SAJCH Vol 11, No 2 (2017) by HMPG

CHILD HEALTH THE SOUTH AFRICAN JOURNAL OF

JUNE 2017

• • • • • •

Volume 11

No. 2

Risk factors for IVH in VLBW infants Endoscopic management of oesophageal strictures Dysphagia in a NICU How well do childcare facilities feed their children? Recovery from severe acute malnutrition A review of neonatal sepsis

CHILD HEALTH THE SOUTH AFRICAN JOURNAL OF

JUNE 2017

Volume 11

No. 2

CONTENTS Editorial

61 Making every baby count: Reflection on the Helping Babies Breathe Program to reduce birth asphyxia in sub-Saharan Africa

E N Odjidja

64 The nursing crisis in paediatrics in South African state hospitals - an unaddressed problem S G Lala, N Lala, Z Dangor

Research

66 Prevalence of and risk factors for cranial ultrasound abnormalities in very-low-birthweight infants at Charlotte Maxeke Johannesburg Academic Hospital

A Ghoor, G Scher, D E Ballot

71 An audit of the management of oesophageal stricture in children in Durban, KwaZuluNatal Province, South Africa

O S Moumin, G P Hadley

75 Risks associated with suspected dysphagia in infants admitted to a neonatal intensive care unit in a South African public hospital

J Schoeman, A Kritzinger

80 Nutritional adequacy of menus offered to children of 2 - 5 years in registered childcare facilities in Inanda, KwaZulu-Natal Province, South Africa

P F Nzama, C E Napier

86 The impact of HIV infection and disease stage on the rate of weight gain and duration of refeeding and treatment in severely malnourished children in rural South African hospitals

M Muzigaba, B Sartorius, T Puoane, B van Wyk, D Sanders

93 Screening for retinitis in children with probable cytomegalovirus infection at Tygerberg Hospital, Cape Town, South Africa

J F Engelbrecht, N Freeman, R M Rautenbach

96 Presentation and pattern of childhood renal diseases in Gusau, Nort-Western Nigeria

B I Garba, A S Muhammad, A B Obasi, A O Adeniji

Review 99

Neonatal sepsis: Highlighting the principles of diagnosis and management

M Coetzee, N T Mbowane, T W de Witt

EDITOR J M Pettifor FOUNDING EDITOR N P Khumalo EDITORIAL BOARD Prof. M Adhikari (University of KwaZuluNatal, Durban) Prof. M Kruger (Stellenbosch University) Prof. H Rode (Red Cross War Memorial Children's Hospital, Cape Town) Prof. L Spitz (Emeritus Nuffield Professor of Paediatric Surgery, London) Prof. A Venter (University of the Free State, Bloemfontein) Dr T Westwood (Red Cross War Memorial Children's Hospital, Cape Town) Prof. D F Wittenberg (University of Pretoria) HEALTH & MEDICAL PUBLISHING GROUP: CEO AND PUBLISHER Hannah Kikaya EXECUTIVE EDITOR Bridget Farham MANAGING EDITORS Naadia van der Bergh Claudia Naidu TECHNICAL EDITORS Naadia van der Bergh Kirsten Morreira PRODUCTION MANAGER Emma Jane Couzens DTP AND DESIGN Travis Arendse Clinton Griffin CHIEF OPERATING OFFICER Diane Smith | Tel. 012 481 2069 Email: dianes@hmpg.co.za ONLINE SUPPORT Gertrude Fani | Tel. 021 532 1281 Email: publishing@hmpg.co.za FINANCE Tshepiso Mokoena HMPG BOARD OF DIRECTORS Prof. M Lukhele (Chair), Dr M R Abbas, Mrs H Kikaya, Dr M Mbokota, Dr G Wolvaardt HEAD OFFICE Block F, Castle Walk Corporate Park, Nossob Street, Erasmuskloof Ext. 3, Pretoria, 0181 EDITORIAL OFFICE Suite 11, Lonsdale Building, Lonsdale Way, Pinelands, 7405 Tel. 021 532 1281 | Cell. 072 635 9825 Email: publishing@hmpg.co.za ISSN 1999-7671

Case report

104 Chediak-Higashi syndrome presenting in the accelerated phase S Palaniyandi, E Sivaprakasam, U Pasupathy, L Ravichandran, A Rajendran, F R Suman, S R Prasad

107

CPD Questions

ublished by the Health and Medical Publishing Group, P Suite 11, Lonsdale Building, Lonsdale Way Pinelands 7405 apers for publication should be addressed to the Editor, P via the website: www.sajch.org.za Tel: 072 635 9825 E-mail: publishing@hmpg.co.za Cover: Thato, Red Cross War Memorial Children's Hospital Primary School

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This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.

EDITORIAL

Making every baby count: Reflection on the Helping Babies Breathe Program to reduce birth asphyxia in sub-Saharan Africa For decades, the world has seen an overwhelming number of neonatal deaths. In 2015 alone, the UN inter-agency estimation group estimated 19.2 deaths per every 1 000 births,[1] the majority of which come from low- and middle-income countries (LMIC) in South East Asia and sub-Saharan Africa.[2] Birth asphyxia, a condition traditionally referred to as the inability of a full-term baby to adequately establish breathing at birth, interrelated with other acute intrapartum events,[3] accounts for 717 000 deaths each year and is the second leading cause of neonatal deaths,[4] of which 85% are experienced in LMIC.[4] The Helping Babies Breathe Program (HBBP) is a global response to asphyxia that was endorsed by the World Health Organization (WHO). It was first introduced by the American Academy of Pediatricians (AAP) in partnership with USAID and Save the Children.[5] After nearly 6 years of implementation, this paper takes a critical look at this programme in sub-Saharan Africa.

Global response to asphyxia through the HBBP

In response to the global increase in neonatal mortality,[6] the WHO and the AAP launched the HBBP in 2010.[5] Key to this intervention was capacity building of skilled birth attendants using simulation-based methods. [5] By the end of 2015, 42 countries in subSaharan Africa had scaled up the HBBP nationally.[2] However, to date, complementary government strategies to support basic newborn care have not been implemented effectively and therefore many targets have not been reached in most African countries.[7] Dickson et al.[7] observed that investments towards establishing robust health information systems to capture the magnitude of birth asphyxia in most African countries had lagged. This undoubtedly has had policy implications as only 47% of African countries had prioritised birth asphyxia in the respective national maternal, neonatal and child health policies.[8]

countries, observed that only 10% of national health programmes adequately incorporated components of Comprehensive Emergency Obstetric and Newborn Care (CEmONC) into routine maternal healthcare. Similarly, a study conducted in Tanzania identified overpopulation of babies in a maternity ward, understaffing, and the absence of essential equipment, as the leading causes of 40 asphyxia-induced deaths.[10] Penwell[11] classified these factors as a violation of fundamental human rights to life. To achieve the golden minute,[1] the AAP recommends that health centres and hospitals have basic resuscitative equipment at every level of care.[5] Sadly, progress in this regard has fallen below expectation in many countries. In Malawi for instance, 6 years after scaling up the HBBP nationally,[12] data from the service provision assessment showed that the basic equipment to support sustainability of the programme was inadequate at almost every level of care (Table 1).[13] Table 1 gives a further insight on the state of affairs. The resounding question that emanates from Table 1 is how can the fight against asphyxia be won when basic equipment such as single suction apparatus is lacking in clinics? How can HBB training make an

Table 1.[14] Availability of basic resuscitation equipment and essential medicine in Malawi Availability, n (%) District and Central Hospitals

Health Centre

Clinic

Availability of IMPAC guidelines

17 (56.7)

182 (43.3)

8 (44.4)

Emergency transport

6 (14.4)

141 (9.8)

10 (20.4)

Suction apparatus (mucus extractor)

18 (60.0)

308 (73.3)

13 (72.2)

Manual vacuum extractor

19 (67.9)

136 (32.4)

4 (22.2)

Vacuum aspirator or D&C kit

14 (58.3)

74 (17.6)

3 (16.7)

Injectable uterotonic (oxytocin)

27 (96.4)

400 (95.2)

17 (94.4)

Injectable antibiotic

23 (82.1)

211 (50.2)

10 (55.6)

Injectable magnesium sulphate

28 (100)

362 (86.2)

5 (27.8)

Injectable diazepam

25 (89.3)

334 (79.5)

11 (61.1)

Skin disinfectant

21 (75.0)

216 (51.40)

9 (50.0)

Intravenous fluids with infusion set

20 (71.4)

281 (66.9)

14 (77.8)

Item

Availability of essential medicines for delivery

Health systems â&#x20AC;&#x201C; can the centre hold with just the HBBP?

One critical factor to improve on is a strengthened healthcare system that delivers safe and quality service intra- and postpartum.[9] Lawn et al.,[8]in a study of 32

indelible impact when a manual vacuum extractor is absent in a health facility? Another crucial area in the fight against asphyxia is an effective referral system that responds to emergencies in a timely fashion.[7] According to Hussein et al.,14] there is a significant negative correlation between effective referral system and neonatal deaths (odds ratio (OR) 0.56; 95% confidence interval (CI) 0.32 - 0.96). Similarly, Pembe et al.[15] posit that implementing an effective referral mechanism has almost twice the potential of reducing risk factors of severe neonatal complications (OR 1.6; 95% CI 0.34 - 7.8). Nevertheless, ineffective referral systems continue to hamper neonatal health especially in rural facilities. For instance, a study in rural facilities found that 62.5% with neonatal deaths were directly associated to late referrals due to transportation bottlenecks.[10] Community surveillance has been identified by Kilonzo et al.[16] as a prime factor necessary for well-coordinated and effective public health planning. Yet, fragmented community surveillance in most African countries has created an overwhelming deficit in planning for overall neonatal and maternal public health.[17] For

IMPAC = integrated management of pregnancy and childbirth; D&C = dilation and curettage

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EDITORIAL instance, a study in Tanzania found that the fragmented nature of documenting neonatal outcomes at birth had resulted in high rates of uncompleted perinatal registers.[10] Integration of MNCH data is the first step towards ensuring a community surveillance strengthening backed with strong data management teams at every level of care. In this instance, Ghana’s approach to community and district surveillance is worth emulating.[18]

Technical challenges of the HBBP – translation into clinical practice and sustainability

Using Kirkpatrick’s model of evaluation, Ersdal et al.[19] found that 39 skilled birth attendants trained in the implementation of the HBBP failed to translate it to clinical practice 7 months after initial training. Surprisingly, the authors further observed that the birth attendants’ ability to conduct face mask ventilation (FMV) in delivery rooms had reduced from 8.4% to 7.5% after their training. Similar to this finding, an evaluation of the HBBP in Malawi found that only 57.1% of healthcare workers could attain the golden minute 1 year after training.[12] High rates of attrition among healthcare workers[12] and inadequate local funding streams[20] have been identified as the prevailing threats to sustaining the HBBP. Until 2015, donors had been the main funders of the HBBP, with >80% of funding for the programme coming from a consortium of private and international donor organisations.[5] Almost 17 years after the Abuja declaration, only Rwanda has committed a minimum 15% of its total budget to healthcare provision.[21] Lessons from other developing countries after the post Global Fund to fight AIDS, Tuberculosis and Malaria funding has taught us the ramifications of having donor-dominated health programmes. Staff attrition continues to threaten the sustainability of the HBBP. In Tanzania, Sepeku and Kohi[10] found that 1 year after implementation of the HBBP, staff turnover had almost doubled. Likewise, in Kenya, a study found that knowledge on asphyxia management in primary healthcare facilities had dissipated, largely due to high attrition rates among healthcare workers.[22]

Conclusion

While a 1-day HBB training programme may result in skills enhancement of birth attendants, its translation into clinical practice is unassured. For this reason, a comprehensive health system-strengthening strategy will be necessary to avoid preventable neonatal deaths. It is worth acknowledging that birth asphyxia is currently the second leading cause of neonatal death, after low birth weight,[4] and now exceeds pneumonia, making it the second leading cause of under-5 mortality as well.[4] This implies that a comprehensive and integrated strategy for asphyxia management along with other perinatal complications will be a giant step towards the achievement of the United Nations’ Sustainable Development Goal number 3 in sub-Saharan Africa. Until sub-Saharan countries strengthen health systems and prioritise perinatal health, the expected progress of reducing under-5 mortality, while increasing life expectancy and the human development index, will remain below target. Governments must fulfil the Abuja declaration and increase health budgetary allocations to 15%, alongside a minimum healthcare spending of 5%. The training of perinatal specialists should be prioritised to improve the conditions of service for birth attendants in remote settings and to remove geophysical barriers to services. Interventions at the household and community levels are crucial in reducing the possible risk factors that could affect the health of babies. For this reason, public healthcare planners should lead national efforts in educating pregnant women, especially those who are least educated. The implementation of community health workers (CHW) will be critical in achieving this objective and it would be worthwhile for other sub-Saharan countries to invest in CHW programmes, such as those in Rwanda and Nigeria.[23] 62

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At the management level, governments should invest in efforts to provide clear-cut policies that allow training institutions to incorporate the HBBP into teaching curricula. Health authorities should prioritise quality improvement and routine in-service training as a complement to the HBBP, and focus on other perinatal capacity building programmes, such as Essential Care for Every Baby (ECEB). It is apparent that the world’s singular targeted response to asphyxia, the HBBP, is inadequate. I therefore join other colleagues to call for global action towards establishing a more integrated, comprehensive, and responsive approach to perinatal health. Emmanuel Nene Odjidja MSc Institute for Global Health and Development, Queen Margaret University, Scotland, UK emmaodjidja@gmail.com S Afr J Child Health 2017;11(2):XX-XX. DOI:10.7196/SAJCH.2017.v11i2.1324

1. You D, Hug L, Ejdemyr S, et al. Global, regional, and national levels and trends in under-5 mortality between 1990 and 2015, with scenario-based projections to 2030: A systematic analysis by the UN Inter-agency Group for Child Mortality Estimation. 2017. https://doi.org/10.1016/S0140-6736(15)00120-8 2. Berkelhamer SK, Kamath-Rayne BD, Niermeyer S. Neonatal resuscitation in low-resource settings. Clinics Perinatol 2016;43(3):573-591. https://doi. org/10.1016/j.clp.2016.04.013 3. Lawn JE, Manandhar A, Haws RA, Darmstadt GL. Reducing one million child deaths from birth asphyxia – a survey of health systems gaps and priorities. Health Res Policy Syst 2007;5(1):4. https://doi.org/10.1186/1478-4505-5-4 4. Liu L, Johnson HL, Cousens S, et al. Global, regional, and national causes of child mortality: An updated systematic analysis for 2010 with time trends since 2000. Lancet 2012;379(9832):2151-2161. https://doi.org/10.1016/s0140-6736(12)60560-1 5. American Academy of Pediatrics (AAP). Helping Babies Survive Washington: AAP, 2010. http://www.helpingbabiesbreathe.org/ (accessed 30 September 2016). 6. Oza S, Lawn JE, Hogan DR, Mathers C, Cousens N. Neonatal cause-of-death estimates for the early and late neonatal periods for 194 countries: 2000 - 2013. Bull World Health Organ 2015,93:19-28. http://dx.doi.org/10.2471/BLT.14.139790 7. Dickson KE, Simen-Kapeu A, Kinney MV, et al. Every newborn: Healthsystems bottlenecks and strategies to accelerate scale-up in countries. Lancet 2014;384(9941):438-454. https://doi.org/10.1016/s0140-6736(14)60582-1 8. Lawn JE, Kinney M, Lee AC, et al. Reducing intrapartum-related deaths and disability: Can the health system deliver? Int J Gynecol Obstet 2009;107:S123-S142. https://doi.org/10.1016/j.ijgo.2009.07.021 9. Spector JM, Daga S. Preventing those so-called stillbirths. Bull World Health Organ 2008;86(4):315-316. https://doi.org/10.2471/BLT.07.049924 10. Sepeku A, Kohi TW. Treatment outcomes of neonatal asphyxia at a national hospital in Dar es Salaam, Tanzania. Afr J Nurs Midwifery 2011;13(2):43-56. 11. Penwell V. A hidden tragedy: Birth as a human rights issue in developing countries. Eugene: Midwifery Today, Inc., 2010. https://www.midwiferytoday. com/articles/hiddentragedy.asp (accessed 30 September 2016). 12. Gupta S, Kazembe A, Mupfudze T, et al. Evaluation of the Helping Babies Breathe (HBB) Initiative Scale-Up in Malawi. Lilongwe: Maternal and Child Survival Program 2014. 13. Ministry of Health (MoH) Malawi, ICF International. Malawi Service Provision Assessment 2013 - 14. Lilongwe, Malawi, and Rockville, Maryland, USA: MoH and ICF International, 2014. 14. Hussein J, Kanguru L, Astin M, Munjanja S. The effectiveness of emergency obstetric referral interventions in developing country settings: A systematic review. PLoS Med 2012;9(7):e1001264. https://doi.org/10.1371/journal. pmed.1001264 15. Pembe AB, Carlstedt A, Urassa DP, Lindmark G, Nyström L, Darj E. Effectiveness of maternal referral system in a rural setting: A case study from Rufiji district, Tanzania. BMC Health Services Res 2010;10(1):326. https://doi. org/10.1186/1472-6963-10-326 16. Kilonzo A, Kouletio M, Whitehead SJ, Curtis KM, McCarthy BJ. Improving surveillance for maternal and perinatal health in 2 districts of rural Tanzania. Am J Pub Health 2001;91(10):1636-1640. https://doi.org/10.2105/ ajph.91.10.1636 17. Calain P. From the field side of the binoculars: A different view on global public health surveillance. Health Policy Plann 2006;22(1):13-20. https://doi. org/10.1093/heapol/czl035

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EDITORIAL 18. Amoakoh-Coleman M, Kayode GA, Brown-Davies C, et al. Completeness and accuracy of data transfer of routine maternal health services data in the greater Accra region. BMC Res Notes 2015;8(1). https://doi.org/10.1186/s13104-015-1058-3 19. Ersdal HL, Vossius C, Bayo E, et al. A one-day ‘Helping Babies Breathe’ course improves simulated performance but not clinical management of neonates. Resuscitation 2013;84(10):1422-1427. https://doi.org/10.1016/j. resuscitation.2013.04.005 20. Vossius C, Lotto E, Lyanga S, et al. Cost-effectiveness of the ‘Helping Babies Breathe’ program in a missionary hospital in rural Tanzania. PLoS ONE 2014;9(7):e102080. https://doi.org/10.1371/journal.pone.0102080

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21. Jowett M, Brunal MP, Flores G, Cylus J. Spending targets for health: No magic number. Health financing working paper No. 1. Geneva: WHO, 2016. http://apps.who.int/iris/bitstream/10665/250048/1/WHO-HIS-HGFHFWorkingPaper-16.1-eng.pdf (accessed 29 September 2016). 22. Bang A, Patel A, Bellad R, et al. Helping Babies Breathe (HBB) training: What happens to knowledge and skills over time? BMC Pregnancy Childbirth 2016;16(1):364. https://doi.org/10.1186/1471-2393-14-116 23. Singh P, Sachs JD. 1 million community health workers in sub-Saharan Africa by 2015. Lancet 2013; 382(9889):363-365. https://doi.org/10.1016/s01406736(12)62002-9

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EDITORIAL

This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.

The nursing crisis in paediatrics in South African state hospitals - an unaddressed problem South African (SA) state hospitals face a myriad of problems, ranging from the deterioration of physical structures to drug shortages, and a lack of human resources. The shortage of trained nurses of all ranks – professional, enrolled and auxiliary – is perhaps the most severe. In paediatrics, nursing is an essential component of care because children require near-constant supervision. In addition to their need for emotional support and comfort, hospitalised children are absolutely dependent on nurses for the monitoring of their general condition and vital signs, administration of medication, delivery and monitoring of intravenous fluids, feeding, bathing, and nappy changes. Nurses also need to cope with enormous administrative and bureaucratic burdens; they act as porters, cooks, and cleaners when called to do so. They are the interface between parents, caregivers, and other health service providers and the burden of their clinical workload is arguably much heavier than that of the rest of the healthcare team. Ironically, nursing staff numbers are dwindling at a time when medical staffing is relatively robust owing to the 2-year internship programme and community service obligations, which have generally bolstered the ranks of junior doctors in the paediatric wards. In the past 2 years (2015 - 2016), our 39-bed ward, which is one of four general paediatric wards at the Chris Hani Baragwanath Academic Hospital, has had a night-time nursing team comprising of four individuals on average: a professional nurse and three enrolled or auxiliary nurses. Staff numbers were marginally better during the day, when we had an average seven-member nursing team of three to four professional nurses, and the remainder comprising of enrolled and/or auxiliary nurses. During this time, we admitted ~2 600 children to our ward. The majority of these patients suffered from lower respiratory tract infections and required supplemental oxygen. Neonates, who generally require more intensive nursing, comprised about 20% of all admissions. Because at any given time there can also be children with medical complexities (e.g. severe neurological impairment) who need intensive and prolonged nursing during a period of prolonged hospitalisation in the ward at any one time, the nursing staff often struggle to provide adequate care to all admitted children. This has consequences: there is an increased risk of nosocomial infections, medication administration errors are likely to occur more frequently, and the supervision and administration of feeding becomes difficult. These adverse events are more likely to affect children with medical complexity, which further increases the duration of their hospitalisation. Furthermore, in medicolegal cases, nurses may be blamed for causing patient harm despite the fact that staff shortages may have indirectly contributed to suboptimal patient management; for example, a nurse may be blamed if a child suffered circulatory, neurological, vascular, or muscular damage after failing to notice and remove a tourniquet timeously post venous cannulation. This creates a vicious cycle where the working conditions in the paediatric wards make it difficult to recruit and retain new nursing staff – this lowers the morale of existing staff and perpetuates the nursing crisis. Notwithstanding the nursing shortage in SA, a great proportion of healthcare delivery, especially in rural and underserved areas, is dependent on nurse-based systems. If we continue to fail to deal with the existing nursing crisis, we risk further collapse of the healthcare system. Nursing has been described as a ‘profession in peril’[1] and the National Department of Health estimated that there was a shortage of ~45 000 professional nurses in the state sector in 2010; that year, only ~3 600 professional nurses registered with 64

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the South African Nursing Council.[1] Rispel and Bruce[1] have identified several critical problem areas that need to be tackled to solve the nursing crisis: (i) nursing education reforms, (ii) the lack of nursing involvement in policy-making, (iii) the use of nursing agencies to provide temporary nursing staff and moonlighting services, and (iv) measures to improve the work experiences of nurses (such as lessening the clinical workload, reducing the risk of physical and psychological harm, and offering professional support and prospects for professional development and job satisfaction). Nonetheless, even if drastic measures are taken to tackle these problems immediately, the nursing shortage is likely to persist for the next decade or so.

In the meantime, what can be done to help nurses?

Firstly, there is an urgent need to define what the minimum nursing paediatric workloads are, and the time and nursing staff numbers (across all categories – professional, enrolled and auxiliary) needed to complete a defined number of paediatric nursing procedures or activities, e.g. the time needed to feed a neonate using a cup and spoon or the time required to accurately draw up and administer an intravenous antibiotic. Although ideal nursing ratios for professional, enrolled, and auxiliary nurses have been proposed for the SA state health system,[2] these norms are unlikely to be reached in the short term. It is critically important that activity-based guidelines be developed urgently, so that task shifting can be planned, with registered nurses supervising enrolled and auxiliary nurses to provide safe and effective paediatric nursing care.[3] Secondly, doctors need to improve on their communication with nursing staff, and include the senior nursing staff in discussions about patient management in the context of the nursing staff numbers. Without endangering patient outcomes and likely improving them, doctors need to evaluate if nursing-intensive procedures and activities are essential – for example, the continued administration of intravenous antibiotics where an oral substitute is suitable. In the context of the nursing crisis, avoiding prolonged hospitalisation should be a medical priority and options to manage stable children as outpatients should be fully explored. Doctors should inform parents, legal guardians, and caregivers about the challenges that nurses face in providing the best care for their children under difficult situations. For children with medical complexity, doctors and the allied medical staff, including dieticians, physiotherapists, speech and occupational therapists, need to discuss their respective management plans with the nursing staff and determine which activities and procedures could be reasonably performed with a certain degree of competence by the nursing staff. In addition, many stable children are often unnecessarily left to wait in wards for procedures, such as specialised radiological investigations, which have no direct bearing on the child’s management. The power dynamics within doctor-nurse relationships will almost certainly require recalibration so that nurses have improved opportunities to suggest, implement, and monitor the effects of innovative methods that have been devised to optimise nursing care, lessen job stress, and minimise bureaucratic tasks. Thirdly, senior competent nurses who have passed retirement age, and who would like to remain in state service, should be kept in fulltime employment with appropriate remuneration. Urgent interventions are required to resolve the nursing crisis in state hospital-based paediatric practice. As paediatricians we need to serve as advocates, not only for the children we treat, but also for the nursing care that children depend on.

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EDITORIAL S G Lala, N Lala, Z Dangor

Department of Paediatrics and Child Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa sanjay.lala@wits.ac.za S Afr J Child Health 2017;11(2):63-64. DOI:10.7196/SAJCH.2017.v11i2.1432

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1. Rispel L, Bruce J. A profession in peril? Revitalising nursing in South Africa. In: Padarath A, King J, English R, eds. South African Health Review 2014/15. Durban: Health Systems Trust; 2015. 2. Uys LR, Klopper HC. What is the ideal ratio of categories of nurses for the South African public health system? S Afr J Sci 2013;109(5/6):a0015. https:// doi.org/10.1590/sajs.2013/a0015. 3. Bateman C. Izindaba: Legislating for nurse/patient ratios ‘clumsy and costly’ – experts. S Afr Med J 2009;99(8):565-568.

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RESEARCH

This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.

Prevalence of and risk factors for cranial ultrasound abnormalities in very-low-birth-weight infants at Charlotte Maxeke Johannesburg Academic Hospital A Ghoor, MB ChB; G Scher, MB BCh, FC Paed (SA), MMed (Paed); D E Ballot, MB BCh, FCPaed (SA), PhD

Department of Paediatrics and Child Health, University of the Witwatersrand and Charlotte Maxeke Johannesburg Academic Hospital, Johannesburg, South Africa Corresponding author: A Ghoor (azra.ghoor@gmail.com)

Background. Periventricular-intraventricular haemorrhage (IVH) and cystic periventricular leukomalacia (cPVL) contribute to neonatal mortality and morbidity. Low birth weight and gestational age are among the risk factors for IVH and cPVL. Objectives. To assess how many very low birth weight (VLBW) infants had cranial ultrasound screening at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) and to determine the prevalence of cranial ultrasound abnormalities. To compare the characteristics and risk factors of those VLBW infants with cranial ultrasound abnormalities to those with normal cranial ultrasound findings. Methods. This was a retrospective case-controlled study of infants <1Â 500 g admitted to CMJAH from 1 January 2013 to 31 December 2015. Cases were identified as infants with IVH or cPVL. Controls were matched 1:2 based on birth weight and gender. Results. Only 55% (856/1 562) of VLBW infants had undergone cranial ultrasound screening. The final sample included 803 VLBW infants. IVH was identified in 26.7% of cases (n=215; 95% confidence interval (CI) 23.8 - 29.9) and 0.9% had cPVL (n=8; 95% CI 0.5 - 1.9). A total of 197 cases were identified and matched with 394 controls. Antenatal care attendance was lower in the cases (71% v. 79%; p=0.039). Sepsis, ventilation, metabolic acidosis and patent ductus arteriosus were all significantly higher in the cases. The use of antenatal steroids was significantly higher in the grades I - II IVH/no-IVH group v. grades III - IV IVH group (44% v. 25%; p=0.017). Conclusion. The prevalence of IVH in our setting was consistent with that of developed countries. Improving antenatal care, infection control, and adequate early resuscitation could decrease the incidence of IVH and cPVL. All VLBW infants should undergo cranial ultrasound screening. S Afr J Child Health 2017;11(2):66-70. DOI:10.7196/SAJCH.2017.v11i2.1167

Periventricular-intraventricular haemorrhage (IVH) and white matter injury (WMI), particularly cystic periventricular leukomalacia (cPVL), are major contributors to mortality and long-term morbidity in preterm infants.[1,2] The immature blood-brain barrier combined with fluctuation in cerebral blood flow, or platelet and coagulation disorders, form the basis for IVH pathogenesis. Risk factors for IVH include low birth weight (LBW), gestational age (GA), prematurity, lack of antenatal steroids, asphyxia, prolonged labour, respiratory distress syndrome, recurrent tracheal suctioning, hypoxia, hypercarbia, acidosis, patent ductus arteriosus (PDA), rapid infusion of sodium bicarbonate and interhospital transfer.[3] Preterm infants with cPVL, without IVH, appear to have a different risk pattern, although the pathogenesis does involve both hypoxic-ischaemic and haemorrhagic processes. It also appears that intrauterine inflammation and cytokine release result in oxidative stress to white matter.[4,5] IVH can be graded according to severity, from grades I to IV, with the most commonly used classification being that of Papile et al.[6] The incidence of IVH in developed countries is about 20 - 25% in very low birth weight (VLBW) infants. More than 50% of those with severe IVH develop intellectual disability or cerebral palsy.[7] Research in southern Africa showed a higher incidence of between 20% and 50% of IVH in VLBW infants, although the prevalence of severe IVH is similar to that of developed countries.[8-10] Most neonatal units have a screening protocol in place to detect IVH and cPVL. The American Academy of Neurology suggests that cranial ultrasound screening should be performed at two time points for all infants with a GA <30 weeks: between weeks 1 and 2 of life, and at 36 - 40 weeks postmenstrual age.[7] More recent studies have shown that magnetic resonance imaging (MRI) performed at the term equivalent age could be helpful in identifying white matter abnormalities that could cause neurocognitive delay as a long-term outcome.[11] However,

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cranial ultrasound is still the first tool for assessing neurological injury in preterm infants, as it allows for bedside investigation and sequential evaluation of evolving lesions. As neonatal and obstetric care improves, there is an increase in the survival rate of preterm infants, and an associated newer burden of disease in the form of neurodevelopmental impairment.[2,12] In order to improve the screening and management of IVH at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH), we needed to investigate the prevalence of IVH and cPVL, and identify the specific risk factors important in our population. LBW and GA are risk factors for IVH, therefore we chose to conduct a study that controlled for these possible confounders.[13] Our aim was to assess how many VLBW infants had cranial ultrasound screening and to determine the prevalence of cranial ultrasound abnormalities in our VLBW population. We also wanted to compare the characteristics, risk factors, and short-term outcomes of VLBW infants with cranial ultrasound abnormalities with those of VLBW infants, with normal cranial ultrasound results.

Methods

Data from the CMJAH neonatal database were used in this retrospective, case-controlled study. The study population included all VLBW infants admitted to the neonatal unit, including the intensive care unit, from 1 January 2013 to 31 December 2015. CMJAH is a tertiary hospital located in Johannesburg, South Africa (SA). It acts as a referral centre for surrounding clinics and district hospitals. The study population included both inborn and outborn infants. Infants born with a birth weight â&#x2030;¤1 500 g qualified as VLBW. All VLBW infants who had the following ultrasound abnormalities were identified as cases: IVH, post-haemorrhagic hydrocephalus, or cPVL. Cases were matched with control infants based on birth weight category and gender on a 1:2 basis.

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RESEARCH The two most suitable controls born closest to the study patient were selected. Grading of IVH was based on the classification described by Papile et al:[6] grade I included bleeds restricted to the germinal matrix; grade II bleeds were those extending into the ventricles and filling ~50% of the ventricle; grade III bleeds caused ventricular dilatation; and grade IV included parenchymal haemorrhage. Grade III and IV bleeds constitute severe IVH. There were four birth weight categories: ≤750 g; 751 - 1 000 g; 1 001 - 1 250 g; and 1 251 - 1 500 g. Infants with major congenital abnormalities of any organ system were excluded. Infants with cranial ultrasound revealing abnormalities such as absent corpus callosum, schizencephaly or findings with questionable significance, such as periventricular echodensities, were also excluded.

Data collection

Data were collected from the neonatal database at CMJAH, which is stored using REDCap (Research Electronic Data Capture).[14] It is a secure web-based application that is linked to the Vermont Oxford Network (VON).[15] The VON includes ~1 000 centres around the world that submit data about high-risk newborn infants. It is a nonprofit voluntary collaboration of health professionals aiming to improve neonatal care. Its members include both public and private units from North America, South America, Europe, the Middle East, Asia and southern Africa, to name a few. Sixty-four units in SA are members of the VON. The following maternal variables were extracted from the database for each infant: antenatal care attendance, antenatal steroids, magnesium sulphate administration, chorioamnionitis, HIV, attempted termination of pregnancy, hypertension, diabetes, and mode of delivery. Newborn variables included the place of birth (inborn, midwife obstetric unit (MOU), another hospital, or home), GA, birth weight, head circumference, gender, multiple gestation, Apgar at 5 min, birth resuscitation, temperature on admission, and metabolic acidosis. Birth resuscitation included oxygen, bag mask ventilation, intubation, cardiopulmonary resuscitation and/or intravenous adrenaline. Ultrasound findings were also recorded, particularly grade of IVH and presence of cPVL. The neonatal course was documented and included respiratory diagnosis, respiratory support, days on continuous positive airway pressure (CPAP), days mechanically ventilated, surfactant therapy, supplementary oxygen on day 28, indomethacin or ibuprofen exposure, and bacterial sepsis (early or late). Early sepsis constituted a positive blood culture within 72 hours of birth and late sepsis was a positive blood culture >72 hours after birth. Other neonatal diagnoses noted were pneumothorax, PDA, necrotising enterocolitis, neonatal jaundice, blood transfusion, HIV testing and major birth defects. Short-term outcome, namely survival to discharge, was also recorded. Infants who were well enough to be transferred to other hospitals were considered survivors.

Statistical methods

Statistical analysis was performed using SPSS Statistics version 23 (IBM Corp., USA). Data were described using standard statistical methods. Continuous data with a normal distribution were described using means and standard deviations (SDs), while skewed data were described using median and range values. Categorical variables were described using frequencies and percentages. Univariate analysis was performed to describe differences between the case and control groups using the Pearson χ2 or Fisher’s exact test for categorical variables. Continuous variables were compared using independent t-tests or non-parametric tests (Mann-Whitney) as appropriate, depending on data distribution. Basic demographic data of the group who had not undergone cranial ultrasound were compared with the final study sample that had undergone ultrasound to establish if the selected sample was random. Sub-analysis also included comparison between those with mild/no IVH with those with severe IVH and cPVL, respectively. A p-value ≤ 0.05 was considered significant. The variables on univariate analysis with p<0.1 were analysed further in a stepwise logistic regression

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model to determine risk factors for IVH and cPVL. Only valid cases were reported for all variables in the analysis, i.e. missing data were excluded.

Ethics

The Human Research Ethics Committee at the University of the Witwatersrand, Johannesburg, approved the study (ref. no. M151195).

Results

There were 1 562 VLBW infants born between 1 January 2013 and 31 December 2015 at CMJAH. Cranial ultrasounds were performed on 856 (55%) infants. Table 1 shows the prevalence of cranial ultrasound abnormalities at CMJAH. Of the 856 patients with cranial ultrasounds, 13 were excluded from the study due to major birth defects. The remaining infants (N=843) who underwent cranial ultrasound were then divided into normal (N=580) and abnormal (N=263) cranial ultrasound groups. Forty infants in the abnormal group (15%) were excluded due to sonar findings that did not meet inclusion criteria. A further 26 infants with abnormal cranial ultrasounds had no matching controls with the correct weight category or gender and were excluded. There were 186/580 (32%) in the normal group who could not be matched with an ‘abnormal’ infant. There were therefore 197 cases and 394 controls selected from the infants who had undergone cranial ultrasound (Fig. 1). Basic demographic data showed that 47% (729/1 562) of infants admitted were males, median birth weight was 1 150 g and mean gestational age was 29 weeks. The mortality of the overall group was 27% (415/1 562). There were fewer males in the group who had not undergone ultrasound (417/702; 45%) compared with the case/control group (303/591, 51%; p=0.029). The median weight was higher in the group with no ultrasound (1 180 g v. 1 090 g in the case/control group; p=0.05). The mean GA of 29 weeks was the same for both groups. Mortality in the group who had not undergone ultrasound was higher (39% v. 17%). This result had a significant p-value of 0.026. The higher mortality in this group could be accounted for by the large number of infants who were ≤750 g and who had not undergone ultrasound (13% v. 3%). When comparing cases and controls, we found that the gender distribution was the same, with males constituting 49% in both groups. The mean birth weight was 1 097 g for cases and 1 065 g for controls. The mean gestational age was 29 weeks for both groups. The above parameters had no statistical significance, which confirmed that cases and controls were matched. The data in Table 1 include all those VLBW infants who had a cranial ultrasound and were included in the study (N=803) to calculate the prevalence over the specified time period. The data in Tables 2 - 5 include only those VLBW infants selected as cases (n=197) or controls (n=384). The univariate comparison between case and control groups is shown in Table 2. A higher proportion of cases were outborn. Sepsis, metabolic acidosis, ventilation and PDA were all significantly higher in the cases, and antenatal care and Apgar at 5 minutes were lower. However, there was no significant difference between the two groups in the use of antenatal steroids. The logistic regression analysis included location of birth, antenatal care, maternal hypertension, maternal HIV, mode of delivery, Apgar at 5 minutes, initial resuscitation with oxygen, early and late bacterial sepsis, PDA and ventilation (Table 3). The analysis showed that antenatal care attendance (odds ratio (OR) 0.59; 95% CI 0.37 - 0.95) and Apgar >7 at 5 minutes (OR 0.53; 95% CI 0.34 - 0.84) were associated with a lower risk of abnormal cranial ultrasound. Ventilation carried a higher risk of cranial ultrasound abnormality (OR 2.44; 95% CI 1.62 - 3.69), and early bacterial sepsis followed this trend (OR 3.32; 95% CI 1.3 - 8.34). The rest of the variables were not significantly different between the groups.

Sub-analyses

Severe IVH within the selected cases was compared with mild/no IVH within the case and control groups. Significant results are shown in Table 4. The use of antenatal steroids was higher in the mild/no IVH group (44%) compared with the severe IVH cases (25%; p=0.017).

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RESEARCH Table 1. Prevalence of ultrasound abnormalities in VLBW infants at CMJAH (N=803) Classification CMJAH, n(%) 95% CI Normal cranial ultrasound Grade I Grade II Grade III Grade IV cPVL

580 (72.2)

(69.0 - 75.2)

63 (7.8) 91 (11.3) 34 (4.2) 27 (3.3) 8 (0.9)

(6.2 - 9.9) (9.3 - 13.7) (3.0 - 5.8) (2.3 - 4.8) (0.5 - 1.9)

VLBW = very low birth weight infants; CMJAH = Charlotte Maxeke Johannesburg Academic Hospital; CI = confidence interval.

VLBW infants in database (N=1 562) No cranial ultrasound (N=706) Infants who had cranial ultrasound (N=856) Birth defects (N=13) No major birth defects (N=843)

Normal cranial ultrasound (N=580)

Controls without suitable cases (N=186)

Matched controls (N=394)

Abnormal cranial ultrasound (N=263)

Inclusion criteria not met (N=40)

Cases matched (N=197) Cases final sample (N=197)

Controls final sample (N=394)

Fig. 1. Flow diagram showing the sample selection process.

Logistic regression analysis revealed that both outborn and ventilated VLBW infants had a higher risk of severe IVH. An Apgar score of ≥7 had indicated a lower risk of severe IVH (Table 3). The sample of infants with cPVL was compared with those with mild/no IVH (Table 5). The significant factors associated with cPVL on univariate analysis were sex (female), chorioamnionitis, blood transfusion, late bacterial sepsis, as well as ventilation. Logistic regression analysis (Table 3) revealed that chorioamnionitis (OR 45.73; 95% CI 6.27 - 333.68) and ventilation (OR 15.92; 95% CI 1.54 - 164.36) hold high risks of cPVL.

Discussion

The main objectives of this study were to analyse the prevalence of cranial ultrasound abnormalities and associated risk factors. According to the screening protocol at CMJAH, every VLBW should have an ultrasound within the first 7 days of life, at 10 - 14 days of life, and before discharge.[16] Only 55% of VLBW infants admitted during the study period had a cranial ultrasound, much lower than the prevalence in the VON database, where 90% of VLBW infants had cranial sonars.[15] Reasons for the low coverage rate in our unit included staff shortages

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Characteristic Outborn Mortality Maternal factors Antenatal care Antenatal steroids Maternal HIV Hypertension Mode of delivery Vaginal Caesarean Neonatal factors Apgar at 5 min <7 ≥7 Resuscitation at birth with oxygen Early bacterial sepsis Late bacterial sepsis Metabolic acidosis Mechanical ventilation PDA Maximum bilirubin level, mean (SD)

Controls n/N (%)* 60/392 (15) 53/393 (14)

Cases n/N (%)* 45/196 (23) 46/197 (23)

307/390 (79) 174/386 (45) 111/392 (28) 105/386 (27)

137/194 (71) 73/191 (38) 72/197 (37) 37/197 (19)

139/385 (36) 246/385 (64)

83/185 (45) 102/185 (55)

p-value 0.03 0.004 0.039 0.14 0.059 0.041 0.054

65/360 (18) 295/360 (82)

52/173 (30) 121/173 (70)

0.002

324/394 (82)

148/197 (75)

0.037

10/392 (3)

13/197 (7)

0.023

156/394 (40) 18/394 (5)

99/197 (50) 22/197 (11)

0.02 0.005

102/380 (27)

95/197 (48)

<0.001

57/393 (15)

45/192 (23)

0.015

167 (44)

179 (55)

0.036

*Unless otherwise specified.

Inclusion criteria met (N=223)

Cases not matched (N=26)

Table 2. Overall characteristics of cases and controls

at times, but more importantly, the lack of appropriate equipment to perform ultrasound. The unit only has one sonar machine that is often not functional. The patients who did not undergo cranial ultrasound had a higher mortality rate than those who had undergone an ultrasound. This is partly explained by the fact that 13% (n=92) of infants in that group were ≤750 g. These infants make up a high-risk group related to their extreme prematurity and are likely to have demised before an ultrasound could be performed. VLBW infants who were admitted with higher birth weights were often well enough to be transferred to the kangaroo mother care ward and were discharged quickly, without undergoing cranial ultrasound screening. The prevalence of IVH (26%) appears to be consistent with that of studies conducted in developed countries and was similar to that reported in the VON over the same time period.[7] With improvement in perinatal care, the prevalence appears to have decreased when compared with a study done at our sister unit at Chris Hani Baragwanath Hospital in Soweto 20 years ago, which showed a prevalence of 52% in VLBW infants.[8] The prevalence of severe IVH in the present study (7%) is less than that reported in the VON, and studies from both developed and developing countries.[7-9] This study confirms what is already known: infants with IVH have higher mortality, and lack of antenatal care, birth asphyxia, and sepsis appear to be associated with the development of IVH. Mechanical ventilation and PDA also had an increased association with IVH and this can be explained by fluctuations in cerebral blood flow.[3] The prevalence of IVH in inborn patients was less compared with those who were outborn, and there are many factors that could explain the higher risk, including delay in transfer, inadequate monitoring, and lack of appropriate management at referring centres. Contrary to other

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RESEARCH Table 3. Parameters influencing the development of IVH, severe IVH and cPVL, identified by logistic regression analysis Parameter All cases Antenatal care Apgar ≥7 at 5 min Early bacterial sepsis Mechanical ventilation Severe IVH Outborn Apgar ≥ at 5 minutes Mechanical ventilation cPVL Sex (male) Chorioamnionitis Mechanical ventilation

95% CI

p-value

0.59 0.53 3.32 2.44

0.37 - 0.95 0.34 - 0.84 1.32 - 8.34 1.62 - 3.69

0.03 0.006 0.011 <0.001

3.0 0.21 3.64

1.22 - 7.41 0.10 - 0.43 1.73 - 7.62

0.017 <0.001 0.001

0.11 45.73 15.92

0.01 - 1.22 6.27 - 333.68 1.54 - 164.36

0.072 <0.001 0.02

OR = odds ratio.

Table 4. Severe IVH compared with mild IVH/no IVH Characteristic Outborn Mortality Maternal factors Antenatal care Antenatal steroids Neonatal factors Apgar at 5 min <7 ≥7 Early bacterial sepsis Oxygen on day 28 Metabolic acidosis Mechanical ventilation

Mild IVH/No abnormality n/N (%) 81/534 (15) 78/535 (15)

Severe IVH n/N (%) 17/47 (36) 17/47 (36)

410/531 (77) 232/527 (44)

28/46 (61) 11/44 (25)

91/485 (19) 394/485 (81) 18/535 (3) 205/517 (40) 31/536 (6) 161/519 (31)

24/41 (59) 17/41 (41) 5/47 (11) 23/41 (56) 7/47 (15) 29/46 (63)

p-value 0.001 <0.001 0.019 0.017 <0.001 0.031 0.047 0.026 <0.001

studies, which showed a decrease in IVH with antenatal steroids, our study did not show a significant difference between the use of antenatal steroids in the case and control groups.[3] This may be due to the fact that the administration of antenatal steroids in our setting was lower than in other settings. Only 43% of mothers of VLBW infants had received steroids compared with 83.5% of those in the VON during the same period, which may have been due to late presentation of unbooked mothers.[17] However, the sub-analysis showed that those with severe IVH had less exposure to antenatal steroids than the mild/ no IVH group. Maternal hypertension was also associated with a lower incidence of overall IVH and this was consistent with other studies.[13] In terms of the logistic regression analysis for all IVH cases, the major protective factors were antenatal care and Apgar ≥7 at 5 minutes. Sepsis and mechanical ventilation showed a ~3-fold increase in IVH and both of those factors can be modified by preventive measures. Severe IVH had similar association on logistic regression analysis to overall IVH, but infants that were outborn were shown to have a 3-fold higher risk of severe IVH, which could be prevented by transport of mothers in premature labour to centres with appropriate neonatal services, before delivery.

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In this study, the prevalence of cPVL was only 1%, although mortality was highest in this group, which was consistent with previous studies.[2] As explained previously, MRI is a better tool to assess WMI, but in our setting this was not feasible owing to a lack of adequate MRI facilities to service the neonatal unit. Studies seeking to describe a difference between cPVL and IVH have shown that the two are not mutually exclusive and that there is a possible causal relationship between the two, although cPVL can be seen as a single pathology in some cases.[4,5] Our sub-analysis showed that the female gender, chorioamnionitis, and blood transfusion had significant associations with cPVL, as well as sepsis and mechanical ventilation, which were both additional risk factors for IVH. However, on multivariate logistic regression analysis, the gender association was shown to have an insignificant 95% CI and only chorioamnionitis and mechanical ventilation appeared significant, although CIs were wide owing to the small sample size.

Study limitations

The retrospective study design was a limitation. The disadvantages included information bias and difficulty in establishing the temporal relationship between certain variables. Incomplete and/or missing records affected the dataset. Another limitation was the lack of resources, including both staff and equipment, which resulted in deviations from the ultrasound screening protocol and 45% of VLBW infants not being screened. WMI may be largely underestimated by cranial ultrasound alone. In our setting, the access to MRI was inadequate.

Conclusion

This retrospective, matched case-control study showed that the prevalence of IVH was consistent with that of developed countries and it was encouraging to note that severe IVH was lower in our unit. It confirmed that the risk factors for IVH and cPVL at CMJAH are in keeping with those found globally. The increased mortality and morbidity in infants with IVH would suggest that we should modify the risk factors found to be significant in our population. Access and awareness of early antenatal care is an important factor in preventing poor perinatal outcome. Neonatal resuscitation training in clinics and hospitals should be given priority, as well as correct protocols for transfer of infants, and possible early transfer of mothers in preterm labour to appropriate centres. Infection control and methods to decrease the need for mechanical ventilation are important interventions that could decrease the incidence of IVH. In terms of ultrasound screening, early detection of lesions gives infants a chance to receive early intervention services. Therefore, efforts should be made to ensure that all VLBW infants undergo ultrasound screening. Furthermore, early identification of patients with poor prognostic factors could assist with decisionmaking regarding the maximum level of care offered and the equitable allocation of resources. Acknowledgements. The authors thank all the staff involved in data collection in the neonatal unit at CMJAH. Author contributions. AG, GS and DEB designed the study and developed the methodology. AG collected the data, performed the analyses and prepared the manuscript. The process was supervised by DEB and GS. The final manuscript was reviewed and edited by DEB and GS. Funding. This study was funded by the authors. Conflicts of interest. None. 1. Brouwer AJ, Groenendaal F, Benders MJNL, de Vries LS. Early and late complications of germinal matrix-intraventricular haemorrhage in the preterm infant: what is new? Neonatology 2014;106(4):296-303. http://dx.doi. org/10.1159/000365127 2. Whyte HE, Blaser S. Limitations of routine neuroimaging in predicting outcomes of preterm infants. Neuroradiology 2013;55(Suppl 2):3-11. http:// dx.doi.org/10.1007/s00234-013-1238-6

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RESEARCH 3. Ballabh P. Pathogenesis and prevention of intraventricular hemorrhage. Clin Perinatol 2014;41(1):47-67. http://dx.doi.org/10.1016/j.clp.2013.09.007 4. Larroque B, Marret S, Ancel PY, et al. White matter damage and intraventricular hemorrhage in very preterm infants: The EPIPAGE study. J Pediatr 2003;143(4):477-483. http://dx.doi.org/10.1067/S0022-3476(03)00417-7 5. Kusters CDJ, Chen ML, Follett PL, Dammann O. ‘Intraventricular’ hemorrhage and cystic periventricular leukomalacia in preterm infants: How are they related? J Child Neurol 2009;24(9):1158-1170. http://dx.doi. org/10.1177/0883073809338064 6. Papile LA, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: A study of infants with birth weights less than 1 500 g. J Pediatr 1978;92(4):529-534. 7. McCrea HJ, Ment LR. The diagnosis, management, and postnatal prevention of intraventricular hemorrhage in the preterm neonate. Clin Perinatol 2008;35(4):777-792. http://dx.doi.org/10.1016/j.clp.2008.07.014 8. Sandler DL, Cooper PA, Bolton KD, Bental RY, Simchowitz ID. Periventricularintraventricular haemorrhage in low-birth-weight infants at Baragwanath Hospital. S Afr Med J 1994;84(1):26-29. 9. Mulindwa MJ, Sinyangwe S, Chomba E. The prevalence of intraventricular haemorrhage and associated risk factors in preterm neonates in the neonatal intensive care unit at the University Teaching Hospital, Lusaka, Zambia. Med J Zambia 2012;39(1):1-6. 10. Adhikhari M. Cranial imaging in very low birth weight babies: A review. Obstet Gynaecol Forum 2008;18(3):87-90.

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11. Benders MJ, Kersbergen KJ, de Vries LS. Neuroimaging of white matter injury, intraventricular and cerebellar hemorrhage. Clin Perinatol 2014;41(1):69-82. http://dx.doi.org/10.1016/j.clp.2013.09.005 12. Bolisetty S, Dhawan A, Abdel-Latif M, Bajuk B, Stack J, Lui K. Intraventricular hemorrhage and neurodevelopmental outcomes in extreme preterm infants. Pediatrics 2014;133(1):55-62. http://dx.doi.org/10.1542/peds.2013-0372 13. Linder N, Haskin O, Levit O, et al. Risk factors for intraventricular hemorrhage in very low birth weight premature infants : A retrospective casecontrol study. Pediatrics 2003;111(5):e590-e595. https://doi.org/10.1542/ peds.111.5.e590 14. Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde GJ. Research electronic data capture (REDCap) - A metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 2009;42(2):377-381. http://dx.doi.org/10.1016/j. jbi.2008.08.010 15. Vermont Oxford Network. Report of very low birth weight infants born in 2015. Burlington: VON, 2016. 16. Cooper PA, Ballot DE, Chirwa P, Ramdin T. Neonatal Protocols. Johannesburg: Charlotte Maxeke Johannesburg Academic Hospital, Neonatal Unit, 2014:27. 17. Sarkar S, Bhagat I, Dechert R, Schumacher RE, Donn SM. Severe intraventricular hemorrhage in preterm infants: Comparison of risk factors and short-term neonatal morbidities between grade 3 and grade 4 intraventricular hemorrhage. Am J Perinatol 2009;26(6):419-424. http:// dx.doi.org/10.1055/s-0029-1214237

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RESEARCH

This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.

An audit of the management of oesophageal stricture in children in Durban, KwaZulu-Natal Province, South Africa O S Moumin,1 MB ChB, High Dip Surgery (SA), FCS (SA); G P Hadley,2 MB ChB FRCS (Edin.), FCS (SA) Department of Surgery, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa Professor Emeritus, Department of Paediatric Surgery, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa 1 2

Corresponding author: O S Moumin (omarmoumin@gmail.com) Objective. To determine the outcome of the endoscopic management of oesophageal strictures (OSs) of varying aetiology in children in a tertiary centre. Methods. A retrospective chart review was conducted of all children aged <14 years at department of paediatric surgery who underwent endoscopic dilatation of OSs at Inkosi Albert Luthuli Central Hospital in Durban, KwaZulu-Natal Province, South Africa, between July 2002 to December 2010. Management status at 3 years after presentation was used to define outcome. Results. A total of 39 patients aged between 1 month and 13 years were reviewed, and 18 (46%) were males. Thirty-six (92.3%) were black South Africans, and 11 (28%) were HIV-infected. Among the types of strictures, postoperative (35%) and corrosive (30.8%) OSs were more prevalent than HIV-related (20.5%) OSs. The mean number of dilatations needed per patient was 7.3, and those patients with corrosive OSs needed more dilatation sessions (median (interquartile range)) than others (10 (5 - 14) v. 6.5 (5 - 10)). Out of 287 attempted dilatations, oesophageal perforations occurred in 8 (2.8%) cases. Mitomycin C was applied topically in 4 (10.3%) patients, with excellent results. A good response to endoscopic treatment was seen in 27 (69%) cases. The worst outcome was noted in HIV-infected patients. Conclusion. Endoscopic treatment of OSs in children yields good results and has a low rate of treatable complications. Patients should be treated on an individual basis, even if they have strictures of the same aetiology. S Afr J Child Health 2017;11(2):71-74. DOI:10.7196/SAJCH.2017.v11i2.1179

Oesophageal strictures (OSs) are common in resource-poor countries. In children, OSs may result from surgery to the oesophagus, such as repair of oesophageal atresia, or following repeated sclerotherapy for oesophageal varices; however, OSs are most commonly caused by chemical injuries.[1] OSs are occasionally seen in children with untreated gastro-oesophageal reflux, most notably in those with neurological impairment, and also after oesophageal infections, especially in HIV-positive children.[1-3] The goals of management are to relieve dysphagia, ensure adequate nutrition for growth and development, and to prevent aspiration pneumonia and recurrence of the stricture by oesophageal dilatation, stenting, or replacement surgery.[4,5] There are several parameters that have been used to define the outcome of patients suffering from OSs, of which the clinical resolution of dysphagia is considered the most relevant. Many patients report significantly improved symptoms shortly after dilatation, but these gradually worsen over time.[1,4,6] The aim of this study was to describe the aetiology and outcomes of the management of OSs in children in Durban, KwaZulu-Natal Province (KZN), South Africa (SA).

Methods

The study design was approved by the Biomedical Research Ethics Committee of the University of KwaZulu-Natal (ref. no. BE044/14), the Department of Health and the management of Inkosi Albert Luthuli Central Hospital. A retrospective chart review was conducted of all paediatric patients aged <14 years, who had been admitted for management of OSs at Inkosi Albert Luthuli Central Hospital in Durban, KZN, SA from July 2002 to December 2010. Management status at 3 years after presentation was used to define outcome. Data collected from the patientsâ&#x20AC;&#x2122; files were manually entered into a Microsoft 71

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Excel spreadsheet. Patient demographics included age, gender, race, comorbidities, aetiological factors, diagnostic investigations, type of endoscope used, location and number of strictures, duration of treatment, complications, recurrence, adjuvant therapy, and patient outcomes. Diagnosis of OS was made endoscopically and radiologically. Operative procedures were performed under general anaesthesia by different paediatric surgeons and trainees.

Results

Thirty-nine patients were identified and included in our review. Their ages ranged from 1 month to 13 years, and there were 18 (46%) males and 21 (54%) females. Most participants were black South Africans (36 (92%)), in keeping with the demographics of the population served. Eleven children (28%) were HIV-infected, (5%) were HIVexposed, and 23 (59%) children had not been tested for HIV. Strictures secondary to surgical correction of oesophageal atresia (14 (35.9%)) were the most common, followed by OSs due to corrosive injury (12 (30.8%)). HIV-related strictures were seen in 8 (21%) children, while gastro-oesophageal reflux (2 (5%)), and foreign body (FB) ingestion (3 (7.6%)) were less common. The most common stricture site was the middle-third of the oesophagus (51%), with 33.3% in the upper-third, and 16% in the lower-third. Most of the patients had a single stricture (36 (92%)). OSs secondary to acid ingestion were in the upper- and middle-thirds of the oesophagus, and those following alkali ingestion were in the lower-third of the oesophagus. There was no statistical relationship between the cause of the OS and the site thereof (Table 1). Dysphagia was reported by 32 patients (82%) on presentation. Seven (18%) patients reported no dysphagia, of whom five were treated for oesophageal atresia and were still breastfeeding. Dysphagia was most frequent in patients with alkali- and HIV-

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RESEARCH Table 1. Relation between the causes and sites of oesophageal strictures Cause of stricture

Upper-third, n (%)

Middle-third, Lower-third, n (%) n (%)

Total, N p-value

Acid

3 (50)

0 (0)

Alkali

2 (33)

1 (17)

3 (50)

Post-surgery

4 (29)

10 (71)

0 (0)

GORD

0 (0)

1 (50)

HIV Complications

3 (38)

4 (50)

1Â (13)

1 (33)

Total

13 (34)

20 (51)

6 (15)

0.08

GORD = gastro-oesophageal reflux disease; FB = foreign body.

related strictures although this observation was not statistically significant (Table 2). Contrast oesophagograms were used in the diagnosis and in the follow-up of most patients (32 (82%)). The mean duration of treatment per patient was 29.5 months. Overall, 287 dilatations were performed in 39 patients using either Savary-Gilliard or balloon dilators. The median (interquartile range (IQR)) number of dilatations per patient was highest for those with acid- and alkali-related injuries (10 (5 - 14) and 6.5 (5 - 10), respectively), and lowest for those related to FB ingestion (2.5 (2 - 3)) (Table 3). Perforation occurred in 8 (3.1%) cases, out of 287 attempted dilatations. Over a 3-year follow-up period, recurrence of the OS was observed in 12 (32.4%) patients and was most frequent following alkali ingestion (50%). Mitomycin C was applied locally in 4 (10.3%) patients with a mean (standard deviation (SD)) of 8.7 (2.8) applications per patient. Mitomycin C application was associated with stricture resolution in all patients. Stenting was performed in 2 (5.1%) patients: one following acid ingestion with failure to maintain a lumen by dilatation, and the other in an HIV-infected child with a presumed vasculopathy following perforation during dilatation. Oesophageal replacement was performed for 3 (7.6%) patients following caustic injury. Five (13%) patients died: two following perforations,

including the HIV-infected patient who underwent oesophageal stenting; one following surgical replacement of the oesophagus; and two from unrelated sepsis. Seven (18%) patients were lost to followup, and three (8%) were referred to general surgeons for follow-up (Table 4).

Discussion

The causes and prevalence of OSs in the paediatric population varies with the geographical region, and management should be tailored to the available resources and the prevalent socio-educational environment. Well-trained medical and nursing teams, with properly equipped neonatal intensive care units, have resulted in improved survival of neonates with congenital malformations, including oesophageal atresia. Postoperative morbidity now accounts for a significant proportion of the burden of the disease, and despite the recent refinements of operative techniques and improvements in perioperative management, anastomotic stricture after repair of oesophageal atresia remains frequent and develops in nearly 40% of operated patients.[7-10] Improved survival has increased the number of children with oesophageal anastomotic strictures referred for treatment, and they now account for 35.9% of patients with OSs in our unit. Strictures secondary to the surgical correction of oesophageal atresia often show

a good response to endoscopic treatment augmented by an anti-reflux procedure. In developing countries, caustic ingestion is still frequent among children, and causes OSs due to the circumferential injury extending into the muscularis propria, followed by subsequent fibrosis.[5,11,12] Such strictures are often complex, multisegmented, rigid, tortuous, and extensive. Owing to their refractory nature, they tend to be difficult to dilate.[4] In our cohort, we noted that the median number of dilatations was the highest for the caustic injury group. HIV and its complications have become a massive clinical burden in developing countries. Candidiasis is the most common cause of oesophageal symptoms in HIVinfected patients and repeated episodes progressively damage the oesophageal mucosa, resulting in scarring, fibrosis, and stricture formation.[13,15] Viral oesophagitis, especially due to cytomegalovirus (CMV) infection, and idiopathic oesophageal ulcers are also important causes of oesophageal strictures in HIV-infected children.[16] In many HIV-infected patients no specific secondary pathology can be identified and HIV-related vasculitis has been suggested as the underlying cause of OS formation. In adults, gastro-oesophageal reflux increases in patients on HAART and this may further contribute to idiopathic oesophageal strictures in the lower third of oesophagus in HIV patients.[14,17,18] Treatment of OSs caused by the complications of HIV, infection has been infrequently reported. Eight of our patients (20.5%) presented with OSs related to HIV. The strictures were mainly in the proximal- and middle-thirds of the oesophagus and we noted that the prognosis of these patients was affected negatively and management became more difficult for these patients if they have low CD4 counts. OSs related to gastro-oesophageal reflux are the consequence of repeated insults of the oesophageal mucosa with gastric acids, which are normally limited by a competent lower oesophageal sphincter and rapidly cleared by normal oesophageal peristalsis.

Table 2. The relation between the degree of dysphagia and the cause of stricture

Acids

Without Dysphagia to dysphagia, n (%) solids, n (%)

Dysphagia to Dysphagia to semisolids, n (%) liquids, n (%)

Dysphagia to saliva, n (%)

Not assessed for dysphagia, n (%) Total, N

1 (17)

0 (0)

2 (33)

1 (17)

Alkali

0 (0)

2 (33)

1 (17)

0 (0)

Post-surgery

0 (0)

2 (14)

3 (21)

4 (29)

0 (0)

5 (35)

GORD

0 (0)

2 (100)

0 (0)

HIV complications

0 (0)

3 (38)

1 (13)

3 (38)

0 (0)

1 (13)

0 (0)

3Â (100)

0 (0)

Total

1 (3)

14 (36)

7 (18)

9 (23)

2 (5)

6 (15)

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RESEARCH Table 3. The relation between the cause of OSs, and the need for endoscopies and the number of dilatations Cause of stricture

n (%)

Number of endoscopies

Number of dilatations

Median

IQR

Acid

10.5

5 - 16

5 - 14

Alkali

7 - 12

6.5

5 - 10

Postoperative

5.5

2-8

4.5

2-7

GORD

3-3

2.5

2-3

HIV-related

6.5

2.5 - 18

3 - 16.5

3.5

3-4

2.5

2-3

FB battery

2-2

1-1

Total

3 - 12

3 - 10

OS = oesophageal stricture; IQR = interquartile range; GORD = gastro-oesophageal reflux disease; FB = foreign body.

Table 4. Management outcomes at 3 years following presentation (N=39) Outcome, n (%) HIV status

Discharged

Died

Defaulted

Referred

Total

Negative

19 (68)

2 (7)

6 (21)

1 (4)

Positive

5 (45)

3 (27)

1 (9)

2 (18)

Total

24 (62)

5 (13)

7 (18)

3 (8)

Most of these strictures are found in the distal-third of the oesophagus.[19] In this study, 5% of OSs were secondary to gastrooesophageal reflux disease. Generally, this type of OS responds well to dilatation, and complete resolution occurs in 70 - 90% of cases when dilation is combined with treatment with proton pump inhibitors.[19,20] Children account for about 80% of cases of FB ingestion. The most frequently ingested FBs are coins, bones, and button batteries, which can damage the oesophagus and lead to strictures. Button batteries are easily swallowed by children and may cause severe injuries due to electrochemical burns when in contact with the oesophageal mucosa, and/or the release of caustic substances when fragmented.[21-23] Dysphagia is the classic presentation of an OS, which may occur when more than half of the oesophageal lumen is narrowed. Children on a liquid diet generally present later and, in infants, the dominant symptom may be reluctance to feed. Patients with advanced strictures often fail to thrive and present with respiratory problems, ranging from a cough to recurrent pneumonia. Patient history and clinical examination can determine the cause of dysphagia in >75% of patients.[3,4] In our study, dysphagia was the dominant symptom in 85% of patients. Contrast studies and ďŹ&#x201A;uoroscopy are essential to determine the characteristics of the stricture. Rigid or fibre-optic endoscopy, as well as a biopsy, is necessary to evaluate luminal and mucosal pathology and has the

advantage of direct visualisation to determine the location, diameter, length, extent, and possible aetiology of a stricture.[3,5,24] Most OSs can be managed with periodic endoscopic dilatations. Gradual dilatation is essential and the procedure is largely individualised, as the optimal frequency and timing has not been established. The time interval between procedures is based on the effects of the previous dilatations and the recurrence of symptoms.[5] Dilators apply either radial or axial forces, or both. In complex strictures, such as those seen after caustic injury, balloon dilators, which apply a radial force only, are favoured although there are no data to support this view.[6] In our unit, we predominantly use Savary-Gilliard dilators as they are available, affordable, and yield satisfactory results. The ideal final diameter of the oesophageal lumen after dilatation can be determined by the patientsâ&#x20AC;&#x2122; clinical condition, considering the improvement of dysphagia, nutritional status and extent of normal oesophageal mucosa. Patients were usually discharged when they became asymptomatic and after re-epithelialisation of the lesion had been observed on subsequent endoscopy. Most strictures are amenable to dilatation, although it has been estimated that ~7% of strictures cannot be successfully dilated and such patients become candidates for oesophageal replacement.[6,25,26] Additional therapy may be attempted in patients with refractory strictures, including topical application of mitomycin 73

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C to the stricture site in an attempt to prevent new collagen formation, which decreases the incidence of recurrence.[12,27] After endoscopic dilatation, mitomycin C can be applied to the dilatation wound by using a rigid endoscopy.[28] All our patients who had mitomycin C applied locally had shown failure of stricture resolution after 10 standard oesophageal dilatations. Following application of mitomycin C, they all had complete resolution of the stricture and were discharged before 3 years of follow up. Mitomycin C application started as a technique for refractory strictures but has now become routine for chemical injury. In children, oesophageal perforation remains the most dreaded complication of oesophageal dilatation. Complex OSs (narrower, angulated), especially causticinduced strictures, seem to be associated with an increased risk of oesophageal perforation.[29,30] In our assessment of 287 dilatations, we had 8 perforations (2.8%). Early diagnosis is the most important prognostic factor to reduce morbidity and mortality, which is reported to range between 0% and 33%.[7,29] There are several parameters that have been used to describe the outcome of patients suffering from OSs. Resolution of dysphagia is considered the most relevant parameter but the potential weakness of this endpoint is that many patients with refractory stenosis report significantly improved symptoms shortly after dilatation, but they gradually worsen over time.[7,9] In our study, HIV-infected patients did poorly, compared with those who were either negative or not tested for HIV. All HIV-infected patients who died had established AIDS with a low CD4 count. In these patients, any contribution of the OS to their death, by preventing the ingestion of essential medication, remains speculation. Successful treatment by dilatation varies from centre to centre and depends mainly on the aetiology. An adequate lumen should be re-established within 6 months to 1 year, with progressively longer intervals between dilatations.[3,7,31] If, during the course of treatment, an adequate lumen cannot be established or maintained, more aggressive intervention should be considered.

Conclusion

Endoscopic dilatation of OSs often yields good results and has low rates of treatable complications. Patients with OSs secondary to caustic ingestion have higher morbidity and need more dilatation sessions. OSs related to complications of retroviral disease have increased and seem to be difficult to manage. Patients should be treated on an individual basis, even if they have strictures with the same aetiology.

RESEARCH Acknowledgements. None. Author contributions. OSM conceptualised the study, acquired and analysed data, and drafted the manuscript. GPH revised the manuscript. Funding. None. Conflict of interest. None.

1. Khan KM. Endoscopic management of strictures in pediatrics. Tech Gastrointest Endosc 2013;15(1):25-31. https://doi.org/10.1016/j.tgie.2012.10.002 2. Azizkhan RG, Stehr W, Cohen AP, et al. Esophageal strictures in children with recessive dystrophic epidermolysis bullosa: An 11-year experience with fluoroscopically guided balloon dilatation. Journal of Pediatr Surg 2006;41(1):55-60. https://doi.org/10.1016/j.jpedsurg.2005.10.007 3. Shehata SM, Enaba ME. Endoscopic dilatation for benign oesophageal strictures in infants and toddlers: Experience of an expectant protocol from North African tertiary centre. Afr j Paediatr Surg 21012;9(3):187. https://doi. org/10.4103/0189-6725.104717 4. Ul-Haq A, Tareen F, Bader I, Burki T, Khan N-u-Z. Oesophageal replacement in children with indolent stricture of the oesophagus. Asian J Surg 2006;29(1):1721. https://doi.org/10.1016/s1015-9584(09)60287-6 5. Forte V, Chait P, Sommer D. Endoscopic management of tracheal and esophageal strictures. Semin Pediatr Surg 2003;12(1):71-79. https://doi. org/10.1016/S1055-8586(03)70009-2 6. Chang C-F, Kuo S-P, Lin H-C, et al. Endoscopic balloon dilatation for esophageal strictures in children younger than 6 years: Experience in a medical center. Pediatr Neonatol 2011;52(4):196-202. https://doi.org/10.1016/j. pedneo.2011.05.005 7. Bittencourt PF, Carvalho SD, Ferreira AR, et al. Endoscopic dilatation of esophageal strictures in children and adolescents. Jornal de Pediatria 2006;82(2):127-131. http://dx.doi.org/10.1590/S0021-75572006000200009 8. Mendelson AH, Small AJ, Agarwalla A, Scott FI, Kochman ML. Esophageal anastomotic strictures: Outcomes of endoscopic dilation, risk of recurrence and refractory stenosis, and effect of foreign body removal. Clin Gastroenterol Hepatol 2015;13(2):263-271.e1. https://doi.org/10.1016/j.cgh.2014.07.010 9. Serhal L, Gottrand F, Sfeir R, et al. Anastomotic stricture after surgical repair of esophageal atresia: Frequency, risk factors, and efficacy of esophageal bougie dilatations. J Pediatr Surg 2010;45(7):1459-1462. https://doi.org/10.1016/j. jpedsurg.2009.11.002 10. Koivusalo AI, Pakarinen MP, Rintala RJ. Modern outcomes of oesophageal atresia: Single centre experience over the last twenty years. J Pediatr Surg 2013;48(2):297-303. https://doi.org/10.1016/j.jpedsurg.2012.11.007 11. Contini S, Garatti M, Swarray-Deen A, Depetris N, Cecchini S, Scarpignato C. Corrosive oesophageal strictures in children: Outcomes after timely or delayed dilatation. Digestive Liver Dis 2009;41(4):263-268. https://doi.org/10.1016/j. dld.2008.07.319 12. El-Asmar KM, Hassan MA, Abdelkader HM, Hamza AF. Topical mitomycin C application is effective in management of localized caustic esophageal stricture: A double-blinded, randomized, placebo-controlled trial. J Pediatr Surg 2013;48(7):1621-1627. https://doi.org/10.1016/j.jpedsurg.2013.04.014 13. Lortholary O, Petrikkos G, Akova M, et al. ESCMID* guideline for the diagnosis and management of Candida diseases 2012: Patients with HIV infection or AIDS. Clin Microbiol Infec. 2012;18(Suppl 7):68-77. https://doi. org/10.1111/1469-0691.12042 14. Karpelowsky J, Millar AJW. Surgical implications of human immunodeficiency virus infections. Semin Pediatr Surg 2012;21(2):125-135. https://doi. org/10.1053/j.sempedsurg.2012.01.005

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15. Werneck-Silva AL, Pagliari C, Patzina RA, da Silva WF, Galo LK, Duarte MIS. Su1952 TH17 pathway promotes mucosal host defense against esophageal candidiasis in HIV-infected patients. Gastroenterol 2014;146(5) Suppl 1:S506-S507. https://doi.org/10.1016/s0016-5085(14)61832-1 16. Loveland JA, Mitchell CE, van Wyk P, Beale P. Esophegeal replacement in children with AIDS. J Pediatr Surg 2010;45(10):2068-2070. https://doi. org/10.1016/j.jpedsurg.2010.06.026 17. Wilcox CM. Esophageal disease in the acquired immunodeficiency syndrome: Etiology, diagnosis, and management. Am J Med 1992;92(4):412-421. https:// doi.org/10.1016/0002-9343(92)9027218. Bonacini M. Medical management of benign oesophageal disease in patients with human immunodeficiency virus infection. Digest Liver Dis 2001;33(3):294-300. https://doi.org/10.1016/s1590-8658(01)80722-2 19. Zouari M, Kamoun H, Bouthour H, et al. Peptic oesophageal stricture in children: Management problems. Afr J Paediatr Surg 2014;11(1):22-25. https:// doi.org/10.4103/0189-6725.129206 20. Pearson EG, Downey EC, Barnhart DC, et al. Reflux esophageal stricture - a review of 30 years' experience in children. J Pediatr Surg 2010;45(12):23562360. https://doi.org/10.1016/j.jpedsurg.2010.08.033 21. Samad L, Ali M, Ramzi H. Button battery ingestion: Hazards of esophageal impaction. J Pediatr Surg 1999;34(10):1527-1531. https://doi.org/10.1016/ s0022-3468(99)90119-7 22. Lin VY, Daniel SJ, Papsin BC. Button batteries in the ear, nose and upper aerodigestive tract. Int J Pediatr Otorhinolaryngol 2004;68(4):473-479. https:// doi.org/10.1016/j.ijporl.2003.10.020 23. Laugel V, Beladdale J, Escande B, Simeoni U. [Accidental ingestion of button battery.] Archives de Pediatrie 1999;6(11):1231-1235. https://doi.org/10.1016/ s0929-693x(00)86309-5 24. Hamza AF, Abdelhay S, Sherif H, et al. Caustic esophageal strictures in children: 30 years’ experience. J Pediatr Surg 2003;38(6):828-833. https://doi. org/10.1016/s0022-3468(03)00105-2 25. Lan LCL, Wong KKY, Lin SCL, et al. Endoscopic balloon dilatation of esophageal strictures in infants and children: 17 years’ experience and a literature review. J Pediatr Surg 2003;38(12):1712-1715. https://doi.org/10.1016/j. jpedsurg.2003.08.040 26. De Peppo F, Zaccara A, Dall'Oglio L, et al. Stenting for caustic strictures: Esophageal replacement replaced. J Pediatr Surg 1998;33(1):54-57. https://doi. org/10.1016/s0022-3468(98)90361-x 27. Heran MKS, Baird R, Blair GK, Skarsgard ED. Topical mitomycin-C for recalcitrant esophageal strictures: A novel endoscopic/fluoroscopic technique for safe endoluminal delivery. J Pediatr Surg 2008;43(5):815-818. https://doi. org/10.1016/j.jpedsurg.2007.12.017 28. Olutoye OO, Shulman RJ, Cotton RT. Mitomycin C in the management of pediatric caustic esophageal strictures: A case report. J Pediatr Surg 2006;41(5):e1-e3. https://doi.org/10.1016/j.jpedsurg.2005.12.051 29. Fayek M, Gerdes H. Risks of esophagogastroduodenoscopy and esophageal dilation. Tech Gastrointest Endosc 2008;10(1):2-6. https://doi.org/10.1016/j. tgie.2007.08.004 30. Schmidt SC, Strauch S, Rosch T, et al. Management of esophageal perforations. Surg Endosc 2010;24(11):2809-2813. https://doi.org/10.1007/s00464-0101054-6 31. Pearson FG. Surgical therapy for esophageal disease: Lessons from a master. Ann Thorac Surg 2010;89(6):S2180-S2182. https://doi.org/10.1016/j. athoracsur.2010.03.076

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RESEARCH

This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.

Risks associated with suspected dysphagia in infants admitted to a neonatal intensive care unit in a South African public hospital J Schoeman, B Com Pathol, M Com Pathol; A Kritzinger, DPhil Department of Speech-Language Pathology and Audiology, Faculty of Humanities, University of Pretoria, South Africa Corresponding author: J Schoeman (jacolineschoeman2gmail.com) Background. The prevalence of neonatal dysphagia is increasing, as medical advances contribute to the survival of critically ill and preterm infants. Additional factors such as low birth weight (LBW), gastro-oesoephageal reflux disorder, failure-to-thrive (FTT), and HIV may increase the complexity of dysphagia symptoms. Knowledge of context-specific risk factors for dysphagia may lead to an effective pathway of diagnosis and management in vulnerable neonates. Objective. To describe the feeding characteristics and categories of underlying medical conditions in infants of gestational age 24 - 42 weeks. Methods. The study was a retrospective review of 231 purposively selected medical and speech-language therapy records. Participants had a mean stay of 28.5 days in a neonatal intensive care unit in a peri-urban public hospital and were referred for a swallowing and feeding assessment. An existing seven-category framework for the classification of suspected dysphagia was used. Results. Most participants (90.0%) presented with multiple medical conditions. Underlying neurological conditions (48.5%) and feeding difficulties secondary to systemic illness (65.8%) contributed mostly to suspected dysphagia in the sample. It was found that 71.0% of infants presented with feeding difficulties secondary to other conditions such as LBW and prematurity, highlighting the need for an expanded dysphagia classification framework. Conclusion. The results concur with the outcomes of previous studies and confirm the need for a unique classification framework in South Africa. Dysphagia is a complex condition and frequently cannot be attributed to a single risk factor. S Afr J Child Health 2017;11(2):75-79. DOI:10.7196/SAJCH.2017.v11i2.1186

Dysphagia in children is ever-increasing, mostly due to the improved survival rate of infants and children with life-threatening conditions and multiple associated health problems.[1,2] Dysphagia, a swallowing disorder secondary to a problem in one or more of the four phases of swallowing, is managed by speech-language therapists (SLTs) who are qualified to assess the dysfunction and provide intervention.[3-5] Infants with risks such as prematurity, congenital or acquired medical conditions, or those with prolonged stays in neonatal intensive care units (NICUs) are at greater risk of developing dysphagia and nutritional problems than typically developing, healthy neonates.[4,6] Also, infants requiring continued intervention for dysphagia are frequently those who were previously admitted to a NICU.[6] Infants with the most complex or severe medical conditions are most at risk of presenting with disorganised or dysfunctional feeding patterns.[4] When preterm infants present with disorganised feeding patterns, it is generally due to immaturity, whereas dysfunctional sucking patterns may be more severe and are usually associated with neurological involvement.[4] It therefore appears that a close relationship exists between dysphagia, the infantâ&#x20AC;&#x2122;s medical diagnosis, associated conditions, and the severity thereof. Limited research regarding risk factors associated with dysphagia in infants admitted to the NICU is currently available.[4,7,8] This is a concern in developing countries, where the burden of disease is high.[9] In a developing country such as South Africa (SA), numerous additional challenges, such as the effects of poverty and HIV, may contribute to dysphagia in infants.[9] HIV may affect all phases of swallowing as a result of oral thrush, odynophagia and gastro-oesophageal reflux disorder (GERD), which can lead to failure-to-thrive (FTT).[10] The prevalence of dysphagia and 75

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GERD among children with HIV is poorly recorded, but frequently encountered in clinical practice and may contribute significantly to the morbidity of infants with exposure to the virus.[10] The incidence of dysphagia in typically developing children is estimated at 25 45%, and even higher, up to 80%, in children with developmental disabilities.[11] The prevalence of neonatal dysphagia is unknown, but represents a universal problem, as dysphagia may carry over to infancy and toddler-age groups.[12] It is important to identify dysphagia as soon as possible after birth, while the infant is still in the hospital, so that the appropriate short- and long-term dietetic and SLT management and parent training can commence.[4] SLTs should be able to state when an infant is not ready for oral feeding and maximise oral feeding skills and safety in those infants who are ready to feed orally.[1,5] Left unidentified and untreated, dysphagia can lead to FTT, GERD, aspiration pneumonia and an inability to establish and sustain vital nutrition and hydration.[13] The objectives of the study were to describe the feeding characteristics of infants admitted to a NICU and referred for suspected dysphagia in a public hospital, and to determine which medical conditions were associated with the participants. Identifying risk factors can contribute to a better understanding of infants with suspected dysphagia, which may lead to improved referral guidelines and SLT staff-planning to ensure adequate intervention for all. A holistic understanding of the diversity of context-specific risk factors, associated with suspected dysphagia in infants who are already compromised by medical conditions, may be attained.

Methods

The study was a retrospective review of medical and SLT records from 2010 to 2014 and included infants, aged 24 - 42 weeks' gestational age

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RESEARCH (GA) at birth, who were admitted to a peri-urban public hospital. GA was determined using the mother’s last menstrual period. Birth weight was defined as: normal (>2 500 g); low birth weight (LBW; <2 500 g), very LBW (<1 500 g) and extremely LBW (<1 000 g). All participants were referred by medical doctors, nurses, audiologists, SLTs, and dieticians for a clinical swallowing evaluation.

deviations were calculated. Descriptive statistics were used to identify the feeding characteristics and risk factors. Table 1. Participant characteristics (N=231) Characteristic

n (%)*

Nationality of mother

Participants

A total of 312 infants were referred for dysphagia assessments within the study period, of which 231 complete data sets were available. Inclusion criteria were that the infants had to present with symptoms of dysphagia, be referred for a feeding or swallowing evaluation by a healthcare professional, admitted to the NICU and assessed for dysphagia by a SLT. Common symptoms of dysphagia in the participants include oral phase symptoms such as absent oral reflexes, absent or poor primitive reflexes, weak suck, uncoordinated suck, immature biting, poor bolus propulsion and poor bolus containment. Abnormalities in triggering of the swallow include absent swallow, delayed trigger of swallow, suck-swallow-breathing (SSB) incoordination, and pharyngeal phase symptoms include laryngeal penetration, aspiration, choking, pharyngeal residue and nasopharyngeal reflux.[14] Common criteria by healthcare professionals for referral of infants and children for feeding and swallowing evaluation included: suckling and swallowing incoordination, weak suck, breathing disruptions or apnoea during feeding, excessive gagging or recurrent coughing during feeds, diagnosis of disorders associated with dysphagia or under-nutrition, severe irritability during feeding, history of recurrent pneumonia and feeding difficulty, concern for possible aspiration during feeds, lethargy or decreased arousal during feeds, tedious feeding times and nasopharyngeal reflux during feeding.

Materials

The materials used during data collection included the Neonatal Patient Discharge Report, which is available in electronic format from the local NICU database, and the SLT records, including a dysphagia assessment form.[15-17] Data were independently collected over five years by seven different SLTs who were trained to use the same data collection instrument. A classification framework described by Arvedson and Brodsky[1] to determine the aetiology or risk factors of paediatric dysphagia was used to categorise each participant. These categories included conditions with neurological involvement (such as asphyxia and convulsions), anatomical and structural impairments (including laryngomalacia), genetic and chromosomal disorders (including trisomy 21), dysphagia secondary to systemic illness (including pneumonia), psychosocial factors (including oral deprivation) as well as dysphagia secondary to resolved medical conditions (including hospital-acquired infections). In a local study, Fourie[7] expanded on the framework by adding a seventh category, ῾other᾽, as the prevalence of prematurity, LBW, GERD, and FTT is high in SA, and does not fit within any of the other six categories.[7]

Procedures

The Research Ethics Committees of two different universities granted approval for the study. Data were manually captured from the printed records to an Excel spreadsheet and analysed using SPSS version 22 (IBM Corp., USA). Being a retrospective study, there was no direct contact with mothers or infants. Variables included those in Arvedson and Brodsky’s[1] framework for categorisation of risks for dysphagia, which was expanded by Fourie[7] to include prenatal risks (such as age of mother, number of antenatal visits), perinatal risks (such as type of delivery, Apgar scores), and postnatal medical risks (such as enteral and parenteral feeding). Pivot tables were used to determine the distribution of each participant within the different categories of medical conditions associated with suspected dysphagia. Standard 76

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South African

204 (88.3)

Non-South African

27 (11.7)

Gender Male

111 (48.1)

Female

120 (51.9)

GA at birth (weeks), mean (SD)

34.9 (3.9)

Birth weight Normal

105 (45.5)

LBW

82 (35.5)

Very LBW

38 (16.4)

Extremely LBW

6 (2.6)

Time spent in NICU (days), mean (SD)

28.5 (36.9)

HIV status of mother (N=196) Negative

135 (69.6)

Positive

59 (30.4)

GA = gestational age; SD = standard deviation; LBW = low birth weight; NICU = neonatal intensive care unit. *Unless otherwise specified.

Results

Participant description

The participant characteristics are described in Table 1. Most mothers were SA citizens. There were slightly more female (51.9%) than male (48.1%) participants, and the mean (standard deviation (SD)) GA of participants was 34.9 (3.9) weeks. The participants were mostly late preterm. More than half of the participants (54.5%) were LBW, very LBW or extremely LBW (Table 1). The mean (SD) stay in the NICU was 28.5 (36.9) days. The percentage of mothers who were HIV-positive and, by implication, had infants exposed to the virus, corresponds with the 2012 antenatal sentinel HIV prevalence survey.[18] The estimated HIV prevalence in the survey was 29.5% in pregnant women and in this study, 30.4% of mothers were HIV-positive.[18] It is not known how many of the mothers were receiving antiretroviral treatment.

Feeding characteristics of participants

Table 2 shows the feeding characteristics of the participants. All participants presented with one or more symptoms of dysphagia. This can explain the frequency of parenteral (14.4%) and enteral feeding (65.0%), as infants with dysphagia often require alternative feeding methods to obtain adequate nutrients and fluids.[1] Thirty-six (15.6%) participants presented with severe feeding difficulties or signs of aspiration. An instrumental assessment, a video fluoroscopic swallow study (VFSS) was only conducted in 14 (38.8%) of those participants. Instrumental assessments are recommended if there are concerns about risks for aspiration, safety of the airway, or possibilities of GERD.[1] The reasons why VFSS was not conducted in the 22 remaining participants referred for the procedure included: participants demised before VFSS could be conducted (n=7); VFSS screening machine was not functioning (n=1); participant was ventilated (n=1); participant was lethargic (n=1); unstable or desaturating during feeding (n=3); clinically

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RESEARCH Table 2. Feeding characteristics of participants (N=231)

Table 3. Underlying medical conditions in participants (N=231)

n (%)

Characteristic

Category

Previous parenteral feeding Yes

33 (14.4)

198 (85.6)

Previous enteral (NGT/OGT) feeding Yes

150 (65.0)

61 (26.4)

Unknown

20 (8.6)

Referred for VFSS by doctors and SLTs (N=36) Yes

6 (15.6)

30 (84.4) 14 (38.8)

22 (61.2)

Manner of feeding at discharge Mixed

127 (55.1)

Exclusive breastfeeding

69 (29.7)

Gastrostomy

14 (6.1)

Exclusive bottlefeeding

12 (5.2)

Cup

6 (2.6)

Syringe

3 (1.3)

NGT = nasogastric tube; OGT = orogastric tube; VFSS = video fluoroscopic swallow study; SLTs = speech-language therapists.

aspirating but no suck/swallow palpable (n=4), clinical swallow present even though there were risks for aspiration (n=5). More than half of participants (55%) used a mixed manner of feeding such as breast- and cupfeeding, or cup- and syringe feeding. Only 29.7% of participants could breastfeed exclusively, which was related to preterm birth and LBW in most of the participants. The use of mixed feeding methods among the participants may indicate that the infants experienced breastfeeding difficulties, as establishing successful breastfeeding may be a challenge for many preterm infants and their mothers, owing to neonatal feeding difficulties.[19] These difficulties may be due to incoordination of SSB as the suckling patterns of preterm infants often remain significantly less efficient than those of full-term infants at term age and beyond.[2,19] Furthermore, 6.1% of the participants required long-term tube feeding, such as a gastrostomy. In another study conducted in SA, it was found that infants and children requiring gastrostomies were likely to present with multiple diagnoses, of which neurological and/ or gastrointestinal impairments were the most prominent medical conditions.[20]

Underlying medical conditions in participants

Underlying medical conditions in participants were classified according to the framework by Arvedson and Brodsky,[1] expanded by Fourie,[7] to determine the aetiology or risk factors of dysphagia (Table 3). Since most participants were not classified in a single category, and presented with multiple risks, the total in Table 3 does not add to 100%. The majority of the infants (71.0%) presented with conditions that were not included in the risks of dysphagia described by Arvedson and Brodsky,[1] a classification system developed for conditions in a developed country such as the USA. The risks included FTT, 77

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n (%)

Neurological conditions

112 (48.5)

Anatomical and structural conditions

19 (8.2)

Secondary to systemic illness

152 (65.8)

Chromosomal (genetic) conditions

18 (7.8)

Psychosocial conditions

4 (1.7)

Secondary to resolved medical condition

32 (13.9)

Other (FTT, LBW, prematurity)

164 (71.0)

FTT = failure-to-thrive; LBW = low birth weight.

VFSS conducted (in referrals) Yes

Description

GERD, LBW as well as HIV exposure. It was found that 65.8% of participants had feeding difficulties secondary to a systemic illness, such as respiratory distress syndrome, cardiac abnormalities, and pneumonia. This could be due to the fact that preterm infants with LBW are more at risk of developing systemic illnesses,[13] and more so in a developing country, such as SA.[7] Results indicated that 48.5% of participants had a condition with neurological involvement, such as asphyxia. The literature suggests that infants with neurological conditions, birth trauma, as well as pre- and perinatal asphyxia, are commonly found to have feeding difficulties.[1] The conditions that occurred the least in the participants were feeding difficulties secondary to resolved medical conditions (13.9%), including iatrogenic conditions such as hospital-acquired infections. A total of 8.2% of the participants presented with anatomical or structural conditions, such as cleft lip and palate, laryngomalacia and tracheo-oesophageal fistula, while only 7.8% of the 231 participants presented with genetic or chromosomal abnormalities, which included infants with trisomies 13, 18 and 21, and other syndromes. Only 1.7% of the participants presented with psychosocial conditions such as oral deprivation and under-nutrition due to social problems. When analysing the results, it became clear that a true profile of multiple underlying conditions to feeding difficulties in the participants could not have been obtained if single categories of risk were considered.

Combinations of risk conditions associated with suspected dysphagia

Combinations of risk categories in participants are described in Table 4. The results indicate that 90.0% of participants presented with multiple medical conditions, therefore revealing the complexity of combinations of different categories. A total of 36 different combinations were found, ranging from a single category to five different combinations. Most of the participants presented with two (50.2%) or three (28.1%) categories of risk factors and a total of 11.7% participants presented with four or five categories of risks. The minority (10.0%) of participants presented with a single category of risk for dysphagia. The results display the diversity and complexity of medical conditions in infants with symptoms of dysphagia. The results are in agreement with Jadcherla,[12] who states that neonatal dysphagia can rarely be associated with a single aetiology.

Discussion

Dysphagia symptoms were accompanied by multiple medical conditions in most of the participants. As was found in other local studies,[7,20] participants presented with a great variety of medical conditions and combinations of these conditions that either directly or indirectly affected their feeding ability.[7] The high number of participants with neurological conditions in this sample can be explained by the fact that infants with neurological

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RESEARCH Table 4. Combinations of risks for dysphagia (N=231) Category

n (%)

Single risk category

23 (10.0)

Neurological

6 (2.6)

Anatomical

2 (0.9)

Dysphagia SSI

10 (4.3)

Other

5 (2.2)

Two risk categories

116 (50.2)

Anatomical, genetic

1 (0.4)

Neurological, SSI

33 (14.3)

Neurological, other

7 (3.0)

SSI, other

65 (28.1)

Anatomical, SSI

4 (1.7)

SSI, SRMC

1 (0.4)

SSI, neurological

1 (0.4)

SSI, genetic

4 (1.7)

Three categories

65 (28.1)

Neurological, SSI, other

39 (16.9)

Neurological, SRMC, other

1 (0.4)

Anatomical, SSI, other

4 (1.7)

SSI, SRMC, other

10 (4.3)

SSI, genetic, other

2 (0.9)

Neurological, SSI, SRMC

4 (1.7)

SSI, psychosocial, SRMC

1 (0.4)

Neurological, anatomical, SSI

1 (0.4)

SSI, psychosocial, other

1 (0.4)

Neurological, other, SSI

1. (0.4)

Neurological, SSI, genetic

1 (0.4)

Four risk categories

Conclusion

Dysphagia frequently occurs in infants and is highly complex in nature.[12] Within the context of a developing country, classifying dysphagia can be challenging and therefore an expanded framework may be beneficial. The eight-category framework can be used by healthcare personnel to refer infants for dysphagia assessment and intervention, and can be used by SLTs to identify infants at risk for dysphagia. Being a retrospective study, various limitations were present, including missing data as well as the restricted geographical location. The outcomes of the current study correspond with international research describing several risk factors for dysphagia related to the primary medical diagnosis and its sequelae, and may be present throughout the infants’ hospitalisation.[8,12] Due to the increased survival rate of preterm infants and infants with complex medical conditions, it is suggested that more research regarding neonatal dysphagia in developing countries should be conducted.

22 (9.5)

Anatomical, SSI, genetic, other

3 (1.3)

Neurological, SSI, SRMC, other

9 (3.9)

Anatomical, SSI, SRMC, other

1 (0.4)

Neurological, anatomical, SSI, other

3 (1.3)

SSI, genetic, SRMC, other

1 (0.4)

Neurological, SSI, psychosocial, other

1 (0.4)

Neurological, Genetic, SSI, Other

1 (0.4)

SSI, Psychosocial, SRMC, Other

1 (0.4)

Neurological, SSI, Genetic, Other

2 (0.9)

Five risk categories

Acknowledgements. None. Author contributions. JS was the researcher and prepared the manuscript. AK co-authored the manuscript and supervised the research. Funding. None. Conflicts of interest. None.

5 (2.2)

Neurological SSI, Genetic, SRMC, Other

1 (0.4)

Anatomical, SSI, Genetic, SRMC, Other

1 (0.4)

Neurological, Anatomical, SSI, Psychosocial, Other

2 (0.9)

Neurological, Anatomical, SSI, Psychosocial, Other

1 (0.4)

SSI = secondary to systemic illness; SRMC = secondary to resolved medical condition.

conditions are commonly found to have feeding difficulties.[1,13] It is estimated that 85 - 90% of infants and children with neurological conditions, such as cerebral palsy, will present with dysphagia 78

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at some point in their lives.[1] Further, the high incidence of systemic illnesses, such as pneumonia, in paediatric populations with dysphagia is linked to specific diagnoses, such as trisomy 21, asthma, GERD, lower respiratory tract infection, and moist cough.[14] Literature indicated that paediatric patients with multisystem diagnoses, in addition to dysphagia, appear to be at greatest risk for developing pneumonia.[14] It is therefore evident that infants can present with multiple variations of swallowing impairments, such as those found in the participants of this study.[14] The results indicate that the seven-category framework used for classification of risks for dysphagia in participants was successful to describe the complexities of different risk categories that may underlie neonatal dysphagia. Fourie[7] found that 52% of participants had aetiological factors for dysphagia pertaining to the ‘other’ category.[7] In the current study, the high rate of 71.0% participants in the ῾other᾽ category included those with HIV exposure, as there was no dedicated category for infants exposed to HIV. Therefore, the results indicated a need for an expanded classification system and the importance of an additional risk category was highlighted. It is proposed that the framework as described by Arvedson and Brodsky should be expanded to an eight-category classification framework that includes a category for prematurity, LBW and related conditions (described by Fourie[7] as ‘other’) as well as a category for infants exposed to HIV. HIV exposure in infants is associated with preterm birth.[21] As a result of prematurity and LBW, the infant is at risk for dysphagia after birth[19] and when HIV infection becomes apparent, feeding and swallowing can be affected due to encephalopathy. An additional category would provide information regarding feeding characteristics, and aid in early identification of dysphagia.

1. Arvedson JC, Brodsky L. Pediatric swallowing and feeding: Assessment and management. 2nd ed. New York: Delmar Cengage Learning, 2002. 2. Kakodkar K, Schroeder JW. Pediatric dysphagia. Pediatr Clin N Am 2013;60:969-977. https://doi.org/10.1016/j.pcl.2013.04.010 3. Bell H, Sheckman Alper MA. Assessment and intervention for dysphagia in infants and children: Beyond the neonatal intensive care unit. Semin Speech Lang 2007;28(3):213-222. http://doi.org/10.1055/s-2007-984727 4. Hawdon JM, Beauregard N, Slattery J, Kennedy G. Identification of neonates at risk of developing feeding problems in infancy. Dev Med Child Neurol 2000;42(4):235-239. https://doi.org/10.1055/s-2007-984727

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RESEARCH 5. American Speech-Language-Hearing Association. Roles of speech-language pathologists in swallowing and feeding disorders: Technical report. www.asha. org/policy (accessed 8 August 2015). 6. Sundseth Ross E, Browne V. Developmental progression of feeding skills: An approach to supporting feeding in preterm infants. Semin Neonatol 2002; 7:469-475. https://doi.org/10.1055/s-2007-984727 7. Fourie A. The aetiology and nature of paediatric dysphagia (0 - 18 months) in state hospitals [dissertation]. Johannesburg: University of the Witwatersrand; 2011. 8. Rommel N, De Meyer AM, Feenstra L, Veereman-Wauters G. The complexity of feeding problems in 700 infants and young children presenting to a tertiary care institution. J Pediatr Gastroenterol Nutr 2003;37(1):75-84. https://doi. org/10.1097/00005176-200307000-00014 9. Olusanya BO, Ruben RJ, Parving A. Reducing the burden of communication disorders in the developing world. An opportunity for the Millennium Development Project. J Am Med Assoc. 2006;296(4):441-444. https://doi. org/10.1001/jama.296.4.441 10. Rabie H, Marais BJ, van Toorn R, et al. Important HIV-associated conditions in HIV-infected infants and children. SA Fam Pract 2007;49(4)19-23. https://doi. org/10.1080/20786204.2007.10873538 11. Arvedson JC. Assessment of pediatric dysphagia and feeding disorders: Clinical and instrumental approaches. Dev Disabil Res Rev 2008;14:118-127. https:// doi.org/10.1002/ddrr.17

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12. Jadcherla S. Dysphagia in the high-risk infant: Potential factors and mechanisms. Am J Clin Nutr 2016;20:1-7. https://doi.org/10.3945/ajcn.115.110106 13. Prasse JE, Kikano GE. An overview of pediatric dysphagia. Clin Pediatr 2009;48(3):247-251. https://doi.org/10.1177/0009922808327323 14. Dodrill P, Gosa MM. Paediatric dysphagia: Physiology, assessment, and management. Ann Nutr Metab 2015;66(5):24-31. https://doi.org/10.1159/000381372 15. McGrath JM. Feeding. In: Kenner C, McGrath JM, eds. Developmental Care of Newborns & Infants: A Guide for Professionals. USA: Mosby, 2004:321-342. 16. Hall KD. Paediatric Dysphagia Resource Guide. Canada: Singular-Thomson Learning, 2001. 17. Fraker C, Walbert L. From NICU to Childhood: Evaluation and Treatment of Pediatric Feeding Disorders. Austin: PRO-ED, 2003. 18. National Department of Health, 2013. The 2012 National antenatal sentinel HIV and Herpes simplex type-2 prevalence survey in South Africa, 2012. https://www.health-e.org.za/wp-content/uploads/2014/05/ASHIVHerp_ Report2014_22May2014.pdf (accessed 16 February 2016). 19. Dodrill P. Feeding difficulties in preterm infants. ICAN 2011;3(6):324-331. https://doi.org/10.1177/1941406411421003 20. Norman V, Singh SA, Hittler T, et al. Indications, medical conditions and services related to gastrostomy placement in infants and children at a tertiary hospital in South Africa. S Afr J Child Health 2011;5(3):86-89. 21. Short CS, Taylor GP. Antiretroviral therapy and preterm birth in HIV-infected women. Expert Rev Anti Infect Ther 2014;12(3):293-306. http://doi.org/10.158 6/14787210.2014.885837

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RESEARCH

This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.

Nutritional adequacy of menus offered to children of 2 - 5 years in registered childcare facilities in Inanda, KwaZulu-Natal Province, South Africa P F Nzama,1 HDE, MAppSc; C E Napier,2 DTech, FSM 1 2

Department of Food and Nutrition, Durban University of Technology, South Africa Department of Food and Nutrition, Institute of Systems Science, Durban University of Technology, South Africa

Corresponding author: P F Nzama (phindilen1@dut.ac.za) Background. The number of children that spend a large part of the day at childcare facilities (CCFs) has risen worldwide. The parent relies on caregivers in CCFs to provide children with balanced meals. Studies in various parts of South Africa (SA) that analysed CCF menus have found that the menus do not satisfy the daily requirements of energy and micronutrients for children. With increasing numbers of children attending CCFs, and an increase in the global prevalence of obesity, information with regards to food presented at the facilities was of interest not only to compare the energy, macro- and micronutrient intake, but also to consider the dietary diversity offered to the children on a daily basis. Objectives. To analyse menus offered to children in CCFs in Inanda, KwaZulu-Natal for nutritional adequacy and to calculate the contribution the meals make to the dietary reference intakes for children in the 2 - 5-year age category. Methods. Permission from the Department of Social Development (DSD) in Durban was obtained to approach the CCFs to participate in the study. Ten CCFs in the Inanda area were randomly selected from the DSD list of 45 registered CCFs. The researcher gathered menus, recipes and serving sizes from each of the 10 CCFs. Food Finder version 3 software (MRC, SA), adjusted to include fortified wheat and bread products, was used to analyse the recipes. Results. The CCFs in Inanda served breakfast and lunch to the children daily. The top 20 list of foods offered cereal-based staples of rice and maize meal more frequently than meat, dairy products and fruit and vegetables. None of the CCFs met 60% of daily requirements for energy, fibre and calcium for children in this age group. Conclusion. Menus offered to children aged 2 - 5 years in registered CCFs in Inanda are nutritionally inadequate. S Afr J Child Health 2017;11(2):80-85. DOI:10.7196/SAJCH.2017.v11i2.1192

The South African Paediatric Food-Based Dietary Guidelines (SAPFBDG) state the necessity to provide sufficient nutrients in meals to support optimal growth and development in children.[1] Childhood is an intermediary nutritional passage from dependence on a caregiver regarding food choices, to children making individual food choices. Furthermore, at this stage children establish eating habits and individual feeding behaviour that will eventually have an impact on society, as the development of diet-related diseases in adulthood is prevented by establishing healthy eating habits from childhood.[1,2] Therefore, meals served at childcare facilities (CCFs) to children from 6 months to 6 years should have dietary variation and ideally contain ingredients from all the major food groups. The minister of social development stated that Early Childhood Development (ECD) programmes are mainly a strategy for alleviating poverty. The programmes should be planned to deal with the total well-being of children by making certain that children grow up, among other things, healthy and well-nourished.[3] In 2009, the Department of Social Development (DSD) reported that in South Africa (SA), the ECD sites as well as children’s enrolment in those sites had increased to 646 491 children aged <4 years in 13 736 registered ECD sites, and 620 223 5-year-olds registered for grade R in schools and ECD sites that are run by non-profit organisations. The government’s subsidy for ECD programmes ranged from ZAR9 to ZAR12 allocated per child to be used towards the full stay of the child including food, stationery and salaries and is one of the strategies for poverty eradication. The subsidy is intended to fund day-care site employees and overheads as well as nutrition.[4] Biersteker and Dawes[5] concurred that high-quality ECD service provision for poor children was a justified cost, as it not only improves the child’s well-being, but also prevents problems related to childhood poverty in later stages of life.

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In SA, the Child Care Act of 1983, Regulation 38, provides the conditions for ECD facilities for children’s meals. The regulation states that the place of care shall operate for a minimum of 8 hours a day, and meals and refreshments shall be served to the child who is present at meal times or tea times.[6] The Children’s Act of 2005 and regulations thereof enable and regulate the provision of ECD services to young children and the DSD created the Guidelines for Early Childhood Development Services (GECDS) to provide direction on how to support the nutritional needs of young children in ECD programmes. According to Neelon and Briley,[7] CCFs that operate for 4 - 7 hours should provide 33.3% of the everyday nutritional needs of preschool children. Furthermore, a CCF that operates for 8 or more hours should provide at least 50% to 66.6% of a child’s daily nutritional requirements. Food should also be served in the correct quantities to balance the energy and nutrient requirements of children of different ages.[7] The deficiency of macro- and micronutrients such as protein, carbohydrates, energy, dietary fibre, calcium, iron, zinc and vitamin A in the diet of children result in stunted growth, wasting, underweight and poor brain development. These deficiencies can also result in a low resistance to infections. Low immunity may cause specific diseases and increase the severity of infectious diseases and chronic illnesses, which ultimately has an influence on the child’s well-being and poses a risk of mortality.[8,9-12] According to Briley and Roberts-Gray,[13] offering children a variety of foods at each meal improves nutrient intake and encourages the establishment of good eating habits, personal preferences, and continued contributions to growth and development. The age of the children and the stage of mental development should be considered when planning meals. In children, eating habits contribute to meeting nutritional requirements, nutritional adequacy, and the promotion of growth.[13] As

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RESEARCH CCFs determine the child’s daily routine, including meal plans, these facilities are platforms for the improvement of the child’s nutritional and physical status.[14]

Methods

Study design and setting

The study was descriptive, cross-sectional, and observational, and included interviews, observations and plate waste studies, which were carried out at all participating CCFs. According to the DSD, 45 CCFs were registered in Inanda at the time of the study. Each CCF served an average of 80 children per meal time. Inanda has nearly half a million residents in what is one of the largest conglomerations of informal settlements in SA. It is situated 20 km from the central business district of Durban and is described as a low-income residential area with a high number of poorly educated and unemployed youth.[15]

Ethical considerations

The study was approved by the Faculty Research Committee at the Durban University of Technology (DUT) and adhered to the SA Medical Research Council (SAMRC)᾽s research ethics guidelines. An ethics registration number was not issued as the children were not included in the study and therefore it was classified as low-risk. The request to conduct the study was acknowledged in writing by the regional director of the DSD. Written consent was obtained from each of the 10 managers at the randomly selected facilities. Anonymity of the data was ensured by allocating a number to each of the CCFs.

Sampling

The study respondents were CCFs accommodating children aged 3 - 5 years. The first contact was made through communication with the DSD to obtain permission to conduct the study among registered CCFs. The DSD provided a list of registered CCFs to the researcher; thereafter, 10 CCFs were randomly selected and approached to participate in the study. On the first visit to a CCF, the researcher met with the owner and/or supervisor to explain the requirements of the study and to obtain signed consent for participation.

Data collection methods and analysis

The researcher spent 5 days of the week in each facility to collect the facility’s menu plans and recipes, and to conduct plate-waste studies for the meals that the CCFs offered. No standardised recipes were available at any of the facilities. Ingredients were weighed uncooked and peeled. The mass and volume of ingredients were recorded on a list of ingredients and the method was written on a recipe sheet from observation and questioning of the food handler (FH). The researcher used a menu sheet to record daily menu plans for each CCF, on 5 days of the week, while the FH was preparing meals. Plate waste studies incorporated a weighed method for accurate measurement of nutrient intake and portion sizes.[16] All meals served to the children in the sample group (n=20 per CCF) were weighed on a Digi DS-708 electronic kitchen scale prior to serving. Plates were weighed again after meal consumption and plate waste was documented. Actual food intake was recorded after deducting plate waste from the served portion sizes. The mean intake and average portion size consumed per age group was subsequently calculated and used for nutrient analysis. These measurements were conducted at breakfast and lunch times, 5 days a week in each CCF. All breakfast and lunch menus, average portion sizes and recipes from the weighed food records were captured using Excel 2007. The data were analysed using Food Finder version 3 software (MRC, South Africa),[17] which was updated to include fortified bread and wheat product recipes, to obtain the top 20 foods served at the 10 CCFs. The software was also used to determine the nutrient contribution of the menus to the nutritional requirements of the children. The nutrient contribution of

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the CCF menus was compared to 60% of the dietary reference intakes (DRIs) for children 3 - 5 years of age using the DRIs from the Institute of Medicine,[18] as 50 - 66% nutrient compliance is recommended for CCFs operating 8 or more hours a day.[7]

Results

Nutrient analysis

The tables present the energy contribution of macronutrients, protein, carbohydrates and fibre, as well as the micronutrients calcium, iron, zinc and vitamin A, as adequacy of these nutrients is essential in childhood. Table 1 presents the menu contribution to the daily nutrient intake of boys and girls aged 2 - 3 years old. Meals at CCFs 1, 2, 5, 7, and 10 met the requirements for protein and carbohydrates, while CCF 9 met the requirements for carbohydrates. All the CCFs failed to meet the energy needs of the children, except CCF 2 where the energy requirement for girls was adequate although boys were slightly below the DRI at 59.3%. At all CCFs the mean dietary fibre provided by both meals was below 30% of the World Health Organization (WHO)’s recommendation of >25 g/day or >15 g (60%) for 2 - 3 year olds. None of the CCF meals met the requirements for calcium. The only meals exceeding 60% of the DRIs for vitamin A (210 µg) were found in CCFs 2 and 7, which contributed >100% of the DRIs. The results also show that for this age category, only 5 CCFs met the requirements for zinc and 5 met the requirements for iron. Table 2 indicates the results of the nutrient analysis for all CCFs for the 4 - 5-year-old children. None of the five CCFs met the requirements for a 60% contribution to energy intake, dietary fibre and calcium. Only CCFs 4 (49.2 (45.2) g) and 8 at 57.6 g (15.6) were below the 60% requirements for carbohydrates. More than 60% of DRIs for protein were met by meals at CCFs 1 (16.2 (4.8) g), 2 (19.1 (1.7) g), 5 (12.2 (6.3) g) and 7 (14.6 (4.8) g). CCFs 1, 2 and 7 also met the requirements for zinc and vitamin A, and the meals in CCFs 3 and 7 provided >60% of the DRIs for iron.

Top 20 food intake

All participating CCFs opened at 07h00 and closed at 15h00 or 16h00. The 5-day menu plans recorded onsite were used to identify the top 20 food items served by the CCFs. CCF 10 did not provide meals for 2-yearolds. Table 3 illustrates the top 20 foods that were served at the CCFs collectively for the 5 days of the week, ranked by total intake of all CCFs. The top 20 list is presented for each age group, as each age group has different nutritional needs. Maize meal and rice were offered almost daily as part of the breakfast and lunch menu at all the CCFs. Maize meal was offered in the form of porridge, crumbly phuthu and stiff pap. The CCFs served maize meal porridge with milk, sugar, peanut butter, margarine and Morvite. CCFs 4, 7 and 10 served Morvite on Fridays. Maltabella, a breakfast cereal made from sorgum grains, was served by CCFs 8 and 10 once a week and biweekly at CCF 1. Two CCFs served cornflakes for breakfast once during a 5-day period. All CCFs (except CCF 10) served rice to 2-year-olds, as rice is considered soft and palatable for younger children. Rice was also the starch of choice for the older age groups at lunch. At teatime, CCF 6 served sliced brown or white bread with tea to 5-year-olds. On Fridays, CCF 4 served Morvite and polony sandwiches made from brown bread, with diluted, sweetened juice because there was no electricity to cook meals. Other sources of carbohydrates for the younger children included dhal soup, dhal and bean soup, baked bean soup, and samp and beans with fish soup. Soup powders were used to thicken soups and curries in all CCFs. Milk was only offered at breakfast time, with porridge, in some CCFs. In one CCF, 375 g Nespray powdered milk was added to a 25 L pot of porridge. Milk was also served with cornflakes for breakfast at two CCFs. Milk quantities were stretched by adding 500 mL of water to 1 L of milk. Some CCFs also served maas and phuthu once a week. Canned fish was widely offered as fish soup ranked number three on the top 20 list for both age groups. The fish bones were removed from the fish before preparing the soup. For the 2- to 3-year-olds, as illustrated

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23.3 (16.7) 11.1 11.2

40.5 0.9 (0.2) 44.1

39 1.2 (0.2) 61.3

2.6 13.2 (4.6) 12.6

15.4 2.9 (0.5) 9.8

53.5

94.6 (68.1) 94.6

51.2

45.3 26.7

41.8

109.2

100

82.7

24.8

23.4

91.3

30.5

24.7

5.8

43.9

27.1

74.1

60.7

7.9

21.3

39.5

Contribution to DRIs (%)

102.4

Mean (SD)

41.6

964.9 (581.5) 964.9 (581.5) 5.8 (3.6) 43.9 (23.1) 2.3 (1.2) 29.1 (33.5) 0.7 (0.6) 0.7 (0.4) 50.5 (54.9)

Contribution to DRIs (%)

41.4

Mean (SD)

23.2

2254.0 (849.6) 2254.0 (849.6) 14.0 (4.2) 91.3 (47.5) 4.5 (3.3) 124.2 (171.3) 2.5 (1.3) 2.2 (1.6) 229.4 (149.0)

51.3

Contribution to DRIs (%)

107

Mean (SD)

54.1

1113.6 (416.0) 1113.6 (416.0) 7.0 (2.7) 41.8 (13.6) 1.9 (1.2) 62.7 (57.9) 1.8 (1.8) 1.0 (0.4) 23.5 (35.4)

25.4

Contribution to DRIs (%)

26.1

47.7

36.7

9.7

42.8

41.5

22.5

Contribution to DRIs (%)

23.7

1734.0 (235.2) 1734.0 (235.2) 13.3 (4.7) 71.0 (1.6) 4.1 (1.3) 39.3 (11.9) 1.8 (0.4) 1.6 (0.4) 56.9 (27.2)

Mean (SD)

SAJCH

JUNE 2017 Vol. 11 No. 2

25.1

56.4

7.3

18.6

52.7

38.4

89.8

111.8

126.7

36.2

25.6

116.5

45.6

60.9

66.7

18.9

17.2

61.3

210 Vitamin A (RE) (µg) (EAR)

2.2

500

100

Total protein (g) (RDA) Carbohydrates avail. (g) (EAR) Total dietary fibre(g) (AI) Calcium (mg) (AI) Iron (mg) (EAR) Zinc (mg) (EAR)

Nutrient/day

DRIs age group 1 to 3 years

Energy (kJ) (EER)

Mean (SD)

4 393 Boys 4 166 Girls 13

1504.5 (844.9) 1504.5 (844.9) 9.4 (4.5) 61.3 (27.3) 3.3 (1.3) 94.3 (74.2) 2.0 (1.5) 1.3 (0.6) 95.7 (99.7)

34.3

Contribution to DRIs (%)

72.3

Mean (SD)

36.1

2603.9 (225.4) 2603.9 (225.4) 14.1 (0.8) 116.5 (8.4) 4.9 (0.5) 181.2 (33.9) 3.8 (0.1) 2.5 (0.2) 188.5 (26.6)

59.3

Contribution to DRIs (%)

108.5

Mean (SD)

62.5

1249.1 (125.8) 1249.1 (125.8) 5.0 (0.9) 52.7 (6.5) 3.5 (0.6) 36.5 (15.7) 2.5 (0.2) 1.2 (0.1) 52.7 (7.8)

28.4

Contribution to DRIs (%)

987.4 (829.6) 987.4 (829.6) 5.4 (4.1) 42.8 (37.5) 2.5 (2.6) 46.8 (61.5) 1.1 (1.1) 1.1 (1.1) 54.7 (100.5)

Mean (SD)

EAR = estimated average requirement; EER = estimated energy requirement; SD = standard deviation; AI = adequate intake; RE = retinol equivalent; RDA = recommended daily allowance; kJ = kilojoules; g = grams; µg = micrograms.

52.6

63.6

11.9

17.4

63.2

79.1

35.5

33.7

1478.2 (380.0) 1478.2 (380.0) 10.3 (5.0) 63.2 (16.5) 3.3 (1.3) 59. 5 (53.9) 1.6 (0.8) 1.4 (0.7) 110.4 (88.2) 42.9

1884.9 (1085.6) 1884.9 (1085.6) 6.7 (2.3)

9 Mean (SD)

Menus served in all Inanda CCFs did not provide >60% of the DRIs for energy, dietary fibre and calcium. Various studies have concluded that CCF meals usually do not meet the requirements for energy and micronutrients in children.[19-21] Results of studies conducted in 40 New York- and 20 Texasbased childcare centres showed that meals were below the RDAs for micronutrients and energy.[21,22] The use of fats, salt and sugar in meals in the Inanda CCFs was in line with the SAPFBDGs, as these condiments were used sparingly during food preparation, as seen in the top 20 foods list in Table 3. On the other hand, this resulted in menus not meeting the energy needs of the children. In childhood, energy is needed for increased activity and growth.[18,23] In developing countries, factors such as the burden of infectious diseases such as diarrhoea and parasitic infections, micronutrient deficiencies and catch-up growth increases the need for energy in children.[24] The meals served at the CCFs in Inanda (n=10) were nearly identical, with very little variation in the food items employed in menu construction. The mean portion served for starch items, as seen in Table 3, is above the recommended 40 and 60 g for children aged 1 - 3 and 4 - 6 years old, respectively. For children aged 1 - 3 years, the portion sizes for meat and vegetable dishes should be 70 - 80 g, of which 40 - 50 g is the recommended portion size for protein; 30 g is recommended for the vegetable portion, excluding soup. Children aged 4 - 5 years should be served at least 110 g of mixed meat and vegetable dishes, as 60 g is recommended for protein and 50 g is recommended for vegetables, excluding soup.[25] There was a lack of dietary fibre in meals at the CCFs, because of low consumption of fibre-rich carbohydrate foods such as whole grain cereals, fruits, and vegetables. Children were served refined cereals daily, and beans, dhal and samp once or twice weekly. This is in line with the SA Food Guide and the SAPFBDGs, which illustrates that starch should be consumed with most meals. The SAPFBDGs also state that legumes should be eaten regularly and that the food items consumed should be of good quality, in correct amounts and

Contribution to DRIs (%)

Discussion

Contribution to DRIs (%) Mean (SD)

Table 1. Nutrient adequacy of menus for children aged 2 to 3 years (n=10). 1 2 3

in Table 3, canned fish soup was served with rice in the CCFs. Canned fish was also cooked with dhal and served with rice. Canned fish soup with samp and beans was served in two CCFs. Other sources of protein included minced meat soup, chicken and dhal soup and chicken curry served once in the 5 days at different CCFs. The fruit and vegetable intake of the children was far below the recommended intake of the WHO of >400 g, and >240 g (60%) for a CCF, respectively. Only CCF 2 presented the children with a piece of fruit on four days of the week, at tea time. Generally, each child would receive either half an apple or orange (45 (0) g). Commonly used fresh vegetables included onions, potatoes, green beans, green peppers, tomatoes, spinach and carrots, and frozen vegetables included carrots, green beans and sweetcorn and were used mainly in soups and curries.

RESEARCH

40.2

39.5

7.4

12.1

11.2

38.1

3 ±1.3 59.5 (53.9) 1.6 (0.8) 1.4 (0.7) 110.4 (88.2) 2.8

68.3

13.3

63.2

21.4

54.1 44.1

16.9

38.3

50.7

16.1

3.3 (0.1) 22.5 (8.7) 1.6 (0.3) 1.1 (0.2) 30.9 (28.1) 10.4

57.6

56.1

2.6 (1.5) 128.6 (123.5) 2.1 (1.7) 1.5 (0.7) 46.4 (69.8) 31.7

34.3

30.2

4.7 18.9 (3.7) 135.1 16.9 (184.5) 2.7 64.9 (1.4) 2.4 59.8 (1.8) 247.4 90 (167.5) 9

84.8

9.1

98.8

76.8 56.6

39.3

38.1

3.9

2.3 (1.2) 72.1 (60.6) 1.2 (0.7) 1.4 (0.4) 87.2 (85.5) 12.7

74.5

64.3

22.9 62.9 (116.6) 25.9

1.2 (1.3) 29.3 39.5

78.1

5.9

52.9 6.6 (73.7) 1.2 (1.3) 28.5

3.2 (1.2) 31.3 (20.0) 1.6 (0.7) 1.6 (0.7) 49.4 (29.6) 2.6 (3.1) 10.4 18.4

84.8

129.1

32.4

4.6 (1.1) 47.5 (16.6) 3.2 (0.2) 1.6 (0.1) 71.11 (19.3) 25.6

95.3

104.4

4.9 (0.5) 259.0 (71.7) 5.3 (0.3) 3.4 (0.2) 266.7 (34.5) 30

275

4.1

800

7.5 (2.9) 111.9 (49.7) 4.3 (1.5) 2.6 (1.0) 262 (244.7)

161.2 108.7 100

49.2 49.2 (45.2) 67.2

33.8 100.4 85.2

Total protein (g) (RDA) Carbohydrates avail. (g) (EAR) Total dietary fibre (g) (AI) Calcium (mg) (AI) Iron (mg) (EAR) Zinc (mg) (EAR) Vitamin A (RE) (µg) (EAR)

DRIs age group 4 to 8 years

Energy (kJ) (EER)

Mean (SD)

7 316 Boys 6 896 Girls 19

2439.9 (412.8) 2439.9 (412.8) 16.2 (4.8) 108.7 (14.4)

Contribution to DRIs (%)

35.4

Mean (SD)

33.4

3564.2 (169.0) 3564.2 (169.0) 19.1 (1.7) 161.2 (7.5)

Contribution to DRIs (%)

51.7

Mean (SD)

48.7

1605.6 (104.8) 1605.6 (104.8) 6.4 (0.8) 67.2 (6.0)

Contribution to DRIs (%)

23.3

Mean (SD)

Nutrient/ day

Table 2. Nutrient adequacy of menus for children aged 4 to 5 years (n=10). 1 2 3

Contribution to DRIs (%)

Mean (SD)

1122.3 15.3 (1017.5) 1122.3 16.3 (1017.5) 6.1 (5.2) 32.1

1735.4 (537.7) 1735.4 (537.7) 12.2 (6.3) 74.5 (19.1)

Contribution to DRIs (%)

25.2

Mean (SD)

23.7

1858.7 (572.8) 1858.7 (572.8) 10.6 (4.0) 84.8 (22.8)

Contribution to DRIs (%)

Mean (SD)

25.4

2397.0 (949.5) 2397.0 (949.5) 14.6 (4.8) 98.8 (51.1)

Contribution to DRIs (%)

34.8

Mean (SD)

32.8

1574.0 (537.6) 1574.0 (537.6) 10.7 (4.1) 57.6 (15.6)

Contribution to DRIs (%)

22.8

Mean (SD)

21.5

1521.1 (192.6) 1521.1 (192.6) 8.4 (2.7) 68.3 (8.5)

Contribution to DRIs (%)

22.1

Mean (SD)

20.8

1478.2 (380.0) 1478.2 (380.0) 10.3 (5.0) 63.2 (16.5)

Contribution to DRIs (%)

20.2

RESEARCH

SAJCH

according to the child’s needs to contribute to the total daily intake, which is lacking in the CCFs’ meals.[26] Inadequate quantities of fruits and vegetables were offered, as none of the CCFs met 60% (240 g) of the WHO’s 400 g minimum recommended consumption for the day. The SAPFBDGs state that children should be given fruits and vegetables every day.[27] Vitamins and mineral substances obtained from consuming fruit and vegetables are essential to boost immunity and fight infections and illnesses in the body.[28] A study in Mangaung, Free State Province, SA, found that a cereal-based diet and low intake of fruit and vegetables resulted in low vitamin C and bioavailable iron.[20] Furthermore, the results of a study in the Limpopo Province of SA found that the meals served at CCFs in the province were mainly cereal-based with maize meal porridge. [29] There was a low intake of fruit and vegetables, which contributed to a low vitamin A intake. But a study conducted in rural villages in KwaZuluNatal showed that increasing the intake of dark green leafy vegetables, especially the indigenous types, contributed considerably to the total intake of calcium, vitamin A and riboflavin.[30] Children should also be served about 600 700 mL of milk per day to meet daily requirements. [25] The GECDS recommends that children should be given skimmed milk to drink.[6] CCFs in Inanda do not serve adequate amounts of calcium-rich foods (Table 3). The inadequacy of calcium-rich foods in the menus is contrary to the SAPFBDGs, which recommend that children of 24 months to 5 years should be given milk, maas or yoghurt every day.[27] At this age, calcium is needed as a blood clotting factor, to heal wounds, in the formation of bones and teeth, muscle contraction and nerve transmission.[31] A similar study in Free State Province in SA[20] found that protein was sufficient but the meals were low in iron, zinc, calcium and vitamin A, which suggested that the protein sources were of low quality. In this study, protein consumption was inadequate because high quality protein foods were served in small quantities and only once or twice weekly. The CCFs fell short of SAPFBDGs, which state that children younger than 5 years could eat lean chicken or lean meat or fish or eggs every day or as often as possible. In a study in Cape Town[19] protein exceeded recommended DRIs as CCFs were serving high-quality protein foods such as meat, eggs, fish, cheese and chicken. However, in the same study, meals were low in thiamine, riboflavin, zinc, vitamin D, folate and vitamin E, and DRIs for energy, calcium and iron were never met. Some meals also did not provide vitamins A, B12, C and D at all.[19] Animal protein sources are needed to build and maintain body tissues and red meat is a good source of iron, which assists in the production of red blood cells.[28] Worldwide, there is a problem with CCF feeding, which needs to be addressed and improved. The results of this study show that the Inanda CCFs were not very different from the rest of the world when it came to the nutrient adequacy of menus served to children.

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RESEARCH

Sugar, white 20

45 (0) 90 Orange, peeled 20 26 5 (1.6) 139

104 (0)

104 (0) 104

104 Chicken and vegetable soup

Chicken and dhal soup 18

19 2

3 50 (8.7)

70.5 (77.1) 141

150

Milk, whole 19

Baked beans soup 18

12 (0)

34 (4.8) 135

125 Cold drink, squash diluted

Bread, brown 16

17 2

4 46 (16.0)

91 (0) 182

185

Egg soup 17

Bread, brown 16

81 (0) 162 Egg soup 15 2 96.5 (12.0) 193

Samp & beans 15

6 (2.1)

100 (0) 200

185 Sugar, white

Rooibos tea 13

14 2

2 112 (29.7)

101 (26.9) 202

224

Maltabella, sorghum 14

Dhal & fish soup 13

210 (0)

113 (8.5) 226

210 Phuthu and maas

Dhal and fish soup 11

12 3

3 86 (9.7)

82 (2.7) 246

259

Chicken curry 12

Mince soup 11

78 (24.7)

70 (25.9) 280

233 Mince soup

Chicken curry 9

10 3

3 125 (0)

126 (61.2) 374

375

Dhal soup 10

Rooibos tea 9

84 (35.5)

118 (57.7) 354

337 Vegetable soup

Morvite 7

8 3

4 104 (27.8)

129 (66.3) 386

416

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Morvite 8

Vegetable soup 7

162 (76.2)

74 (37.9) 370

646 Maltabella, sorghum

Baked beans soup 6

5 3

3 146 (66.6)

155 (23.9)

Phuthu & maas 6

5 437

Samp & beans with fish soup 5

109 (74.5)

60 (12.4) 665

653 Samp and beans

Fish soup 3

4 4

11 72 (28.0)

125 (0) 500

792

82 (33.9) 2 857 Rice 2 34 100 (23.1) 3 414

120 (49.3) Maize meal 1 46

4 466

Cold drink, squash diluted 4

SAJCH

Fish soup 3

Rice 2

1. Bowley NA, Pentz‐Kluyts MA, Bourne LT, et al. Feeding the 1 - 7‐year‐old child. A support paper for the South African paediatric food‐ based dietary guidelines. Matern Child Nutr 2007;3(4):281-291. https://doi.org/10.1111/ j.1740-8709.2007.00112.x 2. Schwartz C, Scholten JPAM, Lalanne A, Weenen H, Nicklaus S. Development of healthy eating habits early in life. Review of recent evidence and selected guidelines. Appetite 2011;57(3):796-807. 3. Department of Social Development. 2nd Technical workshop of the Africa Early Childhood Care and Development Initiative. 2010. www.dsd.gov. za (accessed 20 March 2014).

150 (35.2)

Acknowledgements. We thank the owners, teachers, parents and children in the registered CCFs in Inanda for granting us permission and warmly welcoming us and working harmoniously with us in this study. This was all much appreciated. Author contributions. PFN collected and analysed the data, and wrote the manuscript. CEN supervised the research and reviewed the manuscript. Funding. Durban University of Technology. Conflict of interest. None.

6 911

This study has found that menus served to 2 - 5-year-olds in registered CCFs in Inanda were nutritionally inadequate as most CCFs did not meet the 60% daily requirements for many nutrients from menus served in the CCFs. It is almost impossible to provide 60% of the daily requirements for children on the ZAR9 to ZAR12 allowance presented by the government, making it important for government to consider funding CCFs to contribute to poverty alleviation in resourcepoor communities. A follow-up study could assist in developing menus that are nutritionally adequate yet affordable in this context. The sensory evaluation of food on offer should be conducted with the children to ensure that the menu items on offer are culture- and ageappropriate.

5 627 Maize meal 1

Conclusion

Total served Mean served portion Consumption (g or mL) (SD) (g or mL) frequency Table 3. Top 20 foods consumed by the children in all the CCFs ranked by total intake over 5 days (n=10). Children 2 to 3 years old Children 4 to 5 years old Total served Mean served portion Consumption No. Food items (g or mL) (SD) (g or mL) frequency No. Food Items

For this reason the American Dietetic Association created guidelines for childcare nutrition for 2 - 5- year-old children, which stipulate that CCFs should serve fresh, raw or frozen fruit and vegetables rich in vitamin C every day. Vitamin A-rich foods should be served on 3 days of the week, as should wholewheat grain products like bread and oats, which are a good source of dietary fibre. Children should also drink fat-free milk for their vitamin D and calcium requirements.[7] The meals in the Inanda CCFs need to keep in line with the GECDS as well as SA Food Guide and the SAPFBDGs. Training of food handlers and owners of the CCFs could lead to improved menus and optimal use of available funding in making nutrient-dense menu choices.

RESEARCH 4. Department of Basic Education. Education for All South Africa Country Report 2009. 2010. http://www.gov.za/sites/www.gov.za/files/DoBE_EFA%20 Country%20Report%202009_07062010.pdf (accessed 29 August 2016). 5. Biersteker L, Dawes A. Early childhood development. In: Kraak A, Press K, eds. Human resources development review: Education, employment and skills in South Africa. Cape Town: HSRC Press, 2008:185-205. 6. Department of Social Development Republic of South Africa. Guidelines for Early Childhood Development Services. 2008. www.unicef.org/southafrica/ SAFresources_ecdguidelines.pdf (accessed 24 January 2012). 7. Neelon BSE, Briley ME. Position of the American Dietetic Association: Benchmarks for nutrition in child care. J Am Diet Assoc 2011;111(4):607-615. https://doi.org/10.1016/j.jada.2011.02.016 8. Petrou S, Kupek E. Poverty and childhood undernutrition in developing countries: A multi-national cohort study. Soc Sci Med 2010;71(7):1366-1373. https://doi.org/10.1016/j.socscimed.2010.06.038 9. Black MM. Micronutrient deficiencies and cognitive functioning. J Nutr 2003;133(11):3927S-3931S. 10. Buhl A. Meeting Nutritional Needs Through School Feeding: A Snapshot of Four African Nations. Global Child Nutrition Foundation. 2010. 11. Tulchinsky TH. Micronutrient deficiency conditions: Global health issues. Pub Health Rev 2010;32(1):243-255. https://doi.org/10.1007/bf03391600 12. Nordin SM, Boyle M, Kemmer TM. Position of the Academy of Nutrition and Dietetics: Nutrition security in developing nations: Sustainable food, water, and health. J Acad Nutr Diet 2013;113(4):581-595. https://doi.org/10.1016/j. jand.2013.01.025 13. Briley ME, Roberts-Gray C. Position of the American Dietetic Association: Nutrition standards for childcare programs. J Am Diet Assoc 1999;99(8):981988. http://dx.doi.org/10.1016/S0002-8223(99)00235-7 14. Vossenaar M, Panday B, Hamelinck V, et al. Nutrient offerings from the meals and snacks served in four daycare centers in Guatemala City. Nutrition 2011;27(5):543-556. https://doi.org/10.1016/j.nut.2010.06.007 15. Everatt D, Smith M. Building sustainable livelihoods: Analysing a baseline (2006) and measurement (2008) survey in the 22 nodes of the Urban Renewal Programme and Integrated Sustainable Rural Development Programme. Pretoria: Department of Social Development, 2008. 16. Carr D, Levins J, Lindeman A. Plate waste studies. Practical Research. USA: National Food Service Management Institute, 2000. 17. Wolmarans P, Kunneke E, Laubscher R. The use of the South African Food Composition Database System (SAFOODS) and its products in assessing dietary intake data. Part II. S Afr J Clin Nutr 2009;22(2):59-67. https://doi.org/ 10.1080/16070658.2009.11734220

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18. Dietary reference intakes: Applications in dietary planning. National Academies Press, 2003. https://doi.org/10.17226/10609 19. Pietersen C, Charlton K, du Toit M, et al. An assessment of the nutrient content of meals provided and facilities present at state-funded crĂ¨ches in Cape Town. S Afr J Clin Nutr 2007;15:15-24. 20. Dannhauser A, Bester C, Joubert G, et al. Nutritional status of preschool children in informal settlement areas near Bloemfontein, South Africa. Public Health Nutr 2000;3(3):303-312. https://doi.org/10.1017/s1368980000000343 21. Erinosho T, Dixon LB, Young C, et al. Nutrition practices and children's dietary intakes at 40 child-care centers in New York City. J Am Diet Assoc 2011;111(9):1391-1397. https://doi.org/10.1016/j.jada.2011.06.001 22. Padget A, Briley ME. Dietary intakes at child-care centres in central Texas fail to meet Food Guide Pyramid recommendations. J Am Diet Assoc 2005;105(5):790-793. http://dx.doi.org/10.1016/j.jada.2005.02.002 23. Food and Agriculture Organisation (FAO). Report of a joint FAO, WHO, UNU expert consultation. Human Energy Requirements. 2001. http://www.fao.org/ publications/card/en/c/e1faed04-3a4c-558d-8ec4-76a1a7323dcc/ (accessed 9 September 2013). 24. Swart R, Dhansay A. Nutrition in Infants and preschool children. In: Community Nutrition Textbook for South Africa: A Rights-based Approach. Chronic Diseases of Lifestyle Unit: Medical Research Council, 2008:377-440. 25. Gordon-Davis L, van Rensburg L. The Hospitality Industry Handbook on Nutrition and Menu Planning. Cape Town: Juta & Co., 2004:138-144. 26. Department of Health. Guidelines for Healthy Eating for Nutrition Educators. Pretoria: DOH, 2012. 27. Vorster HH, Badham J, Venter C. An introduction to the revised food-based dietary guidelines for South Africa. S Afr J Clin Nutr 2013:26:S5-S12. 28. Faber M, Laurie S, Ball A, et al. A Crop-based Approach to Address Vitamin A Deficiency in South Africa. Medical Research Council - Cape Town/ ARCRoodeplaat, Pretoria: DOH, 2013:35-60. 29. Kwinda PC, van der Spuy E, Viljoen AT. Application of a food-based dietary guidelines as nutrition strategy in crĂ¨ches to enhance vitamin A consumption. J Fam Ecol Consumer Sci 2011;39:56-67. 30. Faber M, van Jaarsveld PJ, Laubscher R. The contribution of dark-green leafy vegetables to total micronutrient intake of two- to five-year-old children in a rural setting. Water SA 2009;3(3):407-412. https://doi.org/10.4314/wsa. v33i3.49153 31. Stein AJ. Global impacts of human mineral malnutrition. Plant Soil 2010;335(1):133-154. https://doi.org/10.1007/s11104-009-0228-2

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This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.

The impact of HIV infection and disease stage on the rate of weight gain and duration of refeeding and treatment in severely malnourished children in rural South African hospitals M Muzigaba,1,2 PhD, MPH, MPhil, BSc; B Sartorius,3 PhD, EPIET, MSc, BSc (Hons), BSc; T Puoane,2 Dr PH, MPH, BCur, BA SocSci; B van Wyk,2 DPhil, MSc, BSc; D Sanders,2 MB ChB, DCH, MRCP, DTPH, DSc School of Clinical Medicine, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa Faculty of Community and Health Sciences, School of Public Health, University of the Western Cape, Bellville, South Africa 3 Discipline of Public Health Medicine, School of Nursing and Public Health, University of KwaZulu-Natal, Durban, South Africa 1 2

Corresponding author: M Muzigaba (mochemoseo@gmail.com) Background. Evidence of the effects of HIV infection and clinical stage on the duration of refeeding and treatment (DRT) and the rate of weight gain (RWG) in severely malnourished children remains inconclusive. Objectives. To determine whether the RWG and DRT differ by baseline clinical characteristics, and to assess the effect of HIV status and disease stage on the relationship between these two clinical outcomes. Methods. This was a retrospective record review of 346 patiens discharged between 2009 and 2013 following treatment for severe acute malnutrition (SAM) at two rural hospitals in South Africa. Results. A third of the sample was HIV-positive, the RWG (measured as g/kg/day) was significantly slower in HIV-positive patients compared with HIV-negative cases (mean 5.2, 95% confidence interval (CI) 4.47 - 5.93 v. mean 8.51; CI 7.98 - 9.05; p<0.0001) and cases at stage IV of HIV infection had a significantly slower RWG (mean 3.97; CI 2.33 - 5.61) compared with those at stages I (mean 7.64; CI 6.21 - 9.07) (p<0.0001) and II (mean 5.87; CI 4.74 - 6.99). The mean DRT was longer in HIV-positive cases and those at advanced stages of HIV infection. HIV-positive cases were renourished and treated for almost 3.5 times longer than their HIV-negative counterparts to achieve a moderate RWG (5 - 10 g/kg/day). Conclusion. This study highlights the need to reconsider energy requirements for HIV-positive cases at different clinical stages, for more rapid nutritional recovery in under-resourced settings where prolonged hospitalisation may be a challenge. S Afr J Child Health 2017;11(2):86-92. DOI:10.7196/SAJCH.2017.v11i2.1194

Within sub-Saharan Africa, HIV infection has become a common comorbidity among children with severe acute malnutrition (SAM) and some evidence of its effect on survival of children with SAM has begun to emerge.[1-3] Some observational studies conducted in Africa have shown that children with SAM who are HIV-positive are more at risk of dying compared with their HIV-negative counterparts,[4-6] especially if they are marasmic.[3,7] In some cases of SAM, HIV is comorbid with other conditions such as lower respiratory tract infections (LRTIs) and tuberculosis.[8] According to Heikens,[9] these comorbidities have led to an epidemic of secondary SAM, which is more frequently associated with poor outcomes than primary SAM due to food shortage and non-HIV/ TB-related infections. However, the evidence of the effect of HIV infection and other baseline comorbidities on nutritional recovery among children with SAM who are <5 years of age, remains sparse and inconclusive. The differential effect of the World Health Organization (WHO) clinical stages of HIV on nutrition recovery has not been sufficiently, if at all, explored; inconsistent findings have been reported in a limited number of studies. For example, some studies in resource-poor sub-Saharan countries have shown that although HIV-positive, severely malnourished children can achieve normal nutritional status when treated according to specific treatment guidelines, the recovery is slower when compared with HIVnegative children.[2,5,10] Fergusson and colleagues, on the other hand, have reported similar nutritional recovery (mean 8.9 v. 8.0 g/kg/day) among HIV-positive and HIV-negative severely malnourished children who survived.[11] Further to this, the relationship between the rate of weight gain (RWG) and duration of refeeding and treatment (DRT), comparing HIV-positive

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and -negative SAM patients, remains unclear. Initial observations from two hospitals in which this study was conducted revealed that in some instances children were being discharged without due regard to whether they had gained weight sufficiently during the rehabilitation phase. This was partly because the healthcare workers were not sure as to how long the child needed to be in care to achieve optimal weight gain. An enquiry into this aspect of care was important, particularly because of the insufficient resources available to provide prolonged care in the study setting. There was also some speculation among healthcare workers that HIV-positive children would not gain weight at the same rate as their HIV-negative counterparts, no matter how well and for how long the WHO 10-step guidelines were used to treat them. This anecdote is partly supported by the recent WHO update on the WHO 10-step guidelines for management of SAM[12] which highlighted the existing gap in knowledge regarding nutritional recovery among children with SAM who are HIV-positive and are treated according to the current WHO treatment modality. This study sought to assess whether there was a relationship between the RWG and the DRT in a sample of children with SAM who survived, and were discharged, following treatment using the WHO 10-step treatment guidelines for management of severe malnutrition. The study also assessed whether this relationship was affected by baseline clinical characteristics, specifically investigating HIV co-infection, HIV disease stage, and SAM syndromic manifestation. Lastly, the study looked at HIV-negative SAM patients as well as HIV-positive SAM patients, at different HIV disease stages, to estimate how long it took for them to achieve a certain number of units of the RWG. As the nature of this study was operational, assessing these relationships was important not only to promote practices that would ultimately lead

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RESEARCH to better nutritional recovery at ward level, but also to enable the hospital administrators and the clinical teams to make informed decisions regarding resource allocation based on the patient’s clinical condition at baseline.

Methods

Study design

This study was approved by the University of the Western Cape Research Ethics Committee (ref. no. 12/10/37). The study consisted of a retrospective review of medical treatment records of children admitted with SAM in the study setting who survived and were discharged following treatment.

Setting

This study was conducted in two rural district hospitals in the Eastern Cape Province (EC), South Africa (SA). The hospitals were located in the former Transkei, an apartheid-era homeland and one of the most underresourced regions in SA.[13] These hospitals were selected based on the fact that they had participated in the initial province-wide intervention to improve the management of SAM in the EC. They were also found to have implemented the WHO 10-step guidelines more effectively than other hospitals in the region.[13] Throughout the study period - January 2009 to May 2013 - monthly SAM admissions in both hospitals constituted an average of 50% of the total paediatric ward admissions. The hospitals also served a catchment area with high HIV prevalence, with a monthly average HIV co-infection rate of 45% among children admitted with SAM.

Participants

Eligibility and selection

The unit of analysis in this study was the patient’s medical treatment record. The treatment records were purposefully selected by one researcher (MM) during regular visits to each hospital, based on a set of eligibility criteria. In total, 346 medical records were reviewed over the study period. The research team reviewed updated medical records at 3-month intervals during hospital visits. Medical records were eligible for review if they belonged to children aged between 6 and 60 months, who were admitted at any of the two hospitals with SAM between January 2009 and May 2013, and were discharged following treatment. Children were discharged if they: (i) completed the transition to catch up and were eating well; (ii) they had no oedema; (iii) had completed antibiotic treatment; (iv) had received electrolytes and micronutrients for at least 2 weeks; (v) their immunisation was up-to-date; and (vi) their road-to-health card had been updated. The exclusion of patients that died was logical, as most of these patients died during the first three days of admission or earlier before the stabilisation phase. Thus, their RWG could not be determined. Other inclusion criteria included having patient treatment records with clearly defined SAM syndromic classifications based on the Wellcome classification system,[14] having records showing HIV test results and HIV clinical stage for HIVpositive patients, and having had a complete treatment record while in the hospital. A comprehensive written medical examination by a doctor, and the discharge criteria followed for patients who did not die while on treatment, were also used as eligibility criteria.

Patient management and follow-up

Treatment records were accumulated over the study period following standardised treatment of patients admitted with SAM. A patient with SAM brought to the hospital was seen by a doctor in the outpatient department, where the admitting doctor provided the diagnosis and the course of treatment to be followed based on the WHO 10-step guidelines. This information was recorded in standardised patient treatment charts as the basis for follow-up treatment and for record-keeping. For patients that were admitted to the ward, their caregivers were requested to provide consent for their children to take part in the study and also so that they would both be screened for HIV infection. Children who

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tested HIV-positive were identified and their treatment charts set aside for HIV disease staging by the doctor during follow-up ward rounds. Based on the screening results, two broad groups were formed: group A (HIV-negative patients) and group B (HIV-positive patients). Group B was further divided into four categories based on the clinical stage of HIV infection as defined by the WHO guidelines for staging infants and children.[15] The recruitment process is summarised in Fig. 1. All SAM patients were treated at the hospital using the recommended WHO 10-steps guidelines for management of SAM.[16] Children with SAM and HIV co-infection were referred to an HIV clinic situated within the hospital premises for initial or follow-up treatment.

Variable definition and measurement

The outcome variables in this study were DRT and RWG. DRT was defined as the total number of days - from admission to discharge - during which a SAM patient was treated for SAM and other comorbidities as per the WHO treatment guidelines. This was computed from the admission and discharge dates in the patient treatment chart. The RWG was defined as the number of grams gained per kilogram of body weight per day (g/kg/day) during the rehabilitation phase. Patients with the RWG ≤0 g/kg/day were considered as those who lost or did not gain weight; whereas those with ≤5 g/kg/day had poor weight gain; 5 - 10 g/kg/day had moderate weight gain; and >10 g/kg/day had good weight gain. The data used to compute this measure were obtained from a standardised patient weight monitoring chart which was included in Two hospitals (A and B) selected on account of having been the best in the region to optimally implement the WHO guidelines for some time Admission of SAM cases at hospital A – paediatric ward

Admission of SAM cases at hospital B – paediatric ward

HIV screening for all SAM cases (plus caregiver) in each hospital following consent by a parent or guardian

Group A (crude) (HIV-negative SAM cases)

Group B (crude) (HIV-positive SAM cases)

Stage I, II, III, IV Treatment of all SAM cases using the recommended WHO guidelines Retrospective patient record review to document baseline clinical characteristics and treatment outcomes Group A (eligible) (HIV-negative SAM cases; n=258)

Group B (eligible) (HIV-positive SAM cases; n=196)

Group X (eligible) (Group A who survived; n=229)

Group Y (eligible) (Group B who survived; n=117)

Data analysis (N=346) Fig. 1. Flow chart of the participant recruitment and data extraction process.

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RESEARCH the patient treatment record. The weight-for-height z-scores were not considered as a measure of nutritional recovery as the height data were not always recorded in the patient treatment record. Predictor variables and possible confounders included baseline clinical characteristics, such as SAM classification, oedema grade, dermatosis grade, presence of LRTIs, critical illness on admission, presence of other comorbidities, HIV status, and the WHO HIV/AIDS disease stage. Classification of SAM followed the Wellcome system,[14] primarily because there was evidence of inconsistent measurement of patients’ height/ length. HIV testing was done using the HIV polymerase chain reaction (PCR) test, following confidential and private counselling of the caregiver by a professionally trained nurse. HIV clinical staging was done by the admitting doctor as per the WHO guidelines.[15] Oedema and dermatosis were graded on admission as none, mild (+), moderate (++), and severe (+++).[17,18] The LRTIs was an umbrella term used for patients with comorbidities such as pneumonia, bronchitis and other infections below the larynx. Tuberculosis was not a common comorbidity in the treatment records, which may be a result of under-diagnosis or misdiagnosis of the condition in the study setting. Critical illness and other comorbidities were defined based on clinical diagnostic information in the patients’ medical records. Definition of cases as ‘critically ill’ was based on whether or not they were admitted with one or a combination of five clinical features, namely: (i) depressed conscious state (prostration or coma); (ii) bradycardia; (iii) evidence of shock with or without dehydration; (iv) hypoglycaemia and/ or (v) hypothermia, as defined by Maitland et al.[19] Other comorbidities, directly or indirectly related to SAM, were also noted, for example: lethargy, hyponatraemia and hypokalaemia, dehydration, deep acidotic breathing, anaemia and pyrexia, herbal intoxication, presence of diarrhoea, burns and other congenital dysfunctions commonly reported by the doctors in each hospital. A structured and validated questionnaire developed by the International Malnutrition Taskforce and Muhimbili Hospital in Tanzania[20] was used for the extraction of all the data.

Data analysis

All the data were cleaned and analysed using Stata/IC 13.0 (StataCorp., Texas). Subjects’ baseline clinical characteristics were summarised using frequency tables. The RWG and DRT were firstly inspected for normality using the Shapiro-Wilk and Shapiro-Francia tests, which revealed that they were normally distributed. The distributions of these outcomes across all nine baseline clinical profile variables were displayed using Forest Plots with means and 95% confidence intervals (CIs). Inter-group mean differences were assessed using one-way analysis of variance and independent sample t-tests, as applicable. To assess whether there were significant differences between the two study sites in terms of RWG and DRT, an independent samples t-test was used. Exploratory bivariate analyses were conducted using a linear regression model to explore the relationships between each outcome variable (RWG and DRT) and the nine baseline clinical characteristics as predictors. These relationships were further explored using multivariate regression analysis. The model estimates were plotted using the coefplot command in Stata 13.0 which displayed different levels of statistical significance for each predictor variable. To assess the relationship between the RWG and DRT, and whether this was influenced by HIV status or HIV clinical stage, a non-parametric regression analysis using a locally weighted smoothing (LOWESS) technique was used. This technique generated a locally weighted regression of the dependant variable (RWG) on the independent variable (DRT) and two-way locally weighted scatterplot smooths stratified by different levels of HIV status and HIV clinical stages. This nonparametric method was preferred because the relationship between RWG and DRT did not appear to be linear during exploratory analysis. LOWESS was also used because it is known to generate a regression line which follows the data and, as such, provided a more accurate reflection of the relationship between the RWG and DRT.[21]

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Results

Descriptive results

Approximately 88% of the study records for children who were discharged during the study period met the eligibility criteria and were included in this study. Subjects’ baseline clinical characteristics are presented in Table 1, which shows that 33.8% of SAM patients who survived and were discharged were HIV-positive, 15% were admitted in a critical condition, 28% had other comorbidities and 20% had LRTIs. A large proportion (86%) were younger than 25 months and 42% were admitted with kwashiorkor, whereas 33% were admitted with marasmus. It was noteworthy that 28% and 8% of patients were at stages III and IV of HIV infection, respectively.

Inferential results

The comparison of the two hospitals in terms of the distribution of the RWG revealed that there were no statistically significant differences (mean (standard deviation (SD)) 7.788 (3.121) v. 7.186 (3.421) g/kg/day; p=0.236). The means for DRT were also not statistically different (13.15

Table 1. Characterisation of SAM patients by baseline clinical profile (N=346) Variable Age (months) 6 - 12 13 - 24 25 - 36 37 - 60 SAM syndromic classification Marasmus Kwashiorkor Marasmic kwashiorkor Oedema grade None Mild Moderate Severe Dermatosis grade None Mild Moderate Severe LRTIs Yes No Other comorbidities Yes No Critically ill on admission Yes No HIV status Positive Negative HIV/AIDS disease stage 1 2 3 4

n (%)*

112 (33.6) 175 (52.5) 28 (8.4) 18 (5.5) 111 (33.2) 141 (42.2) 82 (24.6) 99 (29.6) 23 (6.9) 96 (28.7) 116 (34.7) 102 (30.5) 79 (23.7) 120 (35.9) 33 (9.9) 67 (20.1) 267 (79.9) 96 (28.7) 238 (71.3) 50 (14.9) 284 (85.1) 113 (33.8) 221 (66.2) 31 (27.4) 41 (36.3) 32 (28.3) 9 (8.0)

SAM = severe acute malnutrition; LRTIs = lower respiratory tract infections. *Unless otherwise specified.

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RESEARCH (3.794) v. 12.011 (3.324) days; p=0.052). Pooled analyses were therefore carried out to determine the distribution of each of the two outcome indicators across various clinical characteristics at baseline, as shown in Figs 2 and 3. The mean RWG was slower with advanced HIV disease stage (p<0.0001), as shown in Fig. 2. Similarly, HIV-positive patients attained a much slower RWG compared with their HIV-negative counterparts (p<0.0001), as did marasmic patients compared with kwashiorkor and marasmic kwashiorkor, although this difference was not statistically significant (p=0.233). Patients who were admitted with other comorbidities, and those who were critically ill, attained a slower RWG than those who were not critically ill, but these differences were also not statistically significant (p=0.169 and p=0.102, respectively). The overall mean RWG was 7.38 g/kg/day (95% CI 6.91 - 7.84). All inter-group differences were not statistically significant at 95% significance level except for HIV status (Fig. 3). HIV-positive patients were hospitalised for notably longer periods (mean 18.59 days; 95% CI 16.96 - 20.22) than their HIV-negative counterparts (mean 14.07 days; 95% CI 13.17 - 14.97). However, there were some patterns of differences in other predictor variables, which are worth noting despite the lack of statistical significance. Marasmic SAM patients who were discharged remained on treatment for longer periods compared with those who were classified as having kwashiorkor or marasmic kwashiorkor. Patients without or with mild oedema (+)stayed a little longer than those with moderate (++) and severe oedema (+++), but there were no notable statistically significant differences in respect of dermatosis grade. The average length of stay was also longer for SAM patients at stage IV of HIV infection compared with other clinical stages. The mean DRTs for all HIV clinical stages were higher than the overall mean DRT for the study sample, which was 15.6 days (95% CI 14.76 - 16.44). Table 2 shows the bivariate relationship between patientsâ&#x20AC;&#x2122; baseline clinical profile and each of the two outcome variables in this study. No. ..... pts No. of patients, n ...

Subgroup Subgroup

SAM syndromic classification 111 Marasmus 147 Kwashiorkor 83 Marasmic kwashiorkor

7.07 (6.24 - 7.90) 7.46 (6.81 - 8.12) 7.63 (6.61 - 8.65)

Oedema grade None Mild Moderate Severe

99 23 98 121

6.80 (5.93 - 7.68) 7.74 (5.78 - 9.71) 7.78 (6.86 - 8.69) 7.45 (6.75 - 8.15)

Dermatosis grade None Mild Moderate Severe

104 82 122 33

7.29 (6.42 - 8.16) 8.10 (7.20 - 9.00) 6.94 (6.20 - 7.69) 7.45 (5.82 - 9.08)

LRTIs No Yes

272 69

7.36 (6.86 - 7.87) 7.43 (6.31 - 8.54)

Other comorbidities No Yes

242 99

7.52 (6.98 - 8.07) 7.01 (6.13 - 7.89)

Critically ill on admission No Yes

288 53

7.41 (6.92 - 7.91) 7.17 (5.92 - 8.43)

224 117

8.51 (7.98 - 9.05) 5.20 (4.47 - 5.93)

32 43 33 9

7.64 (6.21 - 9.07) 5.87 (4.74 - 6.99) 2.30 (1.44 - 3.16) 3.97 (2.33 - 5.61)

341

7.38 (6.91 - 7.84)

HIV infected No Yes

HIV clinical stage I II III IV

Overall (N) 0

Effect (95% CI) Mean (95% CI)

Rate of weight gain (g/kg/day) *Inter-group differences were statistically significant (p<0.0001)

Fig. 2. Mean rate of weight gain (RWG) by HIV status, HIV disease stage and other baseline clinical characteristics: Pooled analysis based on patients who were discharged (2009 - 2013).

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No. .....

Subgroup Subgroup

No of pts patients, n

Effect (95% CI) Mean (95%

CI)

SAM syndromic classification 111 Marasmus 151 Kwashiorkor 84 Marasmic kwashiorkor

17.45 (15.78 - 19.12) 15.32 (14.08 - 16.57) 13.64 (12.29 - 14.99)

Oedema grade None Mild Moderate Severe

99 23 99 125

16.89 (15.07 - 18.71) 17.13 (13.69 - 20.57) 14.48 (13.22 - 15.75) 15.18 (13.80 - 16.56)

Dermatosis grade None Mild Moderate Severe

104 83 124 35

15.78 (14.16 - 17.40) 16.27 (14.54 - 17.99) 15.19 (13.79 - 16.60) 14.91 (12.67 - 17.16)

LRTIs No Yes

276 70

15.34 (14.42 - 16.27) 16.60 (14.57 - 18.63)

Other comorbidities No Yes

246 100

15.33 (14.32 - 16.34) 16.26 (14.73 - 17.79)

Critically ill on admission No Yes

293 53

15.75 (14.81 - 16.69) 14.75 (13.00 - 16.51)

229 117

14.07 (13.17 - 14.97) 18.59 (16.96 - 20.22)

32 43 33 9

16.88 (14.35 - 19.40) 18.00 (15.85 - 20.15) 18.85 (15.43 - 22.27) 26.56 (17.15 - 35.96)

346

15.60 (14.76 - 16.44)

HIV infected No Yes

HIV clinical stage I II III IV Overall (N)

8 10 12 14 16 18 20 22 24 26 28

Duration of refeeding and treatment in days (DRT)

*Inter-group differences were statistically significant (p<0.0001)

Fig. 3. Distribution of the duration of refeeding and treatment (DRT) by HIV status, HIV disease stage and other baseline clinical characteristics: Pooled analysis based on patients who were discharged (2009 - 2013).

As shown in Table 2, the DRT was significantly different among SAM patients depending on their SAM syndromic classification. Marasmic patients stayed significantly longer in the hospital than kwashiorkor and marasmic kwashiorkor patients (p=0.032 and p=0.001, respectively). HIV-positive patients, most of whom were marasmic, stayed longer in the hospital by four daily units compared with their HIV-negative counterparts (p<0.0001), whereas HIV-positive patients who were at stage IV stayed longer by nine daily units compared with those who were at stage 1 (p=0.004). Other baseline clinical characteristics were not significantly associated with the DRT. With regards to the RWG, HIV status and HIV clinical stages were the only clinical characteristics that were significantly associated with the RWG at the bivariate level. HIV-positive patients achieved a slower RWG by 3.3 units compared with HIV-negative patients (p<0.0001). Similarly, HIV-positive patients who were at stages IV, III and II attained a slower RWG by 3, 5 and 1 units, respectively, compared with those who were at stage 1; these results were statistically significant (p=0.006, p<0.0001, p=0.032, respectively). The only predictors which had a statistically significant overall effect on DRT were SAM syndromic classification (F (2, 343); p=0.004) and HIV clinical stage (F (3, 113); p=0.035). The only predictor which had a statistically significant overall effect on RWG was HIV clinical stage (F (3, 113); p<0.000). The multivariate model showed that HIV clinical stage was the only predictor of RWG and DRT at 95% level of statistical significance after adjusting for all other predictors in the model. The sum of all the predictor variables in the multivariate model explained 33% of variability of the RWG and 26% of variability in the DRT. The unexplained variance was most likely due to unmeasured confounders. Since none of the predictors were significantly associated with the RWG and the DRT in a multivariable model, except for HIV disease stage, a multivariate LOWESS regression (MLOWESS) was not necessary

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RESEARCH Table 2. Relationship between baseline clinical characteristics of SAM cases and two outcomes (DRT (days) and RWG (g/kg/day)): Bivariate regression analysis Outcomes DRT (days) RWG (g/kg/day)

Factors SAM syndromic classification Marasmus Kwashiorkor Marasmic kwashiorkor Oedema grade None Mild Moderate Severe Dermatosis grade None Mild Moderate Severe Presence of LRTIs No Yes Other comorbidities No Yes Critically ill on admission No Yes HIV status Negative Positive HIV clinical stage I II III IV

95% CI

p-value

95% CI

p-value

Ref –2.126 –3.907

–4.065 - –0.186 –6.051 - –1.564

0.032 0.001

Ref 0.396 0.559

–0.681 - 1.473 –0.684 - 1.803

0.470 0.377

Ref 0.241 –2.404 –1.713

–3.383 - 3.866 –4.630 - –0.177 –3.820 - 0.394

0.896 0.134 0.111

Ref 0.942 0.974 0.647

–1.039 - 2.924 –0.245 - 2.194 –0.512 - 1.807

0.350 0.117 0.273

Ref 0.486 –0.585 –0.864

–1.834 - 2.806 –2.681 - 1.519 –3.945 - 2.2162

0.680 0.583 0.581

Ref 0.813 -0.343 0.161

–0.449 - 2.075 –1.484 - 0.797 –1.546 - 1.870

0.206 0.554 0.853

Ref 1.255

–0.847 - 3.358

0.241

Ref 0.065

–1.089 - 1.221

0.911

Ref 0.931

–0.934 - 2.795

0.327

Ref –0.514

–1.53 - 0.506

0.322

Ref –0.996

–3.344 - 1.352

0.405

Ref –0.23

–1.517 - 1.043

0.716

Ref 4.51

2.795 - 6.243

<0.001

Ref –3.314

–4.225 - –2.403

<0.001

Ref 1.125 1.973 9.680

–2.932 - 5.182 –2.338 - 6.285 3.123 - 16.238

0.584 0.366 0.004

Ref –1.773 –5.343 –3.67

–3.388 - –0.159 –7.059 - –3.627 –6.282 - –1.063

0.032 <0.001 0.006

SAM = severe acute malnutrition; DRT = duration of refeeding and treatment (days); RWG = rate of weight gain (g/kg/day); CI = confidence interval; Ref = reference group; LRTIs = lower respiratory tract infections.

to determine the adjusted relationship between the two outcome variables. Therefore, a bivariate LOWESS regression was used and the results are presented in Figs 4 and 5. There were notable differences in the RWG between HIV-positive and HIV-negative SAM patients, as shown in Fig. 4. The locally weighted smooths predicted that, while HIV-negative patients who were on treatment for at least 10 days achieved a RWG of around 7.5 g/kg/day, those who were HIV-positive only attained a rate of 3.5 g/kg/day during the same time period (as shown by the vertical dotted lines in Fig. 4). For HIV-negative patients, a moderate RWG (5 - 10 g/kg/day) was achieved by patients who received refeeding and treatment for at least 5 days, whereas HIV-positive patients who attained the same RWG had to receive refeeding and treatment for at least 17 days. However, this analysis did not consider the SAM patients who had a negative RWG. There were 4 such patients from both facilities that were extreme outliers and distorted the position of the locally weighted smoothed lines significantly. It is also important to note that the RWG was consistently higher among HIV-negative patients compared with HIV-positive patients across all time intervals. The locally weighted smoothed regression lines in Fig. 5 show that HIV-positive SAM patients who were at stage I achieved a faster RWG

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in a relatively shorter period of refeeding and treatment compared with those who were at advanced stages of HIV infection.

Discussion

The results of the relationship between HIV status and the RWG both confirm and refute evidence from past research. The current study showed that on average, HIV-negative SAM patients recorded a better RWG than their HIV-positive counterparts. The results were similar in both hospitals. Savadogo et al.[22] also found similar relationships between HIV status and the RWG; however, unlike in the present study, they used the median RWG as a measure of the distribution of the RWG by HIV status. Their results revealed that HIV-positive SAM patients achieved a median of 4.64 g/kg/day v. 9.04 g/kg/day for HIV-negative patients. Several other studies[2,5,10] have also confirmed this relationship. However, Fergusson et al.[11] reported similar RWGs between HIV-positive and -negative SAM patients (mean 8.0 v. 8.9 g/kg/day, respectively). In the present study, the poorer nutritional recovery observed among HIV-positive SAM patients may, in part, be a result of metabolic changes associated with HIV infection, which impact on the nutritional status of the child. These changes include,

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RESEARCH HIV-negative SAM cases

HIV-positive SAM cases

RWG (g/kg/day)

0 0

DRT (days)

RWG (g/kg/day) Fitted values (linear) Locally weighted smooth (LOWESS) for RWG v. LSH (non-linear) Time taken to achieve moderate RWG (5 - 10 g/kg/day)

Fig. 4. Relationship between rate of weight gain (RWG) and duration of refeeding and treatment (DRT) by HIV status: Two-way scatter plot with locally weighted smoothed regression lines and a linear plot overlay. 15

Stage I

Stage II

Stage III

Stage IV

RWG (g/kg/day)

10 5 0 15 10 5 0 0

were able to provide precise quantifiable targets, such as time taken to achieve weight-for-height z-scores, which are oedema-free. In the present study, weight-for-height z-scores were not used as the medical records did not always have data on patient length and height. Perhaps the most important contribution to the literature from our study is the estimation of the relationship between HIV disease stage and the RWG. The study showed that the mean RWG became smaller with advanced HIV disease stage. The relationship between the RWG and HIV disease stage can be explained in light of the randomised controlled trial which demonstrated that half the children hospitalised for SAM developed oedema after starting antiretroviral therapy (ART).[26] Oedema may be associated with a slower RWG as children with oedema have to lose weight during the rehabilitation phase before they gain non-oedema-associated weight. Another possible explanation for this observation is that oedematous children are often more ill and unable to adequately metabolise nutrients. The evidence around this physiological process is still poorly understood. Another key finding from this study was the estimation of the relationship between the RWG and DRT and how these variables can be influenced by HIV status and disease stage. The non-linear polynomial regression and scatter plot smooths estimated that the trajectory to better RWG was faster and consistently higher among HIV-negative SAM patients compared with their HIV-negative counterparts. To our knowledge, this finding has not been documented elsewhere in the literature and may need to be verified in future studies, within a variety of contexts. Nevertheless, against the backdrop of this study, where resources for prolonged management of SAM patients may be relatively fewer, the fact that HIV-positive SAM patients took longer to attain the same RWG as their HIV-negative counterparts may have some practical implications to consider. To optimise outcomes in respect of nutritional recovery, it may be important to prioritise resources for HIV-positive SAM patients, particularly the availability of hospital beds and therapeutic feeds, in addition to medication stock for SAM-related comorbidities.

Study limitations

DRT (days) RWG Fitted values (Linear)

Locally weighted smooth (LOWESS) for RWG v. LSH (non-linear)

Fig. 5. Two-way scatter plots with locally weighted smoothed regression curves and linear plot overlays showing the relationship between the rate of weight gain (RWG) and duration of r-enutrition and treatment (DRT) by HIV clinical stage.

for example, hyper-metabolism of energy stores, nutrient losses and malabsorption as a result of inflammation of the gastrointestinal tract, reduced bioavailability of certain nutrients, and altered nutrient utilisation.[23] Poor appetite, which results in inadequate nutrient intake, has also been documented.[12] HIV-positive patients tend to present with severe oral and oesophageal candidiasis which undermine stherapeutic feeding efforts.[24] This finding begs a question as to whether a much more aggressive therapeutic feeding approach and treatment modality for HIV-positive SAM patients with associated comorbidities may be required to counteract these pathophysiological and metabolic challenges that HIV infection presents among SAM patients. The finding related to the relationship between DRT and HIV status agrees with results from a study by Madec et al.,[25] who showed that the duration of refeeding was much longer among HIVpositive patients (mean 22 days) than in HIV-negative patients (mean 12 days). However, these estimates were larger than those found in our study which recorded means of 14.07 and 18.59 days for HIV-negative and HIV-positive SAM patients, respectively. These differences may be related to the concomitant differences in discharge criteria set out in the study. The study by Madec et al.[25] seems to imply that the minimum number of days required to achieve good nutritional recovery is roughly 22 for HIV-positive SAM patients and 12 for HIVnegative patients. However, neither the present nor Madecâ&#x20AC;&#x2122;s study

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The measurement of quality of care for SAM patients and its relationship with the outcome variables (RWG and DRT) was beyond the scope of this study and is encouraged in future research. However, it was encouraging to learn that there were no statistically significant differences between the two hospitals in terms of the distribution of the two outcomes and how they were related to the predictor variables. Furthermore, only 88% percent of the available medication records for children who were discharged during the entire study period met all the eligibility criteria for record review. It is not known what the remaining 12% would have contributed to the direction and strengths of the relationships presented in this study. There is also limited generalisability of the results presented here, as the study was conducted in purposefully selected facilities where the implementation of the WHO treatment modality for SAM was presumed optimal. Lastly, but not least, patient records did not always have an indication of whether the study subjects were already on ART at admission, and for how long they had been on treatment. This information could not be verified since the study involved a retrospective record review. This information would have constituted important variables to assess as potential confounders or predictors of the RWG and DRT. Given the design limitation of this study, the recommendations made in this article in relation to the WHO protocol should not be considered as definitive but rather suggestive.

Conclusions

The findings from this study suggest that nutritional recovery is, in part, a function of HIV status, HIV disease stage and the duration of refeeding. Our findings raise some important research topics to be explored in future research studies, including, for example, the determination of differential energy requirements among SAM patients depending on

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RESEARCH their HIV status. Such studies can also explore the optimal choice of therapeutic feeds during the transition phase for HIV-positive SAM patients and how long it takes SAM patients, with or without HIV infection, to achieve specific targets for nutritional recovery in terms of the weight-for-height z-scores. Acknowledgement. The staff at the two hospitals where this study was conducted are gratefully acknowledged. Author contributions. DS and TP conceived the study, MM conducted the study and analysed the data. BS provided guidance for statistical analysis and commented on the initial drafts of the manuscript. MM prepared the manuscript for all co-authors (DS, TP and BS) to edit. Funding. This study was funded by the SA National Research Foundation (NRF) and in part by the SA Centre for Epidemiological Modelling and Analysis. Conflict of interest. None. 1. Bachou H, Tylleskar T, Downing R, Tumwine JK. Severe malnutrition with and without HIV-1 infection in hospitalized children in Kampala, Uganda: Differences in clinical features, haematological findings and CD4+ cell count. Nutr J 2006;5(1):27. https://doi.org/10.1186/1475-2891-5-27 2. Ndekha MJ, Mnary MJ, Ashorn P, Briend A. Home based therapy with ready to use therapeutic food is of benefit to malnourished, HIV-infected Malawian children. Acta Paediatr 2005;94(2):222-225. https://doi. org/10.1111/j.1651-2227.2005.tb01895.x 3. Kessler L, Daley H, Malenga G, Graham S. The impact of the Human Immunodeficiency Virus type 1 on the management of severe malnutrition in Malawi. Ann Trop Paediatr 2000;20(1):50-56. https://doi. org/10.1080/02724930092075 4. Chinkhumba J, Tomkins A, Banda T, Mkangama C, Fergusson P. The impact of HIV on mortality during inpatient rehabilitation of severely malnourished children in Malawi. Trans R Soc Trop Med Hyg 2008;102(7):639-644. https:// doi.org/10.1016/j.trstmh.2008.04.028 5. Ticklay IM, Nathoo KJ, Siziya S, Brady JP. HIV infection in malnourished children in Harare, Zimbabwe. East Afr Med J 1997;74:217-220. 6. Mgone CS, Mhalu FS, Shao JF, et al. Prevalence of HIV-1 infection and symptomatology of AIDS in severely malnourished children in Dar Es Salaam, Tanzania. J Acquir Immune Defic Syndr 1991;4(9):910-913. https://doi. org/10.1097/00126334-199109000-00013 7. Prazuck T, Tall F, Nacro B, et al. HIV infection and severe malnutrition: A clinical and epidemiological study in Burkina Faso. AIDS 1993;7(1):103-108. https://doi.org/10.1097/00002030-199301000-00016 8. De Maayer T, Saloojee H. Clinical outcomes of severe malnutrition in a high tuberculosis and HIV setting. Arch Dis Child 2011;96(6):560-564. https://doi. org/10.1136/adc.2010.205039 9. Heikens GT. How can we improve the care of severely malnourished children in Africa? PLoSMed 2007;4(2):e45. https://doi.org/10.1371/journal. pmed.0040045 10. Sandige H, Ndekha MJ, Briend A, Ashorn P, Manary MJ. Home-based treatment of malnourished Malawian children with locally produced or imported ready-to-use food. J Pediatr Gastroenterol Nutr 2004;39(2):141-146. https://doi.org/10.1097/00005176-200408000-00003

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11. Fergusson P, Tomkins A. HIV prevalence and mortality among children undergoing treatment for severe acute malnutrition in Sub-Saharan Africa: A systematic review and meta-analysis. Trans R Soc Trop Med Hyg 2009;103(6):541-548. https://doi.org/10.1016/j.trstmh.2008.10.029 12. World Health Organization. Guideline: Updates on the management of severe acute malnutrition in infants and children. WHO Library Cataloguingin-Publication Data. Geneva: WHO, 2013. http://apps.who.int/iris/ bitstream/10665/95584/1/9789241506328_eng.pdf (accessed 16 May 2016). 13. Puoane T, Sanders D, Ashworth A, Ngumbela M. Training nurses to save lives of malnourished children. Curationis 2006;29(1):73-78. https://doi. org/10.4102/curationis.v29i1.1055 14. Murgod R, Ahmed M. Instant nutrition assessment in children with protein energy undernutrition. Int J Appl Bio Pharma Tech 2015;6(1):171-177. 15. World Health Organization. Interim WHO clinical staging of HIV/AIDS and HIV/AIDS case definitions for surveillance (African Region). Geneva: WHO, 2005. http://www.who.int/hiv/pub/guidelines/casedefinitions/en/index.html (accessed 15 May 2016). 16. World Health Organization. Management of severe malnutrition: A manual for physicians and other senior health workers. Geneva: WHO, 1999. http:// whqlibdoc.who.int/hq/1999/a57361.pdf (accessed 12 May 2016). 17. Latham MC. The dermatosis of kwashiorkor in young children. Semin Dermatol 1991;10(4):270-272. 18. World Health Organization. WHO child growth standards and the identification of severe acute malnutrition in infants and children. A joint statement by the World Health Organization and the United Nations Children’s Fund. Geneva: WHO, 2009. http://apps.who.int/iris/ bitstream/10665/44129/1/9789241598163_eng.pdf (accessed 10 May 2016). 19. Maitland K, Berkley JA, Shebbe M, Peshu N, English M, Newton CRJC. Children with severe malnutrition: Can those at highest risk of death be identified with the WHO protocol? PLoS Med 2006;3(12):e500. https://doi. org/10.1371/journal.pmed.0030500 20. World Health Organization. Improving the Inpatient Management of Severe Acute Malnutrition: Toolkit to monitor current management of severe acute malnutrition. Geneva: WHO, 2010. http://www.cmamforum.org/Pool/Resources/ Toolkit-to-monitor-management- SAM-2010.pdf (accessed 12 May 2016). 21. Royston P. Lowess smoothing. Stata Technical Bulletin 1991;3:7-9. Reprinted in Stata Technical Bulletin Reprints, vol. 1, pp. 41-44. College Station, TX: Stata Press, 1991. 22. Savadogo GL, Donnen P, Kouéta F, Kafando F, Hennart P, Dramaix M. Impact of HIV/AIDS on mortality and nutritional recovery among hospitalised severely malnourished children before starting antiretroviral treatment. Open J Pediatr 2013;3(4):340-345. https://dx.doi.org/10.4236/ojped.2013.34061 23. Mehta NM, Corkins MR, Lyman B, et al. Defining paediatric malnutrition: A paradigm shift toward aetiology-related definitions. J Parenter Enteral Nutr 2013;37(4):460-481. https://dx.doi.org/10.1177/0148607113479972 24. Trehan I, O’Hare A, Phiri A, Heikens GT. Challenges in the management of HIV–infected malnourished children in Sub-Saharan Africa. AIDS Res Treat 2012;2012:1-8. https://dx.doi.org/10.1155/2012/790786 25. Madec Y, Germanaud D, Moya-Alvarez V, et al. HIV prevalence and impact on refeeding in children hospitalised for severe malnutrition in Niger: An argument for more systematic screening. PLoS ONE 2011;6(7):e22787. https:// dx.doi.org/10.1371/journal.pone.0022787 26. Prendergast A, Dangarembizi BM, Kitaka BS, et al. Hospitalisation for severe malnutrition among HIV-infected children starting antiretroviral therapy. AIDS 2011;25(7):951-956. https://dx.doi.org/10.1097/QAD.0b013e328345e56b

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This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.

Screening for retinitis in children with probable systemic cytomegalovirus infection at Tygerberg Hospital, Cape Town, South Africa J F Engelbrecht, MB ChB, Dip Ophth; N Freeman, MB ChB , FC Ophth(SA), MMed Ophth; R M Rautenbach, MB ChB, FC Ophth(SA), MMed Ophth, MSc Med Ophthalmology Department, Stellenbosch University, Tygerberg Hospital, Cape Town, South Africa Corresponding author: J F Engelbrecht (edrich.engelbrecht@gmail.com) Background. The incidence of immunocompromised children with probable systemic cytomegalovirus (CMV) infection is increasing. Currently, there is no protocol for screening children for CMV retinitis in South Africa. Screening for CMV retinitis may prevent permanent visual impairment. Objectives. To determine the prevalence of retinitis in children with probable systemic CMV infection. To assess the value of clinical and laboratory data in identifying risk factors for the development of CMV retinitis in children. Methods. A retrospective, cross-sectional study design was used. All children (≤12 years) with probable systemic CMV infection who underwent ophthalmic screening over a 5-year period, were included. Presumed CMV retinitis was diagnosed by dilated fundoscopy. All cases were evaluated to identify possible risk factors for the development of CMV retinitis. Results. A total of 164 children were screened. Presumed CMV retinitis was diagnosed in 4.9% of participants. Causes of immunosuppression were HIV infection (n=7) and chemotherapy (n=1). HIV infection showed a definite trend towards association with the development of CMV retinitis in our study population (p=0.064). Conclusion.The prevalence of CMV retinitis was 4.9% in our sample. Other than HIV, we were not able to identify additional risk factors for CMV retinitis. Our results show that CD4 levels are possibly not a reliable indicator to predict CMV retinitis. S Afr J Child Health 2017;11(2):93-95. DOI:10.7196/SAJCH.2017.v11i2.1205

Cytomegalovirus (CMV) infection may be due to vertical transmission (congenital CMV), or it may be horizontally acquired. Systemic CMV infection is more widespread in developing countries and in communities with a lower socioeconomic status, and it represents the most significant viral cause of birth defects in industrialised countries.[1] CMV infection is typically subclinical and therefore asymptomatic in healthy individuals; however, it can be life-threatening for the immunocompromised; such as HIVpositive patients, organ transplant recipients, and newborn babies.[2] Similar to other herpes viruses, CMV enters a latent state in which the virus is continually suppressed by cell-mediated immunity. CMV remains latent unless the patient suffers from a significant local or systemic immunodeficiency. Recurrent CMV infections are primarily associated with pneumonitis, colitis, encephalitis, and retinitis.[3] CMV retinitis is known to occur in immunocompromised adults, affecting up to 30% of HIV-positive adults and 5% of immunocompromised children.[4] CMV retinitis has been reported to be more likely in HIV-positive children with CD4 counts of <100 cells/µL, or CD4% <10%.[4] While it is reported that CMV retinitis presents less frequently in children than in adults, children may not report visual loss or associated symptoms, making detection more difficult in the paediatric population.[5] According to our literature review, the prevalence of retinitis in children with probable systemic CMV infection in South Africa (SA) is still unknown. Permanent visual impairment in children with CMV retinitis may be prevented by timely diagnosis and treatment. This study aimed to determine the prevalence of CMV retinitis, and to assess the value of clinical and laboratory data in identifying risk factors for the development of the disease in the study population.

Methods

Ethical considerations

The study was approved by the Health Research Ethics Committee of Stellenbosch University (ref. no. N13/01/012). Internationally 93

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accepted ethical standards and guidelines were respected and patient confidentiality was protected.

Study population and sampling

A retrospective, cross-sectional study design was used. All children ≤12 years admitted to Tygerberg Academic Hospital (TBH), with laboratory evidence of systemic CMV infection and who were referred for ophthalmological screening between 1 January 2009 and 31 December 2013, were included in the study. TBH is a tertiary-level referral hospital in Cape Town, SA. Ophthalmological screening consisted of a thorough examination of the central and peripheral retina by means of indirect ophthalmoscopy through dilated pupils. The screening was performed by a registrar and/or consultant in the Department of Ophthalmology. Presumed CMV retinitis was diagnosed on the characteristic clinical appearance on ophthalmoscopy. All cases with presumed CMV retinitis were reviewed by a consultant ophthalmologist. The study cohort was screened to determine the prevalence of presumed CMV retinitis. All cases were evaluated to identify possible risk factors for the development of CMV retinitis. The immune status of all screened cases was evaluated and classified: nil immunodeficiency, prematurity, congenital immunodeficiency syndrome, perinatal vertical HIV exposure, HIV-positive organ transplantation, chemotherapy or other. Demographic, clinical and laboratory data of all children who underwent ophthalmological screening were collected and included the following: age, gender, T-lymphocyte subsets (including absolute CD4 and CD4/total lymphocyte count (CD4%)), site of systemic CMV infection, laboratory test type performed to detect CMV infection, and the nature of the specimen in which CMV was detected.

Laboratory analysis

Cases of probable systemic CMV infection were identified by CMV polymerase chain reaction (PCR), CMV pp65 antigenaemia test, CMV

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RESEARCH viral culture, and CMV serology. If the qualitative PCR was positive, quantitative PCR was performed. Probable systemic CMV infection had an accompanying quantitative PCR that was higher than detectable limits. HIV was diagnosed by means of HIV PCR in children <18 months of age, and by PCR or viral antibody tests for children >18 months. CD subsets were analysed to determine the absolute CD4 and CD4%. All white cells were counted and marked with CD3, CD4, and CD8 antibodies to determine the absolute CD count. CD4% was calculated by analysing the cells that exclusively contained the marker as a percentage of the total cells. Laboratory tests were performed by the National Health Laboratory Service.

Data management and statistical analysis

IBM SPSS version 22 (IBM Corp., USA) was used to analyse the data. The data were summarised using mean and standard deviation in the case of normally distributed continuous data, and frequency tables and percentages in the case of categorical data. The prevalence of CMV retinitis in children with probable systemic CMV infection was calculated. Associations between the risk factors identified and the development of CMV retinitis were assessed using Fisher’s exact 2-sided tests for categorical variables, and non-parametric MannWhitney tests were used to compare non-normally distributed continuous variables between the groups.

Results

Demographic and clinical data profile of the sample

A total of 164 cases with probable systemic CMV infection were referred for ophthalmological examination to assess the presence or absence of CMV retinitis. The median age was 3.1 months (range 1 day to 131.6 months), and the ratio of male to female was 1.1:1. The most common sites of presumed CMV infection were the respiratory system (n=122), hepatobiliary system (n=17), cardiovascular system (n=8), central nervous system (n=6), and gastrointestinal tract (n=3) (Table 1).

Underlying immunodeficiency

We identified 91 cases that were immunocompromised. Causes for immunosuppression were HIV infection (n=84), other immunodeficiency (n=6), and chemotherapy for leukaemia (n=1) (Fig. 1). HIV infection was diagnosed in 51.2% (n=84) of the screened cases. In our study population there was a definite trend towards association between HIV infection and the development of CMV retinitis (p=0.064). However, due to small numbers, this association could not be confirmed. Highly active antiretroviral therapy (HAART) was initiated 78 (93%) participants of the HIV-positive or HIV-exposed cases at the time of screening. A total of 55 (33.5%) premature infants were screened.

CMV retinitis group

CMV retinitis was diagnosed in 4.9% (n=8) of the cases screened. Age ranged from 3 months to 11 years and the male to female ratio

Presumed infected system

Cases, n (%)

Respiratory

122 (74.4)

Hepatobiliary

17 (10.4)

Cardiovascular

8 (4.9)

CNS

6 (3.6)

GIT

3 (1.8)

Unspecified

8 (4.9)

6 HIV (n=76)

HIV and prematurity (n=8)

Prematurity (n=55)

Chemotherapy (n=1) Other (n=6)

Fig. 1. Causes of underlying immunosuppression (n=91)

was 1:4. The causes of immunosuppression in this group were HIV infection (n=7) and chemotherapy for leukaemia (n=1). All of the HIV-infected patients were on HAART. Two of the HIV-positive cases were also premature, but due to small numbers the significance of prematurity as a risk factor for CMV retinitis could not be proven.

Laboratory data

Laboratory evidence of CMV infection was confirmed by the following tests: CMV PCR (n=136), CMV pp65 antigenaemia test (n=15), CMV viral culture (n=9), and CMV serology (n=4). All qualitative CMV PCR tests had an accompanying quantitative PCR higher than detectable limits. The HIV-positive group had a median absolute CD4 cell count of 598 cells/µL between HIVpositive cases with and without CMV retinitis (p=0.032). The median CD4 cell count in those with CMV retinitis was 334 (range 21-767), while in those without retinitis it was 622 cells/ µL. CD4 as a percentage of the total lymphocyte count (CD4%) ranged between 2.1 and 64.3%, with a median of 16.6%. There was no significant difference between those with and without CMV retinitis in terms of CD4% (p=0.668).

Discussion

There was an exponential increase in the number of paediatric cases with probable systemic CMV infection screened for retinitis at the Department of Ophthalmology, TBH, SA over a 5-year period (Fig. 2), with a resultant increased load on our already overburdened ophthalmology service. In 2006, the estimated number of SA children infected with HIV was 293 000.[6] Due to the HIV pandemic, paediatric CMV infection is becoming more prevalent and CMV infection has been identified in up to 51% of HIV-positive children admitted to SA paediatric intensive care units.[7] Patients on immunosuppressive therapy or with immunodeficiency syndromes are predisposed to CMV infections.[5] The distinctive features of active CMV retinitis are: ‘a fulminant picture of retinal vasculitis and vascular sheathing with areas of yellow-white, full thickness, retinal necrosis producing retinal oedema associated

Screenings, n

Table 1. Site of presumed CMV infection (N=164)

45 40 35 30 25 20 15 10 5 0

2012

2013

36 24

2009

2010

2011 Year

CMV = cytomegalovirus; CNS = central nervous system, GIT = gastrointestinal tract.

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Fig. 2. CMV retinitis screenings at the Department of Ophthalmology, Tygerberg Hospital, Stellenbosch University, SA.

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RESEARCH with haemorrhage and hard exudatesâ&#x20AC;&#x2122;.[8] The indolent variant is described as having less oedema and no haemorrhage or vascular sheathing.[8] In children, CMV retinitis is most often bilateral and can lead to a destructive retinitis of the posterior pole, resulting in permanent visual impairment.[8] Recent developments have led to rapid laboratory detection techniques for systemic CMV and treatment regimens for CMV infection have been improved and are more readily available.[9] Current treatment regimens include intravenous ganciclovir (6 mg/kg, 12 hourly) as the drug of choice, and oral valganciclovir and intravenous foscarnet as alternatives.[4] Although CMV-specific antiviral treatment may cause regression of retinitis, visual acuity may not improve due to macular or optic nerve involvement. Prolonged CMV antiviral treatment is needed to reduce recurrences of retinitis in children that remain immunocompromised.[10] Several international studies have reported the incidence of CMV retinitis in HIV-positive cases: Rwanda 1.8%;[11] USA 2.3%[12]; and Canada 5%.[10] To our knowledge, this is the first study in SA to document the prevalence of presumed CMV retinitis in children with presumed systemic CMV infection. The gold standard for detecting congenital CMV in newborn children is viral isolation in the urine or saliva within the first 3 weeks of life, but serum PCR is reported to be equally sensitive and specific.[9] All the cases in our study population were diagnosed after the age of 3 weeks. We were therefore not able to distinguish congenital from acquired CMV infection. Gender, prematurity, and site of systemic CMV infection were not significant risk factors for the development of retinitis in our paediatric sample. Screening for CMV retinitis in HIV-positive children with probable systemic CMV is imperative in South Africa. In our sample, 7 of the 8 CMV retinitis cases identified were HIV-positive. Only one child in the HIV-negative group developed retinitis; this patient was on chemotherapy for the treatment of leukaemia. CD4 count and CD4% may prove to be valuable in identifying cases at high risk of developing CMV retinitis;[4] however, we could not confirm this association in our study. We would therefore recommend that caution be taken when using CD4 and/or CD4% as criteria for retinitis screening as some cases might remain undiagnosed. International guidelines reported that CD4 cell level is less predictive of risk for CMV disease in young infants with HIV, and CMV infection can occur in HIV-infected children with higher CD4 counts.[4] With appropriate protocols in place, children could be screened and diagnosed early, managed effectively, and possibly have more favourable visual outcomes.

Conclusion

The prevalence of probable CMV retinitis in our study population was 4.9%. Other than HIV, we were not able to identify additional

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risk factors for CMV retinitis. Our results show that CD4 levels are possibly not a reliable guide to predict CMV retinitis. We recommend a multi-centre study to establish a robust screening protocol that may lessen the impact of the ever-increasing numbers of children at risk of CMV retinitis on ophthalmic services. Acknowledgements. The authors would like to thank Dr J Maritz (Department of Virology, Stellenbosch University) for his contributions. Author contributions. None. Funding. None. Conflict of interest. None. 1. Caruso C, Buffa S, Candore G, et al. Mechanisms of immunosenescence. Immun Ageing 2009;6(1):10. https://doi.org/10.1186%2F1742-4933-6-10 2. Kenneth JR, Ray CG. Sherris Medical Microbiology. 4th ed. New York: McGraw-Hill, 2003;439-451. 3. Gallant JE, Moore RD, Richman DD, et al. Incidence and natural history of cytomegalovirus disease in patients with advanced human immunodeficiency virus disease treated with zidovudine. J Infect Dis 1992;166(6):1223-1227. https://doi.org/10.1093%2Finfdis%2F166.6.1223 4. Mofenson LM, Brady MT, Danner SP, et al. Guidelines for the Prevention and Treatment of Opportunistic Infections among HIV-exposed and HIVinfected children: Recommendations from CDC, the National Institutes of Health, the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep 2009;58(RR-11):1-166. https://doi. org/10.1086%2F427295 5. Du LT, Coats DK, Kline MW, et al. Incidence of presumed cytomegalovirus retinitis in HIV-infected pediatric patients. J Am Assoc Pediatr Opthalmol 1999;3(4):245-249. https://doi.org/10.1016%2Fs1091-8531%2899%2970010-8 6. Meyers T, Moultrie H, Naidoo K, Cotton M, Eley B, Sherman G. Challenges to pediatric HIV care and treatment in South Africa. J Infect Dis 2007;196(s3):S474-S481. https://doi.org/10.1086%2F521116 7. Rabie H, de Boer A, van den Bos S, Cotton MF, Kling S, Goussard P. Children with human immunodeficiency virus infection admitted to a paediatric intensive care unit in South Africa. J Trop Pediatr 2007;53(4):270-273. https:// doi.org/10.1093%2Ftropej%2Ffmm036 8. Wren SME, Fielder AR, Bethell D, et al. Cytomegalovirus retinitis in infancy. Eye 2004;18(4):389-392. https://doi.org/10.1038%2Fsj.eye.6700696 9. Nassetta L, Kimberlin D, Whitley R. Treatment of congenital cytomegalovirus infection: Implications for future therapeutic strategies. J Antimicrob Chemother 2009;63(5):862-867. https://doi.org/10.1093%2Fjac%2Fdkp083 10. Baumal CR, Levin AV., Read SE. Cytomegalovirus retinitis in immunosuppressed children. Am J Ophthalmol 1999;127(5):550-558. https://doi.org/10.1016%2 Fs0002-9394%2899%2900031-8 11. Kestelyn P, Lepage P, Karita E, van de Perre P. Ocular manifestations of infection with the human immunodeficiency virus in an African pediatric population. Ocul Immunol Inflamm 2000;8(4):263-273. https://doi. org/10.1076%2Focii.8.4.263.6455 12. Chandwani S, Kaul A, Bebenroth D, et al. Cytomegalovirus infection in human immunodeficiency virus type 1-infected children. Pediatr Infect Dis J 1996;15(4):310-314. https://doi.org/10.1097%2F00006454-199604000-00006

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This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.

Presentation and pattern of childhood renal diseases in Gusau, North-Western Nigeria B I Garba,1 MBBS, FMCPaed, Dip Allerg, MSc (Med); A S Muhammad,2 MBBS, FMCP, MSc (Med); A B Obasi,1 MBBS; A O Adeniji,1 MBBS 1 2

Department of Paediatrics, Ahmad Sani Yariman Bakura Specialist Hospital, Gusau, Zamfara State, Nigeria Department of Medicine, Ahmad Sani Yariman Bakura Specialist Hospital, Gusau, Zamfara State, Nigeria

Corresponding author: B I Garba (bgilah@yahoo.com ) Background. Studies from different parts of Nigeria and the world have reported variable patterns of renal diseases in childhood. There is a paucity of data to guide resource allocation in Zamfara, Nigeria, despite the rising incidence of kidney diseases in children in Nigeria, and globally. Objectives. To determine the prevalence, presentation, pattern, and outcomes of renal diseases among hospitalised children in Gusau, Zamfara State, Nigeria. Methods. A retrospective study was conducted of children aged 1 month to 14 years, who were admitted to the paediatric wards of our hospital over a period of 30 months (October 2013 to March 2016). Relevant information was retrieved from the patientsâ&#x20AC;&#x2122; medical records and data were analysed accordingly. Results. A total of 2 658 children were admitted, of which 3.2% (n=84) had renal diseases; however, only 70 folders were utilised for the study. The male:female ratio was 1.19:1. Fever (63%), reduction in urine volume/frequency (46%), body swelling (43%) and abdominal pain (40%) were the most common symptoms. Hypertension (33%) and heart failure (17%) were common findings. Urinary tract infection (UTI) (34%), acute glomerulonephritis (AGN) (24%) and acute kidney injury (AKI) (20%) were the the most common diagnoses. Most of the children were discharged with good renal function and mortality was low (10%). Conclusions. The prevalence of renal disease in our setting was low, with males predominating. UTI was the most common cause of renal disease, requiring hospitalisation in Gusau, while congenital anomalies and malignancies were rare. These data could be utilised by researchers and stakeholders in resource-poor settings like ours to plan for preventive nephrology as UTI, AGN and AKI are largely preventable., S Afr J Child Health 2017;11(2):96-98. DOI:10.7196/SAJCH.2017.v11i2.1222

Childhood renal diseases are common causes of morbidity and mortality; studies from different parts of Nigeria and the world have reported variable patterns of renal diseases in childhood. Abdurrahman et al.[1] in Zaria, Ocheke et al.[2] in Jos, and Adedoyin et al.[3] in Ilorin carried out evaluations of childhood renal diseases prevalent in Northern Nigeria. Morbidities of importance noted by these researchers included urinary tract infection (UTI), acute glomerulonephritis (AGN), acute kidney injury (AKI) from varying causes, nephrotic syndrome, congenital urinary tract obstructions and malignancies, with varying rates. A recent editorial on childhood kidney diseases in developing countries highlights flawed epidemiological data on renal diseases, especially in Africa, with a paucity of data to guide for resource allocation, despite the rising incidence of kidney diseases in children.[4] Regular audits in different hospitals could provide data that would guide healthcare stakeholders in planning for preventive nephrology, which is necessary to reduce the morbidity and mortality from renal diseases. To our knowledge, the burden of childhood renal diseases in Gusau, Zamfara State, North-Western Nigeria, has not been investigated. In this study, we aimed to determine the prevalence, presentation, pattern and outcome of renal diseases among hospitalised children in Gusau, Zamfara State, Nigeria.

Methods

This was a retrospective study of children aged 1 month to 14 years, who were admitted to the paediatric wards (emergency paediatric unit and paediatric medical ward) of Ahmad Sani Yariman Bakura 96

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Specialist Hospital (ASYBSH), Gusau, Nigeria, over a period of 30 months between October 2013 and March 2016. We reviewed the records of all patients with a diagnosis of renal disease. Incomplete records and readmissions were excluded from the study. Information about age, gender, history, examination, urine microscopy, and urinalysis was carefully recorded. Depending on the provisional diagnoses, further investigations were carried out, including: serum urea and creatinine; serum protein; lipids; throat swab microscopy, culture and sensitivity; abdominal ultrasound; other imaging studies and renal biopsy. Haemodialysis is available to children aged â&#x2030;Ľ10 years (depending on their body size) at ASYBSH; however, there are no facilities for peritoneal dialysis. Diagnosis was based on the primary disease, e.g. children with UTIs and background nephrotic syndrome were classified as nephrotic syndrome, and those with AGN and renal failure were classified as AGN, not AKI. This was to avoid recruiting patients more than once simultaneously because of multiple diagnoses. Hypertension was defined as blood pressure above the 95th percentile for the age and sex of the child. Proteinuria was determined using a urine dipstick and was not quantified. Some children with nephrotic syndrome were diagnosed before initiation of the study period and were already on steroids, their proteinuria had reduced to + or ++. Nephrotic syndrome was diagnosed based on proteinuria, serum protein level, and cholesterol, in addition to clinical features. UTI was diagnosed as presumptive, and was confirmed on receipt of urine culture results. Antenatal screening for congenital malformations was not captured as the children were post neonatal. Outcome measures were: discharged due to recovery of renal

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RESEARCH function; significant improvement but not full renal recovery discharged against medical advice; or death. Patients were followed up as outpatients at the nephrology clinic for variable periods. Ethical approval was obtained from the hospital ethics committee. Data entry and analysis were performed using Statistical Package for Social Science (SPSS) version 17 (SPSS Inc., USA).

Results

A total of 2 658 children were admitted during the 30-month study period. Eighty-four (3.2%) of the children were managed for various renal diseases; however, only 70 folders were utilised for the study as some had incomplete data, while others were missing. There were 38 (54%) males and 32 (46%) females, giving a male: female ratio of 1.19:1. The mean (standard deviation (SD)) age was 88 (44) months, with a range of 1 - 168 months. Most children presented with a history of fever and reduction in urine volume (Table 1). On examination, most of the children were febrile and had facial swelling (Table 2). Proteinuria was seen in most of the children (Table 3), while blood was not seen in the urine samples of most cases (Table 4). However, microscopy revealed that only 14 (20%) had red blood cells in their urine, while 35 (50%) had no red blood cells. Microscopy results were unavailable for 21 (30%) children. The diagnoses included UTI, had posterior urethral valve disorder (PUV), AGN, AKI with varying causes (mainly diarrhoea, sepsis and malaria), chronic kidney disease (CKD) with varying causes (chronic glomerulonephritis, nephrotic syndrome and others), and schistosomiasis (presented with severe anaemia) (Table 5). PUV disorder was the only congenital anomaly observed and no malignancy was identified in any of the cases. Renal biopsy was not performed in eligible children owing to a lack of funds. Table 1. Symptoms of renal disease on presentation (N=70)

Fifty-nine (84%) children were discharged, 47 (67%) had normal renal function, and 12 (17%) had residual renal function, i.e. were still on dialysis or still had deranged urea or creatinine. Seven (10%) children died, while 4 (6%) childrenâ&#x20AC;&#x2122;s caregivers signed against medical advice and left the hospital. The children that died included 4 (57%) with AGN, 2 (29%) with AKI, and 1(14%) with CKD, of which 4 (57%) were males and 3 (43%) were females.

Discussion

This study was the first in Gusau, Zamfara State, North-Western Nigeria to determine the prevalence, presentation, pattern and outcomes of childhood renal diseases. Studies from different parts of Nigeria and the world have reported variable patterns of renal diseases in children. Though our prevalence of 3.2% was low and may not be significant, it was similar to the 3.2% obtained in Calabar,[5] 3.9% in Lagos,[6] 3.0% in Libya,[7] and 3.3% in Pakistan.[8] However, it was lower than the 4.0% reported by Okoro et al.[9] in Enugu and 6.3% by Bhatta et al.[10] in Nepal. These variations could be related to methodology, especially with respect to the type and duration of the study, sample size, and variations in the rates of the renal disorders. More males presented than females, which was similar to results obtained in Lagos,[6] Libya,[7] Enugu,[9] and Jordan,[11] although the differences were marginal. Complaints on presentation were similar to what was obtained in Sudan,[12] though with varying frequencies. Table 3. Proteinuria dipstick results (N=70) Result

n (%)

23 (33)

12 (17)

+++

3 (4)

++++

Symptom*

n (%)

Negative

24 (34)

Fever

44 (63)

No result

8 (11)

Reduction in urine volume/frequency

32 (46)

Body swelling

30 (43)

Abdominal pain

28 (40)

Vomiting

26 (37)

Dysuria

19 (27)

Macroscopic haematuria

7 (10)

Headache

6 (9)

Body rashes

3 (4)

Convulsion

1 (1)

*Some children presented with multiple symptoms.

Table 2. Clinical features on presentation (N=70)

Table 4. Presence of blood on dipstick (N=70) Result

n (%)

10 (14)

13 (19)

+++

3 (4)

++++

2 (3)

Negative

34 (49)

No result

8 (11)

Table 5. Diagnosis of renal diseases (N=70)

Sign*

n (%)

Diagnosis

n (%)

Febrile

29 (41)

UTI

24 (35)

Facial swelling

28 (40)

AGN

17 (24)

Pedal oedema

27 (39)

AKI

14 (20)

Ascites

24 (34)

Nephrotic syndrome

8 (11)

Hypertension

23 (33)

CKD

6 (9)

Renal angle tenderness

17 (24)

Schistosomiasis

1 (1)

Features of heart failure

12 (17)

UTI = urinary tract infection; AGN = acute glomerulonephritis; AKI = acute kidney injury; CKD = chronic kidney disease.

*Some children presented with multiple signs.

SAJCH

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RESEARCH The reason for the similarity may be because UTI was the most common diagnosis in the Sudanese study. The childhood renal diseases identified in our study were similar to what was obtained in studies conducted elsewhere in Nigeria[1,2,5,6,13,14] and the world;[7,15-17] however, with varying rates. This observation could be explained by the fact that environmental factors, such as poor hygiene, poverty, and socioeconomic conditions, as well as genetic factors and late presentation, may have influenced the rates of childhood kidney diseases in our setting. In our study, UTI was the most common renal disorder, which was similar to the findings of studies conducted in Pakistan,[8] Sudan,[12] Benin,[13] Port Harcourt,[14] and Venezuela,[16] but differed from findings in Jos,[2] Calabar,[5] Lagos,[6] Enugu,[9] and Iran.[15] This was followed by AGN and AKI, which showed that infectious agents play a role in renal diseases in Gusau, as seen in other reports.[9,13,14] Congenital renal anomalies and malignancies were uncommon findings. Most of our patients were discharged with good renal function, which was similar to the outcomes of the studies conducted in Enugu[9] and Sudan.[12] Considering the fact that our study was conducted in a resource-poor setting with inadequate facilities for paediatric dialysis, the mortality rate of 10% was relatively low and similar to the 6.8% observed in Sudan,[12] although higher than the <1.0% reported in Libya,[7] and significantly lower than the 17.7% reported in Lagos. Mortality was highest among children with AGN, similar to reports from Lagos.[6] The reason for the mortality can be explained by the fact that most of the children had AKI and, in our setting, some patients present late to the hospital. All the deaths recorded in our study were due to AGN, AKI, or CKD. This observation may be attributed to a lack of dialysis for younger children, as peritoneal dialysis is not available in Zamfara State, late presentation, and cost of haemodialysis, all of which were common findings in various studies.[1,9,11]

Study limitations

This was a retrospective study, and therefore there may be inaccuracies in the data. Owing to a lack of adequate and sophisticated facilities, many renal disease cases may have been missed and poor socioeconomic conditions, along with the high cost of investigations, meant that investigations could not be performed for some of the children. A lack of peritoneal dialysis and the high cost of haemodialysis affected our mortality rate. Indeed, with these limitations, the true incidence of renal diseases may be underestimated. Our study can be improved upon by conducting a prospective study and obtaining grants for research to include appropriate investigations in the future.

Conclusion

Our study highlighted that the prevalence of childhood renal diseases in Gusau, Zamfara State, Nigeria was low, with males predominating. Fever, reduction in urine volume and frequency,

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body swelling, and abdominal pain were the most common presenting symptoms. UTI was the most common cause of renal disease requiring hospitalisation, followed by AGN. Congenital anomalies and malignancies were rare. Most of the children were discharged with normal renal function and the mortality was highest in children with AGN. These data could be utilised by researchers and stakeholders in a resource-poor setting, such as ours, to plan for preventive nephrology, as UTI, AGN and AKI are largely preventable. Acknowledgements. None. Author contributions. GBI conceptualised and designed the study, and analysed and interpreted the data. All authors drafted the manuscript and approved the final version. Funding. None. Conflicts of interest. None. 1. Abdurrahman MB, Babaoye FA, Aikhionbare HA. Childhood renal disorders in Nigeria. Pediatr Nephrol 1990;4(1):88-93. https://doi.org/10.1007/bf00858449 2. Ocheke IE, Okolo SN, Bode-Thomas F, Agaba EI. Pattern of childhood renal disease in Jos, Nigeria: A preliminary report. J Med Trop 2010;12(2):52-55. https://doi.org/10.4314/jmt.v12i2.69316 3. Adedoyin OT, Adesiyun OA, Mark F, Adeniyi A. Childhood renal disorders in Ilorin, North Central Nigeria. Niger Postgraduate Med J 2012:19(2):88-91. 4. Bhimma R, Kalo U. Childhood kidney diseases in developing countries: Is it a forgotten disease? S Afr J Child Health 2016;10(2):103-104. https://doi. org/10.7196/SAJCH.2016.v1012.1144 5. Etuk IS, Anah MU, Ochighs SO, Eyong M. Pattern of paediatric renal disease in inpatients in Calabar, Nigeria. Trop Doct 2006;36(4):256. https://doi. org/10.1258/004947506778604968 6. Onifade EU. A ten year review of childhood renal admissions into the Lagos University Teaching Hospital, Nigeria. Nig Q J Hosp Med 2003;13(3-4):1-5. https:// doi.org/10.4314/nqjhm.v13i3-4.12644 7. Elzouki AY, Amin F, Jaiswa OP. Prevalence and pattern of renal diseases in Eastern Libya. Arch Dis Child 1983;58(2):106-109. https://doi.org/10.1136/ adc.58.2.106 8. Iqbal J, Rahman MA, Khan MA. Pattern of renal diseases in children. J Pak Med Assoc 1994;44(5):118-120. 9. Okoro BA Okafor HU. Pattern of childhood renal disorders in Enugu. Niger J Paed 1999;26(1):14-18. 10. Bhatta NK, Shrestha P, Budhathoki S, et al. Profile of renal diseases in Nepalese children. Kathmandu Uni Med J 2008;6(2):191-194. 11. Hazza I, Mughraby H, Najada A. Spectrum of paediatric renal diseases in Jordan. Saudi J Kidney Dis Transpl 1997;8(3):314-316. http://www.sjkdt.org/ text.asp?1997/8/3/314/39362 12. Ali EM, Abdurrahman AH, Karrar ZA. Pattern of outcome of renal diseases in hospitalised children in Khartoum State, Sudan. Sudan J Paediatr 2012;12(2):52-59. 13. Ibadin OM, Ofovwe EG. Pattern of renal disease in children in mid western zone of Nigeria. Saudi J Kidney Transpl 2003;14(4):539-544. 14. Eke FU, Eke NN. Renal disorders in children: a Nigerian study. Pediatr Nephrol 1994;8(3):383-386. https://doi.org/10.1007/bf00866371 15. Derakhshan A, Al Hashemi GH, Fallahzadeh MH. Spectrum of in-patient renal diseases in children: A report from southern part of Islamic Republic of Iran. Saudi J Kidney Dis Transpl 2004;15(1):12-17. 16. Orta-Sibu N, Lopez M, Moriyon JC, Chavez JB. Renal diseases in children in Venezuela, South America. Pediatr Nephrol 2002;17(7):566-569. https://doi. org/10.1007/s00467-002-0892-4 17. Abdurrahman MB, Elidrissy ATH. Childhood renal disorders in Saudi Arabia. Paediatr Nephrol 1988;2(3):368-372. https://doi.org/10.1007/bf00858694

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REVIEW

This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.

Neonatal sepsis: Highlighting the principles of diagnosis and management M Coetzee, MB ChB, DCH, FCPaed, MMed (Paed), Cert Neonatology (SA); N T Mbowane, MB ChB, FCPaed; T W de Witt, MB ChB, MMed (Paed), FCPaed, DTE Division of Neonatology, Department of Paediatrics and Child Health, School of Medicine, University of Pretoria, South Africa Corresponding author: M Coetzee (mel.coetzee@up.ac.za) Neonatal sepsis is a clinical syndrome consisting of nonspecific symptoms and signs of infection, accompanied by a bacteraemia in the first 28 days of life. The risk of neonatal sepsis and death increases with decreasing birth weight and gestational age. South African data have reported the overall incidence of neonatal sepsis to be 8.5 - 10%, with late-onset sepsis accounting for most of these infections. The diagnosis of neonatal sepsis is not always straightforward, and the initiation and continuation of antimicrobials in these situations relies on good clinical judgment. The need for empirical antimicrobials is driven by the existence of risk factors for early-onset sepsis and clinical symptoms and signs of late-onset sepsis. Antimicrobial stewardship programmes should be in place to guide clinicians to either stop, change, or continue antimicrobials. Institution-specific knowledge of the most common pathogens and the antimicrobial susceptibility pattern is important to prevent the emergence of further antimicrobial resistance. S Afr J Child Health 2017;11(2):99-103. DOI:10.7196/SAJCH.2017.v11i2.1244

Neonatal sepsis is a clinical syndrome consisting of nonspecific symptoms and signs of infection accompanied by bacteraemia in the first 28 days of life.[1,2] Early-onset sepsis (EOS) presents within the first 72 hours of life, and late-onset sepsis (LOS) presents after 72 hours of life.[3-6] The nonspecific features of sepsis may include lethargy, poor feeding or feeding intolerance, irritability, temperature instability, brady- or tachycardia, glucose instability, poor perfusion, apnoea, and a bleeding tendency.[1,2] EOS is primarily the result of intrapartum vertical transmission of bacteria from the mother to the neonate, either transplacentally or due to ascending infection from the genital tract.[2-4,6] LOS is the result of horizontal transmission of bacteria from the environment and healthcare providersâ&#x20AC;&#x2122; hands,[3,6] and has a peak incidence at between 15 and 17 days of life.[2]

Incidence and mortality

The risk of neonatal sepsis and death increases with decreasing birth weight[6] and gestational age,[4,7] with better outcomes in neonates that receive early empirical antimicrobial treatment.[3] However, ~95% of neonates initiated on empirical antimicrobials for suspected EOS were shown to have no laboratory evidence of infection.[7] Available South African (SA) data have reported the overall incidence of neonatal sepsis to be 8.5 - 10%, with LOS accounting for the majority of these infections (83.2 - 94.3%).[8-9] The mortality rate was found to vary between 24.2% and 40%, and 19.7% and 22.5% for EOS and LOS, respectively, with an overall mortality of 20.8 - 23%.[8,9] Death due to Gram-negative sepsis is more common (69.2 - 80%).[8,9]

Making the diagnosis of neonatal sepsis

The gold standard for confirming neonatal sepsis is a positive culture from a sterile site, including blood,[6,10] cerebrospinal fluid (CSF)[7] or urine.[11] Culture results may only become available after 48 - 72 hours, and initiation and continuation of antimicrobials in these situations often rely on good clinical judgement. Blood investigations, including the full blood count and acutephase reactants, such as C-reactive protein (CRP) and procalcitonin (PCT), are time-dependent and should be performed 6 - 12 hours after delivery to allow for an inflammatory response.[4,8] The total white cell count has a poor positive predictive value for neonatal sepsis and is 99

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not useful in making the diagnosis.[4,5] While neutropenia has a better specificity for neonatal sepsis, values are dependent on gestational age, time after birth, and delivery method.[4,5] The immature-to-totalneutrophil ratio (I:T ratio) has the best sensitivity of all the neutrophil indices, but the positive predictive value is only 25%.[4] The I:T ratio is best used to exclude neonatal sepsis, with a negative predictive value of 99%.[4] CRP values start to increase 6 - 8 hours after infection and peak at ~24 hours,[4] with only 35 - 65% of neonates having a raised CRP at the onset of illness.[3] Serial CRP values at 24 - 48 hours after the onset of sepsis have a better sensitivity and specificity when compared with a single CRP value.[3] Two consecutive CRP values of <10 mg/L, obtained 24 hours apart, have a negative predictive value of 99%.[3-5] PCT is slightly more sensitive than CRP, but with a lower specificity,[4] as it may increase physiologically in the first 24 hours post-delivery, and may increase in response to non-infectious conditions.[4,5] PCT values increase 2 hours after infection and peak ~12 hours later.[4] A PCT value of <0.1 ng/mL is considered normal in a neonate >72 hours old.[5] At least 1 mL of blood should be collected for sterile blood cultures, with appropriate measures taken to reduce contamination. Suggested factors to differentiate between true infection and contamination include the identity of the organism, the number of positive cultures of the same organism, the time taken to flag positive, the quantity of bacterial growth, and the source or site of the culture.[10] The positive predictive value for true bacteraemia improves when multiple cultures (â&#x2030;Ľ2) grow the same organism,[12,13] with the presence of only one positive culture out of at least two being suggestive of contamination.[10] Cultures that flag positive after 48 - 72 hours are more likely to be contaminants.[10,12,13] Limited evidence exists for using the quantity of bacterial growth to differentiate true bacteraemia from contamination, and low colony counts in a high-risk population should not be dismissed as contamination.[10] Lastly, cultures taken from a vascular catheter may represent true bacteraemia, contamination, or catheter colonisation. To distinguish between these, it is recommended that cultures are taken from both the catheter and peripherally.[10] Coagulase-negative staphylococci (CoNS), which are skin commensals and represent ~80% of contaminated blood cultures,[10] have recently emerged as pathogenic organisms causing LOS,

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REVIEW especially in premature and very-low-birth-weight (VLBW) neonates.[2,5,6] To exclude contamination, most clinicians require at least 2 positive cultures of CoNS.[2] Another study has shown that ≤15 hours’ time to positivity for CoNS had a positive predictive value of 84% for true bacteraemia.[10] CoNS is responsible for more than 50% of cases of LOS in developed countries, and 35 - 46.5% in developing countries, with a mortality rate of up to 10.2% in VLBW neonates.[2] Indwelling medical devices are the largest contributing factor for CoNS sepsis in VLBW infants.[2] The sensitivity for diagnosing invasive fungal sepsis on blood culture remains poor (<50%).[14-15] Risk factors for fungal sepsis include extremely low birth weight (ELBW), gestation <28 weeks, previous exposure to antibiotics (third-generation cephalosporins or carbapenems), thrombocytopenia, central venous lines, mechanical ventilation, use of antacids (histamine-2 blockers or proton-pump inhibitors), use of total parenteral nutrition, delayed enteral feeding, and prolonged hospital stay (>7 days).[3,14,16] A clinical predictive model for candidaemia is available (Table 1),[14,16] with a combined score of 2 having a sensitivity of 85%, and a moderate specificity of 47% for neonatal candidaemia.[16] Considering the high mortality for invasive fungal sepsis in neonates, it may be acceptable to use the candidaemia scoring model in empirical antifungal decision-making. The detection of (1,3)-β-D glucan to diagnose invasive fungal sepsis in neonates has also been proposed, although very few studies have included neonates. If adult reference ranges are used, where >80 pg/ mL is considered positive, 60 - 80 pg/mL is considered equivocal, and <60 pg/mL is considered negative, the assay has a sensitivity of 70.7% and a specificity of 77.4%. These values should, therefore, be used as an adjunct to the clinical picture, haematological values, and the candidaemia score in the diagnosis of invasive fungal sepsis.[15] All patients with a positive fungal culture should have a full systemic evaluation (urine, blood, CSF, renal sonar, and fundoscopy) for invasive fungal sepsis.[16] Sterile urine specimens should be collected for urinalysis and culture in neonates suspected to have LOS ≥6 days of life.[4,5,11,17] Although there are no clear criteria for the diagnosis of urinary tract infections (UTIs) in neonates,[18] many clinicians use the following guide: growth of any urinary pathogen (≥1 000 CFU/mL) from a suprapubic specimen, or if a catheter specimen was taken, growth of ≥50 000 CFU/mL of a single uropathogen, or between 10 000 and 50 000 CFU/mL of a single uropathogen with evidence of pyuria.[11] A lumbar puncture (LP) should be performed on all neonates with suspected sepsis, as nearly one-quarter of neonates with blood-culture-positive sepsis have concurrent meningitis,[4,5] and up to 38% of neonates with proven meningitis have a negative blood culture.[4,5] CSF indices indicating neonatal meningitis are controversial,[4] as there is considerable overlap between CSF values in neonates, with and without meningitis.[19,20] Adjusting the CSF white blood cell (WBC) count for the number of red blood cells in the CSF is unreliable, resulting in loss of sensitivity for only a slight gain in specificity.[4,5,7,20] Lab CSF values suggestive of neonatal meningitis include a WBC count >21 cells/µL,[7,20] with a sensitivity and specificity of ~80%.[7,20] The CSF protein varies inversely with gestational age,[4,5] with a value >1.5 g/L in a preterm neonate and >1.0 g/L in a term neonate being highly suggestive of bacterial meningitis.[20] Of all the variables, a low CSF glucose has the greatest specificity for meningitis.[4] The ratio of CSF to serum glucose is not useful in neonates, and a CSF glucose of <1.1 mmol/L in a preterm, and <1.7 mmol/L in a term neonate is suggestive of bacterial meningitis.[20] If the diagnosis of meningitis is questionable due to marginal WBC counts or other parameters, but the clinical picture is suspicious, the LP should be repeated within 24 - 48 hours.[7,20] It remains controversial whether tracheal aspirates should be taken from neonates suspected to have ventilator associated pneumonia (VAP),[21] defined as the presence of a new pneumonia in a patient 100

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who has required assisted ventilation through an endotracheal tube in the previous 48 hours.[21,22] Tracheal aspirates have a low sensitivity, low specificity, and poor positive predictive value in the diagnosis of VAP.[21] They may, however, identify the organisms colonising the airway, guiding the choice of antimicrobial therapy.[21] An organism may be considered significant if ≥106 CFU/mL are present.[23] A negative tracheal aspirate culture has a high negative predictive value for excluding a VAP.[21] The radiographic picture, clinical, and laboratory criteria may be used to make the diagnosis of VAP without a culture result.[21,22] Table 1. Variables of the Candidaemia Score[14,16] Variable

Score

Unexplained thrombocytopenia (<150 000/µL) on the day of blood culture

2 points

Third-generation cephalosporin or carbapenem use in the 7 days prior to blood culture

1 point

Gestational age 25 - 27 weeks

1 point

Gestational age ≤24 weeks

2 points

Osteomyelitis, although uncommon, is another consideration in a neonate suspected of sepsis, and may be accompanied by positive blood cultures in severe disease.[24]

Pathogenic organisms and contaminants

The most common organisms, accounting for ~70% of cases of EOS in the developed world, are Streptococcus agalactiae (Group B Streptococcus (GBS)) and Escherichia coli (E. coli).[1,3-5] The majority of LOS (70%) in the developed world is due to Gram-positive infections,[1,3,25] with CoNS,[6] Staphylococcus aureus, Enterococcus spp., and GBS being most common in VLBW infants.[3] Approximately 18 - 20% of LOS is due to Gram-negative infections (mostly Enterobacteriaceae spp.), and 12% due to fungal infections (Candida spp.).[3] EOS in the developing world is most commonly caused by E. coli, Klebsiella spp. and S. aureus.[3] LOS is mainly caused by Grampositive organisms, such as CoNS,[6] S. aureus, S. pneumoniae and S. pyogenes,[3] although the proportion of LOS caused by Gram-negative organisms is rising.[25] An SA study published in 2005 reported that Gram-negative organisms (E. coli) are responsible for the majority of EOS, and Gram-positive organisms (CoNS, Enterococcus faecalis, viridans streptococci) are the major contributors to LOS (57.9%).[8] This contrasts with two more recent SA studies, which reported that LOS and healthcare-associated infections are predominantly due to Gram-negative organisms, such as Acinetobacter spp., Klebsiella spp., Enterobacter spp., and E. coli (46.1 - 48.2%).[9,26] The most common Gram-positive organism was CoNS in one study,[9] and S. aureus and Enterococcus spp. in the other.[26] However, the result of the latter study may have been skewed, as all CoNS cultures were excluded and it was considered a contaminant.[26] Other pathogenic organisms include Listeria monocytogenes, Neisseria meningitides, N. gonorrhoeae, Haemophilus influenzae, Pseudomonas aeruginosa, members of the Bacteroides fragilis group, and Cryptococcus neoformans.[10] Microorganisms that may be considered as contaminants in the majority of cases include Corynebacterium spp., Bacillus spp. other than Bacillus anthracis, Propionibacterium acnes, Micrococcus spp., and Clostridium perfringens.[10]

Identifying neonates at risk for sepsis

The need for empirical antimicrobial therapy is driven by the existence of risk factors for EOS, and clinical symptoms and signs for LOS.[1-3] Chorioamnionitis, maternal intrapartum pyrexia (temperature

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REVIEW >38°C), prematurity (<37 weeks’ gestation), low birth weight, assisted instrumental delivery, low Apgar scores, maternal colonisation with GBS or a previous neonate with a GBS infection, and prolonged rupture of membranes before delivery of >18 hours are all risk factors for EOS.[3-5] Prematurity, prolonged hospital admission, repeated invasive procedures, deep intravenous lines, intravenous lipids in total parenteral nutrition, prolonged antimicrobial administration, and mechanical ventilation are risk factors for LOS.[2,6]

Recommended empirical antimicrobial regimens

Knowledge of the most common pathogens and the antimicrobial susceptibility patterns is important to select the appropriate empirical antimicrobial(s).[3] Empirical antimicrobial therapy can be targeted when the culture result becomes available.[27] In developed countries, all GBS isolates are sensitive to penicillin, ampicillin and vancomycin.[3] Ninety-six percent of E. coli isolates are sensitive to gentamycin or a cephalosporin, and 78% of E. coli isolates are resistant to ampicillin.[3] In combination, ~94% of EOS isolates (GBS, CoNS, non-pyogenic streptococci, and E. coli) are sensitive to a combination of penicillin plus gentamicin, and 100% of these organisms are sensitive to the combination of amoxicillin plus cefotaxime;[3] however, routine use of cefotaxime has been shown to rapidly increase bacterial resistance and prolonged use increases the risk for invasive fungal infections.[4,5] In SA, all GBS isolates are sensitive to ampicillin and 85.7% of E. coli isolates are sensitive to amikacin, with 100% sensitivity of both organisms to cefotaxime.[9] Although empirical therapy for EOS should be individualised per hospital or region, a widely accepted empirical regimen is a combination of ampicillin plus an aminoglycoside.[3,4] Empirical antimicrobial therapy for suspected LOS should, ideally, cover both Gram-positive and Gram-negative organisms.[3,6] In developed countries, 95% of organisms causing LOS are sensitive to a combination of gentamicin with either amoxicillin or flucloxacillin,[6] or amoxicillin plus cefotaxime.[3] Only 79% of organisms are sensitive to cefotaxime alone.[3] In countries where invasive CoNS is increasing, vancomycin may be recommended as part of empirical therapy.[3] In developing countries, LOS due to gram-negative organisms, such as K. pneumoniae, E. coli, Pseudomonas spp., and Acinetobacter spp., is rising.[3] Approximately 70% of K. pneumoniae and E. coli are resistant to the combination of ampicillin plus gentamycin, and 50% are resistant to cefotaxime.[3] S. aureus is a common Gram-positive organism causing LOS, with methicillin resistance increasing.[3] In SA, ~40% of Gram-negative organisms are multidrug-resistant (75.6% Klebsiella spp., 86.5% Enterobacter spp., and 33.3% E. coli), including 14% of Acinetobacter spp. that are pan-drug resistant.[26] Gram-negative organisms are most resistant to ampicillin, gentamicin, and cefotaxime.[9] Of the Gram-positive organisms, 90 - 100% of S. aureus isolates and 55% of CoNS isolates are methicillin-resistant, and therefore require vancomycin.[8,9,26] Taking these antimicrobial resistance patterns into consideration, as well as the wide variety of organisms, there is insufficient evidence to recommend any antimicrobial regimen above another for the empirical management of suspected LOS.[3] The combination of intravenous ampicillin plus an aminoglycoside should cover most urinary pathogens for the treatment of neonatal UTIs. Ampicillin may need to be substituted with vancomycin for the treatment of hospital-acquired UTIs, as the predominant organisms include CoNS, S. aureus and Enterococcus spp. Ideally, the urine culture should be repeated after 48 hours to document sterilisation.[11] The recommended empirical antimicrobials for suspected earlyonset meningitis are ampicillin plus an aminoglycoside[3,4] or ampicillin 101

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plus cefotaxime.[3,5] For late-onset meningitis, a combination of vancomycin plus a third-generation cephalosporin, with or without an aminoglycoside, is recommended.[3] Once the Gram stain, capsular antigen, or culture results are available, antimicrobials can be targeted.[28] Empirical antifungal therapy must be determined by the institution's resistance pattern of fungal isolates, and can be targeted when the culture result is available.[14,16] The most common empirical antifungals used are amphotericin B and fluconazole, although fluconazole should not be used as empirical therapy if it had been administered as fungal prophylaxis.[16] Amphotericin B is the preferred antifungal for suspected fungal meningitis.[29,30] Antimicrobial management of a VAP should be guided by local data on pathogens and sensitivity, and usually includes a broadspectrum antimicrobial.[21,22] Osteomyelitis requires a two-pronged management plan, including surgical drainage of pus and prompt initiation of antimicrobials targeted against the most common organisms. Gram-positive organisms, such as S. aureus, group A Streptococcus, GBS and alpha-haemolytic streptococci are responsible for most cases of osteomyelitis. Therefore, a combination of oxacillin plus an aminoglycoside is recommended as empirical therapy until culture results are available. If a unit has a high incidence of methicillinresistant S. aureus (MRSA), oxacillin may be substituted with vancomycin.[24]

Antimicrobial duration

Stopping antimicrobials timeously is important as they disturb the neonate’s faecal flora, disrupting the normal development of the nascent immune system.[7] Additionally, unnecessary antimicrobial administration is increasing antimicrobial resistance worldwide. The appropriate duration of empirical antimicrobial therapy for culture-negative suspected EOS is debated, but standard practice is to stop antimicrobials if the culture remains negative for 48 - 72 hours and the patient has no clinical or haematological signs of infection.[3,5,6] There are limited randomised controlled trials evaluating the outcome of shorter or longer antimicrobial courses for neonatal pneumonia and proven bacterial sepsis without meningitis or deepseated infections. In a cohort of neonates of ≥32 weeks gestation and ≥1 500g, there was no difference in outcome or the need for readmission in the group receiving a short course (4 days) of antimicrobials for the management of pneumonia, provided the neonate was asymptomatic for the preceding 48 hours.[3] Antimicrobial durations of 7 - 14 days were compared in a similar group of neonates with blood-culture positive sepsis. As all of the neonates had a similar outcome, a duration of 7 days seems reasonable, provided the neonate is both clinically asymptomatic and has a CRP <10 mg/L by day 5 of treatment.[3] Longer antimicrobial courses of 10 - 14 days may still be appropriate for smaller or sicker neonates.[3] Neonates with positive fungal blood cultures should receive an antifungal for a total duration of 14 - 21 days after the first confirmed negative culture,[29] and fungal clearance should be confirmed by two negative blood cultures, 24 hours apart.[16] When amphotericin B is used, a cumulative dose of 25 - 30 mg/kg is recommended to prevent relapse.[29] The duration of empirical antifungals for culturenegative suspected fungal sepsis is unknown, but it is recommended to continue antifungals until the culture is reported as negative (incubated for at least 5 days).[12,16] Definite data for the duration of treatment of neonatal UTI is lacking, but 7 - 14 days of antimicrobials are usually sufficient.[11,18] Renal ultrasound examination is recommended for all neonates diagnosed with the first UTI. [11,18] Meningitis due to GBS should be treated for 14 - 21 days,[4] Listeria monocytogenes meningitis treated for ≥21 days and Gramnegative meningitis for ≥21 days.[3,4] Meningitis secondary to Grampositive organisms (other than GBS and L. monocytogenes) may be

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REVIEW treated with 14 days of antimicrobials.[28] Currently, the adjunctive use of dexamethasone in neonatal bacterial meningitis cannot be recommended, owing to insufficient evidence.[3] Antifungals for confirmed fungal meningitis must be continued until the CSF parameters (protein, glucose, and WBC count) have returned to normal and the CSF culture is negative, which may take weeks to months.[30] Repeated LPs are not recommended, with the exception of neonates who do not respond adequately to 48 hours of treatment, and to document CSF sterilisation in neonates with Gram-negative[3] and fungal meningitis.[30] The management of CSF culture-negative suspected meningitis should be guided by the blood culture result and CSF parameters.[20] If both the CSF and blood cultures taken prior to initiation of antimicrobials are negative, antimicrobial therapy may be discontinued after 48 - 72 hours.[28] Neonates with a positive blood culture, but negative CSF culture, and with raised CSF WBC should be treated for meningitis - 10 days of antimicrobials for Grampositive bacteraemia and 14 days for Gram-negative bacteraemia.[28] If the LP was delayed and antimicrobials were administered, resulting in negative CSF and blood cultures, the duration of therapy should be guided by the CSF parameters.[28] If the CSF WBC count is raised, suggesting meningitis, antimicrobial therapy should be individualised (no standard duration), but if the CSF WBC is normal, antimicrobials can be discontinued after 48 - 72 hours.[28] The combination of the clinical condition, biomarkers of infection, and radiographic picture can aid in determining when to discontinue antimicrobials for a VAP, although a duration of 7 - 10 days is usually sufficient.[22] Osteomyelitis must be treated for a total duration of 4 - 6 weeks with intravenous antimicrobials; however, a longer duration of therapy is recommended if the causative organism is S. aureus (methicillin-sensitive or resistant).[24]

Antimicrobial stewardship

The core principles common to all antimicrobial stewardship (AMS) programmes are: (i) correctly identifying patients who need antimicrobial therapy; (ii) using local and regional antibiograms to guide prescribing; (iii) avoiding antimicrobials with overlapping activity; (iv) administering the correct dose at the correct intervals; (v) regularly reviewing the culture results and adjusting antimicrobials appropriately; (vi) monitoring drug levels and adjusting the dose accordingly; and (vii) stopping antimicrobials promptly when guided by negative cultures.[13] The Department of Health Advisory Committee on Antimicrobial Resistance and Healthcare Associated Infection has developed the ‘Start Smart – Then Focus’ principles of AMS to guide clinicians on the appropriate use of antimicrobials (Table 2).[7]

Conclusion

Sepsis is a leading cause of death during the neonatal period, and clinicians must have a high index of suspicion, as neonates present with nonspecific clinical signs and symptoms. Early empirical antimicrobial treatment is associated with better outcomes in neonatal sepsis, but antimicrobials must be discontinued timeously to prevent the emergence of further antimicrobial resistance. Acknowledgements. The authors would like to thank Prof. R J Green for his professional guidance and valuable support. Author contributions. MC wrote the initial draft, critically reviewed the manuscript, and participated in revising the manuscript. NTM critically reviewed the manuscript and participated in revising the manuscript. TWDW critically reviewed the manuscript and participated in revising the manuscript. All authors approved the final version to be published. Funding. None. Conflicts of interest. None.

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Table 2. Antimicrobial stewardship programmes: A guide for clinicians[7] Start Smart • Do not start antimicrobials without clinical evidence of infection • Initiate prompt (within 1 hour of diagnosis) and effective antimicrobials in patients with a suspicion or evidence of sepsis • Comply with local prescribing guidelines when choosing an appropriate antimicrobial • Record the clinical indication for antimicrobials, dose and route of administration on the drug chart and medical notes • Record a review/stop date or recommended duration of antimicrobials • Where possible, obtain all relevant cultures prior to commencing antimicrobials Then Focus • Review the clinical diagnosis and microbiology (culture results) to decide on the continuing need for antimicrobials by 48 - 72 hours • Document the plan of action - ‘Antimicrobial prescribing decisions’ relevant to neonates are: stop, change or continue antimicrobials • Document the next review date or stop date 1. Shah BA, Padbury JF. Neonatal sepsis: An old problem with new insights. Virulence 2014;5(1):1-9. https://doi.org/10.4161/viru.26906 2. Dong Y, Speer CP. The role of Staphylococcus epidermidis in neonatal sepsis: Guarding angel or pathogenic devil? Int J Med Microbiol 2014;304:513-520. https://doi.org/10.1016/j.ijmm.2014.04.013 3. Sivanandan S, Soraisham AS, Swarnam K. Review article: Choice and duration of antimicrobial therapy for neonatal sepsis and meningitis. Int J Pediatr 2011;2011:1-9. https://doi.org/10.1155/2011/712150 4. Polin RA. Management of neonates with suspected or proven early-onset sepsis. Pediatr 2012;129(5):1006-1013. https://doi.org/10.1542/peds.2012-0541 5. Simonsen KA, Anderson-Berry AL, Delair SF, Davies HD. Early-onset neonatal sepsis. Clin Microbiol Rev 2014;27(1):21-47. http://doi.org/10.1128/ CMR.00031-13 6. Dong Y, Speer CP. Late-onset neonatal sepsis: Recent developments. Arch Dis Child Fetal Neonatal Ed 2014;100(3):F257-F263. https://doi.org/10.1136/ archdischild-2014-306213 7. Bedford Russel AR, Kumar R. Early onset neonatal sepsis: Diagnostic dilemmas and practical management. Arch Dis Child Fetal Neonatal Ed 2015;100(4):F350-F354. https://doi.org/10.1136/archdischild-2014-306193 8. Motara F, Ballot DE, Perovic O. Epidemiology of neonatal sepsis at Johannesburg Hospital. South Afr J Epidemiol Infect 2005;20(3):90-93. 9. Lebea MM. Evaluation of culture-proven neonatal sepsis at a tertiary care hospital in South Africa (dissertation). University of the Witwatersrand, 2015. http://wiredspace.wits.ac.za/handle/10539/19970 (accessed 12 August 2016). 10. Hall KK, Lyman JA. Updated review of blood culture contamination. Clin Microbiol Rev 2006;19(4):788-802. http://doi.org/10.1128/CMR.00062-05 11. O’Donovan DJ. Urinary tract infections in neonates. UpToDate 2016. https:// www.uptodate.com/contents/urinary-tract-infections-in-neonates (accessed 10 November 2016). 12. Doern GV. Blood cultures for the detection of bacteremia. UpToDate 2016. Available at: https://www.uptodate.com/contents/blood-cultures-for-thedetection-of-bacteremia (accessed 08 November 2016). 13. Patel SJ, Saiman L. Principles and strategies of antimicrobial stewardship in the neonatal intensive care unit. Semin Perinatol 2012;36(6):431-436. https://doi. org/10.1053/j.semperi.2012.06.005 14. Benjamin DK, DeLong ER, Steinbach WJ, Cotton CM, Walsh TJ, Clark RH. Empirical therapy for neonatal candidemia in very low birth weight infants. Pediatrics 2003;112(3):543-547. https://doi.org/10.1542/peds.112.3.543 15. Mackay CA, Ballot DE. Serum 1,3-ßD-glucan assay in the diagnosis of invasive fungal disease in neonates. Pediatric Reports 2011;3(2):45-48. https://doi. org/10.4081/pr.2011.e14 16. Hsieh E, Smith B, Benjamin DK, et al. Neonatal fungal infections: When to treat? Early Hum Dev 2012;88(S2):S6-S10. https://doi.org/10.1016/s03783782(12)70004-x 17. Weisman LE, Pammi M. Clinical features and diagnosis of bacterial sepsis in the preterm infant (<34 weeks gestation). UpToDate 2016. http://www. uptodate.com/contents/clinical-features-and-diagnosis-of-bacterial-sepsis-inthe-preterm-infant-less-than34-weeks-gestation (accessed 08 August 2016). 18. Santoro JD, Carroll VG, Steele RW. Diagnosis and management of urinary tract infections in neonates and young infants. Clin Pediatr 2012;52(2):111-114. https://doi.org/10.1177/0009922812471713 19. Majumdar A, Jana A, Jana A, Biswas S, Bhatacharyya S, Bannerjee S. Importance of normal CSF parameters in term versus preterm neonates. J Clin Neonatol 2013;2(4):166-168. http://doi.org/10.4103/2249-4847.123089

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REVIEW 20. Edwards MS. Bacterial meningitis in the neonate: Clinical features and diagnosis. UpToDate 2016. https://www.uptodate.com/contents/bacterialmeningitis-in-the-neonate-clinical-features-and-diagnosis. (accessed 7 November 2016). 21. Garland JS. Ventilator-associated pneumonia in neonates: An update. NeoReviews 2014;15(6):e225-e235. https://doi.org/10.1542/neo.15-6-e225 22. Cernada M, Brugada M, Golombek S, Vento M. Ventilator-associated pneumonia in neonatal patients: An update. Neonatology 2014;105(2):98107. https://doi.org/10.1159/000355539 23. Aelami MH, Lofti M, Zingg W. Ventilator-associated pneumonia in neonates, infants and children. Antimicrob Resist Infect Control 2014;3:30. https://doi. org/10.1186/2047-2994-3-30 24. Fisher RG. Neonatal osteomyelitis. NeoReviews 2011;12(7):e374-e380. 25. Future directions in the evaluation and management of neonatal sepsis. NeoReviews 2012;13:e103-10. http://doi.org/10.1542/neo.12-7-e374

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26. Velaphi S, Wadula J, Madhi S. Pathogens isolated from blood stream of neonates diagnosed with healthcare associated infections: Antimicrobial susceptibility and case fatality rates. Presented at the 34th Conference on Priorities in Perinatal Care in South Africa, Drakensberg, South Africa, 17 - 20 March 2015. 27. Neonatal sepsis: An old issue needing new answers. Lancet 2015;15(5):503-505. http://dx.doi.org/10.1016/S1473-3099(14)71016-3 28. Edwards MS. Bacterial meningitis in the neonate: Treatment and outcome. UpToDate 2016. https://www.uptodate.com/contents/bacterial-meningitis-inthe-neonate-treatment-and-outcome (accessed 8 November 2016). 29. Pammi M. Treatment of candida infection in neonates. UpToDate 2016. https:// www.uptodate.com/contents/treatment-of-candida-infection-in-neonates (accessed 8 November 2016). 30. Kauffman CA. Candida infections of the central nervous system. UpToDate 2016. https://www.uptodate.com/contents/candida-infections-of-the-centralnervous-system (accessed 8 November 2016).

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CASE REPORT

This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.

Chediak-Higashi syndrome presenting in the accelerated phase S Palaniyandi,1 MD; E Sivaprakasam,1 DCH, DNB; U Pasupathy,1 MD; L Ravichandran,1 DCH, DNB; A Rajendran,1 MD, DM; F R Suman,2 MD; S Rajendra Prasad,1 DCH 1 2

Department of Paediatrics, Sri Ramachandra University, Chennai, India Department of Pathology, Sri Ramachandra University, Chennai, India

Corresponding author: E Sivaprakasam (elayaped@gmail.com) Chediak-Higashi syndrome (CHS) is an extremely rare autosomal recessive disorder characterised by recurrent pyogenic infections, partial oculocutaneous albinism, and mild bleeding. The most reliable finding that helps in diagnosis is abnormally large granules in leukocytes and other granule-containing cells. Herein we report a case of CHS in a 3-month-old girl who presented to us in the accelerated phase of the disease. The case is reported because of the extreme rarity of CHS presenting in the accelerated phase at diagnosis. S Afr J Child Health 2017;11(2):104-106. DOI:10.7196/SAJCH.2017.v11i2.1277

A 3-month-old female child, the third child born of a second-degree consanguineous marriage and developmentally normal with a normal birth history, presented to us with complaints of fever for 3 days. There was a history of hypopigmentation over the skin for the past month, with a history of recurrent respiratory tract infections. There was no family history of similar complaints. Examination revealed an active, anthropometrically normal, febrile child with axillary lymphadenopathy and hepatosplenomegaly. The child had silvery hair with patchy areas of skin hypopigmentation over the face, trunk and limbs (Fig. 1). Other systems were normal. Evaluation showed bicytopenia (low haemoglobin of 6.6 g/dL and platelets of 60 000/ÂľL) with elevated serum triglyceride (323 mg/dL)

and ferritin (2 734 ng/mL) â&#x20AC;&#x201C; features suggestive of haemophagocytic lymphohistiocytosis (HLH). A familial or infectious cause was suspected. Blood and urine cultures were sterile. Toxoplasmosis, rubella, cytomegalovirus, herpes simplex and HIV (TORCH) screening was also negative. Ultrasonography of the abdomen revealed mild ascites. Radiographs of the chest and skull were normal. Peripheral smear (Fig. 2) and bone-marrow aspirate (Fig. 3) showed characteristic giant cytoplasmic granules suggestive of Chediak-Higashi syndrome (CHS). Skin biopsy (Fig. 4) revealed irregularly placed giant melanosomes, consistent with CHS. Ophthalmic evaluation was normal. Ebstein-Barr virus work-up (IgG and IgM) was negative. CHS presenting with features of HLH

Fig. 1. Child presented with silvery hair and patchy areas of skin hypopigmentation.

Fig. 2. Peripheral smear showing giant intracellular granules (arrow).

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CASE REPORT Discussion

Fig. 3. Bone-marrow aspirate showing characteristic giant cytoplasmic granules (arrow).

Fig. 4. Skin biopsy showing giant irregularly placed melanosomes (arrow).

was taken as the accelerated phase. Genetic testing for CHS1/LYST gene mutations is not available in India, and therefore this test could not be performed. T-cell subset levels were not done because of financial constraints. The child was treated with intravenous piperacillin, tazobactam, and amikacin, which were later changed to meropenem and fluconazole owing to persistent high-grade fever spikes. Initiation of chemotherapy was planned as per the HLH 2004 protocol,[1] and a bone-marrow transplant was to be considered; however, the parents did not opt for any escalation of treatment and wanted to continue with the conservative management. The child was discharged at their request and succumbed to her illness 2 days after discharge.

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CHS is a rare disease that follows an autosomal recessive pattern of inheritance. Less than 500 cases have been reported worldwide. The first case in India was diagnosed in 1982.[2] Genetic studies suggest a mutation in the lysosomal trafficking regulator (CHS1/LYST) gene located at 1q42, resulting in abnormal organellar protein trafficking and aberrant fusion of vesicles, further resulting in a failure to transport lysosomes to the appropriate site of action.[3] Altered lysosomes/granules are found in all cell types in CHS, and are the hallmark of the disease. CHS can be suspected on presentation of partial oculocutaneous albinism with a history of recurrent infections.[3] Staphylococcus aureus is the predominant cause while Streptococcus pyogenes and Pneumococcus spp. are the other common infectious organisms. Most of the cases also present with leukopenia, thrombocytopenia and coagulopathy. Photosensitivity has been reported in many cases. Differential diagnosis includes Hermansky-Pudlak syndrome and Griscelli syndrome.[4,5] Hermansky-Pudlak syndrome, an autosomal recessive disorder, is characterised by partial oculocutaneous albinism and a platelet storage pool deficiency. Griscelli syndrome is another autosomal recessive disorder that is characterised by similar partial oculocutaneous albinism with immunodeficiency, which is attributed to a mutation in one of three intracellular trafficking genes. Defective neutrophil chemotaxis, degranulation and bactericidal activity could be the reason for recurrent infections. Pathological aggregation and uneven distribution of melanosomes play a role in hypopigmentation. The degree of hypopigmentation varies. The hair can be light blonde, grey or white with a metallic sheen. In darkly pigmented races, hypopigmentation is appreciated more in sun-exposed areas. Iris and retinal pigmentation is also reduced; light-coloured eyes are seen. Impaired platelet aggregation may contribute to the mild bleeding diathesis found in some cases. The mild coagulation defect in such cases can result in easy bruising and abnormal bleeding, especially noted in mucosal tissue. Diagnosis can be made with a simple peripheral smear for the classic giant azurophilic granules, which are peroxidase-positive, in all granule-containing cells including the peripheral blood and bone marrow.[6] Giant melanosomes can be seen on skin melanocytes. Genetic testing for CHS1/LYST gene mutations can confirm the diagnosis. This gene is large with most mutations being unique, and therefore identifying the exact mutation is a challenge. Prenatal diagnosis is made by amniocentesis or chorionic villus sampling for enlarged lysosomes – this helps in early diagnosis and treatment before the accelerated phase.[7] There are two phases in the progress of the disease: a stable or chronic phase; and a progressive or accelerated phase. The stable phase is characterised by recurrent infections. This phase can be managed with appropriate use of antibiotics or antifungal agents with adequate hygiene. About 10% of patients survive early childhood despite serious infections, but develop severe, debilitating neurological manifestations such as mental retardation, peripheral neuropathy and seizures in adolescence and early adulthood. The accelerated phase may occur soon after birth, as in our case, or years later, and is usually fatal unless intervention occurs rapidly. It mimics a lymphoma-like scenario and is considered a form of familial HLH.[8] Epstein-Barr virus and a lack of natural killer cell function has been implicated in the accelerated phase.[9] There is lymphohistiocytic infiltration of virtually all organs with more profound immune deficiency. Affected individuals present with fever, increased hepatosplenomegaly and lymphadenopathy, with worsening pancytopenia and bleeding.[10] Other presentations can include unexplained hepatosplenomegaly and unexplained neurological abnormalities, especially in an older child, in the form of ataxia, tremors, muscle weakness, sensory loss, cranial nerve

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CASE REPORT palsies, progressive intellectual decline and seizures. Movement disorders, such as Parkinson’s disease and dementia can also occur. The accelerated phase is treated with chemotherapy as per the HLH 2004 protocol. Haematopoietic stem cell transplant is the ultimate treatment for the immunological and haematological manifestations of CHS.[11,12] However, it has no effect on the neurological symptoms and oculocutaneous albinism. Successful transplantation depends on having an HLA-identical donor. HLA-non-identical transplant remains an experimental approach. There has been a report of successful bone-marrow transplantation in a 2-year-old male with CHS in the accelerated phase with hereditary elliptocytosis, the boy being clinically well post transplant.[13] Most patients with CHS die in their first decade if a stem-cell transplant is not done, although patients have been reported as old as 27 years.[14] In a study of 35 children with CHS, the 5-year prognosis post transplantation was 62%. Prognosis is better if the transplant is done before the onset of the accelerated phase. Atypical presentation of CHS can include subtle or absent oculocutaneous albinism, insignificant or less frequent infections, subtle bleeding manifestations and progressive neurological findings that are highly variable and nonspecific.[15] A carefully examined peripheral smear can clinch the diagnosis. Early detection facilitates early bone-marrow transplant, which is the only curative approach for CHS. Acknowledgements. None. Author contributions. All authors were involved in the management of the patient. SP drafted the manuscript. UP, LR, and SRP reviewed the manuscript. AR and FRS provided haematolgy and pathology expertise, respectively. ES critically reviewed the manuscript. Funding. None. Conflict of interest. None. 1. Henter J-I, Horne AC, Arico M, et al. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 2007,48(2):124-131. https://doi.org/10.1002/pbc.21039

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2. Seth P, Bhargava M, Kalra V. Chediak-Higashi syndrome. Indian Paediatr 1982;19(11):950-952. 3. Kaplan J, De Demenico I, Ward DM. Chediak-Higashi syndrome. Curr Opin Hematol 2008;15(1):22-29. https://doi.org/10.1097/moh.0b013e3282f2bcce 4. Diukman R, Tangiawara S, Cowan MJ, Golbus MS. Prenatal diagnosis of Chediak-Higashi syndrome. Prenat Diagnosis 1992;12(11):877-885. https:// doi.org/10.1002/pd.1970121105 5. De Saint Basile G. Chediak-Higashi and Griscelli syndromes. Immunol Allergy Clin North Am 2002;22(2):301-317. 6. Burkhardt JK, Wiebel FA, Hester S, Argon Y. The giant organelles in beige and Chediak-Higashi fibroblasts are derived from late endosomes and mature lysosomes. J Exp Med 1993;178(6):1845-1856. https://doi.org/10.1084/ jem.178.6.1845 7. Valente NY, Machado MC, Boggio P, et al. Polarised light microscopy of hair shafts aids in the differential diagnosis of Chediak-Higashi and GriscelliPrunieras syndrome. Clinics 2006;61(4):327-332. https://doi.org/10.1590/ s1807-59322006000400009 8. Nargund AR, Madhumathi DS, Premalatha CS, Rao CR, Appaji L, Lakshmidevi V. Accelerated phase of Chediak-Higashi syndrome mimicking lymphoma: A case report. J Pediat Hematol Oncol 2010;32(6):e223-e226. https://doi. org/10.1097/mph.0b013e3181e62663 9. Merino F, Henle W, Ramirez-Duque P. Chronic active Epstein Barr virus infection in patients with Chediak-Higashi Syndrome. J Clin Immunol 1986;6(4):299-305. https://doi.org/10.1007/bf00917330 10. Scherber E, Beutel K, Ganschow R, Schulz A, Janka G, Stadt U. Molecular analysis and clinical aspects of four patients with Chédiak-Higashi syndrome (CHS). Clin Genet 2009;76(4):409-412. https://doi.org/10.1111/j.13990004.2009.01205.x 11. Ayas M, Al-Ghonaium A. In patients with Chediak-Higashi syndrome undergoing allogenic SCT, does adding etoposide to the conditioning regimen improve the outcome of bone marrow transplant? Bone Marrow Transplant 2007;40(6):603. http://dx.doi.org/10.1038/sj.bmt.1705774. 12. Eapen M, DeLaat CA, Baker KS, et al. Hematopoietic cell transplantation for Chediak Higashi syndrome. Bone Marrow Transpl 2007;39(7):411-415. https:// doi.org/10.1038/sj.bmt.1705600 13. Islam AS, Hawsawi ZM, Islam MS, Ibrahim OA. Chédiak-Higashi syndrome: An accelerated phase with hereditary elliptocytosis. Ann Saudi Med 2001; 21(34):221-224. https://doi.org/10.5144/0256-4947.2001.221 14. Gallin JI, Elin RJ, Hubert RT, et al. Efficacy of ascorbic acid in Chediak-Higashi syndrome: Studies in humans and mice. Blood 1979;53:226-234. 15. Karim MA, Suzuki K, Fukai K, et.al. Apparent genotype-phenotype correlation in childhood, adolescent, and adult Chediak-Higashi syndrome. Am J Med Genet 2002;108(1):16-22. https://doi.org/10.1002/ajmg.10184

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CPD June 2017 The CPD programme for SAJCH is administered by Medical Practice Consulting. CPD questionnaires must be completed online at www.mpconsulting.co.za

True (T) or false (F): Regarding cranial ultrasound abnormalities in very low birthweight (VLBW) infants 1. More than 50% of VLBW infants have evidence of intraventricular haemorrhage. 2. In a Johannesburg Academic hospital, >90% of VLBW infants have a cranial ultrasound investigation during their initial hospital stay. 3. Cystic periventricular leukomalacia is associated with chorioamnionitis. Regarding the management of oesophageal strictures (OSs) in children 4. The most common cause of OSs was repair of oesophageal atresia. 5. Mitomycin-c administration aggravated the stricture in all patients. Regarding dysphagia in neonates admitted to a neonatal intensive care unit 6. There are three phases of swallowing in normal neonates. 7. Nearly 50% of neonates investigated for dysphagia had neurological abnormalities. Nutritional adequacy of menus in registered child care facilities 8. A child care facility (CCF) open for 6 hours/day should provide one-third of a childâ&#x20AC;&#x2122;s daily nutritional requirements. 9. The majority of CCFs provided the required protein content in the diet. 10. None of the CCFs investigated provided the required calcium content in the diet.

Regarding treatment of severely malnourished children 11. Among HIV-positive children with severe acute malnutrition, those with marasmus have an increased mortality compared to HIV-negative children with severe acute malnutrition (SAM). 12. Good weight gain during recovery from SAM was defined as >20 g/kg/day. 13. HIV infection did not influence the rate of recovery or of weight gain. Regarding screening for cytomegalovirus (CMV) retinitis 14. CMV retinitis was found in the majority of referred children with probable systemic CMV infection. 15. CMV polymerase chain reaction was positive in >80% of children with probable systemic CMV infection. 16. The majority of children with CMV retinitis were HIV-positive. Regarding childhood renal disease 17. Glomerulonephritis was the most common renal disease in children admitted between 1 month and 14 years of age. 18. Proteinuria was present in one-third of children admitted with renal disease. Regarding neonatal sepsis 19. Blood, cerebrospinal fluid, and urine are sterile sites in the neonate. 20. Early-onset sepsis is considered to have occurred if the infection is detected within 5 days of neonatal life.

A maximum of 3 CEUs will be awarded per correctly completed test. CPD questionnaires must be completed online via www.mpconsulting.co.za. After submission you can check the answers and print your certificate. Accreditation number: MDB015/172/02/2017 (Clinical)

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