CHILD HEALTH THE SOUTH AFRICAN JOURNAL OF
April 2015
• • • •
Volume 9
No. 2
Hypoxaemia and pneumonia severity Apartheid and healthcare access Audiological practices post HPCSA position statement Mother-to-child transmission of HIV despite PMTCT interventions • Early renal surveillance and tuberous sclerosis complex
CHILD HEALTH THE SOUTH AFRICAN JOURNAL OF
April 2015
Volume 9
No. 2
CONTENTS Editorial
EDITOR J M Pettifor FOUNDING EDITOR N P Khumalo EDITORIAL BOARD: SAJCH Prof. M Adhikari (University of KwaZulu-Natal, Durban) Prof. M Kruger (Stellenbosch University) Prof. H Rode (Red Cross 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 Hospital, Cape Town) Prof. D F Wittenberg (University of Pretoria)
35
Acute lower respiratory infections in children
J M Pettifor
Opinion
L B Lewandowski, C Scott
Research
A Kanji, J Opperman
DEPUTY EDITOR Bridget Farham
41
The Micral-Test as a screening tool to detect microalbuminuria in children 5 - 15 years old with sickle cell anaemia, Lagos State University Teaching Hospital
SCIENTIFIC EDITOR Ingrid Nye
A U Solarin, F O Njokanma
TECHNICAL EDITORS Emma Buchanan Paula van der Bijl
36 Apartheid and healthcare access for paediatric systemic lupus erythematosus patients in South Africa
EDITOR-IN-CHIEF Janet Seggie
38 Audiological practices and findings post HPCSA position statement: Assessment of children aged 0 - 35 months
45 The use of nasal CPAP at the Charlotte Maxeke Johannesburg Academic Hospital
HEALTH & MEDICAL PUBLISHING GROUP:
C Jardine, D E Ballot
CONSULTING EDITOR J P de V van Niekerk
NEWS EDITOR Chris Bateman
49 Determinants of mother-to-child transmission of HIV despite PMTCT interventions in Enugu, Nigeria
CEO AND PUBLISHER Hannah Kikaya
HEAD OF PUBLISHING Robert Arendse
K K Iloh, O N Iloh, A N Ikefuna, N S Ibeziako, A C Ubesie, I J Emodi
53 Hypoxaemia as a measure of disease severity in young hospitalised Nigerian children with pneumonia: A cross-sectional study
PRODUCTION MANAGER Emma Jane Couzens
M B Abdulkadir, R M Ibraheem, A A Gobir, W B R Johnson
Case Reports
ART DIRECTOR Brent Meder
S K John, R Nalla, V Kumar, P L N G Rao, S Prabhu, S P Thotan, B Kharga
59
Neuroregression in an infant: A rare cause
P Subramani, C Gomathi Saranya, G M Chand, R Sowmiya Narayani, S James, P N Vinoth
57
Early renal surveillance: A necessity in a child with tuberous sclerosis complex
61
An unusual case of Trisomy 13
C Feben, J Kromberg, A Krause
63
Accidental podophyllin poisoning in a 3-year-old child
T de Wit, T Bisseru
65
Achalasia cardia in children: A report of two cases
N Khan, C Liebenberg, F Suleman
Conference Report
67 68
DISTRIBUTION MANAGER Edward Macdonald HEAD OF SALES AND MARKETING Diane Smith (012) 481 2069 | dianes@samedical.org ISSN 1994-3032
The fifth South African Child Health Priorities Conference
CPD Questions ublished by Health and Medical Publishing Group, P Suites 9 & 10, Lonsdale Building Gardner Way Pinelands, 7405 apers for publication should be addressed to the Editor, P via website: www.sajch.org.za Tel: (021) 681-7200 E-mail: publishing@hmpg.co.za
Cover: 'Snail' by Sibelo, Red Cross Children's Hospital Primary School
DTP, LAYOUT & SETTING Carl Sampson
©Copyright: Health and Medical Publishing Group (Pty) Ltd
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EDITORIAL
Acute lower respiratory infections in children In this South African Journal of Child Health issue, we publish an article from Nigeria on the association of hypoxaemia with the outcome in children under the age of 5 years admitted with pneumonia.[1] In this study, children with hypoxaemia (pulse oximetry SpO2 <90%) were 48 times more likely to die, and those who survived were likely to spend almost twice as long in hospital as those who were not hypoxaemic. The overall mortality rate of admitted children with pneumonia was 8.5%, but all the deaths occurred in those who were hypoxaemic on admission (giving a mortality rate of 20% in that group). In a very recent systematic review of risk factors for mortality from acute lower respiratory infections (ALRIs) in <5-yearold children in low- and middle-income countries[2] (95% of all deaths from ALRIs occur in these countries), the major risk factors were the diagnosis of very severe pneumonia using the World Health Organization (WHO) definition, being <2 months of age, and having underlying chronic disease, HIV or severe malnutrition. The usual socioeconomic and environmental factors also contributed, namely young maternal age, low maternal education, second-hand smoke exposure and indoor air pollution. The most common bacterial causes of pneumonia have typically been Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus;[3] however, the increasing use of Haemophilus influenza type b and pneumococcal vaccines in the Expanded Programme of Immunization in many countries has dramatically reduced the role of the latter two organisms in the pathogenesis of the disease, and has also reduced the importance of bacterial pathogens as a cause of ALRI. In HIV-negative children, the 9-valent pneumococcal vaccine has reduced invasive pneumococcal disease by 83% and ALRIs by 20%.[4] In a study conducted in South Africa and published this year, viral pathogens were found in 78% of children <5 years of age with ALRIs.[5] As expected, the most common viruses were rhinovirus (37%), respiratory syncytial virus (RSV) (26%), adenovirus (26%) and influenza virus (7%). As an aside, the actual role of rhinovirus and adenovirus in the pathogenesis of ALRI is unclear, as the two viruses are frequently found in healthy controls. The case fatality rate in the cohort of children with ALRIs was 2%, but it is difficult to draw comparisons with the Nigerian study quoted above. HIV-infected children had up to a three-fold greater incidence of ALRIs than HIVnegative children, but this increased risk appears to have declined over the years of the study, from 3.7 in 2009 to 1.8 in 2012, possibly because of the greater use of highly active antiretroviral therapy. The mortality among HIV-positive children was 7% compared with 1% in HIV-negative children. These figures highlight the urgent need for effective interventions against respiratory syncytial and influenza viruses, not only to reduce mortality but also hospital admissions from ALRIs. RSV infection is the major cause of ALRI globally and of morbidity especially in infants <1 year of age[6] and those with underlying chronic diseases or a history of prematurity. Anecdotally, RSV infections account for the large upsurge in admissions to the paediatric wards at Chris Hani Baragwanath Academic Hospital during the autumn and winter
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months. Some 80% of children at 2 years of age have been infected with RSV, of whom one-third will have developed an ALRI, usually bronchiolitis. Vaccines have been developed but have yet to be proven efficacious in preventing RSV infections in infants and young children. The reason is that the natural immune response to RSV is complex. After an infection, protection against repeat infection is short-lived and incomplete, so that infants may be reinfected with the same RSV strain within the same year. Reinfections with antigenically similar strains of RSV occur throughout life, despite there being relative antigenic stability.[7] Maternal IgG antibodies against RSV do cross the placenta and are present in the neonate, but levels decline rapidly. The presence of sufficient levels of antibodies in the young infant does help to protect the infant from severe infection, but these do not last. As RSV disease is most severe in infants <12 months of age, any effective vaccine is going to have to ensure that it stimulates adequate antibody levels in this age group, and this is currently a challenge. It appears that we still have a long way to go before we see an effective RSV vaccine available to protect young infants from the most common cause of bronchiolitis and severe lower respiratory infection globally. J M Pettifor MB BCh, FCPaed (SA), PhD (Med), MASSAf Editor, South African Journal of Child Health
References 1. Abdulkadir MB, Ibraheem RM, Gobir AA, Johnson WBR. Hypoxaemia as a measure of disease severity in young hospitalised Nigerian children with pneumonia: A cross-sectional study. S Afr J Child Health 2015;9(2):53-56. [http://dx.doi.org/10.7196/SAJCH.901] 2. Sonego M, Pellegrin MC, Becker G, Lazzerini M. Risk factors for mortality from acute lower respiratory infections (ALRI) in children under five years of age in low- and middle-income countries: A systematic review and metaanalysis of observational studies. PLoS One 2015;10(1):e0116380. [http:// dx.doi.org/10.1371/journal.pone.0116380] 3. Principi N, Esposito S. Management of severe community-acquired pneumonia of children in developing and developed countries. Thorax 2011;66(9):815-822. [http://dx.doi.org/10.1136/thx.2010.142604] 4. Klugman KP, Madhi SA, Huebner RE, et al. A trial of a 9-valent pneumococcal conjugate vaccine in children with and those without HIV infection. N Engl J Med 2003;349(14):1341-1348. [http://dx.doi.org/10.1056/NEJMoa035060] 5. Cohen C, Walaza S, Moyes J, et al. Epidemiology of viral-associated acute lower respiratory tract infection among children <5 years of age in a high HIV prevalence setting, South Africa, 2009 - 2012. Pediatr Infect Dis J 2015;34(1):6672. [http://dx.doi.org/10.1097/INF.0000000000000478] 6. Nair H, Nokes DJ, Gessner BD, et al. Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: A systematic review and meta-analysis. Lancet 2010;375(9725):1545-1555. [http://dx.doi. org/10.1016/S0140-6736(10)60206-1] 7. Lambert L, Sagfors AM, Openshaw PJM, Culley FJ. Immunity to RSV in earlylife. Front Immunol 2014;5:466. [http://dx.doi.org/10.3389/fimmu.2014.00466] S Afr J CH 2015;9(2):35. DOI:10.7196/SAJCH.947
APRIL 2015 Vol. 9 No. 2
OPINION
Apartheid and healthcare access for paediatric systemic lupus erythematosus patients in South Africa L B Lewandowski,1 MD; C Scott,2 MB ChB, FCPaed 1 2
uke University Medical Center, Duke Global Health Institute, Pediatric Rheumatology, Global Health, Durham, USA D Head of Paediatric Rheumatology, Red Cross War Memorial Children’s Hospital, University of Cape Town, South Africa
Corresponding author: L B Lewandowski (laura.lewandowski@dm.duke.edu) South Africa (SA) still faces the legacy of apartheid: the history, politics and economics have a lasting, indelible effect on the health of its people. Here, we discuss the challenges of caring for patients with chronic disease, focusing on paediatric systemic lupus erythematosus (SLE), as a framework for evaluating the structural challenges to accessing care in SA. Prior reports have demonstrated numerous factors influencing access for SA patients with chronic disease.[1] This article explores the economic, social and political vestiges of apartheid as it affects the healthcare system and subsequently, our patients. SLE is a life-threatening autoimmune disease, which we will use to highlight the challenges of identifying and treating chronic diseases in SA. Paediatric SLE (pSLE) is more severe than the adult disease, and children with SLE in Africa are potentially at high risk for poor outcomes based on race and age.[2-4] We have initiated a study of the pSLE population in SA. Over half of the cohort presented with severe manifestations, such as renal failure or stroke, at time of diagnosis, leading to serious and irreversible organ damage in many of our patients. We propose that postapartheid and related economic obstacles may delay the diagnosis of pSLE and other chronic diseases, leading to advanced disease burden and poor outcomes. Access to care in SA is a complex outcome with many facets. This analysis borrows a model from the world of economics: the theory of transaction costs used to explain market failures.[5] The transaction cost of travel (including risk of travel, time and expense) often creates a barrier to market participation. Utilising this theory of transaction costs, we describe the personal and economic pressures that drive medical access decisions in postapartheid SA. Through this model, we will attempt to understand the factors that limit access to care. SA is a low-to-middle-income country, yet the income disparities are vast. The Gini coefficient (a measure of income inequality ranging from 0 to 1) grew in postapartheid SA from 0.56 in 1995 to 0.76 in 2005, although it did decrease slightly to 0.7 in the most recent report.[6,7] Other studies have highlighted the effects of poverty on health, and the detrimental effects of income disparity on the health of SA.[8] During apartheid, laws and policies were put in place that targeted the marginalisation of black African and coloured people.*[6,9] Through a series of legislative acts, including pass laws and the Land Act, black African families were relocated to rural areas.[10] The infrastructure of roads and these laws combined to limit access and mobility for people of colour. This has led to a fragmentation of land, services and access, often according to racial and socioeconomic status. The vestiges of that system have continued consequences for the poor of those areas today.[11] Previous studies have linked the length of travel time and access to care. Limited availability of ambulances creates a travel barrier, as emergency care may be unable or unwilling to enter informal settlements. Roads and addresses in these areas can be poorly marked or nonexistent. Maternity studies highlight this problem: 36
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most women who delivered outside of a facility did so while waiting for emergency transport. Interviews revealed that ambulances can or will not attempt to enter their settlements.[12] A study of patients with chronic disease revealed that ambulance disrepair and poor staff availability are also causes for lack of emergency transport options.[1] There is no reliable system of centralised public transportation in SA. Public transportation safety is a serious concern.[13] One study revealed that 64% of South Africans were dissatisfied with personal security on the walk to train stations and on the trains themselves. [14] In 2011, there were over 5 000 deaths in SA from traffic accidents. [15] Minibus taxi users were the most unsatisfied about safety from accidents (67%), lack of facilities (64%), and lack of vehicle roadworthiness (60%).[16] Poor people living in rural areas are least likely to have access to a private car, yet may not have emergency vehicle or public transport options available in times of illness. Cost for transport further compounds this matter. Minibus taxis are expensive relative to income and are not subsidised by the state. In almost half of the poorest households (monthly income <ZAR500, ~USD50 equivalent), it is shown that members spend more than 20% of their income on public transportation at baseline.[15] In addition to fees, time is often an underappreciated cost. In one study, if transportation time exceeded 1 hour, there was a marked decline in a patient’s likelihood to seek care.[12] Travel time is often underestimated, as many roadmaps are inaccurate, and variations in the rainy season and other hindrances can turn a 5-km walk into a 10-hour trip. Studies have shown that in SA, the average wait time in clinics is 150 - 160 minutes.[12,17] This time is additive with the travel time to the clinic. A final invisible cost to consider is job security. SA has a high number of migrant workers and day labourers. The time spent waiting for transport and care can translate into a day of missed work. Without job security, this may mean loss of livelihood. Current estimates of the unemployment rate are 27%,[14] therefore a lost job is unlikely to be restored. Transportation cost may be a more prominent obstacle in seeking healthcare for initial symptoms of chronic conditions. These first, milder symptoms can continue unchecked until they develop into an emergency.[18] When patients present with advanced disease, it may have caused irreversible damage, leading to anger and frustration. This can result in a cycle of distrust between the patient and providers (Fig. 1). Reflecting on all the major costs listed above, it is remarkable that families under these circumstances ever access healthcare. In our study, the majority of children have severe damage, such as blindness or renal failure. We recognise that the costs of transportation, both visible and unseen, may be just one component of delay in care. Based on the evidence presented in this article, it seems likely that the cost of transport will prove to create a barrier to care, and addressing this impediment could improve the care of chronic disease in SA.
APRIL 2015 Vol. 9 No. 2
OPINION Poor road access from rural and peri-urban (township) areas
Poor pubic transportation options
Vestiges of apartheid spatial separation of racial and economic groups
Long transport from home to medical care facility
Fear of lost wages/job
High traffic accident mortality
Delay in seeking care Provider frustration
Increase in irreversible organ damage
Patient mistrust
Poor outcomes Fig. 1. Conceptual framework of barriers to healthcare access.
*Note: All categories of race described in this article are utilised according the scheme used by Statistics SA, and include the following groups: black African, coloured, Indian/ Asian, white and other. Acknowledgements. This work was funded by Duke Immunology/Rheumatology under T32 Training grant award number 3020466 and the Fogarty International Center of the National Institute of Health under award number R25TW009337. This study was approved by the University of Cape Town ethics committee and the Duke University Institutional review board. We would like to acknowledge Dr N Thielman for thoughtful manuscript review.
References 1. Goudge J, Gilson L, Russell S, Gumede T, Mills A. Affordability, availability and acceptability barriers to health care for the chronically ill:
Longitudinal case studies from South Africa. BMC Health Serv Res 2009;9:75. [http://dx.doi. org/10.1186/1472-6963-9-75] 2. Brunner HI, Gladman DD, Ibañez D, Urowitz MD, Silverman ED. Difference in disease features between childhood-onset and adult-onset systemic lupus erythematosus. Arthritis Rheum 2008;58(2):556-562. [http://dx.doi.org/10.1002/ art.23204] 3. Ardoin SP, Schanberg LE. Paediatric rheumatic disease: Lessons from SLE: Children are not little adults. Nat Rev Rheumatol 2012;8(8):444-445. [http://dx.doi.org/10.1038/ nrrheum.2012.109] 4. Uribe AG, McGwin G Jr, Reveille JD, Alarcón GS. What have we learned from a 10-year experience with the LUMINA (Lupus in Minorities; Nature vs. nurture) cohort? Where are we heading? Autoimmun Rev 2004;3(4):321-329. [http://dx.doi.org/10.1016/j. autrev.2003.11.005] 5. De Janvry A, Fafchamps M, Sadoulet E. Peasant household behaviour with missing markets: Some paradoxes explained. Econ J 1991;101(409):14001417. 6. Coovadia H, Jewkes R, Barron P, Sanders D, McIntyre D. The health and health system of South
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Africa: Historical roots of current public health challenges. Lancet 2009;5;374(9692):817-834. [http://dx.doi.org/10.1016/S0140-6736(09)60951-X] 7. Statistics South Africa. Living conditions of households in South Africa, 2008/2009. http:// b e t a 2 . st at ss a . gov. z a / ? p age _ i d = 7 3 9 & i d = 1 (accessed October 2014). 8. Mayosi BM, Benatar SR. Health and health care in South Africa: 20 years after Mandela. N Engl J Med 2014;371(14):1344-1353. [http://dx.doi. org/10.1056/NEJMsr1405012] 9. Posel D. Race as common sense: Racial classification in twentieth-century South Africa. Afr Stud Rev 2001;44(2):87-113. 10. Marks S, Andersson N. Issues in the political economy of health in Southern Africa. J South Afr Stud 1987;13(2):177-186. [http://dx.doi. org/10.1080/03057078708708140] 11. Mayosi BM, Lawn JE, van Niekerk A, Bradshaw D, Abdool Karim SS, Coovadia HM. Health in South Africa: Changes and challenges since 2009. Lancet 2012;380(9858):2029-2043. [http://dx.doi. org/10.1016/S0140-6736(12)61814-5] 12. Silal S, Penn-Kekana L, Harris B, Birch S, McIntyre D. Exploring inequalities in access to and use of maternal health services in South Africa. BMC Health Serv Res 2012;12(1):120. [http://dx.doi. org/10.1186/1472-6963-12-120] 13. Czeglédy AP. Getting around town: Transportation and the built environment in post-apartheid South Africa. City Soc 2004;16(2):63-92. [http:// dx.doi.org/10.1525/city.2004.16.2.63] 14. Walters J. Overview of public transport policy developments in South Africa. Res Transportation Economics 2008;22(1):98-108. [http://dx.doi. org/10.1016/j.retrec.2012.05.021] 15. Statistics South Africa. P0309.3: Mortality and causes of death in South Africa, 2011: Findings from death notification. http://beta2.statssa. gov.za/publications/P03093/P030932011.pdf (accessed October 2014). 16. Meel BL. Trends in fatal motor vehicle accidents in Transkei region of South Africa. Med Sci Law 2007;47(1):64-68. 17. Tanser F, Gijsbertsen B, Herbst K. Modelling and understanding primary health care accessibility and utilisation in rural South Africa: An exploration using a geographical information system. Soc Sci Med 2006;63(3):691-705. [http:// dx.doi.org/10.1016/j.socscimed.2006.01.015] 18. Goudge J, Gilson L, Russell S, Gumede T, Mills A. The household costs of health care in rural South Africa with free public primary care and hospital exemptions for the poor. Trop Med Int Health 2009;14(4):458-467. [http://dx.doi.org/10.1111/ j.1365-3156.2009.02256.x]
S Afr J CH 2015;9(2):36-37. DOI:10.7196/SAJCH.869
RESEARCH
Audiological practices and findings post HPCSA position statement: Assessment of children aged 0 - 35 months A Kanji, MA (Audiology); J Opperman, BA (Speech and Hearing Therapy) Department of Speech Therapy and Audiology, University of the Witwatersrand, Johannesburg, South Africa Corresponding author: A Kanji (amisha.kanji@wits.ac.za)
Background. Early detection of hearing loss is important to ensure optimal development, and may be influenced by the audiological assessment process. Objective. To describe the actual practices and audiological findings with regard to the assessment of 0 - 35-month-old children referred for a hearing assessment at a public hospital. Methods. A retrospective record review was conducted. The study sample comprised 100 participant files. Results. The mean age of initial hearing screening was 13.1 months. Of the participants, 99% received an initial hearing screening and 44% received a second hearing screening. Only four of the eight participants who were referred underwent auditory brainstem response testing and were diagnosed with hearing loss. These four participants were diagnosed after the age of 2 years. The audiological protocol differed from that recommended by the Health Professions Council of South Africa, resulting in limited diagnostic assessment results. Conclusion. The study highlighted gaps in the practice of recommended, age-appropriate audiological protocols as well as the ages at which the initial hearing screenings were conducted, which affects early diagnosis of hearing loss. S Afr J CH 2015;9(2):38-40. DOI:10.7196/SAJCH.778
The professional board for speech, language and hearing professions of the Health Professions Council of South Africa (HPCSA) released a position statement that outlines the Early Hearing Detection and Intervention (EHDI) programme in South Africa (SA).[1] The purpose of the EHDI programme is to detect, diagnose and treat newborns and infants with hearing loss at an early age. A recent survey suggested that 53% of private hospitals offer some form of newborn hearing screening, and only 15% offer true universal newborn hearing screening.[2] In comparison, an earlier study revealed that only 7.5% of public hospitals in SA had implemented some form of newborn hearing screening.[3] Although EHDI has proven benefits, its implementation in SA is not yet a reality.[4] A recent study by Swanepoel et al.[5] in a university clinic setting indicated that of the 65 participants with bilateral sensorineural hearing loss within their study sample, 47% were diagnosed after 36 months, 20.4% before 18 months and 30.6% before 24 months. They also reported that 75% of the participants with unilateral hearing loss (n=8) had been diagnosed after 36 months. These ages for diagnosis and intervention are delayed when compared with the stipulated guidelines by the HPCSA position statement.[1] There is limited published literature regarding the audiological practices to assess hearing in children within the SA public healthcare sector. Late detection of hearing loss may also be influenced by the audiological assessment process, from initial assessment to final diagnosis. It is necessary for audiologists to use a test battery, so as to base the diagnosis on collective results.[6] Hospitals are required to follow an inclusive audiological test battery when assessing neonates and infants.[1] The HPCSA has recommended a test battery between the ages of 0 and 36 months to allow for accountable testing and diagnosis of hearing loss (Figs 1 and 2).[1] Apart from the recommended electrophysiological measures, high-frequency tympanometry (using a 1 000-Hz probe tone) has also been recommended as a measure that should be made available at tertiary and secondary hospitals for differential diagnosis when a ‘refer result’ is obtained for otoacoustic emissions (OAEs).[1] 38
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Objective
To describe the actual practices and audiological findings with regard to the assessment of 0 - 35-month-old children referred for a hearing assessment at a public hospital.
Methods
Research design and site
The research study employed a descriptive, retrospective research design. The research site was a secondary hospital located in Johannesburg. The Audiology Department has two permanent audiologists and one community service audiologist, and is located near the Ear, Nose and Throat (ENT) Department. There is only one audiology booth with an audiometer, an OAE screener, an immittance machine using a 226-Hz probe tone and noise makers.
Sampling strategy and sample
A purposive sampling method was used. For the purposes of this study, patient files of children aged 0 - 35 months, assessed between January 2010 and December 2012, were utilised. The sample comprised 100 participant files that met the inclusion criteria. The initial audiological assessment had to be of children within 0 - 35 months old, between 2010 and 2012. The participant files had to include information on at least the initial audiological assessment.
Data analysis
The data collected were analysed using descriptive statistics.
Ethical considerations
Ethical clearance was obtained from the Medical Human Research Ethics Committee of the University of the Witwatersrand (clearance certificate number: M130365) and permission was obtained from relevant personnel at the hospital prior to commencement of the study. Anonymity was ensured by using a participant code system instead of participant names.
APRIL 2015 Vol. 9 No. 2
RESEARCH
Case history information
Observation of infant’s response to sound
Electrophysiological measure (ABR/ASSR)
assessment was 31.5 months and the median age was 11 months. Results indicated that 44% (n=44) of the participants underwent a second hearing screening, four of which underwent diagnostic auditory brainstem response (ABR) from another nearby tertiary hospital. The mean age for the second hearing screening was 16 months, which was conducted ~3 months after the initial hearing screening. The four participants diagnosed with hearing loss were diagnosed at a mean age of 32.5 months.
Audiological evaluation of children following hearing screening
Immitance audiometry
DPOAE
Fig. 1. Recommended audiological test battery for infants <6 months old.[1]
Case history information
Behavioural response audiometry including speech audiometry
Parental report on hearing abilities
Very few participant files indicated referral for diagnostic audiological evaluation. Of the 100 participants, 6 of the 66 participants who were >6 months were referred for visual reinforcement audiometry, and 8 participants were referred for diagnostic ABR. Of these 14 participants, only 4 (4%) were clinically diagnosed with hearing loss, despite 35 having had an OAE referral without any suspected middle-ear pathology. All four of the participants diagnosed with hearing loss presented with bilateral hearing loss. Three of the participants were diagnosed with sensorineural hearing loss, and one was diagnosed with conductive hearing loss. The initial age of hearing screening was after 2 years of age (range 25 - 32 months). Participants were diagnosed with hearing loss through diagnostic measures ~3.5 months after the initial audiological screening. From the initial OAE screenings (N=100), 73% had a bilateral refer result and 26% had a unilateral refer result. Of the 44 participants who received a second screening, 11 presented with a unilateral refer, while 33 presented with a bilateral refer result.
Audiological protocol used for diagnosis of hearing loss
Communication and language screening
ABR/ASSR and OAE at initial consultation
Fig. 2. Recommended audiological test battery for children aged 6 - 36 months.[1]
Results
The age of participants at the time of initial audiological assessment ranged from 2 weeks to 32 months, with 34 participants being <6 months old. Of the 100 participants, 99 had an OAE refer result (9 for the left ear only, 17 for the right ear only and 73 bilaterally). One participant could not be screened using OAEs. Twenty-seven of the bilateral OAE refer results were accompanied by type A tympanograms bilaterally, 13 by type B tym panograms bilaterally, 19 by unilateral type
A and type B tympanograms, 8 by unilateral type A and type As tympanograms, and 6 by unilateral type B and type As tympanograms. Overall, 75 participant files indicated a need for a recheck, and 19 indicated the need for referral to the ENT specialist.
Age of initial audiological assessment
The mean age of initial audiological assessment was 13.5 months (range 2 weeks - 32 months). The age range for the initial 39
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Case history interviews and immittance audiometry (tympanometry 226-Hz probe tone) were routine procedures conducted on all participants diagnosed with hearing loss. Tympanometry with a 226-Hz probe tone was routinely used, even though a 1 000-Hz probe tone is recommended for children between 0 and 6 months of age. OAE screening was also commonly conducted at the initial audiological evaluation, even when contraindicated by the presence of suspected conductive pathology. One participant was referred directly for an ABR assessment following a case history interview and tympanometry, without any assessment through behavioural audiometry. One participant received a diagnostic distortion product OAE (DPOAE) from a referral tertiary hospital. All four children diagnosed with hearing loss underwent a diagnostic ABR from a referral tertiary hospital.
RESEARCH Discussion
Four children were diagnosed with hearing loss between 2010 and 2012. It must be noted that this may be an underrepresentation, as these children were reportedly the only children who underwent a comprehensive audiological assessment; the remaining participants who did not receive complete assessments may include some children with undiagnosed hearing loss. The late diagnosis of hearing loss in developing countries is attributed to the reality that hearing diagnosis in developing countries relies highly on family concerns.[7] Families often notice developmental delays when the child reaches the age of language acquisition, which is after 1 year of age. Results showed that participants were receiving their initial hearing screening at an average age of 13.5 months. In contrast, a study conducted in Malaysia identified that children were receiving initial evaluation before 3 months of age, as a result of an early screening programme, with detection of hearing impairment through diagnostic ABR between 2.4 and 5.2 months of age.[8] According to the HPCSA,[1] hospital-based screening should involve screening of infants before the age of 1 month. Appropriate EHDI programmes have evidently not been successfully implemented. This was further noted in a study done by Van der Spuy et al.[9] The implications of these results are that children with hearing loss are not receiving intervention at an appropriate age. The four children diagnosed with hearing loss in the current study were diagnosed at a mean age of 32.5 months, following ABR assess ment. Although the results of the diagnosed children in this study are not representative of the population, they correlate with results from other studies.[5,10] However, it is recommended that hearing loss be diagnosed by 3 months of age to allow for optimal development.[1] The late age of diagnosis may be influenced by the audiological protocol used to assess children between 0 and 35 months of age and poor follow-up return rate. Results from the current study indicated that 55% of the participants did not have a follow-up screening, despite the initial refer result from OAE screening. According to the HPCSA,[1] a rescreen after an OAE refer is critical to eliminate false positives, and screening should be monitored monthly to allow for hearing loss diagnosis to occur by 3 months of age. The follow-up screening in the current study occurred ~3 months after the initial screening, resulting in further delay with regard to diagnosis of hearing loss. Assessment using OAEs is not sufficient in isolation.[11] Further testing, such as ABR, is necessary for this population in order to assist in decreasing false positives, which take up time and resources, and cost money. Therefore, a screening protocol should comprise a reliable test battery to eliminate high referral rates and false positives. The protocol documented in the sample population included case history taking, OAE screening, otoscopy, 226-Hz tympanometry and speech awareness thresholds. The recommended protocol at hospital level includes an ABR/ automated ABR, DPOAE, immittance audiometry, speech audiometry and case history.[1] It is evident from the results that the protocol currently being implemented differs from the recommended guidelines in terms of electrophysiological measures. According to the HPCSA position statement,[1] children <6 months require ABR/ auditory steady state response (ASSR), DPOAE and/or high-frequency tympanometry (1 000-Hz probe tone) for appropriate diagnosis. These assessment measures were not available at the hospital in the current study. Children between the ages of 6 and 36 months require an ABR/ ASSR and behavioural audiometry,[1] which was not evident in the current study. An unpublished study by Teixeira (Master’s research report, University of the Witwatersrand, 2012) found that audiologists were overreliant on diagnostic electrophysiological measures for paediatric hearing assessment. The research site used in the current study was not equipped with diagnostic electrophysiological measures and needed to refer to a nearby tertiary hospital for ABR, diagnostic DPOAE or 40
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ASSR testing. OAEs and ABRs are the only reliable tools in identifying hearing loss in infants,[11] but a lack of equipment and staff has been identified as a challenge to screening and assessment in the SA context.[3] The lack of appropriate audiological equipment may have contributed to only 4% of the sample population being diagnosed with a hearing loss. Although a recheck is recommended by the HPCSA position statement[1] in screening infants, no further records were available regarding the recheck results. This suggests that a significant number of participants were not followed up, possibly due to poor follow-up return rates and/or poor record keeping. Record keeping is essential as it allows for appropriate tracking of patients who have not returned for follow-up appointments, and further allows for continuation of care for those who return.[12] Follow-up return rate is a growing concern in SA. The factors contributing to children being ‘lost’ before their follow-up include insufficient services, such as qualified audiologists and necessary equipment, a lack of professional knowledge involved in hearing screening, the difficulty parents face in bringing their children for screening and the gap in communication among professionals.[13]
Conclusion
The number of participants with reported hearing loss may not be accurate, as very few participants underwent comprehensive, diagnostic assessment. The current study identified that infants are still not being diagnosed at the recommended age as stipulated by the HPCSA position statement, the implications of which are far reaching into the child’s development and communication. Results also showed gaps in age-appropriate assessment protocols, which has significant implications for the diagnosis of hearing loss in this age group. Findings may be further influenced by poor follow-up return rate, and challenges faced by audiologists working within the public healthcare sector context in terms of availability of equipment and resources, especially at tertiary and secondary levels of care. Acknowledgement. The authors would like to thank the staff at the research site.
References 1. Health Professions Council of South Africa. Early Hearing Detection and Intervention Programmes in South Africa, Position Statement Year 2007. http:// www.hpsca.co.za/hpcsa/default.aspx?id=137 (accessed 7 February 2014). 2. Meyer ME, Swanepoel D. Newborn hearing screening in the private health care sector: A national study. S Afr Med J 2011;101(9):665-667. 3. Theunissen M, Swanepoel D. Early hearing detection and intervention services in the public health care sector in South Africa. Int J Audiol 2008;47(Suppl 1):S23-S29. [http://dx.doi.org/10.1080/14992020802294032] 4. Swanepoel D, Störbeck C, Friedland P. Early hearing detection and intervention in South Africa. Int J Pediatr Otorhinolaryngol 2009;73:783-786. 5. Swanepoel D, Johl L, Pienaar D. Childhood hearing loss and risk profile in a South African population. Int J Pediatr Otorhinolaryngol 2013;77(3):394-398. [http://dx.doi.org/10.1016/j.ijporl.2012.11.034] 6. Butler I. Identification and management of childhood hearing loss. Continuing Medical Education 2012;30(9):314-317. 7. McPherson B, Olusanya BO. Screening for hearing loss in developing countries. In: McPherson B, Brouillette R, eds. Audiology in Developing Countries. New York: Nova Science Publishers, 2008:75-106. 8. Ahmad A, Mohamad I, Mansor S, Daud MK, Sidek D. Outcome of a newborn hearing screening program in a tertiary hospital in Malaysia: First five years. Ann Saudi Med 2011;31(1):24-28. [http://dx.doi.org/10.4103/0256-4947.75774] 9. Van der Spuy T, Pottas L. Infant hearing loss in South Africa: Age of intervention and parental needs for support. Int J Audiol 2008;47(Suppl 1):S30-S35. [http:// dx.doi.org/10.1080/14992020802286210] 10. Khoza-Shangase K, Barratt J, Jonosky J. Protocols for early audiology intervention services: Views from early intervention practitioners in a developing country. S Afr J Child Health 2010;4(4):100-108. 11. Swanepoel D. Identifying infant hearing loss: Never too early, but often too late. Continuing Medical Education 2009;27(8):368. 12. Joubert K, Casoojee A. Hearing-screening record-keeping practices at primary healthcare clinics in Gauteng. S Afr J Commun Disord 2013;60:27-30. [http:// dx.doi.org/10.7196/sajcd.233] 13. Shulman S, Besculides M, Saltzman A, Ireys H, White KR, Forsman I. Evaluation of the universal newborn hearing screening and intervention program. Pediatrics 2010;126(Suppl 1):S19-S27. [http://dx.doi.org/10.1542/peds.2010-0354F]
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RESEARCH
The Micral-Test as a screening tool to detect micro albuminuria in children 5 - 15 years old with sickle cell anaemia, Lagos State University Teaching Hospital A U Solarin,1,3 FWAC (Paed), Cert Nephrology (SA) (Paed); F O Njokanma,2 FWAC (Paed), FMC (Paed) Renal (ISN/IPNA) Fellow, Department of Paediatric Nephrology, Red Cross War Memorial Children’s Hospital, Cape Town, South Africa Department of Paediatrics, Lagos State University Teaching Hospital, Lagos, Nigeria 3 Department of Paediatrics, Babcock University Teaching Hospital, Ilishan-Remo, Ogun State, Nigeria 1 2
Corresponding author: A U Solarin (asolar234@gmail.com) Objective. To determine the sensitivity, specificity, and positive and negative predictive values of the Micral-Test in determination of microalbuminuria (MA). Methods. Eighty children aged 5 -15 years with sickle cell anaemia (SCA) (HbSS) in a steady state attending the Lagos State University Teaching Hospital were recruited. The subjects were age-, sex- and social-class-matched with controls of genotype AA (HbAA). This prospective, descriptive and cross-sectional study lasted for 3 months, between October and December 2009. Morning random spot urine was used to assess the Micral-Test and the albumin/creatinine ratio (ACR). The performance of the Micral-Test was determined using the ACR as the gold standard. Result. The sensitivity and specificity of the Micral-Test were 84.6% and 81.0%, respectively. The sensitivity and specificity were 100% and 86.6%, respectively, in children <10 years of age compared with 80% and 73.8%, respectively, in those >10 years old. The positive predictive value was 28.2% and the negative predictive value was 98% among the study subjects. Conclusion. The sensitivity and specificity of the Micral-Test make it a good screening tool to detect MA in children with SCA. The MicralTest is cheaper than quantitative measurement of ACR. Patients with a single positive Micral-Test should be followed up with two more Micral-Tests over a 3-month period to confirm persistent MA. S Afr J CH 2015;9(2):41-44. DOI:10.7196/SAJCH.755
Sickle cell anaemia (SCA) accounts for more than three-quarters of the >300 000 children born world wide with a serious Hb disorder.[1] SCA is inherited as an autosomal recessive disorder and is the most common inherited condition affecting red blood cells among blacks. There is a high burden of the disease in Africa, particularly in Nigeria, where the heterozygous (AS) carrier rate is ~25% and homozygous rate (SS) is ~3%.[2,3] SCA accounts for 5% of <5-year-old deaths on the African continent, more than 9% of such deaths in West Africa and up to 16% in individual West African countries.[4] The disease contributes to up to 26.5% of deaths in children aged 5 - 15 years in Nigeria; this high disease burden makes SCA a major cause of mortality in Nigeria.[5,6] SCA is associated with alterations in the functions of many organ systems, including the kidney.[7] Renal abnormalities associated with SCA include concentration defects, impaired urinary acidification, disruption of medullary vasculature, cortical scarring, proteinuria and uraemia.[7] Renal failure, a major complication, has been found to affect 5 - 18% of all patients with SCA, and leads to early death.[8] Derangement of renal function observed in SCA is partly explained by hyperfiltration and hyperperfusion. Essentially, these two processes are consequences of significant insult to the glomerular basement membrane, resulting in excessive loss of albumin in the urine. This glomerulopathy is responsible for proteinuria and progressive renal insufficiency.[9,10] An albumin excretion rate of <20 μg/min (i.e. 30 mg/24 hours) is considered normal in healthy individuals. [11] However, in SCA, early in the process of altered renal function, albumin is lost in the urine in minute quantities above the acceptable range but below the level (30 mg/dL) detectable by routine dipstick analysis. The excretion of proteins by the kidneys above the ‘normal’ range but below the level of standard dipstick 41
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detection is termed microalbuminuria (MA).[12] MA is a prelude to the development of overt proteinuria. The use of MA in the prediction of future development of overt renal disease in diabetes and hypertension has been established in diseases such as diabetes and hypertension. Methods employed include the 24-hour urine albumin test, the overnight urine albumin test (these are timed collections) and the spot urine test for albumin and/or albumin/creatinine ratio (ACR) (these are earlymorning or random urine tests). The most accurate microalbumin measurement is the 24-hour urine test, but this is cumbersome in children and relies on patient compliance, which may be limited. When urinary creatinine measurement is performed along with a spot microalbumin test, the resulting ACR approaches the accuracy of the 24-hour microalbumin test without the extended collection difficulties.[10] An alternative to the 24-hour microalbumin test is the spot microalbumin test (spot urine). The ease of specimen collection, performance of the test and universal acceptance of results have made this alternative attractive.[10] The objective of the current study was to determine the usefulness (accuracy) of a spot test (Micral-Test) compared with ACR as the gold standard.
Methods
This study was conducted between October and December 2009 at the Sickle Cell Clinic of the Lagos State University Teaching Hospital, Lagos, Nigeria. The subjects included 80 children aged 5 - 15 years with Hb genotype SS (HbSS), matched for age and sex with 80 children with Hb genotype AA (HbAA). Equal numbers of boys and girls were recruited. The number of subjects recruited from each age group depended on the proportions of the different age groups of patients on the clinic register.
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RESEARCH Hb genotype was determined by electrophoresis using cellulose acetate paper. Both subjects and controls tested negative for MA by dipstick urinalysis. Subjects were in a steady state at the time of investigation, defined as the absence of fever, acute illness or crisis in the previous 4 weeks or more, and taking no other medication than routine folic acid and prophylactic antimalarial medication.[13] Written informed parental consent and assent of the subject, where applicable, and Institutional Ethics Review Board approval were obtained before commencement of the study. Sample size was calculated using the formula for determining single proportions.[14] The assumed prevalence of MA from a previous study was 19.2%.[15] An effort was made to ensure an even age and gender representation in the sample. The following subjects were excluded from the study: children with symptoms and signs suggestive of urinary tract infection or pre-existing renal disease, children with ongoing menstruation or vaginal/penile discharge, and children with a history of exposure to drugs such as oxytetracycline within 72 hours of the study. For each child, a detailed history was obtained, including age, sex and relevant medical history including recurrent admissions, blood transfusions, cigarette smoking, family history of hypertension, and drugs taken within the preceding 72 hours. Each child was awarded a socioeconomic index based on the occupations and educational attain ment of parents or their caregivers, using the method described by Oyedeji.[16] Those in social classes I and II were regarded as in the upper socioeconomic stratum, those in social class 3 were regarded as in the middle socioeconomic stratum, while those in social classes IV and V were in the lower socioeconomic stratum. A thorough physical examination was carried out on each child. Axillary temperature was recorded in degrees Celsius (°C). A child was regarded as febrile if the temperature was >37.5°C.[17] Weight and height were recorded, and body surface area (BSA) and body mass index (BMI) were derived using standard formulae.[18] The blood pressure (BP) reading was taken on arrival at the clinic and only repeated on departure if the initial reading was very high. This was to minimise white-coat hypertension. The BP was recorded using an Accoson (UK) sphygmomanometer using standard methods. [19] Hypertension was defined as an average systolic BP that was ≥95th percentile for sex, age and height.[19]
Ratios of 30 - 300 mg/g were classified as MA. Based on the results of the urine screening, children were classified as follows: MA absent, i.e. urine microalbumin <30 mg/g, or MA present, i.e. urine microalbumin 30 - 300 mg/g.
Statistical analysis
Data for 160 subjects (80 sickle cell patients and 80 controls) were analysed using SPSS version 16.0 (IBM, USA). Descriptive statistics (means and standard deviations (SDs)) were calculated for continuous variables. Differences between mean values were evaluated using Student’s t-test, while discrete variables were compared using χ2 tests or odds ratios at 95% confidence limits.
Results
A total of 160 children comprising 80 subjects with HbSS and 80 HbAA controls were recruited into the study. Table 1 shows the distribution of subjects and controls according to age, gender and socioeconomic class. By design, equal numbers of males and females were recruited. The mean (SD) age of HbSS subjects was 9.58 (3.26) years, and of the controls was 9.62 (3.40) years (p=0.988). The majority of families were of the upper and middle social strata, both accounting for >80% of either HbSS subjects or HbAA controls. Overall, HbSS subjects weighed significantly less than controls (p=0.001). Similarly, the mean height (131.20 (16.12) cm), mean body surface area (BSA) (0.9 (0.26) m2) and mean BMI (14.80 (2.04) kg/m2) of HbSS subjects were significantly lower compared with HbAA controls (136.30 (16.01) cm, 1.1 (0.28) m2 and 17.40 (5.23) kg/m2 for height, BSA and BMI, respectively) (p=0.045, p<0.001 and p<0.001, respectively). The mean systolic BP was comparable in the two groups (99.4 (12.7) mmHg for HbSS and 98.8 (12.3) mmHg for HbAA, p=0.763). The diastolic BP was lower in the SCA subjects (98.80 (12.28) mmHg) compared with that of the controls (60.74 (10.66) mmHg, p=0.001). Percentages are of total number of HbSS subjects (n=80) or HbAA controls (n=80), as applicable.
Concordance of Micral-Test and ACR
ACR was used as the gold standard and the Micral-Test as the screening test at this phase. All subjects, HbSS and HbAA, were
Specimen collection
All subjects were provided with three universal bottles for the collection of morning random urine samples: one bottle for macroalbuminuria using Combi-screen strips (combi-10 multistrips) and the other two bottles for the Micral-Test and ACR, respectively. Only subjects whose Combi-screen results were negative were evaluated for MA by Micral-Test and microalbumin/creatinine quantification. Caregivers and the subjects were instructed on how to collect a midstream urine sample. The morning urine samples for ACR were sent to the diagnostic laboratory within 2 hours of collection. About 2 mL of venous blood were collected from each patient by venepuncture, using aseptic procedure. The blood sample was for confirmation of Hb genotype, which was determined by paper electrophoresis using tris buffer at pH 8.6.[20] Urine specimens were screened for MA using Micral-Test strips (Roche Diagnostics, USA). The urine samples were tested according to manufacturer’s instructions. Screening was considered positive when values of ≥20 mg/L were obtained. Urine microalbumin was measured using the MA reagent in conjunction with Synchron CX System and Synchron CX MA Calibrator (Beckman Coulter, USA) in our diagnostic laboratory. The MA reagent was used to measure the albumin concentration by a turbidimetric method. Urine creatinine was measured using the alkaline picrate method.[21] Urine ACR was mathematically derived. 42
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Table 1. Demographic characteristics of study subjects HbSS subjects, n (%)
HbAA controls, n (%)
5-6
18 (22.5)
18 (22.5)
7-8
18 (22.5)
18 (22.5)
9 - 10
12 (15.0)
12 (15.0)
11 - 12
12 (15.0)
12 (15.0)
13 - 14
10 (12.5)
10 (12.5)
15
10 (12.5)
10 (12.5)
Male
40 (50.0)
40 (50.0)
Female
40 (50.0)
40 (50.0)
Upper (I and II)
33 (41.3)
39 (48.8)
Middle (III)
32 (40.0)
29 (36.2)
Lower (IV and V)
15 (18.8)
12 (15.0)
Age (years)
Sex
Socioeconomic index
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RESEARCH Table 2. Performance of the Micral-Test in comparison with ACR as the gold standard in subjects <10 years old* ACR Micral-Test result
Positive, n
Negative, n
Positive
3 (TP)
11 (FP)
Negative
0 (FN)
71 (TN)
TP = true positive; FP = false positive; TN = true negative; FN = false negative. *Sensitivity = 100%; specificity = 86.6%; positive predictive value = 21.4%; negative predictive value = 100%.
Table 3. Performance of the Micral-Test in comparison with ACR as the gold standard in subjects ≥10 years old* ACR Micral-Test result
Positive, n
Negative, n
Positive
8 (TP)
17 (FP)
Negative
2 (FN)
48 (TN)
*Sensitivity = 80%; specificity = 73.8%; positive predictive value = 32%; negative predictive value = 96%.
pooled and analysed as a group. The sensitivity, specificity, positive predictive value and negative predictive value of the Micral-Test were 84.6%, 81.0%, 28.2% and 98.3%, respectively. Next, the concordance analyses were repeated according to age groups (<10 years and >10 years) (Tables 2 and 3, respectively). Sensitivity, specificity and negative predictive value of the Micral-Test were higher in younger subjects, while positive predictive value was higher in older subjects. In spite of observed differences, sensitivity of the Micral-Test remained >80%, specificity >70% and negative predictive value >95%, irrespective of age group. Also, positive predictive value of the Micral-Test was <40% for both age groups.
Discussion
The current study demonstrated high performance of the MicralTest as a screening test, using ACR as the reference standard. The high sensitivity and specificity rates of the Micral-Test for MA (84.6% and 81.0%, respectively) fall within the limits claimed by the manufacturers and corroborate the findings of earlier clinical studies.[22] Mogensen et al.,[23] in a large multicentre study, observed a sensitivity of 96.7% and a specificity of 71% for the diagnosis of MA with the Micral-Test II. The reference standard for MA diagnosis was the measurement of albumin concentration in a spot urine sample (20 mg/L) rather than ACR determination. Incerti et al.[24] demonstrated the sensitivity and specificity of the Micral-Test as 90% and 46%, respectively, using urine albumin excretion rate in 24-hour urine as the reference standard on the receiver operating characteristic curve. A study in the USA found a sensitivity of 88% and specificity of 80%, which are similar to the current study;[12] however, our study observed a lower positive predictive value of 28.2% than the 69% reported in their study. Other authors have also described a higher sensitivity (95.2%) and specificity (84.7%) for MA diagnosis than those observed in the current study.[25] These differences could be due to the performance of strip readings in first morning urine specimens, in which the known diurnal variation in albumin excretion is not present, compared with a random urine specimen. Albumin measurements in a first morning urine specimen correlate more with 24-hour protein excretion than measurements in a random spot urine sample.[26,27] A good screening test is expected to have a very high sensitivity so that very few true positives are missed. This requirement is demonstrated by the Micral-Test, with 84.6% sensitivity. In addition, 43
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the high specificity of 81% and high negative predictive value of 98.3% show the ability of the Micral-Test to identify true negatives and to exclude false negatives. Perhaps the strongest finding with the use of the Micral-Test in this study is the very high negative predictive value of 98.3%. The implication is that in negative cases, the test result is almost uniformly correct. The main limitation of the Micral-Test is its low positive predictive value of 28.2%. This implies that if a test is positive, the patient would need further evaluation to be certain that it is not a case of false positivity. However, the impressive diagnostic indices of the Micral-Test for MA remained high irrespective of age of subjects. Thus, overall, the value of the Micral-Test in the investigation of MA is very good. The average cost of performing the Micral-Test was USD5 (NGN750) per subject, while ACR cost about USD30 (NGN4 200) per test. It is important to note that quantitative ACR can only be done where there is suitable laboratory structure, whereas the Micral-Test does not depend on any prerequisite. In this regard, immediate urine results using the Micral-Test may represent an advantage, especially when a standard quantitative technique is not readily available. According to National Kidney Foundation/Kidney Disease Outcome Quality Initiative (NKF/KDOQI) guidelines,[27] it is usually not necessary to obtain a timed urine collection for MA evaluation, and albumin should be measured in a spot urine sample using either an albumin-specific dipstick or ACR. However, it is important to note that patients with a positive dipstick test should undergo confirmation of MA by a quantitative measurement.[27] Renal failure, a major complication of sickle cell disease, leads to early death.[5] Scheven et al.,[28] in their recent study, identified isolated MA as indicative of a poor medical prognosis. Early detection of the at-risk population of SCA and forestalling progression of disease are important. With the high burden of SCA and the seemingly bleak future for curative nephrology in the resource-poor Nigerian environment, prevention is definitely key.
Conclusion
The sensitivity and specificity of the Micral-Test makes it a good screening tool to detect MA in children with SCA. The Micral-Test is cheaper than the quantitative measurement of ACR. Patients with a single positive Micral-Test should be followed up with two more Micral-Tests over a 3-month period to confirm persistent MA. Our study was a cross-sectional study, therefore we cannot say how many sickle cell subjects have ended up in renal failure and how long after the identification of MA. A longitudinal study would be required to answer these questions. References 1. Akinyanju O, Ohujohungbe A. How to Live with Sickle Cell Disorder. Ibadan, Book Builders Edition Africa, 2006. 2. Akinyanju, OO. A profile of sickle cell disease in Nigeria. Ann N Y Acad Sci 1998;565:126-134. 3. Adekile AD. Haemoglobinopathies. In: Azubuike JC, Nkanginieme KEO, eds. Paediatric and Child Health in a Tropical Region. 2nd ed. Owerri: African Education Services, 1999;194-312. 4. World Health Organization. Sickle cell anaemia. www.who.int/gb/ebwha/pdf_ files/wHA (accessed 12 October 2010). 5. Adeyokunnu AA, Taiwo A, Antia AU. Childhood mortality among 22 225 consecutive admissions in the University College Hospital Ibadan. Niger J Paediatr 1980;7(1):7-15. 6. Fagbule D, Joiner KT. Pattern of childhood mortality at the University of Ilorin Teaching Hospital. Niger J Paediatr 1987;14(1):1-5. 7. Searjeant GR. Sickle cell disease. 2nd ed. Oxford: Oxford Medical Publications, 1992:261-281. 8. McBurney PG, Hancvold CD, Hernandez CM, Waller JL, Mckie KM. Risk factors for microalbuminuria in children with sickle cell anaemia. J Pediatr Hematol Oncol 2002;24(6):473-477. 9. Alvarez O, Montane B, Lopez G, Wilkinson J, Miller T. Early blood transfusion protects against microalbuminuria in children with sickle cell disease. Pediatr Blood Cancer 2006;47(1):71-6. [http://dx.doi.org/10.1002/pbc.20645]
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RESEARCH 10. De Jong PE, Curhan GC. Screening, monitoring and treatment of albuminuria: Public health perspectives. J Am Soc Nephrol 2006;17(8):2120-2126. [http:// dx.doi.org/10.1681/ASN.2006010097] 11. Rowe DJ, Bagga H, Betts PB. Normal variation in rate of albumin excretion and albumin to creatinine ratios in overnight and daytime urine collection in nondiabetic children. Br Med J (Clin Res Ed) 1985;291(6497):693-694. 12. Mogensen CE, Friedman C. Clinicianâ&#x20AC;&#x2122;s Manual on Microalbuminuria. London: Current Medical Group, 2006. 13. Ojuawo A, Adedoyin MA, Fagbule D. Hepatic function test in children with sickle cell anaemia during vaso-occlusive crisis. Central Afr J Med 1994;40(12):342-345. 14. Bland JM, Butland BK, Peacock JL, Poloniecki J, Reid F, Sedgwick P. Statistics guide for research grant applicants. http://www.sgul.ac.uk/depts/chs/disciplinegroups/stat guide/size.cfm (accessed 2 December 2008). 15. Datta V, Ayengar JR, Karpate S, Chaturredi P. Microalbuminuria as a predictor of early glomerular injury in children with sickle cell disease. Indian J Paediatr 2003;70(4):307-309. [http://dx.doi.org/10.1007/BF02723586] 16. Oyedeji GA. Socio-economic and cultural background of hospitalized children in Ilesha. Niger J Paediatr 1985;12(4):111-117. 17. Mato CN, Anochie IC, Uchenna DI, Ikimalo JI. Introduction to clinical medicine: An objective-based learning manual. Port Harcourt: University of Port Harcourt Press, 2007:74. 18. Mosteller RD. Simplified calculation of body surface area. N Engl J Med 1987;317(17):1098. 19. National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents. Pediatrics 2004;114(2 Suppl 4th Report):S555-S556.
44
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20. Nicholson JF, Pesce MA. Reference ranges for laboratory tests and procedures. In: Behrman RE, ed. Nelson Textbook of Paediatrics. 16th ed. Philadelphia: WB Saunders Co, 2000:2182. 21. Knox-Macaulay HM. Molecular biology and inheritance. In: Fleming AF, ed. Sickle Cell Disease: A Handbook for the General Clinician. Edinburgh: Churchill Livingstone Inc, 1982:20. 22. Marouf R, Mojiminiyi O, Abdella N, Kortom M, Al Wazzan H. Comparison of renal function markers in Kuwaiti patients with sickle cell disease. J Clin Pathol 2006;59(4):345-351. (http://dx.doi.org/10.1136/jcp.2005.026799] 23. Mogensen CE, Viberti GC, Peheim E, et al. Multicenter evaluation of the Micral-Test II test strip, an immunologic rapid test for the detection of microalbuminuria. Diabetes Care 1997;20(11):1642-1646. 24. Incerti J, Zelmanovitz T, Camargo JL, Gross JL, de Azevedo MJ. Evaluation of tests for microalbuminuria screening in patients with diabetes. Nephrol Dial Transplant 2005;20(11):2402-2407. [http://dx.doi.org/10.1093/ndt/ gfi074] 25. Lepore G, Maglio ML, Nosari I, Dodesini AR, Trevisan R. Cost-effectiveness of two screening programs for microalbuminuria in type 2 diabetes. Diabetes Care 2002;25(11):2103-2104. 26. Molitch ME, DeFronzo RA, Franz MJ, et al., American Diabetes Association. Nephropathy in diabetes. Diabetes Care 2004;27(Suppl 1):S79-S83. 27. National Kidney Foundation/Kidney Disease Outcome Quality Initiative. NKF/KDOQI Guidelines. http://www2.kidney.org/professionals/KDOQI/ guidelines_ckd/p5_lab_g5.htm (accessed 19 September 2013). 28. Scheven L, Van der Velde M, Lambers Heersprink HJ, De Jong PE, Ganservoort RT. Isolated microalbuminuria indicates a poor medical prognosis. Nephrol Dial Transplant 2013;28(7):1794-1801. [http://dx.doi. org/10.1093/ndt/gft031]
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RESEARCH
The use of nasal CPAP at the Charlotte Maxeke Johannesburg Academic Hospital C Jardine, MB BCh; 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: C Jardine (carlsjardine@gmail.com) Background. Nasal continuous positive airway pressure (NCPAP) is well established as a treatment for hyaline membrane disease (HMD) and other respiratory diagnoses in neonates. NCPAP is an affordable intervention that reduces the number of neonatal admissions to the intensive care unit (ICU) for ventilation. At the Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) we have been using NCPAP since April 2006. Objectives. To review the use of early NCPAP in our hospital setting. Methods. This was a retrospective, descriptive study of all neonates ≥750 g admitted to CMJAH between 1 January 2013 and 31 July 2014, who received NCPAP within 72 hours of birth. The characteristics and the survival of all infants who received NCPAP were described using univariate analysis. Results. The NCPAP group (n=481) of neonates <1 500 g was significantly associated with surfactant use (p<0.0005), bronchopulmonary dysplasia (p<0.0005) and late sepsis (p<0.0005). The survival to day 7 and to discharge of infants treated with NCPAP was significantly decreased (p<0.0005). NCPAP alone (without ventilation) improved the survival to discharge (p=0.001). The survival was 95.4% in the ≥1 500 g infants, compared with 87.6% in the very low birth weight infants and 55.2% in the extremely low birth weight infants. Conclusion. NCPAP is an effective intervention for HMD; it is both cost-effective and easy to use in a resource-limited setting, and reduces the morbidity and mortality associated with ICU admission. S Afr J CH 2015;9(2):45-48. DOI:10.7196/SAJCH.859
Nasal continuous positive airway pressure (NCPAP) has become widely used and accepted as a treatment for hyaline membrane disease (HMD) since its first introduction in 1971.[1,2] HMD affects premature babies and causes considerable morbidity and mortality. The use of NCPAP on its own and in combination with the use of surfactant has been shown to improve the outcomes of HMD in premature infants.[3] The incidence of HMD is related to the degree of prematurity of the lungs, and therefore the incidence increases as the gestational age (GA) decreases. The use of antenatal steroids given to mothers where a premature delivery is expected has reduced the incidence and severity of HMD.[4] The administration of surfactant for severe HMD has been shown to improve lung compliance, facilitate weaning off supplemental oxygen and result in fewer neonates needing ventilatory support. Surfactant replacement therapy also significantly reduces the mortality from HMD.[5] NCPAP is not only used in HMD but is also used to treat apnoea of prematurity, respiratory distress due to other aetiologies, some types of upper airway obstruction, and can sometimes be used as an alternative to endotracheal intubation or as a weaning mode of ventilation.[1] The continuous positive pressure provided by NCPAP helps to support and distend the alveoli, preventing their collapse. This results in the recruitment of alveoli, which improves the ventilation perfusion mismatch of the lungs and increases the functional residual capacity and tidal volume, thereby improving oxygenation in the neonate.[1] NCPAP also exerts a distending pressure on the larger airways, thus stabilising them and preventing upper airway collapse.[1] The early use of NCPAP in premature neonates reduces the need for surfactant and results in fewer neonates needing to be intubated and ventilated.[3,6,7] This decreases ventilator-induced lung injury and results in fewer cases 45
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of bronchopulmonary dysplasia (BPD).[3,7] Adverse effects of NCPAP use, including ‘CPAP belly syndrome’,[8] nasal septal necrosis and pneumothorax, may sometimes occur. NCPAP is an affordable intervention that is easy to use in a resource-poor setting. The successful use of NCPAP could result in a considerable reduction in the costs of neonatal care, as there would be a reduction in ventilation and neonatal intensive care unit (NICU) admissions, as well as a decrease in poor outcomes associated with prolonged ventilation. Recently, there have been a number of studies reporting on the survival of extremely low birth weight (ELBW) infants (birth weight <1 000 g). At Charlotte Maxeke Johannesburg Academic Hospital (CMJAH), it was found that the use of NCPAP in ELBW infants was not associated with an improvement in survival. [9] This study was done using data from neonates ≤900 g admitted between January 2006 and December 2010, a period during which fewer ELBW infants were receiving NCPAP than currently. A previous study at CMJAH, which assessed the determinants of survival in very low birth weight (VLBW) neonates (birth weight <1 500 g) found that NCPAP was associated with improved survival. [10] Kirsten et al.[11] at the Tygerberg Children’s Hospital in the Western Cape found that NCPAP practised together with InSurE (intubating to give surfactant and then extubating) in a neonatal high-care ward with limited resources improved the survival of ELBW infants. NCPAP was introduced into the neonatal unit at the CMJAH in April 2006. It is now used as the first line of ventilatory support in neonates with HMD. The objective of this study was to review the use of early NCPAP in neonates at CMJAH.
Methods
This was a retrospective, descriptive study of all neonates with a birth weight ≥750 g admitted to the neonatal unit at CMJAH
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RESEARCH between 1 January 2013 and 31 July 2014, who received NCPAP within 72 hours of birth. Neonates were excluded if there was insufficient information, if NCPAP was used post extubation from conventional mechanical ventilation (CMV) or if they had major congenital abnormalities. All in-born babies, babies born at maternity outpatient units, or babies born before arrival (BBA) were initially observed in the transitional care unit for assessment before being admitted to the neonatal unit, and were included in our statistics. T-piece resuscitators were not available in the labour ward nursery, and bag mask valve resuscitation was used for babies who required resuscitation at birth. The babies were observed for 1 - 2 hours in the transitional care unit and then a decision was made by the attending doctor on whether or not they required NCPAP and surfactant. NCPAP with early rescue surfactant was offered to neonates with respiratory failure due to HMD as per the neonatal unit’s protocol. Respiratory failure was defined as an oxygen saturation <88% in 60% supplemental oxygen, respiratory acidosis on arterial blood gas or clinical signs of severe respiratory distress, including indrawing of the sternum and tachypnoea. Due to insufficient NCPAP machines, not all neonates who qualified for NCPAP could receive it. Neonates who required NCPAP were admitted to the highcare neonatal ward where there were nine Bubble NCPAP (Fisher and Paykel, New Zealand) machines available; NCPAP was not initiated in the NICU. If NCPAP was not available, babies were given surfactant and placed on nasal prong oxygen. The neonatal unit’s policy at the time of the study was that neonates ≥900 g would qualify for ventilation in the NICU if required.
Database
The neonatal records at CMJAH are kept on the REDCap (Research Electronic Data Capture) electronic neonatal database.[12] REDCap is a secure, web-based program that has been designed to aid data capture for the purposes of clinical audit and quality improvement. Data are collected upon discharge of patients and entered into the REDCap database. The information is verified at several different stages of collection. The following data were collected from the database: (i) maternal data – antenatal steroids, place and mode of delivery, multiple gestation; and (ii) infant data – gestational age, birth weight, gender, place of birth, 5-minute Apgar score, necrotising enterocolitis (NEC), intraventricular haemorrhage (IVH), NCPAP with or without surfactant or CMV, respiratory diagnosis, duration of NCPAP and ventilation, late sepsis (occurring after day 3), BPD (defined by oxygen requirement at 28 days of age),
nasal septal necrosis, pneumothorax, and outcome (death or survival) at discharge.
Statistical analysis
The data were entered into an MS Excel (Microsoft, USA) spreadsheet and imported into statistical software package SPSS version 19 (IBM, USA). Categorical variables were described using frequencies and percentages, while continuous variables were described using means and standard deviations (SDs). The data were also stratified into birth weight categories (ELBW <1 000 g, VLBW <1 500 g, low birth weight (LBW) <2 500 g and weight ≥2 500 g), and the proportion of infants in each category receiving NCPAP was determined. Neonates <1 500 g who had not received NCPAP were compared with those who had received NCPAP, with regard to characteristics and survival to discharge. IVH was graded according to the sonographic grading system described by Papile et al.[13] Grades 1 and 2 of IVH were considered together as ‘mild’ and grades 3 and 4 as ‘severe’. The NEC category included grades 2 and 3 of NEC, according to modified Bell’s staging criteria. [14] Infants were regarded as having birth asphyxia if they had Apgar scores of ≤5 at 5 minutes. Babies on NCPAP who developed respiratory failure and required ventilation in the NICU were regarded as having failed NCPAP. Babies who were transferred out and those who were discharged home directly were grouped together as survivors for the purpose of analysis. Univariate analysis was used to compare the characteristics of the two groups, and survival was described. Categorical variables were compared using χ2 tests, and continuous variables using unpaired t-tests (as the distribution was normal). A p-value of <0.05 was considered to be significant. In neonates ≥1 500 g, the characteristics, respiratory diagnosis and survival of those who received NCPAP were described.
Ethics
Ethics approval for the study was granted by the Human Research Ethics Committee at the University of the Witwatersrand, Johannesburg (clearance certificate number M140403).
Results
Infants <1 500g
There were 748 VLBW infants admitted over the 19-month period. Information was not
available on 9 infants, 18 infants had major birth defects, NCPAP was used as a weaning mode of ventilation in 3 infants and NCPAP was started after 72 hours in 7 infants. All of the above were excluded, leaving a total of 711 infants in the study. The majority were female (n=378, 53.2%). The mean birth weight was 1 158 (SD 220) g and GA was 29.5 (2.6) weeks. The majority (n=380, 53.4%) were born by emergency caesarean section, and most (n=591, 83.1%) were inborn. Antenatal steroids were given in 275 (38.7%) cases. NCPAP was provided to 481 (67.7%) of the infants in total. Most babies (n=397, 82.5%) coped on NCPAP alone; in 84 (17.5%), NCPAP failed. Overall, there were 560 (78.8%) survivors. The mean duration of NCPAP was 2.58 (3.52) days with a maximum duration of 35 days. Nasal septal necrosis occurred in 27/481 (5.6%) and pneumothorax occurred in 5/481 (1%) of the infants who received NCPAP. Surfactant was given to 507 (71.3%) infants in total; 43 (8.4%) of these received surfactant without NCPAP. Birth asphyxia occurred in 79 (11.1%) infants. VLBW 1 000 - 1 499 g In this category, there were 517 infants, of whom 453 (87.6%) survived. A total of 308 (59.6%) infants received NCPAP, and surfactant was given to 329 (63.6%) infants. There were 41 (8%) infants with birth asphyxia. The use of NCPAP was significantly associated with death (p=0.001, odds ratio (OR) 0.41, 95% confidence interval (CI) 0.23 - 0.73). Overall, 252 (81.8%) infants coped on NCPAP alone, while 56 (18.2%) infants failed NCPAP. ELBW 750 - 999 g
In this category, there were 194 infants, of whom 107 (55.2%) survived. A total of 173 (89.2%) infants received NCPAP, and surfactant was given to 178 (91.8%) infants. There were 38 (19.6%) infants with birth asphyxia. NCPAP was not significantly associated with survival (p=0.261, OR 0.72, 95% CI 0.39 - 1.35). Overall, 145 (83.8%) infants coped on NCPAP alone, while 28 (16.1%) infants failed NCPAP (these were all >900 g and thus were offered ventilation).
NCPAP v. no NCPAP The entire group of neonates between 750 and 1 499 g was divided into two groups: those who had received NCPAP and those
Table 1. Characteristics of the NCPAP group and no NCPAP group in neonates <1 500 g Variable
NCPAP (n=481), n (%)
No NCPAP (n=230), n (%)
p-value
Surfactant
464 (96.4)
43 (18.7)
<0.0005
BPD
108 (22.4)
18 (7.8)
<0.0005
Late sepsis
125 (25.9)
30 (15.0)
<0.0005
46
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RESEARCH Table 2. Survival of infants who were treated with NCPAP compared with those who were not NCPAP (n=481), n (%)
No NCPAP (n=230), n (%)
p-value
Survival to day 3
450 (93.5)
222 (96.5)
0.104
Survival to day 7
407 (84.6)
218 (94.7)
<0.0005
Survival to discharge
351 (72.8)
209 (90.8)
<0.0005
Table 3. Survival of infants who were treated with NCPAP alone NCPAP alone (n=397), n (%)
Failed NCPAP (n=84), n (%)
p-value
Survival to day 3
370 (93.2)
80 (95.2)
0.489
Survival to day 7
336 (84.6)
71 (84.5)
0.980
Survival to discharge
302 (76.0)
49 (58.3)
0.001
Table 4. Respiratory diagnosis in the ≥1 500 g group who received NCPAP Respiratory diagnosis
LBW <2 500 g, n (%)
≥2 500 g, n (%)
TTN
8 (3.6)
5 (12.2)
Congenital pneumonia
9 (4.1)
5 (12.2)
MAS
2 (0.9)
10 (24.4)
HMD
200 (90.9)
13 (31.7)
Apnoea
8 (3.6)
1 (2.4)
who had not. The characteristics of the two groups were compared and significant differences are shown in Table 1. There was no significant difference in the babies with regards to CMV, pneumothorax, antenatal steroids, IVH or NEC. Mild IVH occurred in 69 (14.4%) infants in the NCPAP group compared with 18 (7.8%) infants not receiving NCPAP, and severe IVH occurred in 20 (4.2%) infants receiving NCPAP compared with 7 (3%) infants not receiving NCPAP. These differences were not significant. The survival of the infants in the two groups was compared in Table 2. The use of NCPAP was associated with an increased risk of death by day 7 and at discharge. When the successful use of NCPAP alone was compared with those who failed NCPAP, there was a significantly higher rate of survival to discharge (Table 3).
section. In the LBW (1 500 - 2 499 g) cate gory, there were 220 (84.3%) infants, and in the ≥2 500 g category, there were 41 (15.7%) infants. The mean birth weight was 2 044 (528) g, with a maximum of 5 250 g, and the mean GA was 33.5 (2.9) weeks with a minimum of 28 weeks. Overall, 249 (95.4%) infants survived. Surfactant was given to 210 (80.5%) infants. The mean duration of NCPAP was 1.62 (1.7) days, with a minimum of <1 day and a maximum of 31 days. There were 33 (12.6%) infants who failed NCPAP. This group of larger infants (≥1 500 g) represented 35.1% (261/742) of all the babies who received NCPAP over the study period. The respiratory diagnosis in the majority of cases was HMD (n=213, 81.6%) but also included transient tachypnoea of the newborn (TTN), congenital pneumonia, meconium aspiration syndrome (MAS) and apnoea (Table 4).
Infants ≥1 500 g
Discussion
A total of 1 997 neonates weighed ≥1 500 g; 1 570 infants did not receive NCPAP, 154 had a major birth defect, 7 had insufficient information and 5 had NCPAP as a weaning mode from CMV. There were thus 261 infants in the NCPAP group. The majority were males (n=164, 62.8%). Most of the infants were inborn (n=217, 83.1%). In 129 (49.4%) infants, the mode of delivery was by emergency caesarean
This was the first study from our unit on how we are using NCPAP in all our neonates from 750 g to 5 250 g. Previously, we had investigated the use of NCPAP as it relates to the survival of both ELBW and VLBW in fants in our unit, but we had not determined the characteristics of the infants receiving NCPAP across all weight categories. The majority of the babies in the ELBW category received NCPAP (89.2%). It was 47
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expected that all the babies in this weight category would have had HMD, requiring NCPAP and surfactant replacement, and it is encouraging that we managed to provide NCPAP to most patients. Only 16.1% of the ELBW infants and 18.2% of the VLBW infants failed NCPAP and were given ventilation. However, in the ELBW category, only infants ≥900 g would have been offered CMV. These figures are appropriate for a resource-poor setting in a high-care nursery such as ours. We have only nine Bubble NCPAP machines available, but most of our babies were able to receive NCPAP. This may be attributed to the fact that babies were able to wean off of the NCPAP relatively quickly, allowing a high turnover of these machines. With the successful use of NCPAP, far fewer premature babies are requiring NICU admission for ventilation. This is both cost-saving and greatly reduces morbidity and mortality associated with the NICU. Our ICU is shared between neonates, paediatrics and paediatric surgery patients. There was a concern that lowering our ICU admission weight category to 900 g would inundate the ICU with premature babies, but – largely due to NCPAP – this has not been the case. However, it is important to note that although babies who require NCPAP do not need NICU admission, they do require adequate high-care facilities with well-trained nursing staff, as they need close monitoring and active weaning off the NCPAP. In the larger (≥1 500 g) babies, only 12.6% failed NCPAP. In these babies, we were using NCPAP for other indications such as TTN, congenital pneumonia, MAS and apnoea, but in the majority of cases it was used for HMD in larger premature babies. It is disappointing to note that in this study there was no improvement in the use of antenatal steroids since the study done in 2010[10] (38.7% in this study v. 36% in the 2010 study). This is largely due to missed opportunities and late presentation once the mother was already in preterm labour.[15] The use of NCPAP was significantly associated with a higher mortality to day 7 (p<0.0005) and discharge (p<0.0005). The increased mortality with NCPAP use may be due to other factors affecting survival, such as late sepsis and NEC, which VLBW infants are prone to. There is also a selection bias, as NCPAP is given to babies with more severe respiratory illness and not routinely offered to all premature babies. Within the NCPAP group, NCPAP alone (without CMV) improved survival to discharge (p=0.001). Prolonged ventilation is associated with increased morbidity, and infants who fail NCPAP have a more severe degree of HMD with higher mortality. Surfactant, BPD and late sepsis were shown to be significantly associated with
RESEARCH the use of NCPAP. The overall incidence of 22.4% BPD was higher than the 8.8% reported in our hospital in 2010.[10] More babies are now offered NCPAP and are surviving long enough to develop BPD than in 2010, where over a 1-year period only 96/474 (20.3%) VLBW infants received NCPAP. VLBW infants are prone to late-onset sepsis[16] and the use of NCPAP has also been associated with this.â&#x20AC;&#x201A;[17] Limited nursing staff and overcrowding in the neonatal nursery further compound this problem. There was a very low rate of complications of NCPAP in our study, with only five infants developing a pneumothorax, and 27/481â&#x20AC;&#x201A; infants developing nasal septal necrosis, while IVH was not found to be significantly associated with NCPAP. When compared with the Vermont Oxford Network, our rate of pneumothoraces was lower (1% v. 4%) and our NCPAP use (67.7% v. 73.5%) was also lower.
Conclusion
NCPAP is cost-effective and easy to use in a resource-poor environment with a small number of Bubble NCPAP machines being able to treat a large number of neonates with HMD. This effectively releases ICU beds, thereby increasing the number of beds that are available for ventilatory support for neonatal and general paediatric patients. References 1. Sankaran K, Adegbite M. Noninvasive respiratory support in neonates: A brief review. Chin J Contemp Pediatr 2012;14(9):643-652. 2. Roberts CL, Badgery-Parker T, Algert CS, Bowen JR, Nassar N. Trends in the use of neonatal CPAP: A population-based study. BMC Pediatrics 2011;11:89. [http://dx.doi.org/10.1186/1471-2431-1189] 3. Pelligra G, Abdellatif MA, Lee SK. Nasal continuous positive airway pressure and outcomes in preterm infants: A retrospective analysis. Paediatr Child Health 2008;13(2):99-103. 4. Wong D, Abdel-Latif ME, Kent AL, et al. Antenatal steroid exposure and outcomes of very premature infants: A regional cohort study. Arch Dis
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Child Fetal Neonatal Ed 2014;99(1):F12-F20. [http://dx.doi.org/10.1136/ archdischild-2013-304705] 5. Polin RA, Carlo WA. Surfactant replacement therapy for preterm and term neonates with respiratory distress. Pediatrics 2014;133(1):156-163. [http:// dx.doi.org/10.1542/peds.2013-3443] 6. Saxena A, Thapar RK, Sondhi V, Chandra P. Continuous positive pressure for spontaneously breathing premature infants with respiratory distress syndrome. Indian J Pediatr 2012;70(9):1185-1191. [http://dx.doi.org/10.1007/s12098-0120722-z] 7. Miksch RM, Armbrust S, Pahnke J, Fusch C. Outcome of very low birth weight infants after introducing a new standard regime with the early use of nasal CPAP. Eur J Pediatr 2008;167(8):909-916. [http://dx.doi.org/10.1007/s00431-007-0646-1] 8. Jaile JC, Levin T, Wung JT, Abramson SJ, Ruzal-Shapiro C, Berdon WE. Benign gaseous distension of the bowel in premature infants treated with nasal continuous airway pressure: A study of contributing factors. AJR Am J Roentgenol 1992;158(1):125-127. 9. Kalimba EM, Ballot DE. Survival of extremely low-birth-weight infants. S Afr J CH 2013;7(1):13-16. [http://dx.doi.org/10.7196/SAJCH.488] 10. Ballot DE, Chirwa TF, Cooper PA. Determinants of survival in very low birth weight neonates in a public sector hospital in Johannesburg. BMC Pediatrics 2010;10:30. [http://dx.doi.org/10.1186/1471-2431-10-30] 11. Kirsten GF, Kirsten CL, Henning PA. The outcome of ELBW infants treated with NCPAP and InSurE in a resource-limited institution. Pediatrics 2012;129(4):e952-e959. [http://dx.doi.org/10.1542/peds.2011-1365] 12. Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. 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] 13. 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. 14. Neu J. Necrotizing enterocolitis: The search for a unifying pathogenic theory leading to prevention. Pediatr Clin North Am 1996;43(2):409-432. 15. Ballot DE, Ballot NS, Rothberg AD. Reasons for failure to administer antenatal corticosteroids in preterm labour. S Afr Med J 1995;85(10):1005-1007. 16. Stoll BJ, Hansen N, Fanaroff AA, et al. Late-onset sepsis in very low birth weight neonates: The experience of the NICHD Neonatal Research Network. Pediatrics 2002;110(2 Pt 1):285-291. 17. Graham PL, Begg MD, Larson E, Della-Latta P, Allen A, Saiman L. Risk factors for late onset Gram-negative sepsis in low birth weight infants hospitalized in the neonatal intensive care unit. Pediatr Infect Dis J 2006;25(2):113-117. [http://dx.doi.org/10.1097/01.inf.0000199310.52875.10]
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RESEARCH
Determinants of mother-to-child transmission of HIV despite PMTCT interventions in Enugu, Nigeria K K Iloh, MBBS; O N Iloh, MBBS; A N Ikefuna, MBBS; N S Ibeziako, MBBS; A C Ubesie, MBBS, MPH; I J Emodi, MBBS Department of Paediatrics, University of Nigeria Teaching Hospital, Ituku/Ozalla, Enugu, Nigeria Corresponding author: A C Ubesie (zionagoz@yahoo.co.uk) Background. The burden of paediatric HIV is unacceptably high in Nigeria. Prevention of mother-to-child transmission (PMTCT) of HIV represents a critical opportunity for reducing the burden of paediatric HIV. Objectives. To determine risk factors of MTCT of HIV following PMTCT interventions. Methods. This was a prospective study over a 12-month period, involving HIV-positive pregnant mothers in their third trimester. A structured, interviewer-administered questionnaire was used to obtain relevant information about mothers and their babies. Maternal HIV RNA levels (viral load) and CD4 counts were also obtained. DNA polymerase chain reaction (PCR) testing was done for all the infants. Data analysis was with SPSS version 15 (Chicago, USA). Results. There was a total of 210 infants, comprising 198 singletons and 6 sets of twins. Two infants had a positive DNA PCR, giving an MTCT rate of 1%. There was significant association between MTCT of HIV and maternal HIV RNA levels (p=0 .009) and mixed feeding (p<0.001). None of the other risk factors studied, namely maternal CD4 count, mode of delivery and duration of rupture of fetal membrane before delivery, had any influence on MTCT. Conclusion. The rate of MTCT can be reduced markedly if there is strict adherence to PMTCT strategies. It is therefore recommended that there be increased access to PMTCT programmes and full participation of mothers in Nigeria. S Afr J CH 2015;9(2):49-52. DOI:10.7196/SAJCH.803
Worldwide, an estimated two million infants of HIV-infected pregnant mothers are exposed to HIV annually.[1] Two hundred and fifty thousand children died of AIDS-related illnesses in 2010 alone.[1] The national seroprevalence rate of HIV in Nigeria stood at 4.1% in 2010.[2] More than 90% of paediatric HIV infections occur through mother-to-child transmission (MTCT).[3] Fifteen to forty per cent of infants born to HIV-infected mothers become infected in utero, during labour and delivery, or by breastfeeding postnatally. [4] For non-breastfeeding populations, 50% of HIV infections are transmitted to infants towards the end of pregnancy, during labour and delivery, while for breastfeeding populations, the postnatal period accounts for most of the HIV infections transmitted to infants.[5] Estimated rates of MTCT among untreated, seropositive women vary between 15 and 25% in Europe, to 25 and 40% in Africa and Asia.[6] In Nigeria, the estimated transmission rate among untreated mothers is reported to be as high as 45%.[7] Transmission rates of HIV are consistently higher in resource-poor countries than in industrialised countries.[6] Transmission rates <2% have been documented in developed countries.[8,9] Studies in Nigeria have reported transmission rates of 4 - 16% following the use of antiretroviral (ARV) drugs and safe obstetric practices.[10-12] The implementation of the PMTCT programme in Nigeria commenced in July 2002.[13] By 2008, there were 640 sites across the country where PMTCT had been integrated into routine antenatal care services. Interventions for the PMTCT of HIV in University of Nigeria Teaching Hospital (UNTH), Enugu, started in 2006 and include the use of ARV drugs for the mother and her baby, safe delivery practices and appropriate infant feeding options. There is a need to evaluate the determinants of MTCT of HIV in Enugu, which is critical for the monitoring, evaluation and updating of preventive strategies. 49
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Methods
Study area and site
This study was carried out at UNTH, Ituku-Ozalla, in Enugu State, Nigeria. The study site was the HIV clinic, comprising a paediatric, an adult and a PMTCT clinic. The clinics have been improved with funding from President’s Emergency Plan for AIDS Relief (PEPFAR). The PMTCT clinic is made up of two units: • The antenatal unit, where infected pregnant women are seen from booking. The pregnant women are followed up until delivery, after which the baby is referred to the exposed babies clinic. • The exposed babies clinic is where the babies born to HIVinfected women are followed up until their definite status is known. The HIV status is determined after 6 weeks of age using DNA polymerase chain reaction (PCR). For the infants who are being breastfed, the DNA PCR is repeated 6 weeks after breastfeeding has been stopped. All HIV-infected babies are referred to the ARV therapy (ART) clinic. HIV-negative babies remain with the follow-up clinic until 18 months of age, when a final ELISA test is done.
Study population
The subjects were HIV-infected pregnant women receiving antenatal care at UNTH, and their infants seen at the PMTCT follow-up clinic in UNTH. PEPFAR supports a full range of HIV services in the hospital: adult, paediatric and PMTCT. Therefore, it is not uncommon for women of reproductive age on treatment for their own health to be linked to the PMTCT services once they become pregnant. HIV-positive pregnant women in their last trimester and their delivered infants seen within 72 hours of delivery were included in the study. Details of the study were explained to each HIVpositive mother by the researcher, and written informed consent was obtained before enrollment into the study. The exclusion criterion was eligible mothers who declined consent.
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RESEARCH Study design
In this prospective cohort study, HIV-infected women who came to the PMTCT clinic who met the inclusion criteria were recruited consecu tively on weekly clinic days until the desired sample size was achieved.
Ethical considerations
Ethical approval was obtained from the Health Research and Ethics Committee of UNTH. The names of all the study subjects were coded in the final soft and hard copies of the proforma to ensure confidentiality. All the relevant data pertaining to the study are in the sole custody of the principal investigator.
Data collection
Gestational age was determined using the mother’s last menstrual period and ultrasound reports. Mothers were interviewed to obtain their sociodemographic profile: age, sex, parity, level of education, occupation, marital status and place of residence. The World Health Organization (WHO) HIV clinical stage and maternal ART use were also documented. CD4 count and viral load (VL) were requested. Infant feeding counselling messages were reinforced. The mothers were assigned a social class using Oyedeji’s[14] social classification scheme (Appendix 1). Each enrolled mother was seen with her baby within 72 hours of delivery, either at the labour room, in the postnatal ward or at the exposed babies clinic. Information on the gestational age at delivery, mode of delivery, duration of rupture of membrane, use of episiotomy and delivery instruments was extracted from the delivery form. Each mother was interviewed again to confirm her infant feeding choice and encouraged to adhere to her choice. The babies were examined and ART prophylaxis was commenced (nevirapine 2 mg/kg stat and zidovudine 4 mg/kg/dose every 12 hours for 6 weeks, according to the National Guidelines[15] (in use at the time of this study). At 6 weeks of age, irrespective of the feeding choice, a dry blood spot specimen was collected from each baby on a Whartman filter paper for HIV status determination using the DNA PCR technique. Pneumocystis pneumonia prophylaxis with co-trimoxazole (at a dose of 6 - 8 mg/ kg/day of trimethoprim component) was commenced and zidovudine stopped. At another scheduled visit, the result of the DNA PCR was discussed with the mother and her partner (if present). HIV-positive babies were referred to the paediatric ART clinic for evaluation and commencement of highly active ART (HAART). Those with negative DNA PCR and on exclusive replacement feeding with infant formula were encouraged to continue their routine follow-ups at the clinic. For babies with negative DNA PCR who were on exclusive breastfeeding, the test was repeated at least 6 weeks after breastfeeding had been stopped.
Early infant diagnosis
The PCR test, Ampliclor 3.2.1 (Roche Molecular Systems, USA) (100% sensitivity after 4 - 6 weeks of delivery[16]) was used for early infant diagnosis. Positive results were repeated on the same sample for confirmation.
Data analysis
Data were analysed using SPSS version 15.0 (IBM, USA). Descriptive statistics were used to summarise quantitative variables (age, weight), while qualitative variables (occupation, marital status, baby’s sex, mode of delivery, DNA PCR status) were summarised by proportions. Student’s t-test, χ2 and Fisher’s exact test were used to test for significance between variables. A p-value <0.05 was considered statistically significant. All reported p-values were two-sided.
Results
Sociodemographic data
A total of 204 of HIV-positive mothers met the inclusion criteria and were recruited and studied over a 12-month period from February 50
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2011 to January 2012. None of them refused consent. The mean age of mothers was 32 (standard deviation (SD) 4.05) years. Ninetyone (44.6%) had secondary education as their highest educational attainment, while 39 (19.1%) and 73 (35.8%) had attained primary and tertiary education, respectively. One (0.5%) had no formal education. The predominant socioeconomic class was social class III (Appendix 1), which accounted for 49.5% of the mothers.
Obstetric characteristics of mothers
The parity of 155 (76%) of the mothers was 2 - 4. A total of 196 (96.1%) of the pregnancies were of term gestation, while 8 (3.9%) were preterm. Overall, 173 (84.8%) mothers delivered vaginally, while 14 (6.9%) and 17 (8.3%) delivered by elective and emergency caesarean section, respectively. Of the 190 mothers who delivered by either par vaginam or through emergency caesarean section, 167 (88.8%) had their fetal membrane ruptured for <4 hours before delivery. Overall, 197 (96.6%) mothers knew their status before the index pregnancy. Most of the mothers (n=143, 70.1%) were in WHO clinical stage 2. A total of 175 (85.8%) were on HAART before the index pregnancy, while 29 (14.2%) had ARV prophylaxis initiated within the pregnancy period. The CD4 count was ≥200 cells/mL in 192 (94.1%) of the mothers, and <200 in 12 (5.9%). HIV RNA levels were <400 viral copies/mL in 141 (69.1%) of the mothers, between 400 and 9 999 viral copies/mL in 36 (17.6%) and ≥10 000 viral copies/mL in 27 (13.2%).
Characteristics of the HIV-exposed infants
There were 210 babies delivered to the 204 HIV-infected mothers, comprising 198 singletons and 6 sets of twins. Of the 210 babies, 100 (47.6%) were males and 110 (52.4%) were females, giving a male:female ratio of 1:1.1. A total of 202 babies (96.2%) were of term gestation. The mean (SD) birth weight of the babies was 3.02 (0.5) kg. All the babies received postnatal ARV prophylaxis. One hundred and thirty-seven infants (65.2%) went exclusively onto infant formula, 71 (33.8%) were exclusively breastfed, and only 2 (1%) had mixed feeding (breastmilk and formula). Sixtyfour (90.1%) of the breastfed babies were exclusively breastfed for 3 months, while 2 (2.8%) and 5 (7.1%) were breastfed exclusively for 2 months and 1 month, respectively (Table 1). All the babies studied had their initial DNA PCR within 6 8 weeks of delivery, and those who were breastfed had a repeat DNA PCR within 6 - 8 weeks after cessation of breastfeeding. Two hundred and eight (99%) were HIV-negative, while 2 (1%) were HIV-positive, giving a transmission rate of 1%.
Risk factors of MTCT of HIV
Maternal HIV RNA VL levels Of the 145 infants whose mothers’ VL was suppressed (<400 viral copies/mL) and 36 infants whose mothers VL was between 400 and 9 999 viral copies/mL, none had positive DNA PCR, whereas 2 of the 29 infants whose mothers’ VL was ≥10 000 viral copies/mL had positive DNA PCR. The association between infants’ DNA PCR results and high maternal HIV RNA levels (≥10 000 viral copies) was statistically significant (p=0.009). CD4 count Whereas 2 of the 197 babies whose maternal CD4 count was ≥200 cells/mL had positive DNA PCR, none of the 13 infants whose maternal CD4 count was <200 cells/mL had positive DNA PCR; however, the difference was not statistically significant (p=1.000). Mode of delivery Two of the 177 of the infants delivered vaginally had positive DNA PCR, whereas none of the infants delivered by elective or emergency caesarean section had positive DNA PCR; however, the difference was not statistically significant (p=1.000).
APRIL 2015 Vol. 9 No. 2
RESEARCH Feeding choice
HIV-positive babies were found only among those who received mixed feeding. There were none who were either exclusively breastfed or exclusively formula fed. The relationship between feeding choice and DNA PCR result was statistically significant (p<0.001).
Discussion
The MTCT rate of 1% in this study was lower than rates reported in previous studies in Nigeria.[7,17,18] A previous study in Nigeria among ARV-naive, HIV-infected pregnant women who had no preventive intervention reported an HIV MTCT rate of 45%.[7] The rates reported in other Nigerian studies where some form of PMTCT interventions were provided varied from 4 to 8%.[17,18] This could be owing to the fact that most of the women in this study knew their status before pregnancy, and had been on HAART with their viral RNA levels significantly suppressed. Additionally, the infants were started on ARV prophylaxis and most of the mothers adhered to the chosen infant feeding choice. None of the women with a VL <9 999 viral copies/mL transmitted the virus to their infants. There have been consistent reports that maternal viral suppression has been associated with a significant reduction in the risk of MTCT of HIV.[8,18] In a multicentre, French perinatal cohort study, Warszawski et al.[8] documented a transmission rate of 0.6% in women whose VL was suppressed <400 viral copies/mL. The importance of marked maternal viral suppression was also documented by Garcia et al.[19] in the USA. Interestingly, the current study documented a transmission rate of 6.9% (2/29) among infants whose mother’s VL was ≥10 000 viral copies/mL. This situation involved only a few mothers, but contributed to 100% of the infected children. Therefore, maternal VL clearly stands out as a key determinant of MTCT risk. Although low CD4 count (<200 cells/mL) has been associated with increased risk of vertical transmission,[20] this was not the finding in
Conclusions
Table 1. Characteristics of the HIV-exposed infants Variable
this study, as the two mothers who transmitted the virus to their infants had CD4 counts of ≥200 cells/mL. The explanation for this is not clear, but may be owing to the small proportion of the subjects studied who had a CD4 count <200 (5.9%) cells/mL. Babies delivered vaginally in this study had a higher rate of transmission than those delivered by elective caesarean section. This finding is in consonance with previous studies that documented increased transmission in babies delivered by the vaginal route compared with those delivered by elective caesarean section.[21] The present study documented that none of the women whose VL was suppressed (<400 copies/mL) and who delivered per vaginam transmitted the virus to their infants. A striking observation from this study was that there was no HIVpositive result among the infants who were exclusively breastfed. The use of HAART among most of our mothers and attendant VL suppression explains this. This finding is similar in a Ugandan study where Homsy et al.[22] observed that none of 114 infants who were exclusively breastfed tested positive for HIV. Other studies have also documented the importance of ART with resultant significant viral suppression in the reduction of risk of MTCT of HIV among infants who were exclusively breastfed.[17,23] Also in this study, no transmission of HIV was found among infants who had exclusive replacement feeding, which agreed with the study in Jos University Teaching Hospital by Achonga.[11] The only two HIV-positive babies found in the current study had mixed feeding. Several studies have documented increased risk of MTCT of HIV among infants who were mixed fed.[17,24,25] It is noteworthy that the transmission rate in this study is comparable with a rate of <2% such as documented in developed countries.[8-10] The results of this study clearly suggest a positive affect of the PMTCT strategies adopted in Nigeria and highlight the fact that the goal of virtual elimination, where no HIV-exposed child becomes infected, is possible even in resource-poor settings. The rate of MTCT of HIV in UNTH, Enugu, among those who fully participated in the PMTCT programme was 1%. Significant risk factors of MTCT of HIV in this study were maternal HIV RNA levels and infant feeding choice.
Frequency (n)
Percentage (%)
Male
100
47.6
Female
110
52.4
Acknowledgement. We are thankful to the mothers and their infants who participated in this study.
<37
8
3.8
References
37 - 42
202
96.2
>42
0
0
24
11.4
2 500 - 3 999
183
87.1
4 000
3
1.4
137
65.2
EBF
71
33.8
Mixed feeding
2
1.0
Gender
Gestational age at birth (weeks)
1. UNAIDS. Global report: UNAIDS report on the global AIDS epidemic 2010. http://www.unaids.org/globalreport/documents/20101123_GlobalReport_ full_en.pdf (accessed 16 January 2014). 2. Federal Ministry of Health Nigeria. A Technical Report on 2010 National HIV sero-prevalence sentinel survey. Abuja: Federal Ministry of Health, 2010. 3. Car LT, van Velthoven MHMMT, Brusamento S, et al. Integrating prevention of mother-to-child HIV transmission programs to improve uptake: A systematic review. PLoS ONE 2012;7(4):e35268. [http://dx.doi.org/10.1371/journal.pone.0035268] 4. Lu D, Liu J, Samson L, et al. Factors responsible for mother-to-child HIV transmission in Ontario, Canada, 1996-2008. Can J Public Health 2014;105(1):e15-e20. 5. Kourtis AP, Lee FK, Abrams EJ, Jamieson DJ, Bulterys M. Mother-to-child transmission of HIV: Timing and implications for prevention. Lancet Infect Dis 2006;6(11):726-732. [http://dx.doi.org/10.1016/S1473-3099(06)70629-6] 6. Working Group on Mother-to-Child Transmission of HIV. Rate of mother-tochild transmission of HIV in Africa, America and Europe: Result of 13 perinatal studies. J Acquir Immune Defic Syndr 1995;8(5):506-510. 7. Odaibo GN, Olaleye DO, Heyndrickx L, Vereecken K, Houwer K, Jansens N. Mother-to-child transmission of different HIV subtypes among ARVnaïve infected pregnant women in Nigeria. Rev Inst Med Trop Sao Paulo 2006;48(2):77-80. [http://dx.doi.org/10.1590/S0036-46652006000200004] 8. Warszawski J, Tubiana R, le Chenadec J, et al. Mother-to-child HIV transmission despite anti-retroviral therapy in ANRS French Perinatal Cohort. AIDS 2008;22(2):289-299. [http://dx.doi.org/10.1097/QAD.0b013e3282f3d63c] 9. Ammann AJ. Human immunodeficiency virus in China: An opportunity to halt an emergency epidemic. AIDS patient care STD 2000;14(1):109-112. 10. Audu RA, Salu OB, Musa AZ, et al. Estimation of the rate of mother-to-child transmission in Nigeria. Afr J Med Sci 2006;35(2):121-124.
Birth weight (grams) <2 500
Feeding choice Infant formula
Duration of EBF (months) 1
5
7.1
2
2
2.8
3
64
90.1
EBF = exclusive breastfeeding.
51
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RESEARCH 11. Achonga M. Infants of HIV-positive mothers at Jos University Teaching Hospital: Pattern of feeding and health status during the first six months of life (Thesis). Jos, Nigeria: National Postgraduate College Nigeria, 2006:33. 12. Ibeziako NS, Ubesie AC, Emodi IJ, Ayuk AC, Iloh KK, Ikefuna AN. Mother-tochild transmission of HIV: The pre-rapid advice experience of UNTH Ituku/ Ozalla, Enugu, South-east Nigeria. BMC Res Notes 2012;5:305. [http://dx.doi. org/10.1186/1756-0500-5-305] 13. Federal Ministry of Health. Evaluation of the prevention of mother-to-child transmission (PMTCT) of HIV pilot programmme in Nigeria. Abuja: Federal Ministry of Health Nigeria, 2005:12. 14. Oyedeji GA. Socio-economic and cultural background of hospitalized children in Ilesha. Nig J Paed 1985;12(4):111-117. 15. Federal Ministry of Health. National Guideline for Paediatric HIV and AIDS Treatment and Care. Abuja: Federal Ministry of Health Nigeria, 2007. 16. Quiagen. Quiagen Genomic DNA Handbook. United States: Pharmacia Biotec, 2001:7. http://www.qiagen.com/ng/resources/resourcedetail?id=97640bc9-e4fe4c4b-83f6-ac7ca4181597&lang=en (accessed 16 January 2014). 17. Okechukwu AA, Abdulrahaman IB. The impact of prevention of mother-tochild transmission of HIV programme in Federal Capital Territory, Abuja. Nig J Med 2008;17(2):191-197. 18. Sadoh WE, Sadoh AE, Adeniran KA, et al. Infant-feeding practices among HIV-infected mothers in an HIV treatment programmme. J Health Popul Nutr 2008;4:463-467.
19. Garcia PM, Kalish LA, Pitt J, et al. Maternal levels of plasma HIV type-1 RNA and the risk of perinatal transmission. N Engl J Med 1999;341(6):394-402. 20. The International Perinatal HIV Group. Duration of rupture of membrane and vertical transmission of HIV: A meta-analysis from 15 prospective cohort studies. AIDS 2001;15(3):357-368. 21. Thorne C, Semenenko I, Pilipenko T, Malyuta R. Progress in prevention of motherto-child transmission of HIV infection in Ukraine: Results from a birth cohort study. BMC Infect Dis 2009;9:40. [http://dx.doi.org/10.1186/1471-2334-9-40] 22. Homsy J, Moore D, Barasa A. Breastfeeding, mother-to-child HIV transmission, and mortality among infants born to HIV-infected women on highly active antiretroviral therapy in rural Uganda. J Acquir Immune Defic Syndr 2010;53(1):28-35. [http://dx.doi.org/10.1097/QAI.0b013e3181bdf65a] 23. Palombi L, Marazzi M, Veotberg A, Magid NA. Treatment acceleration programme and the experience of the DREAM programme in the prevention of mother-to-child transmission of HIV. AIDS 2007;21(Suppl 4):S65-71. [http:// dx.doi.org/10.1097/01.aids.0000279708.09180.f5] 24. Piwoz EG, Humphery JM, Tavengwa NV, et al. The impact of safer breastfeeding practices on postnatal HIV transmission in Zimbabwe. Am J Pub Health 2007:97(7):1249-1254. [http://dx.doi.org/10.2105/AJPH.2006.085704] 25. Coovadia HM, Rollins NC, Bland RM, et al. Mother-to-child transmission of HIV infection during exclusive breastfeeding in the first six months of life: An interventional cohort study. Lancet 2007;369(9567):1107-1116. [http://dx.doi. org/10.1016/S0140-6736(07)60283-9]
Appendix 1. Oyedeji's socioeconomic index scores
Educational attainments: • Class I: University graduates or equivalents • Class II: School certificate holders with teaching or other professional training • Class III: School certificate or Grade 2 teachers’ certificate holders or equivalents • Class IV: Modern 3 or primary six certificate holders • Class V: Cannot read/write or illiterate Occupation of parents: • Class I: Senior public servants, professionals, managers, large-scale traders, businesspeople, contractors • Class II: Intermediate group of public servants and senior school teachers • Class III: Junior public servants and school teachers, drivers, artisans • Class IV: Petty traders, labourers and similar grades • Class V: Unemployed, full-time housewives, students and subsistence farmers Calculation of socioeconomic class (SEC) Four scores were obtained from educational attainment and occupation for the two parents. The socioeconomic grading is obtained by finding the mean of the four scores for the two parents. This is then rounded off to the nearest whole number to get the SEC level of the study participant.
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RESEARCH
Hypoxaemia as a measure of disease severity in young hospitalised Nigerian children with pneumonia: A cross-sectional study M B Abdulkadir, MBBS, FWACP (Paed); R M Ibraheem, MBBS, FWACP (Paed), FMCPaed; A A Gobir, MBBS, FMCPaed; W B R Johnson, MBBS, FWACP (Paed) Department of Paediatrics and Child Health, University of Ilorin and University of Ilorin Teaching Hospital, Ilorin, Nigeria Corresponding author: M B Abdulkadir (docmohng@gmail.com) Background. Pneumonia remains a common cause of mortality among children in developing countries. Hypoxaemia is a common consequence of pneumonia in children. Objectives. To define the relationship between Hb oxygen saturation (SpO2) and parameters of outcome, duration of supplemental oxygen and duration of hospitalisation among children with pneumonia. Methods. A cross-sectional study was carried out at the paediatric wards of a tertiary hospital in North-Central Nigeria. Two hundred children aged between 2 and 59 months with pneumonia seen at the University of Ilorin Teaching Hospital were recruited consecutively. Sociodemographic and clinical information regarding the illness was obtained. Hb SpO2 of subjects was recorded with a pulse oximeter at presentation. The primary outcome was the SpO2 of the children with pneumonia. Secondary outcome measures were disease outcome, duration of supplemental oxygen and duration of hospitalisation among children with pneumonia. Results. The prevalence of hypoxaemia among the children was 41.5% and their mean SpO2 was 90.4% (standard deviation (SD) 8.9%). Surviving children with hypoxaemia had a longer mean (SD) duration of hospitalisation of 6.9 (6.4) days compared with those without hypoxaemia (4.9 (2.7) days; p=0.001). Children with hypoxaemia spent a longer duration receiving supplemental oxygen compared with those without hypoxaemia (p=0.001). The case fatality rate from pneumonia was 8.5% (17 deaths). The risk of death among children with hypoxaemia was 48 times higher than among the non-hypoxaemic children. Conclusion. Hypoxaemia with increasing severity significantly predicts a longer duration of hospitalisation, duration on supplemental oxygen and poorer outcome in children with pneumonia. S Afr J CH 2015;9(2):53-56. DOI:10.7196/SAJCH.901
Globally, pneumonia is a leading cause of death among children <5 years old, accounting for >90% of acute lower respiratory infection-related deaths. In Nigeria, pneumonia-related deaths account for 20 25% of childhood mortality.[1] A previous study from Ilorin in the North-Central region of Nigeria reported a case fatality rate of 10%.[2] Hypoxaemia is a major complication of pneumonia, associated with an increase in the risk of death with increasing severity of hypoxaemia.[3] It is often associated with acidosis, organ dysfunction and multiple complications. Hypoxaemia can be detected via clinical signs, blood gas analysis or pulse oximetry. While blood gas analysis represents the ‘gold standard’ for defining hypoxaemia, its use is limited by its expense, invasiveness and provision of only a single measure per sample. However, pulse oximetry has been shown to be reliable, safe, non-invasive, simple and reproducible, hence most authors accept it as a detection tool.[3] Pulse oximetry has also been found to be superior to the use of clinical signs alone in detecting hypoxaemia.[4,5] It may be a useful tool in ensuring the most efficient use of oxygen therapy, which is especially important in resource-limited settings. Despite the burden of mortality from pneumonia, there is a dearth of knowledge regarding the contribution of hypoxaemia to its outcome in the North-Central region of Nigeria. The objective of the current study therefore is to describe the relationship between various levels of Hb oxygen saturation (SpO2) and duration of hospitalisation, duration on oxygen and mortality, among a group of hospitalised children with pneumonia. 53
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Methods
This was a descriptive cross-sectional study in which the subjects were children aged between 2 months and 5 years of age, who were diagnosed with pneumonia. The study was conducted at the Emergency Paediatric Unit (EPU) and the Paediatric Medical Ward (PMW) of the University of Ilorin Teaching Hospital (UITH). The hospital is a tertiary centre in Ilorin South Local Government Area of Kwara State in the North-Central geopolitical zone. The EPU and PMW cater for children from beyond the neonatal period to the age of 14 years. At the time of this study, the Hb SpO2 levels of children in the emergency room were not routinely measured, and therapeutic oxygen was commenced based on clinical assessment alone. The sample size was calculated using the Fisher formula,[6,7] and a prevalence of pneumonia of 11.1% from a previous study.[2] The calculated minimum sample size was 151; however, a total of 200 children <5 years old were recruited for the study. The subjects were children presenting at the EPU with clinical features comprising a cough of <28 days’ duration, fever, difficult breathing, age-related tachypnoea (>50 breaths/minute for infants aged 2 months - 1 year, and >40 breaths/minute for children aged 12 - 59 months), and auscultatory findings of at least one of reduced breath sound intensity, bronchial breath sounds or crepitations.[4] All consecutive admissions into the EPU with a diagnosis of pneumonia were enrolled. The study was completed within 12 months (March 2010 - February 2011). Children with sickle cell disease, bronchial asthma, severe anaemia (haematocrit ≤15%) and clinical features of shock, such as cold, clammy extremities, weak, thready pulse and other parameters of poor peripheral perfusion were excluded from the study.
APRIL 2015 Vol. 9 No. 2
RESEARCH The study was approved by the Ethics and Research Committee of the University of Ilorin Teaching Hospital. Written informed consent was obtained from all caregivers. A semistructured questionnaire was administered to obtain the clinical and sociodemographic data from each subject’s parent. Clinical observations were made and recorded. Hb SpO2 was measured by attaching a Smartsigns Liteplus CE 0088 pulse oximeter (Huntleigh Healthcare, UK) to a finger using an appropriately sized paediatric sensor. This was done as soon as possible after presentation, before oxygen administration if required. SpO2 was recorded after a stable reading was obtained for at least 1 minute, while the child was breathing room air. For the purpose of the study, hypoxaemia was defined as an SpO2 of <90% as recorded by pulse oximetry.[5] In addition, the various levels of SpO2 were categorised into five groups: >95%, 93 - 95%, 90 - 92%, 86 - 89%, and ≤85%. The severity of pneumonia in each subject was graded as mild, moderate or severe using the British Thoracic Society guidelines on the management of community-acquired pneumonia in children. [8] Subjects with complications of pneumonia at presentation were considered as having severe pneumonia.[8] Chest radiographs were obtained for all subjects within 24 hours of presentation. Radiographic features were recorded as either normal, presence of patchy opacities in one or more lobes, or lobar/segmental consolidation with or without an air bronchogram. The radiograph findings were corroborated by a consultant radiologist. All subjects were treated with the most appropriate medications according to the current institutional guidelines. Each child was followed up to monitor the admission outcome (survived or died). The duration on supplemental oxygen (for those given) and hospitalisation were also documented.
The mean duration of hospital admission among the subjects recruited was 5.7 (4.7) days. Table 2 shows that the children who had hypoxaemia had a significantly longer duration of hospitalisation compared with those without hypoxaemia (p=0.002). The mean duration of hospitalisation increased as SpO2 levels decreased. Furthermore, the mean duration of hospitalisation Table 2. Duration of hospitalisation and hypoxaemia in the children with pneumonia Duration of hospitalisation (days) n (%)
Mean (SD) Range
p-value
Present (<90%)
83 (41.5)
6.9 (6.4)
0.002
Absent
117 (58.5) 4.9 (2.7)
1 - 19
>95
75 (37.5)
4.2 (2.0)*
1 - 10
93 - 95
24 (12.0)
5.4 (2.7)*
Parameter Hypoxaemia
0.2 - 33
Levels of SpO2 (%)
90 - 92
18 (9.0)
6.7 (4.2)*
86 - 89
34 (17.0)
7.9 (7.0)†
≤85
49 (24.5)
6.3 (6.0)*
0.002
1 - 13 †
3 - 19 0.3 - 32
†
0.2 - 33
Admission outcome Discharged
183 (91.5) 6.1 (4.7)
1 - 33
Died
17 (8.5)
0 - 12
1.9 (3.0)
0.001
Type of pneumonia
Statistical analyses
Data were analysed using SPSS version 20.0 (IBM, USA) for Windows. The data collected on the proforma were transferred onto a master sheet using numerical codes. After the generation of frequency tables and simple proportions, the χ2 and Student’s t-tests were used to iden tify significant differences for categorical and continuous variables, respectively. Case fatality rates were calculated for the various cut-offs of SpO2. Relative risk of death among the hypoxaemic children was calculated. A p-value of <0.05 was considered significant.
Bronchopneumonia
168 (84.0) 5.1 (3.8)
0.2 - 33
Lobar pneumonia
32 (16.0)
9.0 (7.2)
0.3 - 32
Moderate
12 (6.0)
3.3 (2.1)
2-9
Severe
188 (94.0) 5.9 (4.8)
0.001
Severity of pneumonia 0.072
0.3 - 33
†
* Duncan multiple range test shows that means with the same symbol are not statistically different at p<0.05.
Results
Two hundred patients were recruited, and all patients completed the study. The mean (SD) age of the children with pneumonia was 14.3 (13.5) months. A total of 113 (56.5%) children were aged <12 months, 46 (23.0%) were aged 12 - <24 months, 26 (13.0%) were aged 24 - <36 months, 4 (2.0%) were 36 - <48 months, and 11 (5.5%) were 48 - <60 months. Overall, 119 (59.5%) patients were male. Using the defined cut-off for hypoxaemia, namely SpO2 <90%, 83 children (41.5%) had hypoxaemia (Table 1). The mean (SD, range) SpO2 was 90.4% (8.9, 47 - 100), while mean (SD) SpO2 values among the hypoxaemic and non-hypoxaemic children were 82.3% (8.1) and 96.2% (2.8), respectively. Table 1. SpO2 levels in children with pneumonia (N=200) Levels of SpO2 (%)
n (%)
SpO2 mean % (SD)
>95
75 (37.5)
98.0 (1.5)
93 - 95
24 (12.0)
93.8 (0.9)
90 - 92
18 (9.0)
91.8 (0.4)
86 - 89
34 (17.0)
88.1 (1.0)
≤85
49 (24.5)
78.2 (8.5)
Table 3. Duration of hospitalisation among survivors with hypoxaemia Duration of hospitalisation among survivors (days) n (%)
Mean (SD)
Range
p-value
Present
66 (36.1)
8.2 (6.4)
3 - 33
0.001
Absent
117 (63.9)
4.9 (2.7)
1 - 19
75 (41.0)
4.2 (2.0)*
Parameter Hypoxaemia
Levels of SpO2 (%) >95
†
1 - 10
93 - 95
24 (13.1)
5.4 (2.7)*
1 - 13
90 - 92
18 (9.8)
6.7 (4.2)†‡
3 - 19
‡
86 - 89
28 (15.3)
8.9 (7.0)
3 - 32
≤85
38 (20.8)
7.7 (6.1)†‡
3 - 33
†‡
0.001
* Duncan multiple range test shows that means with the same symbol are not statistically different at p<0.05.
54
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RESEARCH in children with lobar pneumonia was significantly longer than the corresponding values for those with bronchopneumonia (p=0.001). Among the survivors, the children with hypoxaemia had a longer duration of hospitalisation compared with those without hypoxaemia (p=0.001) (Table 3). The mean (SD) duration of supplemental oxygen therapy among all the subjects was 26.3 (34.5) hours. The mean duration on supplemental oxygen to the children with hypoxaemia was significantly longer than the corresponding value recorded in those without hypoxaemia (p=0.001) (Table 4). The mean duration of oxygen therapy in children with pneumonia increased
significantly as the SpO2 levels decreased (p=0.001). Seventeen of the children with pneumonia died, giving a case fatality of 8.5%. Of these, 10 (58.8%) were aged <12 months, 3 (17.7%) were aged 12 - <24 months, and 4 (23.5%) were aged 24 - <36 months. Twelve (70.6%) of the 17 children who died were male. All the children who died had hypoxaemia (Table 5). The case fatality rate for children with hypoxaemia was 20.5% with a relative risk of death of 48 in children with hypoxaemia compared with those without. Regarding the various cut-offs for hypoxaemia, there was a progressive increase in case fatality rate as SpO2 fell to <90% (Table 5).
Table 4. Duration on oxygen therapy and hypoxaemia in the study population Duration on oxygen (hours) n (%)
Mean (SD)
Range
p-value
Present
83 (41.5)
45.1 (41.9)
5 - 240
0.001
Absent
117 (58.5)
12.9 (19.2)
0 - 96
75 (37.5)
5.8 (11.9)*†
Parameter Hypoxaemia
Levels of SpO2 (%) >95 93 - 95
24 (12.0)
0 - 48 †
0 - 72
†
20.8 (20.6)*
90 - 92
18 (9.0)
31.9 (24.8)*
0 - 96
86 - 89
34 (17.0)
47.2 (47.8)†
6 - 240
49 (24.5)
†
43.7 (37.9)
5 - 194
Moderate
12 (6.0)
2.8 (9.2)
0 - 72
Severe
188 (94.0)
27.8 (35.0)
0 - 240
Discharged
183 (91.5)
26.0 (34.4)
0 - 240
Died
17 (8.5)
29.5 (37.0)
5 - 137
≤85
0.001
Severity of pneumonia 0.015
Admission outcome 0.684
†
* Duncan multiple range test shows that the means with the same symbol are not statistically different at p<0.05.
Table 5. Hypoxaemia and mortality among the children with pneumonia Outcome of admission Discharged, n (%)
Died, n (%)
Case fatality rate, % (95% CI)
Relative risk (95% CI)
Present
66 (79.5)
17 (20.5)
20.5 (13.1 - 30.5)
48.1 (2.9 - 790.0)
Absent
117 (100)
0 (0)
0 (0.00 - 4.82)
-
>95
75 (100)
0 (0)
0.0
-
93 - 95
24 (100)
0 (0)
0.0
-
90 - 92
18 (100)
0 (0)
0.0
-
86 - 89
28 (81.8)
6 (18.2)
17.6
-
≤85
38 (78.0)
11 (22.0)
22.4
-
Total
183
17
8.5
-
Parameter Hypoxaemia
Levels of SpO2 (%)
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The mean SpO2 level recorded of 78.3% (10.9) among the fatal cases was significantly lower than the corresponding value of 91.5% (7.8) recorded among the children who survived (p=0.001). The relationship between the recorded pulse oximeter values and various other parameters is shown in Table 6.
Discussion
The case fatality among the children with pneumonia in this series was 8.5%. While this value is slightly higher than the 7.8% recorded by Johnson et al.[9] in Ibadan, an even higher case fatality value of 10.0% had been identified in an earlier report (some 25 years earlier) by Fagbule et al.[2] in Ilorin, where the present study was carried out. The corresponding values from other countries include 15.0% reported by Nathoo et al.[10] in Zimbabwe and 10.5% by Sehgal et al.[11] in India. It is worrisome that despite advances in pneumonia case management, including appropriate use of antibiotics and deployment of technology, there has been only a paltry 15% decrease in case fatality over the past 25 years. Some of this barely significant decline may be attributed to more prompt home recognition of disease severity, early diagnosis, better defined criteria for referrals, as well as institutional adoption of more effective management strategies in the last few years.[11,12] However, there still exists an urgent need to improve pneumonia case management and its outcome drastically. The fact that the presence of hypoxaemia was associated with a significantly higher pneumonia-related mortality is in accord with earlier reports.[13] Pneumonia interferes with the process of oxygen exchange at the alveoli and increases ventilationperfusion mismatch. Thus, it is conceivable that more-severe disease will further limit oxygen exchange, leading to hypoxaemia. This emphasises the role of SpO2 as a tool for determining initial disease severity. Similar reports have shown the presence of hypoxaemia to correlate with severity of pneumonia.[12] This study further validates the definition of hypoxaemia as SpO2 <90%, as case fatality rate was nil in children with SpO2 >90%, but progressively increased with lower SpO2 levels. The presence of hypoxaemia increased the risk of death 48-fold compared with those who were nonhypoxaemic. The preponderance of children with severe disease in this study as shown by a prevalence of hypoxaemia of 42% compared with 5.8% in The Gambia[14] and 6.4% in Kenya[13] provides some explanation for the wide disparity in the hypoxaemiarelated risk of death. Other reasons may relate to the smaller sample size in this study and the possible differing levels of care provided in these facilities. Nevertheless, the implication of this dramatic increase in
RESEARCH Table 6. Pulse oximeter readings and outcome in the children with pneumonia Pulse oximeter reading (%) n (%)
Mean (SD)
Range
p-value
Present
83 (41.5)
82.3 (8.1)
47 - 89
0.001
Absent
117 (58.5)
96.2 (2.8)
91 - 100
Discharged
183 (91.5)
91.5 (7.8)
55 - 100
Died
17 (8.5)
78.3 (10.9)
47 - 89
Moderate
12 (6.0)
97.1 (2.2)
94 - 100
Severe
188 (94.0)
90.0 (9.0)
47 - 100
Parameter Hypoxaemia
Outcome 0.001
Severity of pneumonia
risk of death is the need to evolve systems for aggressive management of those patients presenting with hypoxaemia in developing countries. In the current study, the duration of hospital stay was found to be significantly longer for hypoxaemic children. This obser vation is similar to the reported findings in some earlier studies.[13,14] Indeed, the mean duration of hospitalisation increased as the levels of hypoxaemia worsened, with decreasing SpO2 levels. This is attributable to the longer time required by hypoxaemic children with pneumonia to recover from the underlying pathophysiological aberrations of alveolar hypoventilation and ventilationperfusion mismatch. Supplemental oxygen is given to children with pneumonia to relieve hypoxaemia. In the current study, the mean duration of supplemental oxygen administration increased with decreasing SpO2 and severity of pneumonia. This has strong implications in developing countries where oxygen may be scarce. An identified limitation of the study was the use of single-point determination of SpO2 rather than a continuous measure, which
0.007
would have provided a more accurate guide to the actual duration for which a patient requires supplemental oxygen. Nevertheless, in situations where oxygen supplies are limited and facilities for monitoring saturation are not available, initial disease severity may be a reliable guide to planning the rationing of such supplies. These data underscore the need to make pulse oximeters available in healthcare facilities with the capacity and wherewithal for administering oxygen therapy to patients.
Conclusion
The prevalence of hypoxaemia in children <5â&#x20AC;&#x201A; years of age hospitalised with pneumonia is 41.5%, and hypoxaemia significantly predicts a worse outcome in terms of mortality, duration of hospitalisation and oxygen therapy. Thus, it would be essential for health facilities in developing countries to have capacity for monitoring SpO2 as a guide to oxygen therapy and aggressive management. Acknowledgements. The authors acknowledge the contributions of all the consultants, residents and entire nursing staff of the EPU,
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and thank the parents who consented to be part of this study.
References
1. Rudan I, Boschi-Pinto C, Biloglav Z, Mulholland K, Campbell H. Epidemiology and etiology of childhood pneumonia. Bull World Health Organ 2008;86(5):408-416. 2. Fagbule D, Adedoyin M, Nzeh D. Childhood pneumonia in the University of Ilorin Teaching Hospital. Nig J Paediatr 1987;14(3,4):73-78. 3. Mower WR, Sachs C, Nicklin EL, Baraff LJ. Pulse oximetry as a fifth pediatric vital sign. Pediatrics 1997;99(5):681-686. 4. Stein RT, Marostica PJC. Community-acquired pneumonia: A review and recent advances. Pediatr Pulmonol 2007;42(12):1095-1103. [http:// dx.doi.org/10.1002/ppul.20652] 5. Hassan A. Non-invasive monitoring of blood gases. In: Hassan A, ed. Handbook of Blood Gas / Acid Base Interpretation. London: Springer-Verlag; 2009:63-95. 6. Araoye MO. Subjects selection. In: Araoye MO, ed. Research Methodology with Statistics for Health and Social Sciences. Ilorin: Nathadex, 2003:115-121. 7. Fisher AA, Laing JE, Stoeckel JE, Townsend JW. Handbook for Family Planning Operations Research Design. 2nd ed. New York: Population Council, 1991:43-46. 8. Harris M, Clark J, Coote N, et al. British Thoracic Society guidelines for the management of community acquired pneumonia in children: Update 2011. Thorax 2011;66(Suppl 2):ii1-23. [http://dx.doi.org/10.1136/thoraxjnl-2011-200598] 9. Johnson WBR, Osinusi K, Aderele WI, Gbadero D. Acute lower respiratory infections in hospitalized urban preschool Nigerian children: A clinical overview. Afr J Med Med Sci 1994;23(2):127-138. 10. Nathoo KJ, Nkrumah FK, Ndlovu D, Nhembe M, Pirie DJ, Kowo H. Acute lower respiratory tract infection in hospitalized children in Zimbabwe. Ann Trop Paediatr 1993;13(3):253-261. 11. Sehgal V, Sethi GR, Sachdev HP, Satyanarayana L. Predictors of mortality in subjects hospitalized with acute lower respiratory tract infections. Indian Pediatr 1997;34(3):213-219. 12. Principi N, Esposito S. Management of severe community-acquired pneumonia of children in developing and developed countries. Thorax 2011;66(9):815-822. [http://dx.doi.org/10.1136/ thx.2010.142604] 13. Onyango FE, Steinhoff MC, Wafula EM, Wariua S, Musia J, Kitonyi J. Hypoxaemia in young Kenyan children with acute lower respiratory infection. BMJ 1993;306(6878):612-615. 14. Usen S, Weber M, Mulholland K, et al. Clinical predictors of hypoxaemia in Gambian children with acute lower respiratory tract infection: Prospective cohort study. BMJ 1999;318(7176):8691.
CASE REPORT
Early renal surveillance: A necessity in a child with tuberous sclerosis complex S K John,1 MBBS, MS, FMAS; R Nalla,2 MBBS; V Kumar,1 MBBS, MS, MCh; P L N G Rao,3 MBBS, MS, MCh; S Prabhu,1 MBBS, DNB; S P Thotan,1 MBBS, MS, MCh; B Kharga,1 MBBS, DNB epartment of Paediatric Surgery, Kasturba Medical College, Manipal University, Manipal, India D Department of Surgery, Kasturba Medical College, Manipal University, Manipal, India 3 Vice-Chancellor, Manipal International University, Nilai, Malaysia 1 2
Corresponding author: S K John (drsijokjohn@yahoo.com) Tuberous sclerosis complex (TSC) is an extremely variable genetic disorder that can affect virtually any organ in the body. Disease manifestations continue to develop over the lifetime of an affected individual. Many manifestations can be life threatening; appropriate surveillance and management are necessary to limit morbidity and mortality in this disease. We report a case of an 8-year-old girl with TSC and bilateral renal cell carcinoma, which is usually thought to be a complication diagnosed in adulthood. Our report emphasises the need for frequent surveillance and renal imaging in paediatric patients with TSC. S Afr J CH 2015;9(2):57-58. DOI:10.7196/SAJCH.828
Tuberous sclerosis complex (TSC) is a genetic disorder that can affect virtually any organ in the body. Many manifestations can be life threatening. We report a case of an 8-yearold girl with TSC and bilateral renal cell carcinoma, which is usually thought to be a complication diagnosed in adulthood.
Case report
An 8-year-old girl presented with diffuse abdominal pain of 4 days’ duration, asso ciated with fever. The patient had been previously diagnosed as a case of tuberous sclerosis complex (TSC). Past history reveal ed infantile spasms managed with sodium valproate, and computed tomography (CT) of the brain showed subependymal nodules protruding into the lateral ventricles. The patient had undergone enucleation of the right eye for an astrocytic hamartoma. Initial evaluation had not revealed any renal lesions. However, no imaging studies had been done in the last 5 years. General examination revealed telangi ectatic papules over the cheeks (Fig. 1 A) and chin (angiofibromas), flesh-coloured soft plaques with prominent follicular openings over the right cheek (Fig. 1 B) and lumbosacral area (shagreen patches), and ash-leaf-shaped macules over the limbs (Fig. 1 C) and abdomen. Dental pits were also noted. Abdominal examination revealed a large mass of 15 × 10 cm involving the right hypochondrium and lumbar region. Ultrasound (US) scan showed bilateral renal masses. CT scan of the abdomen revealed mass lesions in both kidneys
(Fig. 1 D). The lesions showed no fat attenuation, with areas of necrosis and calcifications suggestive of bilateral renal cell carcinoma. The parents refused further evaluation and treatment.
Discussion
Tuberous sclerosis complex (TSC) is an extremely variable genetic disorder that can affect virtually any organ in the body. The most common findings are benign tumours in the skin, brain, kidneys, lungs and heart,
which can lead to organ dysfunction. TSC is highly variable in clinical presentation and findings. Diagnosis is made based on the updated diagnostic criteria established at the Tuberous Sclerosis Complex Consensus Conference in 2012. Disease manifestations continue to develop over the lifetime of an affected individual. Accurate diagnosis is fundamental to implementation of appropriate medical surveillance and treatment, apart from being crucial for optimal quality of life of the affected. Many
A
B
C
D
Fig. 1 A. Telangiectatic papules over the cheeks (angiofibromas); B. Flesh-coloured soft plaques with prominent follicular openings over the right cheek (shagreen patches); C. Ash-leaf-shaped macules over the limbs; D. CT scan of abdomen showing mass lesions in the right and left kidneys, with no fat attenuation and areas of necrosis and calcifications, suggestive of bilateral renal cell carcinoma.
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CASE REPORT manifestations can be life threatening, and appropriate surveillance and management are necessary to limit morbidity and mortality. Renal manifestations occur frequently in TSC, with varying severity. Estimated rates of involvement range from 48 to 80%.[1] The most common renal lesions are angiomyolipomata and renal cysts, the prevalence of both increasing with age. Angiomyolipoma is a benign renal neoplasm comprising vascular, smooth muscle and fat elements. The estimated incidence of renal cell carcinoma in TSC ranges from 2.2 to 4.2%[1,2] and occurs primarily in women.[3] The median age of diagnosis of renal cell carcinoma in TSC is reported as 28 years, 25 years earlier than the average age at diagnosis in the general population. [2,3] Although renal cell carcinoma has been reported in children with TSC as young as 6 months of age,[4] debate continues over whether TSC mutations increase susceptibility to renal cell carcinoma and whether TSC-related angiomyolipoma can progress to renal cell carcinoma.[1] At the time of diagnosis, abdominal imaging should be obtained, regardless of age. Magnetic resonance imaging (MRI) is the preferred modality for evaluation of angiomyolipomata, because many can be fat-poor and hence missed in abdominal CT or US.[5] In CT, the only finding that can distinguish angiomyolipoma from renal cell carcinoma is intralesional fat. Fat-poor angiomyolipomata are not uncommon in patients with TSC. Biopsy is often discouraged, as it may cause highly vascular angiomyolipomata to haemorrhage or scatter malignant cells from a renal cell carcinoma.[1] But if there is doubt and the lesions are growing faster than 0.5 cm per year, a needle biopsy or an open biopsy may be considered.[5] Nephrectomy is to be undertaken with caution, since these patients are predisposed to developing additional masses in the remaining kidney and the operation has a high incidence of complications.[1] Prognosis varies, as these tumours frequently metastasise.[3] This case report illustrates the need for early and frequent renal surveillance and renal imaging in paediatric patients with TSC.
Usually thought to be a complication diagnosed in adulthood, it is important to remember that although scarce, renal cell carcinoma may appear in a paediatric setting. The recommended surveillance protocol was poorly followed in our patient. The current recommendations (Table 1) suggest MRI of the abdomen at the time of diagnosis of TSC and every 1 - 3 years throughout the lifetime of the patient[5] to diagnose polycystic disease, renal cell carcinoma or other tumours, and to monitor changes in angiomyolipoma. Annual clinical assessments of renal function and hypertension are also recommended. Although our case report illustrates renal complications, we would like to emphasise the importance of total surveillance in these patients. Appropriate surveillance and early management are crucial to limit morbidity and mortality in this disease, and improve quality of life of those affected.
References 1. Rakowski SK, Winterkorn EB, Paul E, Steele DJ, Halpern EF, Thiele EA. Renal manifestations of tuberous sclerosis complex: Incidence, prognosis, and predictive factors. Kidney Int 2006;70(10):1777-1782. [http://dx.doi. org/10.1038/sj.ki.5001853] 2. Gil AT, Brett A, Cordinhã C, Gomes C. Bilateral renal cell carcinoma in a paediatric patient with tuberous sclerosis complex. BMJ Case Rep 2013. [http:// dx.doi.org/10.1136/bcr-2013-010015] 3. Bjornsson J, Short MP, Kwiatkowski DJ, Henske EP. Tuberous sclerosisassociated renal cell carcinoma. Clinical, pathological, and genetic features. Am J Pathol 1996;149(4):1201-1208. 4. Breysem L, Nijs E, Proesmans W, Smet MH. Tuberous sclerosis with cystic renal disease and multifocal renal cell carcinoma in a baby girl. Pediatr Radiol 2002;32(9):677-680. [http://dx.doi.org/10.1007/s00247-002-0765-9] 5. Krueger DA, Northrup H, International Tuberous Sclerosis Complex Consensus Group. Tuberous sclerosis complex surveillance and management: Recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. Pediatr Neurol 2013;49(4):255-265. [http://dx.doi. org/10.1016/j.pediatrneurol.2013.08.002]
Table 1. Renal surveillance and management recommendations for TSC[5] Recommendations for newly diagnosed or suspected TSC* Obtain MRI of the abdomen to assess for the presence of angiomyolipoma and renal cysts. Screen for hypertension by obtaining an accurate blood pressure. Evaluate renal function by determining GFR.
Recommendations for patients already diagnosed with definite or possible TSC Obtain MRI of the abdomen to assess for the progression of angiomyolipoma and renal cystic disease every 1 - 3 years throughout the lifetime of the patient.* Assess renal function (including determination of GFR) and blood pressure at least annually.* For asymptomatic, growing angiomyolipoma measuring larger than 3 cm in diameter, treatment with mTOR complex inhibitors is the recommended first-line therapy.* Selective embolisation or kidney-sparing resection are acceptable second-line therapies for asymptomatic angiomyolipoma.† Embolisation followed by corticosteroids is first-line therapy for angiomyolipoma presenting with acute haemorrhage.† Nephrectomy is to be avoided.† GFR = glomerular filtration rate; mTOR = mammalian target of rapamycin. *Recommendation category I: Based on high-level evidence, there is uniform consensus that the intervention is appropriate (supporting evidence: at least one convincing ‡ class I study or at least two convincing and consistent class II studies or at least three convincing and consistent class III studies). †
Recommendation category IIA: Based on lower-level evidence, there is uniform consensus that the intervention is appropriate (supporting evidence: at least one convincing class II study or at least two convincing and consistent class III studies). ‡
Class definitions for supporting evidence: • Class I: evidence provided by a prospective, randomised, controlled clinical trial with masked outcome assessment, in a representative population. • Class II: evidence provided by a prospective matched group cohort study in a representative population with masked outcome assessment. • Class III: evidence provided by all other controlled trials (including well-defined natural history controls or patients serving as own controls) in a representative population, where outcome assessment is independent of patient treatment. • Class IV: evidence provided by uncontrolled studies, case series, case reports or expert opinion.
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CASE REPORT
Neuroregression in an infant: A rare cause P Subramani, MD; C Gomathi Saranya, MBBS; G M Chand, MBBS; R Sowmiya Narayani, MBBS; S James, MD; P N Vinoth, MD, MRCPCH Department of Pediatrics, Sri Ramachandra Medical College, Chennai, India Corresponding author: P N Vinoth (vindoc1977@gmail.com) Neuroregression in infants has diverse aetiologies, and vitamin B12 deficiency is a rare one. Infantile vitamin B12 deficiency is usually secondary to maternal pernicious anaemia or maternal vegetarian diet. We report a 10-month-old infant with developmental regression secondary to vitamin B12 deficiency. Her mother was a strict vegetarian and the patient was exclusively breastfed. Clinical symptoms normalised after vitamin B12 supplementation. S Afr J CH 2015;9(2):59-60. DOI:10.7196/SAJCH.882
Dietary sources of vitamin B12 include foods of animal origin. Vegans with aversion to milk and eggs have inadequate amounts of vitamin B12. Adults can tolerate a vitamin B12-deficient diet for many years without clinical symptoms, owing to their endogenous pool, whereas infants become symptomatic within a few months owing to limited hepatic reserves. Maternal vitamin B12 deficiency is usually secondary to maternal pernicious anaemia or strict vegetarian diet, and can cause ineffective haematopoiesis and severe neurological abnormalities among exclusively breastfed infants. [1] Here, we present a 10-month-old infant with developmental regression associated with vitamin B12 deficiency; the child showed marked clinical improvement after vitamin B12 supplementation.
Case report
A 10-month-old female child, firstborn to non-consanguineous parents, presented with a history of regression of milestones, namely inability to sit with support, roll over or hold her neck. The mother also complained of the child having abnormal movements, especially in the upper limbs. She attained milestones appropriate for her age until 6 months of age. Birth history was normal, and the child was exclusively breastfed for 6 months. On examination, the patient looked apathetic and exhibited lassitude. She could neither hold her neck up nor reach for objects, but recognised her mother’s face. There was no pallor or hyperpigmentation of her oral cavity, the dorsum of her hands or feet. Anthropometric measurements were weight 7.2 kg (<10th centile), head circumference 42 cm (<10th centile) and length 68 cm (10th centile). The child had generalised hypotonia with normal deep tendon reflexes. She displayed abnormal movements in the form of tremors and myoclonic jerks involving the upper limbs. There was no other systemic involvement. She was provisionally diagnosed as having a neurodegenerative disorder and investigated. Investigations revealed a haemoglobin of 10.4 g/dL, total count 7.9 × 109/µL (differential count of polymorphonuclear cells 40%, lymphocytes 48%, eosinophils 2% and monocytes 10%) and platelets 250 × 109/L. Her mean corpuscular volume (MCV) was 105.5 fL with macrocytic red blood cells in the peripheral smear. Liver and renal function tests were within normal limits. In view of the high MCV and macrocytic picture, vitamin B12 deficiency was suspected and serum vitamin B12, folate and homocysteine levels were sent to the lab. Vitamin B12 and folate levels were <83 pg/mL (reference range 208 - 963 pg/mL) and 3.78 ng/mL (2.7 - 17.0 ng/ mL), respectively. Serum homocysteine levels were elevated (>50.0 µmol/L). Electroencephalogram (EEG) and magnetic resonance imaging 59
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brain scans were normal. On further questioning, we found that the mother was on a strict vegetarian diet and her vitamin B12 level was also low (<90 pg/mL), hence the child was diagnosed as having a vitamin B12-associated neuroregression, and started on vitamin B12 injections (1 000 µg). In our centre, for vitamin B12 deficiency in children we administer weekly vitamin B12 injections (1 000 µg) for 4 weeks, then once monthly for 3 months and finally once every 3 months for 6 months. After 2 weeks of treatment with vitamin B12 injections, the patient showed marked improvement in social interaction, with gradual reduction in tremors and myoclonic jerks. At the end of 4 weeks, the child was able to hold her neck up, sit without support and stand with support. Repeat serum vitamin B12 level was 936 pg/mL and serum homocysteine level was 10 µmol/L. She is now on a regular follow-up schedule on an outpatient basis.
Discussion
In a paediatric population, vitamin B12 deficiency can be associated with haematologic, neurologic and psychiatric symptoms. Infantile vitamin B12 deficiency was first reported in six South Indian infants, who presented at 7 - 12 months with megaloblastic anaemia, develop mental regression and skin hyperpigmentation.[2] Infantile vitamin B12 deficiency is a rare but treatable cause of developmental delay and regression, affecting exclusively breastfed infants born to vitamin-B12-deficient mothers. Infant cobalamin status is determined by the cobalamin content in the breastmilk and the maternal cobalamin concentration during lactation. Maternal factors such as pernicious anaemia, vegan diet and malabsorption contribute to infant cobalamin deficiency.[3] Humans are unable to synthesise vitamin B12, and their only dietary sources are products of animal origin, such as meat, liver, fish, eggs or milk. The average body store of vitamin B12 in healthy adults is ~3 mg, compared with 25 µg in neonates, so adults can tolerate deficient diets for many years without visible symptoms, whereas neonates born to a vitamin-B12deficient mother can develop symptoms within a few months.[1] In our patient, vitamin B12 deficiency was attributed to the maternal vegetarian diet. Vitamin B12 deficiency principally affects the central nervous system (CNS) and those tissues with rapid mitotic activity, such as digestive tract epithelium and haematopoietic cells. CNS symptoms generally appear between 2 and 12 months of age, and include vomiting, lethargy and feeding problems. Hypotonia, optic atrophy, adynamia, developmental regression and abnormal movements such as tremors or myoclonus are other hallmarks of the disease. [4] In contrast to severe neurological findings in infantile vitamin B12 deficiency, in adolescents and adults only mild neuropsychiatric
APRIL 2015 Vol. 9 No. 2
CASE REPORT symptoms are observed. Neuroimaging studies may demonstrate cerebral atrophy in infants in comparison with subacute combined degeneration of cord in adults. The molecular basis for these alterations is not well understood.[2,5,6] Neuroimaging studies did not reveal any abnormalities in our patient. Synthesis of methionine and succinyl-CoA depends on the coenzyme activity of cobalamin. For synthesis of methionine, a methyl group is transferred from methyltetrahydrofolate (THF) to methylcobalamin (Cbl). Methionine is finally generated by the transfer of the methyl group to homocysteine. Methionine and THF thus formed are essential for DNA synthesis. THF becomes formyl-THF and provides C1 units in purine synthesis. The lack of neurological symptoms in folate deficiency indicates that methionine synthesis may not be causally related to Cbl-associated neuropathy. The other Cbl-dependent reaction is the conversion of methylmalonyl-CoA to succinyl-CoA. Cobalamin deficiency results in the accumulation of precursor propionyl-CoA, which in turn leads to odd-chain fatty acid synthesis, resulting in incorporation of large amounts of unusual C15 and C17 fatty acids in nerve sheets with altered nerve functions.[7] Abnormal movements such as tremors or myoclonus have been described in vitamin-B12-deficient infants before or during treatment with vitamin B12. The reason for these abnormal movements is not well understood.[2] Hyperglycinaemia causing nonspecific interference with glycine cleavage was suggested to be responsible for abnormal movements. However, normal glycine levels in symptomatic patients excluded this hypothesis.[8,9] GrattanSmith et al.[10] reported that the movement disorder that appeared after treatment is due to the swift availability of cobalamin resulting in intense stimulation of cobalamin and folate pathways, producing a short-term imbalance of metabolic pathways, with local deficiencies or excesses occurring. A metabolite yet to be demonstrated may be responsible for the involuntary movements.[10] Our patient had myoclonic jerks that disappeared after 2 months of treatment with vitamin B12. Vitamin B12 supplementation results in rapid clinical improvement with complete resolution of structural and EEG abnormalities; however, there is a concern for long-term prognosis.[1] Pearson and Turner[11] followed up a child with vitamin B12 deficiency diagnosed at 32 months and found an IQ of 60 at the age of 6 years. Graham et al.[12] identified mild cognitive impairment in 2/4 patients with
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cobalamin deficiency.[12] Von Schenck et al.[1] observed that when a diagnosis is made within 10 months of age, it has been associated with a favourable outcome compared with permanent neurological abnormalities in children whose diagnoses were made after 1 year of age. Special attention should be given to pregnant and breastfeeding women on vegan diets to prevent vitamin B12 deficiency in their infants. Screening for urinary methylmalonic acid can be a useful tool to identify these individuals.[1] It is important to emphasise that vitamin B12 supplementation during pregnancy should be provided for strict vegans and mothers with pernicious anaemia to avoid irreversible neurological damage in exclusively breastfed babies. References 1. Von Schenck U, BenderGötz C, Koletzko B. Persistence of neurological damage induced by dietary Vitamin B12 deficiency in infancy. Arch Dis Child 1997;77(2):137-139. 2. Avci Z, Turul T, Aysun S, Unal I. Involuntary movements and magnetic resonance imaging findings in infantile cobalamin (vitamin B12) deficiency. Pediatrics 2003;112(3 Pt 1):684-686. 3. Agrawal S, Nathani S. Neuro-regression in vitamin B12 deficiency. BMJ Case Rep 2009;2009: bcr.06.2008.0235. 4. Casella EB, Valente M, de Navarroa J M, Kok F. Vitamin B12 deficiency in infancy as a cause of developmental regression. Brain Dev 2005;27(8):592-594. [http://dx.doi.org/10.1016/j.braindev.2005.02.005] 5. Bassi SS, Bulundwe KK, Greeff GP, Labuscagne JH, Gledhill RF. MRI of the spinal cord in myelopathy complicating vitamin B12 deficiency: Two additional cases and review of the literature. Neuroradiology 1999;41(4):271-274. 6. Lövblad K, Ramelli G, Remonda L, Nirkko AC, Ozdoba C, Schroth G. Retardation of myelination due to dietary vitamin B12 deficiency: Cranial MRI findings. Pediatr Radiol 1997;27(2):155-158. 7. Frenkel E. Abnormal fatty acid metabolism in peripheral nerve of patients with pernicious anaemia. J Clin Invest 1973;52(5):1237-1245. 8. Higginbottom MC, Sweetman L, Nyhan WL. A syndrome of methylmalonic aciduria, homocystinuria, megaloblastic anemia and neurologic abnormalities in a vitamin B12-deficient breast-fed infant of a strict vegetarian. N Engl J Med 1978;299(7):317-323. 9. Kühne T, Bubl R, Baumgartner R. Maternal vegan diet causing a serious infantile neurologic disorder due to vitamin B12 deficiency. Eur J Pediatr 1991;150(3):205-208. 10. Grattan-Smith PJ, Wilcken B, Procopis PG, Wise GA. The neurological syndrome of infantile cobalamin deficiency: Developmental regression and involuntary movements. Mov Disord 1997;12(1):39-46. 11. Pearson AGM, Turner AJ. Folate-dependent 1-carbon transfer to biogenic amines mediated by methylenetetrahydrofolate reductase. Nature 1975;258(5531):173-174. 12. Graham SM, Arvela OM, Wise GA. Long-term neurologic consequences of nutritional vitamin B12 deficiency in infants. J Pediatr 1992;121(5 Pt 1):710-714.
APRIL 2015 Vol. 9 No. 2
CASE REPORT
An unusual case of Trisomy 13 C Feben, MB BCh, DCH, MMed, FCMG (SA); J Kromberg, MA, PhD; A Krause, MB BCh, PhD Division of Human Genetics, National Health Laboratory Service and School of Pathology, University of the Witwatersrand, Johannesburg, South Africa Corresponding author: C Feben (candice.feben@nhls.ac.za)
Trisomy 13 is a common chromosome abnormality with a recognisable clinical phenotype, which should prompt its early diagnosis. This case report describes a patient with Trisomy 13 with unusual limb malformations and expands on the clinical phenotype of the disorder. S Afr J CH 2015;9(2):61-62. DOI:10.7196/SAJCH.840
Trisomy 13 (Patau syndrome) is a well-recognised, multiple congenital anomaly syndrome, characterised by the cardinal triad of orofacial clefts, microphthalmia and postaxial polydactyly of the limbs. With an estimated worldwide liveborn prevalence (after the advent of prenatal diagnosis) of 1/10 000, it is an important cause of aneuploidy.[1] Studies conducted in South Africa (SA) many years ago estimated the prevalence of Patau syndrome at 1/24 000.[2] Given that ~4% of birth defects in SA are formally reported (Dr H Malherbe, Chairperson of the South African Inherited Diseases Association, August 2014, personal communication), it is likely that prevalence figures are actually much higher. While postaxial polydactyly remains the most commonly described limb anomaly in affected individuals, isolated reports of other limb anomalies, including thumb hypoplasia, oligodactyly and split hand malformation (SHM), have been documented in the literature.[3-5] A case report follows of a patient diagnosed with Trisomy 13, with multiple congenital anomalies including bilateral SHM. This case expands on the clinical phenotype of Trisomy 13 and highlights why the diagnosis of common genetic conditions should not be confounded by unusual presentations.
pre-auricular tags were noted. The right foot showed type A postaxial polydactyly. The upper limbs showed SHM. On the right, bidactyly was present, with absence of the middle and ulnar ray and a cleft between the presumed thumb and first digit. On the left, oligodactyly was present with a missing middle ray and a cleft between the first and third digits (Figs 1 A - E). Echocardiography and ultrasound (US) evaluation of the renal system and brain did not reveal other structural congenital malformations. A polymerase chain reaction (PCR) aneu ploidy screen performed on a peripheral blood sample diagnosed Trisomy 13. The result was confirmed on karyotype analysis (performed to elucidate the mechanism of aneuploidy) as a non-disjunction Trisomy 13 A
Case report
A genetic consultation was requested for Baby S at the Charlotte Maxeke Johannesburg Academic Hospital in Johannesburg, SA. Baby S was born by normal vaginal delivery at term after an uncomplicated pregnancy. Her parents are a non-consanguineous couple of advanced age. The clinical examination revealed age-appropriate growth measurements, but multiple congenital anomalies. On the face, bilateral severe microphthalmia, a broad nasal tip, bilateral cleft lip, a cleft palate and small ears with
(47, XX + 13). In light of the atypical finding of bilateral SHM, a 180k oligoarray-comparative genome hybridisation (CGH) was performed by a collaborating laboratory in Belgium (Universitaire ziekenhuizen Leuven). The array result (arr Xq13.1 (70 947 014 - 71 192 496) × 3, 13q11q34 (18 348 559 -114 123 757) × 3, 15q11.2 (20 305 022 - 20 697 543) × 1) confirmed Trisomy 13 but also showed an additional small pathogenic deletion on the long arm of chromosome 15, associated with epilepsy and neuropsychiatric abnormalities, as well as a variant duplication on the X chromosome of unknown significance. The patient’s mother received genetic counselling regarding the clinical features of Trisomy 13, their aetiology and significance, B
C
D
E
Fig. 1. A: Bilateral cleft lip and palate; B: Small posteriorly rotated ear with overfolded ear helix and preauricular tag; C: Bidactyly of the right hand; D: Oligodactyly with cleft of the left hand; E: Type A postaxial polydactyly of the right foot.
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CASE REPORT and the poor prognosis. She was referred for palliative care to assist with home care of Baby S. Prenatal genetic counselling with the offer of prenatal testing by chorionic villous sampling (CVS) or amniocentesis was recommended for future pregnancies in view of the mother’s advanced maternal age, which would increase her risk for another baby with a chromosome abnormality.
Discussion
The diagnosis of Trisomy 13 was suspected in Baby S on the basis of the indicative cardinal triad of features. However, the finding of bilateral SHM was very unusual. To date, only five other cases of Trisomy 13 have been described with SHM.[3-5] Prior to the PCR result, the major differential diagnosis in Baby S was ‘ectrodactyly, ectodermal dysplasia, clefting syndrome’ (EEC), which is caused by mutations in the TP63 gene and which is inherited in an autosomal dominant manner.[6] While we have not excluded TP63 mutations (testing is not available in SA) in Baby S and co-occurrence of Trisomy 13 and EEC is possible, this dual pathology has not been previously reported to our knowledge. Furthermore, Baby S did not have clinical features of an ectodermal dysplasia (including hair and nail anomalies), which would make dual pathology less likely. Neither of the two other copy number variations detected by arrayCGH is known to be associated with SHM. We concluded thus that SHM was part of the spectrum of limb malformations in this infant with Trisomy 13. Trisomy 13 is a common condition of aneuploidy worldwide. The majority of cases (80%) are caused by the presence of an additional chromosome 13 owing to non-disjunction (usually in maternal meiosis I); ~10 - 20% are due to translocations, usually an unbalanced 13:14 Robertsonian translocation.[1] Apart from the classic triad of features (in 60 - 70% of cases),[1] multiple other dysmorphic features and congenital anomalies are described. Growth deficiency is common and is related to the aneuploidy as well as to poor feeding associated with orofacial clefts, gastrointestinal malformations and gastro-oesophageal reflux. Cardiac malformations are present in up to 80% of patients,[1,7] with atrial septal defect, patent ductus arteriosus and ventricular septal defect reported as the most common anomalies in one series of cases. [7] Renal pathology, particularly cystic dysplasia, is reported in over 30% of patients.[1,8] Significant ocular pathology (microphthalmia, colobomas, retinal dysplasia and cataracts) occurs in up to 50% of patients, and sensorineural hearing loss has been reported.[1] Other anomalies include limb defects (postaxial polydactyly, oligodactyly, limb deficiency and rarely SHM),[3] omphalocoele, cutis aplasia of the scalp and neural tube defects.[8] Structural malformations of the central nervous system (CNS), including the holoprosencephaly spectrum, cerebellar hypoplasia and hypogenesis of the corpus callosum are described[1] and occurred in 76% of patients in one series.[8] Central apnoea, related or unrelated to CNS malformations, may explain the increased mortality rate, with 90% of affected patients passing away before 1 year of age.[1,8] Surviving patients have profound mental retardation.[1] Pre- and postnatal diagnosis of Trisomy 13 in SA is often made on PCR aneuploidy screen, which detects triplicate copies of short tandem repeat sequences on chromosome 13. The test is also used for confirming the diagnosis of Down syndrome (Trisomy 21) and Trisomy 18. PCR aneuploidy testing does not elucidate the mechanism of the trisomy or provide recurrence risk information, and as such, karyotype analysis can also be used as a first-line investigation in suspected cases. Trisomy 13 can be suspected on antenatal US by 20 weeks’ gestation in 90 - 100% of cases.[9] Apart from structural anomalies, other indicators of Trisomy 13 include intrauterine growth restriction, echogenic cardiac foci, hypotelorism and poly- or oligohydramnios.[8,9] Invasive prenatal testing, including CVS (11 - 13 weeks’ gestation) or amniocentesis (16 - 20 weeks’ 62
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gestation), can be offered to women of advanced maternal age who are at increased risk of aneuploidy or those whose antenatal US has detected fetal anomalies. While it is generally agreed that affected infants have a poor prognosis and significant disability if they survive, recent discourse has questioned the care that should be afforded these individuals. Traditional views of palliative care and the withholding of life-saving treatments are now being challenged by families and healthcare practitioners who advocate life-saving interventions. A review of this discourse is beyond the scope of this report; however, it is recommended that a balanced approach be taken when counselling families at the time of diagnosis and thereafter, and that parental autonomy be seriously considered. Each case should be treated on an individual basis with personalised care, based on the social and financial resources of the family as well as the best interests of the child.[10,11] Genetic counselling is beneficial not only in terms of understanding the diagnosis and its implications, but also in supporting families to make particularly difficult decisions for future care and family planning.
Conclusion
Trisomy 13 can be suspected from the clinical phenotype of the affected infant. While unusual features may suggest a different diagnosis or a more complicated aetiology, they do not exclude the possibility of aneuploidy. As simple tests to detect aneuploidy can be readily accessed, common genetic conditions, including Trisomy 13, should be considered in the differential diagnosis and actively excluded even in the presence of unusual manifestations. Referral to a genetic counselling clinic is advocated whenever possible, although care of the affected infant and support for the family can and should be offered by all healthcare practitioners. Acknowledgments. The authors wish to thank Prof. Thomy de Ravel (Universitaire ziekenhuizen Leuven, Belgium) for his assistance with array-CGH testing. We also wish to thank the patient and her family for their participation in this study, as well as Dr L Bhengu and the Paediatric Department at the Charlotte Maxeke Johannesburg Academic Hospital.
References 1. Carey JC. Trisomy 18 and Trisomy 13. In: Cassidy SB, Allanson JE, eds. Management of Genetic Syndromes. 3rd ed. New Jersey, USA: John Wiley & Sons, 2010. 2. Parrot NM. A study of the three most common chromosome trisomies, 21 (Down syndrome), 18 (Edwards syndrome) and 13 (Patau syndrome) [Research report for MSc]. Johannesburg: University of the Witwatersrand, 1997. 3. Martinez-Frias ML, Villa A, de Pablo RA. Limb deficiencies in infants with Trisomy 13. Am J Med Genet 2000;93(4):339-341. [http://dx.doi. org/10.1002/1096-8628(20000814)93:43.0.CO;2-R] 4. Kushel B, Gillesses-Kaesbach G. Trisomy 13 with bilateral hand oligodactyly. Am J Med Genet 2000;90(1):87-88. [http://dx.doi.org/10.1002/(SICI)10968628(20000103)90:13.0.CO;2-I] 5. Urioste M, Martinez-Frias ML, Aparicio P. Ectrodactyly in Trisomy 13 syndrome. Am J Med Genet 1994;53(4):390-392. [http://dx.doi.org/10.1002/ ajmg.1320530422] 6. Rinne T, Brunner HG, van Bokhoven H. p63-associated disorders. Cell Cycle 2007;6(3):262-268. [http://dx.doi.org/10.4161/CC6.3.3796] 7. Polli JB, de P Groff D, Petry P, et al. Trisomy 13 (Patau syndrome) and congenital heart defects. Am J Med Genet 2013;164(1):272-275. [http://dx.doi. org/10.1002/ajmg.a.36193] 8. Hsu HF, Hou JW. Variable expressivity in Patau syndrome is not all related to Trisomy 13 mosaicism. Am J Med Genet 2007;143A(15):1739-1748. [http:// dx.doi.org/10.1002/ajmg.a.31835] 9. Shipp TD, Benacerraf BR. Second trimester ultrasound screening for chromosomal abnormalities. Prenat Diagn 2002;22(4):296-307. [http://dx.doi. org/10.1002/pd.307] 10. Janvier A, Watkins W. Medical interventions for children with Trisomy 13 and Trisomy 18: What is the value of a short disabled life? Acta Paediatr 2013;102(12):1112-1117. [http://dx.doi.org/10.1111/apa.12424] 11. Carey JC. Perspectives on the care and management of infants with Trisomy 13 and Trisomy 18: Striving for balance. Curr Opin Pediatr 2012;24(6):672-678. [http://dx.doi.org/10.1097/MOP.ob013e3283595031]
APRIL 2015 Vol. 9 No. 2
CASE REPORT
Accidental podophyllin poisoning in a 3-year-old child T de Wit, MB BCh, DCH (SA); T Bisseru, MB BCh, FC Paed (SA) Department of Paediatrics, Pietermaritzburg Hospital Complex, South Africa Corresponding author: T Bisseru (tashmin@live.co.za) Accidental poisoning in children remains a common presentation in healthcare centres worldwide, with the highest rates of fatal poisonings occurring in Africa. Podophyllin, commonly used for genital warts, is a rare agent in poisoning cases. A few cases have been reported in the international literature, with serious systemic and neurological side-effects. We report a case of accidental podophyllin poisoning in a 3-year-old boy, which was complicated with organ dysfunction. The case highlights the severe neurological side-effects of podophyllin poisoning and the importance of accident prevention in our communities. S Afr J CH 2015;9(2):63-64. DOI:10.7196/SAJCH.865
A 3-year-old male was admitted after accidentally ingesting an unknown amount of a podophyllincontaining topical solution, originally prescribed for an adult member of the family. Prior to his hospital admission, milk was given as a home remedy, consequently followed by massive emesis and diarrhoea. He presented to hospital 5 hours post ingestion with an altered sensorium. Activated charcoal was administered via nasogastric tube. He had no known medical conditions or previous admissions to hospital. His growth and development were normal for his age. After initial stabilisation, he was transferred to a tertiary hospital for further intensive care. In the paediatric intensive care unit, the child was assessed to have a Glasgow Coma Scale (GCS) of 5/15 (E = Eyes, 1; V = Verbal, 1; M = Motor, 4). He did not require any airway support or mechanical ventilation, but was placed on nasal prong oxygen. Initially, the peripheral neurological and general examination was normal. Laboratory investigations revealed renal and hepatic impairment, as well as bone marrow suppression (Table 1). Twenty-four hours post podophyllin ingestion, the child’s GCS remained 5/15; however, he had now developed abnormal neurological signs, including hypotonia, areflexia with no clonus and reduced power in all limbs, but with no evidence of a pseudobulbar palsy. He had no signs of autonomic dysfunction; however, he did show deficits in sensation examination with loss of pain and touch. Proprioception and temperature examination were not conclusive owing to the age of the patient and his reduced GCS. He was assessed as having a possible sensory-motor peripheral neuropathy. He was monitored closely and
managed supportively. Feeding was initiated via a nasogastric tube. The child’s GCS improved to 9/15 (E4, V2, M3) 72 hours after ingesting the podophyllin, but he then exhibited signs of a pseudobulbar palsy. After 6 days in high care, the child developed a paralytic ileus, requiring nasojejunal tube placement, bowel rest and antibiotics. During this time, his renal and liver impairment and blood counts steadily improved. Further investigations revealed a normal computed tomography scan of the brain; however, a magnetic resonance image of the brain revealed cortical atrophy that was not in keeping with his age. An electroencephalo gram showed a background of slowing
and of low-amplitude (4 Hz) wave activity, but no focal or epileptiform activity. Nerve conduction studies confirmed a sensorymotor neuropathy. A videofluoroscopic study (modified barium swallow), done to assess the extent of his pseudobulbar palsy, revealed a delay in the triggering of the swallowing reflex. He has regained minimal motor and sensory function, and receives regular physio- and occupational therapy as part of his continued rehabilitation. He awaits a percutaneous gastrotomy to assist with appropriate feeding.
Discussion
Accidental poisoning in children is a common occurrence, making up 10.9% of all
Table 1. Trends of blood results Investigation
Reference range*
Admission
Day 1
Day 3
Day 7
10.5 - 14.5 g/dL
Full blood count Haemoglobin White cell count Platelets
11.3
7.4
9.0
8.1
3
10.9
11.5
4.4
16.8
3
200
79
67
575
5.5 - 15.5 × 10 cells/µL 170 - 380 × 10 µL
Urea and electrolytes Urea
2.5 - 6.5 mg/dL
16.3
20.6
2.5
1.2
Creatinine
<46 µmol/L
90
125
26
21
60 - 320 IU/L
454
288
165
131
Liver function tests ALP ALT
<45 IU/L
69
80
52
16
AST
16 - 69 IU/L
Not done
230
93
62
GGT
<45 IU/L
87
60
35
25
0.8 - 1.2
1.43
2.29
0.96
1.06
Coagulation tests INR
ALP = alkaline phosphatase; ALT = alanine aminotransferase; AST = aspartate transaminase; GGT = gamma glutamyl transpeptidase; INR = international normalised ratio. *National Health Laboratory Services age and gender specific laboratory reference ranges.
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CASE REPORT unintentional injuries worldwide.[1] Africa has the highest incidence of fatal poisonings worldwide, at 4 per 100 000. [1] Poisoning with podophyllin is rare, with most cases documented around the 1970s 1980s. The drug is widely used for the treatment of genital warts. The last known reported case was a paediatric patient in India in 2001.[2] There are very few reports on the toxic effects of this compound, and therefore the serious systemic and neurological effects of podophyllin are not fully appreciated. Podophyllin use began in the 1800s, variously as an emetic and cathartic agent to an antivenom and suicidal agent.[3] Later, its use was extended as a local agent for skin lesions.[3] The widespread use of podophyllin for condyloma acuminatum only began in 1942.[3] The first documented side-effects were reported around 1835, when a woman developed abdominal cramps and pain after ingestion,[3] and the first fatal case after oral administration was reported in 1890. A fatal case relating to topical application was reported in 1954.[3] The active constituent of the drug is podophyllotoxin, a lipid-soluble compound extracted from the resin of Podophyllin plant roots, which readily crosses cell membranes.[2,3] Podophyllotoxin is a cytotoxic agent that inhibits DNA synthesis as well as cell mitosis in metaphase. Podophyllin has both local and systemic effects associated with topical and oral use. It is a severe irritant to mucous membranes, with local effects including erythematous, oedematous and ulcerative skin lesions, burns and conjunctivitis.[4,5] Systemic toxicity causes multiorgan dysfunction. Gastrointestinal irritation in the form of nausea, vomiting, abdominal pain and diarrhoea, and bone marrow suppression with thrombocytopenia and leucopenia, manifest early in the presentation. Renal and hepatic failure with electrolyte disturbances, including hypokalaemia and hypoglycaemia, have been noted in several cases.[2,5] Neurotoxicity is the most severe effect of podophyllin poisoning. [2,5] Initially, the presentation includes altered sensorium ranging from confusion to coma, but may include hallucinations, stupor, seizures and ultimately death.[2,5,6] Peripheral neuropathies can appear early, but mostly present some days later with motor (hypotonia, hyporeflexia) and sensory (paraesthesia, glove and stocking loss of light touch and proprioception) deficits.[2,5] Autonomic neuropathies can also be present, manifesting as paralytic ileus, hypotension, tachycardia, urinary retention and apnoea.[2,5] Our patient had complications of bone marrow suppression, renal and hepatic impairment, as well as peripheral and autonomic neuropathies. The management of podophyllin ingestion and subsequent toxicity is mainly supportive, as no specific antidote exists. Activated
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charcoal is recommended for use after a recent ingestion.[2,5] Adequate management of ventilation and circulation is required, accompanied by monitoring for the abovementioned complications. Haemoperfusion to reduce plasma levels of podophyllin has been reported in the literature; however, its use has only been reported in adults and its effect on outcomes remains unclear.[5] In South Africa, Malangu et al.[7] reported that 17% of total paediatric ward admissions are due to acute poisoning, with the majority being unintentional poisonings and with children <10 years of age comprising 80% of all poisoning victims. Podophyllin is still a widely used treatment, especially as a topical application. Despite podophyllin poisoning being rare, with few reported cases, the toxic side-effects (especially the neurotoxicity) must be highlighted because of the associated morbidity and mortality.[8] Accidental poisoning in children, as in this case, is a preventable injury. Education of parents and healthcare workers on home safety still remains the mainstay of prevention. Most poisoning cases require supportive management, and poison control centres should be contacted early for management guidelines.
Ethical approval
Informed consent for the publication of this case report was obtained from the mother of the child.
References
1. World Health Organization, United Nations Children’s Fund. Chapter 6: Poisoning. World Report on Child Injury Prevention, 2008. Geneva: World Health Organization Press, 2008:123-138. http://www.who.int/violence_ injury_prevention/child/en/ (accessed 8 October 2013). 2. Kumar M, Shanmugham A, Prabha S, Adhisivam B, Narayanan P, Biswal N. Permanent neurological sequelae following accidental podophyllin ingestion. J Child Neurol 2012;27(2):203. [http://dx.doi.org/10.1177/0883073811415682] 3. Miller R. Podophyllin. Int J Dermatol 1985;24(8):491-498. [http://dx.doi. org/10.1111/j.1365-4362.1985.tb05827.x] 4. Rudrappa S, Vijaydeva L. Podophyllin poisoning. Indian Pediatr 2002;39:598599. 5. Afritox. Afritox Poisons Information Centre. www.afritox.co.za (accessed 10 October 2013). 6. Filley CM, Graff-Richard NR, Lacy JR, Heitner MA, Earnest MP. Neurologic manifestations of podophyllin toxicity. Neurology 1982;32(3):308-311. [http:// dx.doi.org/10.1212/WNL.32.3.308] 7. Malangu N, Ogubanjo G. A profile of acute poisoning at selected hospitals in South Africa. S Afr J Epidemiol Infect 2009;24(2):14-16. 8. Moher LM, Maurer SA. Podophyllum toxicity: Case report and literature review. J Fam Pract 1979;9(2):237-240.
APRIL 2015 Vol. 9 No. 2
CASE REPORT
Achalasia cardia in children: A report of two cases N Khan, FC Rad; C Liebenberg, MB ChB; F Suleman, FC Rad Department of Radiology, Faculty of Health Sciences, University of Pretoria, South Africa Corresponding author: N Khan (nausheenkhan5@yahoo.com) Oesophageal achalasia is a neuromuscular disorder of unknown aetiology, characterised by abnormal motility of the oesophagus and failure of the lower oesophageal sphincter to relax. This causes an abnormal dilatation of the oesophagus and resultant symptoms of vomiting/regurgitation, dysphagia, chest pain and at times, signs of lung aspiration and infection. In children, it may present as a chronic cough. The condition usually presents in the 4th and 5th decades and has very rarely been described in children. We describe two cases of achalasia and their imaging findings in adolescents. S Afr J CH 2015;9(2):65-66. DOI:10.7196/SAJCH.855
Case report Case 1
A 13-year-old boy presented to the surgical outpatient department with a history of intermittent vomiting and dysphagia since the age of 3 months. Clinically, he was cachectic with no syndromic features. On oesophagogastroscopy, the oesophagus was markedly dilated, with food residue and a spastic and stiff lower oesophageal sphincter (LES). No fibrotic rings were identified and there were no signs of oesophagitis. The opening was less than 3 mm and it was not possible to pass the scope beyond the stiff LES; hence, manometric studies were not done. A control chest radiograph (Fig. 1A) showed a massively dilated oesophagus with an air-fluid level. A subsequent barium swallow study (Fig. 1B) demonstrated a megaoesophagus, with irregular and abnormal peristalsis in the proximal oesophagus. The oesophagus tapered and narrowed at the gastro-oesophageal junction, with failure of the LES to relax. No aspiration changes were noted in the lung fields. A diagnosis of achalasia was made and the patient was booked for gastroscopy and pneumatic dilatation. The LES was dilated up to 14 mm without complications. The patient was symptom free and was discharged, and requested to come back for a review examination after 6 months. The patient presented again after 3 months with symp toms similar to initial presentation, and a repeat barium swallow again showed a tight stricture at the distal oesophagus, suggesting recurrence of achalasia. As the symptoms recurred within 6 months of dilatation, and as the patient was otherwise young and healthy, surgery was chosen as a treatment of choice as it provides lasting benefits for children with achalasia. Medical treatment with Botox (botulinium) injections was not
selected because it needs to be repeated multiple times a year with a mean duration of symptom relief of about 4 months. A Heller’s myotomy and fundoplication were done without any complications. A followup examination after 2 months and then 1 year showed complete resolution in clinical symptoms with no signs of recurrence to date.
a child presenting with chronic cough due to compression and narrowing of the trachea has been described. [6] A postulated cause of achalasia is the degeneration of the ganglion cells in Auerbach’s plexus of the oesophagus. The A
Case 2
A female patient with juvenile diabetes mellitus and hypogonadism presented with dysphagia and vomiting at the age of 16 years. A barium swallow study confirmed the findings of achalasia (Figs 2A and B). There were no signs of hyperpigmentation or alacrimia to suggest triple AAA syndrome (achalasia, alacrimia, adrenocorticotropic hormone (ACTH) deficiency). Manometric studies confirmed high LES pressure (47.1 mmHg) and a poor relaxation of 30.4%. Medical treatment was not considered as the results have either a short-term success or are not well studied in children. She was treated with Heller’s myotomy, which was complicated by perforation and later severe peritoneal sepsis. The patient subsequently had a long admission to the intensive care unit followed by a high care unit, but despite aggressive therapy for the sepsis in the context of her diabetes mellitus, she died 9 months after the procedure.
B
Discussion
Achalasia cardia is a neuromuscular disorder of unknown aetiology, rarely described in children and adolescents.. The symptoms include dysphagia, vomiting/ regurgitation of food, retrosternal pain, poor growth and respiratory symptoms due to chronic aspiration.[1-3] Few cases have been reported in infants, and some familial forms have been described but are even more rare. [4,5] An unusual case of achalasia in 65
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Fig. 1. A. Control anteroposterior demonstrating a massively dilated oesophagus with an air-fluid level; B. Lateral barium swallow radiograph confirming a mega-oesophagus with air contrast level and a classic ‘bird beak’ appearance of the distal oesophagus of the patient described in Case 1.
CASE REPORT A
B
Fig. 2. Frontal barium swallow images demonstrating: A. a dilated oesophagus with a contrast fluid level in the superior mediastinum; B. a classic ‘bird beak’ appearance of the distal oesophagus in the patient described in Case 2.
result is a lack of relaxation of the LES, with dilatation and hypertrophy of the proximal portion of the oesophagus and disordered peristalsis in the rest of the oesophagus.[1,3,7] Numerous syndromes have been associated
with achalasia, including AAA. Other associations include progressive cerebellar ataxia, parkinsonism, familial glucocorti coid deficiency, mental retardation and Down syndrome. The steroid abnormality of AAA is often not appreciated and may appear as hyperpigmentation or hypoglycaemia-induced symptoms of dizziness or confusion.[2-5,8] The gold standard for diagnosis of achalasia is a barium swallow and manometric studies. A barium swallow demonstrates the presence of mega-oesophagus and the so-called ‘bird beak’ tapering of the lower oesophagus, causing functional obstruction and significant delay of passage of contrast into the stomach. Non-peristaltic tertiary contractions may also be seen.[6,8,9] At endoscopy, a dilated oesophagus with a tight LES that ‘pops’ open with gentle pressure is often observed, as well as retained food and saliva. Signs of oesophagitis may also be seen. A normal oesophagogastroscopy does not exclude the diagnosis, as 40% of endoscopies may be normal.[3,8,9] Oesophageal manometry defines achalasia as the absence of peristalsis or the presence of abnormal peristalsis in the oesophageal body, a stiff LES with a resting pressure of >45 mmHg with poor or incomplete relaxation, and a residual pressure after emptying of >8 mmHg.[3,7,9] Biopsy, if performed, may show lack of myenteric plexus enervation. Treatment options depend on a patient’s willingness to undergo an invasive procedure and on their physical ability to endure it. The medical treatment includes calcium channel blockers such as nifedipine, which inhibits the transmembrane influx of calcium in cardiac and smooth muscle; this has been used primarily in adults to treat achalasia. The use of calcium channel blockers in children, however, is not well studied. Other medical treatment options include endoscopic injection of Botox into the LES. Botox acts on the terminal nerve endings, preventing the release of acetylcholine. This can be both diagnostic and therapeutic; however, in children the optimal dose and injection frequency to relieve achalasia is not determined and the duration of symptom relief is only 4 months, thus often requiring multiple treatments. Pneumatic dilatations have been used in children with a functionally obstructed oesophagus. Multiple dilatations are often required to achieve complete relief of symptoms and can be complicated by
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substernal pain, perforation and gastrooesophageal reflux disease. Surgery is the most definite treatment of choice, and includes Heller’s myotomy with or without fundoplication. Two of the most important complications of surgery include perforation (as in Case 2) and recurrent dysphagia.[1,3,8,9] A newer, relatively less invasive technique called POEM (per oral endoscopic myotomy) has been used for the treatment of achalasia in adults, and directly treats the diseased tissue using an oral approach. POEM is safe and equally effective in children; however, it is not yet widely employed in the management of paediatric achalasia.[1]
Conclusion
Achalasia cardia is a rare motor disorder in children, but should be kept in the differential diagnosis of patients with a history of intermittent chronic regurgitation of food and dysphagia. Alertness on the part of the paediatrician and radiologist with respect to the disease should lead to an early diagnosis and prompt, definite treatment. There are numerous treatment options available, and the choice depends mostly on willingness and compliance of the patient.
References
1. Franklin AL, Petrosyan M, Kane TD. Childhood achalasia: A comprehensive review of disease, diagnosis and therapeutic management. World J Gastrointest Endosc 2014;6(4):105-111. [http:// dx.doi.org/10.4253/wjge.v6.i4.105] 2. Singh S, Wakhlu A, Pandey A, Kureel SN, Rawat J. Retrospective analysis of paediatric achalasia in India: Single centre experience. Afr J Paediatr Surg 2012;9(2):117-121. [http://dx.doi. org/10.4103/0189-6725.99396] 3. Lee CW, Kays DW, Chen MK, Islam S. Outcomes of treatment of childhood achalasia. J Pediatr Surg 2010;45(6):1173-1177. [http://dx.doi. org/10.1016/j.jpedsurg.2010.02.086] 4. Bosher LP, Shaw A. Achalasia in siblings: Clinical and genetic aspects. Am J Dis Child 1981;135(8):709-710. 5. Monnig PJ. Familial achalasia in children. Ann Thorac Surg 1990;49(6):1019-22. 6. Mehdi NF, Weinberger MM, Abu-Hasan MN. Achalasia: Unusual cause of chronic cough in children. Cough 2008;4(6):1-5. [http://dx.doi. org/10.1186/1745-9974-4-6] 7. Francis DL, Katzka DA. Achalasia: Update on disease and its treatment. Gastroenterology 2010;139(2);369-374. [http://dx.doi.org/10.1053/j. gastro.2010.06.024] 8. Zhang Y, Xu CD, Zaouche A, Cai W. Diagnosis and management of esophageal achalasia in children: Analysis of 13 cases. World J Pediatr 2009;5(1):5659. [http://dx.doi.org/10.1007/s12519-009-0010-9] 9. Farrokhi F, Vaezi MF. Idiopathic (primary) achalasia. Orphanet J Rare Dis 2007;2(38):1-9. [http://dx.doi.org/10.1186/1750-1172-2-38]
CONFERENCE REPORT
The fifth South African Child Health Priorities Conference New directions and priorities in SA child health
The fifth South African (SA) Child Health Priorities Conference was convened by the South African Child Health Priorities Asso ciation at the University of the Free State in Bloemfontein from 3 to 5 December 2014. The conference theme was ‘Closing the Gaps – Beyond Child Survival’. A well-constructed conference programme encouraged parti cipants to move away from traditional notions focused on child survival and the absence of disease, towards reflecting on how best to promote the wellbeing, resilience and capability of the country’s children. In the course of the conference three subthemes emerged – taking stock of child survival in South Africa and enhancing local initiatives to improve this; the potential of early childhood development (ECD) activities to close existing gaps; and a long overdue appreciation of the importance of social, adolescent and mental health. The conference opening addresses from Dr Bhardwaj (from UNICEF) and Dr Matela (Free State Provincial Paediatrician), reviewed both global and local progress in child survival as the Millennium Development Goals (MDGs) 2015 endpoint nears. Despite a doubling in the rate of reduction of under-five mortality in countdown countries during 2000-2012 compared with 19902000 and a halving of child deaths since 1990, more than half of the 62 countdown countries, including SA, are unlikely to achieve their MDG child mortality targets. A decline in the under-five and infant mortality rates continues in SA, albeit at a slower pace, but the neonatal mortality rate is unchanged and fluctuates around 12 per 1 000. Dr Bhardwaj emphasised that maintaining the current momentum required ruthless prioritisation of quality delivery at scale for a small number of interventions that address the major causes of child deaths. Fortunately early drafts of the next global step, the Sustainable Development Goals (SDGs), retain the healthrelated MDGs as a subset of their proposed health-related goals. Drs Bhardwaj and Saloojee (University of the Witwatersrand) provided feedback on an independent mid-term review com missioned by the national health department of the department’s Maternal, Newborn, Child and Women’s Health and Nutrition (MNCWH&N) 2012-2016 strategic plan. The evaluation found limited progress in health system functional effectiveness, with, for example, lengthy and cumbersome procurement and human resources processes resulting in stock-outs of medicines and supplies and shortages of critical staff. Swifter decentralisation of responsi bility was identified as a key response. Some progress was noted in organisational and political effectiveness. Improved communication of key messages to staff and the public was another activity identified as requiring substantial attention. The review’s recommendations focus on the need for all health workers to know their own issues, track responses, be accountable, foster teamwork, get the basics right while actively connecting components of the health system (through activities such as facilitating effective transport and referrals). ECD, first introduced as a theme at the 2012 conference, was once again a focus at this conference. Ms Slemming (University of the Witwatersrand) reviewed the background, development and future of the ECD policy and plans for the country. She emphasised the central role of ECD in the realisation of the national development plan goal to reduce poverty and inequality
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in the country and highlighted the five priority areas of the ECD plan – family, home and centre-based support; nutrition; early learning opportunities; support for children with disabilities; and improved public communication. Cabinet was considering adopting a national ECD policy. (Update: The ECD policy was gazetted in March 2015). A presentation on how best to reduce a key ECD target – stunting in SA – emphasised that nutritionspecific interventions alone are almost certainly insufficient, and nutrition-sensitive development needs to be fostered. Current KwaZulu-Natal (KZN) initiatives supporting infant and young child feeding policy implementation were discussed by Ms Spies (KZN health department). These included extending the BabyFriendly initiative to community health centres and clinics, establishment of human breastmilk banks and the employment of lactation advisors within health centres, and support for media messaging (including social media). The third subtheme of the conference introduced participants to issues related to social, mental and adolescent health. A moving case report from Universitas Hospital highlighted the value of palliative care in the holistic care of children with malignancies. Professor Nicol and Ms Mabizela (University of the Free State) respectively, considered the predisposing factors, context and spectrum of childhood mental disorders as well as an approach to addressing these within the Free State health service. Dr Rabie (Tygerberg Hospital) used her experience in an adolescent HIV clinic to highlight the complexities, challenges and rewards of caring for adolescent patients. The role of child health screening in the SA context was debated and, despite well considered arguments from advocates of specific child screening programmes, it was evident that these cannot be justified merely because there is a problem or a suitable test available. The potential for a functional system has to be present to ensure that the benefits of screening outweigh the costs. Few screening procedures meet this criterion in the local context. A conference highlight for many was a session where adolescents with two chronic diseases – diabetes mellitus and HIV – reflected on the effect of the illness on their lives and offered frank and insightful answers to questions from the audience. On a lighter note, this was possibly the first conference where participants had to sing to retain their seats when Professor Westwood introduced the Western Cape’s approach to promoting the use of the Road to Health Book as a child’s passport to health. Conference participants boisterously sang the initiative’s pledge song to the tune of Paul McCartney’s frog song, ‘We All Stand Together’. The South African Child Health Priorities Association is a child health advocacy group, supporting interaction of child health professionals from a variety of fields (such as health, social development and law). Its goals for 2015 include establishing fora where national policy related to National Health Insurance and ECD, and their relevance to children (such as packages of care), can be discussed, followed by the formation of working groups to initiate and lead activity related to both policies. The next Child Priorities conference is scheduled for Pietermaritzburg in December 2015, with Cape Town being the likely venue in 2016. Visit the Association’s website http:// childhealthpriorities.co.za for more detail, and to view PowerPoint presentations from the 2014 conference.
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CPD April 2015 The CPD programme for SAJCH is being administered by Medical Practice Consulting: CPD questionnaires must be completed online at www.mpconsulting.co.za
True (T) or False (F): Regarding access to healthcare for patients with chronic diseases: 1. More than 50% of a cohort of children with systemic lupus erythematosus in South Africa (SA) presented with severe manifestations, such as stroke or renal failure. 2. The Gini coefficient is a measure of socioeconomic status. Regarding the hearing assessment of children between 0 and 35 months: 3. Some form of newborn screening for hearing loss occurs in the majority (>75%) of private hospitals in SA. 4. The Health Professions Council of SA (HPCSA) recommends that infant screening should be done early so that hearing loss can be confirmed by 3 months of age. Regarding sickle cell anaemia in children: 5. The homozygote rate for sickle cell anaemia is approximately 3% in Nigeria. 6. Micro-albuminuria is an early indication of glomerular dysfunc tion in subjects with sickle cell anaemia.
10. Viral load in the mother does not correlate with the risk of HIV transmission to the infant. Regarding hypoxaemia in children with pneumonia: 11. Using a pulse oximeter, hypoxaemia is usually considered to be present if the SpO2 is <85%. 12. In several studies in Nigeria, mortality among children <5â&#x20AC;&#x201A; years of age admitted to hospital is <10%. Regarding tuberous sclerosis complex: 13. Tuberous sclerosis complex is inherited as an autosomal recessive condition. 14. The two most common renal lesions are angiomyolipomata and renal cysts. Regarding vitamin B12 deficiency in an infant: 15. Infantile vitamin B12 deficiency may be secondary to a maternal vegetarian diet. 16. Infantile vitamin B12 deficiency may cause developmental regression in infants.
Regarding the use of nasal CPAP in neonates: 7. Nasal continuous positive airway pressure (NCPAP) reduces the functional residual capacity and tidal volume of treated premature neonates. 8. NCPAP reduces the need for surfactant in preterm infants with hyaline membrane disease.
Regarding Trisomy 13 17. Trisomy 13 is associated with choanal atresia, macrocephaly and syndactyly. 18. Trisomy 13 may be diagnosed by a polymerase chain reaction (PCR) aneuploidy screen.
Regarding mother-to-child transmission of HIV: 9. With appropriate PMTCT programmes in place, as in developed countries, transmission rates to infants are <2%.
Regarding podophyllin poisoning: 19. Podophyllin toxicity may cause thrombocytopenia and leucopenia. 20. Peripheral neuropathies may develop days after ingestion.
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: MDB015/165/02/2015(Clinical)
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APRIL 2015 Vol. 9 No. 2