SAJCH Vol 10, No 4 (2016)

CHILD HEALTH THE SOUTH AFRICAN JOURNAL OF

December 2016

Volume 10

No. 4

• The outcome of CPAP use in VLBW neonates • The reasons for upper GIT endoscopy in a Nigerian hospital • Is acute diarrhoeal disease being appropriately managed?

• An audit of medical admissions to a paediatric ICU • Omphalocoele presentation over the past decade • The management of persistent pulmonary hypertension of the newborn

CHILD HEALTH THE SOUTH AFRICAN JOURNAL OF

DECEMBER 2016

Volume 10

No. 4

CONTENTS Editorial

192 Early hearing screening in South Africa – time to get real about context

A Kanji

Letter

FOUNDING EDITOR N P Khumalo EDITORIAL BOARD Prof. M Adhikari (University of KwaZuluNatal, Durban) Prof. M Kruger (Stellenbosch University) Prof. H Rode (Red Cross War Memorial Children's Hospital, Cape Town) Prof. L Spitz (Emeritus Nuffield Professor of Paediatric Surgery, London) Prof. A Venter (University of the Free State, Bloemfontein) Dr T Westwood (Red Cross War Memorial Children's Hospital, Cape Town) Prof. D F Wittenberg (University of Pretoria) HEALTH & MEDICAL PUBLISHING GROUP:

193 Hypothyroidism and hip pain

EDITOR J M Pettifor

CEO AND PUBLISHER Hannah Kikaya

S Kumar

Review

EXECUTIVE EDITOR Bridget Farham

MANAGING EDITORS Ingrid Nye Claudia Naidu

194 The management of persistent pulmonary hypertension of the newborn: A review L G Lloyd, J Smith

Research

199 Outcome of very-low-birth-weight babies managed with nasal continuous positive airway pressure, with or without surfactant, in a high-care nursery

T Bopape-Chinyanga, R Thomas, S Velaphi

PRODUCTION MANAGER Emma Jane Couzens

207 Upper gastrointestinal endoscopy in children: The Lagos University Teaching Hospital experience

O F Adeniyi, O A Lesi, E A Odeghe, O Adekola, O A Oduwole

215 Management of acute diarrhoeal disease at Edendale Hospital: Are standard treatment guidelines followed?

K Reddy, M E Patrick, C R Stephen

R K Mopeli, D E Ballot, D A White

227 Mothers’ perception of neonatal jaundice in Lagos, Nigeria: An urgent need for greater awareness

V C Ezeaka, E N Ekure, I B Fajolu, B N Ezenwa, P E Akintan

Case Reports

231 Fatal Lemierre’s syndrome as a complication of chronic otitis media with cholesteatoma

M Roos, T Harris, R Seedat

233 Intracardiac and intracerebral thrombosis associated with methylenetetrahydrofolate reductase A1298C homozygote mutation in paediatric steroid-resistant nephrotic syndrome

R Renda, Ö Aydoğ, M Bülbül, E K Çakıcı

237 Rosai-Dorfman disease in a 12-year-old Nigerian male

J C Elo-Ilo, K K Odinaka, C O Ukah

239

CPD Questions ublished by the Health and Medical Publishing Group, P Suite 11, Lonsdale Building, Lonsdale Way Pinelands 7405 apers for publication should be addressed to the Editor, P via the website: www.sajch.org.za Tel: 072 635 9825 E-mail: publishing@hmpg.co.za

Cover: Palesa, Red Cross War Memorial Children's Hospital Primary School

ONLINE SUPPORT Gertrude Fani | Tel. 072 463 2159 Email: publishing@hmpg.co.za FINANCE Tshepiso Mokoena

221 An audit of primary medical conditions in children admitted to the paediatric intensive care unit of Charlotte Maxeke Johannesburg Academic Hospital

DTP AND DESIGN Travis Arendse Clinton Griffon CHIEF OPERATING OFFICER Diane Smith | Tel. 012 481 2069 Email: dianes@hmpg.co.za

211 Omphalocoeles: A decade in review

S Singh, A Madaree

TECHNICAL EDITORS Emma Buchanan Paula van der Bijl

©Copyright: Health and Medical Publishing Group (Pty) Ltd

HMPG BOARD OF DIRECTORS Prof. M Lukhele (Chair), Dr M R Abbas, Dr M J Grootboom, Mrs H Kikaya, Prof. E L Mazwai, Dr M Mbokota, Dr G Wolvaardt HEAD OFFICE Block F, Castle Walk Corporate Park, Nossob Street, Erasmuskloof Ext. 3, Pretoria, 0181 EDITORIAL OFFICE Suite 11, Lonsdale Building, Lonsdale Way, Pinelands, 7405 Tel. 021 532 1281 | Cell. 072 635 9825 Email: publishing@hmpg.co.za ISSN 1999-7671

Use of editorial material is subject to the Creative Commons Attribution – Noncommercial Works Licence. http://creativecommons.org/licenses/by-nc/4.0

EDITORIAL

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

Early hearing screening in South Africa – time to get real about context Review of published literature related to early hearing detection and intervention (EHDI) services in South Africa (SA) between 1995 and 2014 has highlighted progress in terms of the journey toward implementation of paediatric hearing screening services.[1] However, in contrast to developed contexts, there are very few outcome studies from developing countries such as SA that support the efficacy of EHDI. This dearth of evidence from developing countries may be due to the lack of integrated, national EHDI programmes.

The Health Professions Council of South Africa (HPCSA)[2] position statement guidelines and principles for EHDI are primarily based on guidelines from developed contexts with slight contextual adaptations in terms of the time frames for screening and diagnosis. While these guidelines are geared toward universal newborn hearing screening (UNHS) and serve as the gold standard that audiologists in SA should constantly aim towards achieving, they may not necessarily be currently applicable within all healthcare sectors within the SA context. Research and conceptual papers related to EHDI in SA have fortunately acknowledged the impracticalities in attempting to implement developed world models of newborn hearing screening (NHS) in developing countries, where context is evidently different.[1] The current status of NHS[3] coupled with manpower-related challenges may possibly suggest that UNHS is currently not applicable in the SA context, particularly in the public healthcare sector, where over 80% of the population receives healthcare. The manpower demand related to a higher prevalence rate of infant hearing loss in the public healthcare sector in SA is not met, as the majority of registered audiologists work in the private healthcare sector. Moreover, there is currently no established mid-level worker programme in audiology to facilitate hearing screening by personnel other than audiologists.

There is, therefore, an evident shortage of manpower in the public sector, which may influence the ability of audiologists in SA to effectively implement UNHS. However, it is important that an interim approach to early detection of hearing loss be established as a means of potentially identifying newborns and infants with hearing loss, who would ordinarily be missed in the absence of an NHS programme.

The implementation of risk-based or targeted newborn hearing screening (TNHS) programmes, which involve screening of newborns with known risk factors for hearing loss, would be a more feasible interim approach to adopt in order to identify children with hearing loss early. In SA, TNHS has not been formally and systematically implemented as the intermediate, small step towards a larger UNHS programme. Effective implementation of a TNHS is dependent on a number of aspects, such as: the choice of screening measures, and how these measures are to be employed within a screening protocol; the existence of established risk factors for hearing loss; and the various levels of service delivery or contexts within the SA healthcare system.

High-risk factors for hearing loss stipulated by the HPCSA have been based on position statements from developed contexts, and have been faintly adapted to include two conditions that are considered unique to the SA context.[2] While research findings from developed contexts may be of value, findings from these higher-income countries may be costly and more difficult to implement into practice in lowerincome countries as they may be culturally inappropriate and often focus on non-communicable diseases prevalent in developed contexts.

There is therefore a tendency to neglect the specific, local needs of lower-income or developing countries.[4] Hence, contextual research is imperative in guiding clinical and contextually relevant practice. Risk factors for permanent congenital and early-onset hearing loss may also vary across communities and may be influenced by considerable 192

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variation of situations, burden of disease and time periods in different countries.[5] Context-specific risk factors are particularly relevant to ensure appropriate identification of hearing loss in high-risk neonates.

Much ongoing research is therefore needed into the review of highrisk factors for hearing loss within the SA context. Instead of using existing, international high-risk registries for TNHS in SA, it may be more beneficial to screen all neonates with a prolonged hospital stay, whether in neonatal intensive care unit, high care or kangaroo mother care. This will allow for a greater coverage rate and lessen the chances of missed cases in this population. Findings from implemented TNHS programmes could also be used retrospectively to conduct research and consistently update the list of risk indicators associated with hearing impairment.

A variety of healthcare contexts need to be explored as possible platforms for the establishment and provision of NHS services, particularly TNHS as the intermediate approach. This is particularly important as the choice of context may influence coverage rates and follow-up return rates, which are two of the key determinants to effective and successful NHS programmes. Primary healthcare clinics in SA have been proposed as one of the platforms for conducting NHS in order to ensure optimal coverage and follow-up return rate, and this is being piloted in the Western Cape. This was based on statistics in 2002 that indicated a significant number of home births[2] and well babies being discharged soon after birth, making it difficult to co-ordinate screening. However, the number of home births has since decreased, with statistics indicating that 94.1% of live births occur at a health facility.[6] Hence, more initiatives are required at secondary and tertiary levels of service delivery, particularly in highrisk neonates who may have a prolonged hospital stay and scheduled follow-up appointments with paediatricians at these facilities.

The author is of the view that a two-tiered approach may be appropriate, involving early hearing screening of high-risk babies in the hospital setting, with screening of well babies at clinic level. This would address the earlier discharge of well babies, which would result in missed cases in the hospital setting. It would also address follow-up and monitoring of high-risk infants who undergo regular follow-up at specialist clinics within a hospital setting. Audiologists need to play an active role in the piloting, planning, implementation and management of TNHS programmes within the SA public healthcare context.

Amisha Kanji

Department of Speech Pathology and Audiology, School of Human and Community Development, University of the Witwatersrand, Johannesburg, South Africa amisha.kanji@wits.ac.za 1. Moodley S, Storbeck C. Narrative review of EHDI in South Africa. S Afr J Commun Disord 2015;62(1):1-10. http://dx.doi.org/10.4102/sajcd.v62i1.126 2. Health Professions Council of South Africa. Early Hearing Detection and Intervention Programmes in South Africa, Position Statement, Year 2007. http://www.hpcsa.co.za/Uploads/editor/UserFiles/downloads/speech/early_ hearing_detection_statement.pdf (accessed 10 March 2016).

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):S23-29. http://dx.doi.org/10.1080/14992020802294032 4. Chetwood JD, Ladep NG, Taylor-Robinson SD. Research partnerships between high and low-income countries: Are international partnerships always a good thing? BMC Med Ethics 2015;16:36-40. http://dx.doi.org/10.1186/s12910-015-0030-z 5. Olusanya BO, Luxon LM, Wirz SL. Benefits and challenges of newborn hearing screening for developing countries. Int J Pediatr Otorhinolaryngol 2004;68(3):287-305. http://dx.doi.org/10.1016/j.ijporl.2003.10.015 6. South African Government Information. Maternal and Women’s Health. 2011. http://www.info.gov.za/aboutsa/health.htm (accessed 19 July 2011).

DECEMBER 2016 Vol. 10 No. 4

LETTER

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

Hypothyroidism and hip pain To the Editor: Slipped capital femoral epiphysis (SCFE) is the most common hip disorder affecting adolescents and has multifactorial aetiology.[1] Hypothyroidism may present as SCFE.[2] We introduce a patient with such a presentation to highlight the association.

A 14-year-old female child visited our outpatient department with a presenting complaint of left-sided hip pain for the last 6 months, after a trivial trauma, associated with restriction of mobility.

She had history of developmental delay and mental retardation.

She was the product of non-consanguineous marriage with no significant antenatal/perinatal events and a negative family history for hypothyroidism. She had attained menarche 6 months prior to admission. She did not have goiter, polydactyly, facial dysmorphism or opthalamological issues. Her weight was 65 kg and height 142 cm, with a z-score of 1.2 and –2.8 for her age, respectively. Her body mass index was 32 kg/m2. Sonography of the thyroid gland showed normal anatomy. Her liver function tests, renal function tests and abdominal ultrasonography were normal. She had a thyroid-stimulating hormone (TSH) level of ~600 µIU/mL. Her serum follicular-stimulating hormone, luteinising hormone, and prolactin and cortisol levels were within normal limits. Her magnetic

resonance imaging (MRI) brain scan was normal. Hip X-ray of the left side showed SCFE (Fig. 1).

She was started on Eltroxin; her hip pain settled and there was an improvement in mobility. Further orthopaedic management of the SCFE is being sought.

SCFE is characterised by displacement of the capital femoral epiphysis from the metaphysis through the physis. In a study of association of endocrinal disorders with SCFE, hypothyroidism was found in 40% of all the cases studied.[3] A high serum TSH level causes abnormal skeletal development in hypothyroidism via its suppressive effects on the growth plate.[4] The delay in diagnosis – as in our case – severely affected the skeleton and mental development.[5] Through this letter, we highlight the importance of early diagnosis of hypothyroidism and the need for a high index of suspicion in obese children with hip pain.

Santosh Kumar

Senior resident, Department of Pediatrics, Mata Gujri Memorial Medical College and Lions Seva Kendra Hospital, Kishanganj,Bihar, India santoshaiims08@gmail.com

Jasninder Singh

MD student (Pediatrics), Mata Gujri Memorial Medical College and Lions Seva Kendra Hospital, Kishanganj,Bihar, India 1. Gholve PA, Cameron DB, Millis MB. Slipped capital femoral epiphysis update. Curr Opin Pediatr 2009;21(1):39-45. http://dx.doi.org/10.1097/ MOP.0b013e328320acea 2. Heyerman W, Weiner D. Slipped epiphysis associated with hypothyroidism. J Pediatr Orthop 1984;4(5):569-573.

3. Loder RT, Wittenberg B, DeSilva G. Slipped capital femoral epiphysis associated with endocrine disorder. J Pediatr Orthop 1995;15(3):349-356.

4. Endo T, Kobayashi T. Excess TSH causes abnormal skeletal development in young mice with hypothyroidism via suppressive effects on the growth plate. Am J Physiol Endocrinol Metab 2013;305(5):E660-E666. http://dx.doi. org/10.1152/ajpendo.00067.2013 5. Schoenmakers N, Moran C, Peeters RP, Visser T, Gurnell M, Chatterjee K. Resistance to thyroid hormone mediated by defective thyroid hormone receptor alpha. Biochim Biophys Acta 2013;1830(7):4004-4008. http://dx.doi. org/10.1016/j.bbagen.2013.03.018

Fig. 1. Left-sided SCFE.

S Afr J Child Health 2016;10(4):193. DOI:10.7196/SAJCH.2016.v10i4.1221

193

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DECEMBER 2016 Vol. 10 No. 4

REVIEW

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

The management of persistent pulmonary hypertension of the newborn: A review L G Lloyd, MB ChB, DCH (SA), FC Paed (SA), MMed (Paed), Cert Neonatology (SA); J Smith, MB ChB, MMed, FC Paed (SA), PhD (Paed) Division of Neonatology, Department of Paediatrics and Child Health, Stellenbosch University and Tygerberg Children’s Hospital, Cape Town, South Africa Corresponding author: L G Lloyd (lgl@sun.ac.za) Persistent pulmonary hypertension of the newborn is a neonatal emergency with a high mortality rate in spite of several advances in the management thereof. The underlying pathophysiology is complex and multifactorial. The gold standard of treatment is inhaled nitric oxide, yet up to a third of patients will not respond to standard treatment. This article reviews treatment modalities available, as well as the evidence to support the use of these treatment options.

S Afr J Child Health 2016;10(4):194-198. DOI:10.7196/SAJCH.2016.v10i4.1145

The first literary reference to persistent pulmonary hypertension (PH) of the newborn (PPHN) can be found in 1969 by Gersony et al.,[1,2] who described it as persistence of physiologic characteristics of the fetal circulation in the absence of disease. Defined as a failure of normal circulatory transition at birth, or more specifically as failure of the pulmonary vasculature to relax after birth, with continued shunting of non-oxygenated blood into the systemic circulation via fetal channels (ductus arteriosus and foramen ovale), it remains a challenging neonatal emergency to manage.[3-6] Term and nearterm infants are most commonly affected, but PPHN can occur in premature infants.[4] The incidence of PPHN in developed countries has been estimated as 1.9 per 1 000 live births; however, the incidence is likely to be higher in developing countries.[2,3,5,7] PPHN constitutes ~10% of neonatal intensive care unit (NICU) admissions, with the reported mortality rate ranging from 10 to 20%.[4,5,8-10]

systemic vascular resistance with the removal of the low-resistance placenta after umbilical cord clamping.[3,10] The first breath fills the lungs with air, causing an eight-fold increase in pulmonary blood flow. The resulting shear stress and oxygenation up-regulates the expression of endothelial NO synthase (eNOS).[3,4,6] Endothelial NO synthesised from l-arginine activates soluble guanylyl cyclase (sGC), converting cyclic guanosine triphosphate (cGTP) to cyclic guanosine monophosphate (cGMP), which facilitates smooth muscle relaxation.[4-6] Oxygenation also inhibits phosphodiesterase-5 (PDE5), increasing the availability of cGMP.[4] The production of prostaglandin endoperoxides from arachadonic acid in the endothelium, specifically PGI2, stimulates adenylyl cyclase to convert adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP), which also facilitates pulmonary vaso­ dilatation.[4,6] Phosphodiesterase-3 (PDE3) increases the availability of cAMP. Prostaglandins decrease PVR less than does NO.[4]

Physiology

Aetiology and pathophysiology

The normal physiological state of a fetus is best described as hypoxaemic, with PH and reduced pulmonary blood flow, and with the placenta responsible for gas and nutrient exchange.[3,4,6,10] It is important to understand that the fetus is not hypoxic, as adequate oxygen delivery to the tissues is maintained and facilitated by a high cardiac output and high fetal haemoglobin levels with increased oxygen affinity.[3] Factors involved in maintaining an increased pulmonary vascular resistance (PVR) in utero include fluid-filled lungs, decreased nitric oxide (NO) and prostacyclin (PGI2), and increased endothelin-1 (ET-1).[4] Products of the prostaglandin pathway, such as thromboxane and leukotriene, also play a role. Serotonin increases fetal PVR, which brings into question the safety of using selective serotonin reuptake inhibitors (SSRIs) during pregnancy.[3,4,6,11]

Fetal circulation

The systemic and pulmonary circulations of the fetus function in parallel, where both ventricles essentially eject blood into the aorta and use the foramen ovale and ductus arteriosus to bypass the pulmonary circulation. Only 13 - 25% of blood ejected will reach pulmonary circulation.[3,4,6,11]

Transition to extrauterine life

The normal transition from ‘parallel’ to ‘series’ circulation starts with a rapid decrease in PVR with the first breath, and an increase in 194

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When there is failure of the normal transition to extra-uterine life, with the persistence of increased PVR, PPHN occurs. Hypoxia, acidosis and hypercarbia cause vasoconstriction, and play an important role in the underlying pathogenesis.[10] The causes of PPHN can be classified into four groups: underdevelopment, maldevelopment, maladaptation and intrinsic obstruction (Table 1).[3,4,6] Meconium aspiration syndrome (MAS) is the most common cause of PPHN.[4,6] Meconium-stained liquor occurs in 5 - 24% of normal pregnancies, and of these 5% will develop MAS. Meconium causes airway obstruction, inactivation of surfactant and chemical pneumonitis, owing to the release of proinflammatory cytokines. The resultant decreased ventilation/perfusion ratio, with hypoxaemia and hypercarbia, may lead to PPHN.[3] Idiopathic or ‘black-lung’ PPHN occurs in 20 - 25% of cases, with ‘black lung’ referring to the paucity of pulmonary vascularity.[3,4,6,8] There is an absence of parenchymal lung disease, as the underlying problem is vascular smooth muscle hyperplasia of the normally muscle-free arteries. A questionable association with antenatal use of non-steroidal anti-inflammatory drugs and SSRIs exists.[12] Congenital diaphragmatic hernia is associated with lung hypoplasia and the decreased cross-sectional area of the pulmonary vascular bed. Lung damage is often exacerbated by volutrauma, hyperoxia and mechanical ventilation.[6]

DECEMBER 2016 Vol. 10 No. 4

REVIEW Table 1. Pathophysiology of PPHN[3,4,6] Underdevelopment

Maldevelopment

Maladaptation

Intrinsic obstruction

Pathology

Decreased vascular growth Abnormal vascular structure Normal vasculature with High viscosity resulting in hypoxia induced vasospasm intravascular obstruction of pulmonary arteries

Examples

Pulmonary hypoplasia: • CDH • Oligohydramnios • Renal agenesis • Rare causes, e.g. alveolar capillary dysplasia

Idiopathic/ primary PPHN Chronic fetal hypoxia Fetal anaemia Premature closure of ductus arteriosus

Asphyxia Parenchymal diseases: • MAS • RDS • Sepsis/pneumonia

Polycythaemia, e.g. IDM

CDH = congenital diaphragmatic hernia; MAS = meconium aspiration syndrome; RDS = respiratory distress syndrome; IDM = infant of a diabetic mother.

Table 2. Risk factors for the development of PPHN[4-6]

Table 4. Diagnosis of PPHN

Maternal factors African or Asian maternal race Preconceptual maternal obesity (BMI >27) Maternal chronic diseases, e.g. diabetes, asthma Use of SSRIs, e.g. fluoxetine, after 20 weeks’ gestation Maternal use of nicotine Chorioamnionitis, e.g. ureaplasma Birth-related factors Caesarean section Meconium-stained liquor and meconium aspiration syndrome Perinatal acidosis and asphyxia Patient-related factors Male Late preterm Large for gestational age Infection, especially group B Streptococcus Hypothermia Hypocalcaemia Polycythaemia

Pre- and postDifferential ductal saturation cyanosis[3,5,6,10]

BMI = body mass index; SSRI = seletive serotonin uptake inhibitors.

Exclude underlying cardiac abnormalities

To assist therapeutic decisionmaking

TR jet velocity

To calculate RV pressure with modified Bernoulli equation

Direction of ductal shunting

Identify right-to-left shunting

Alignment of the interventricular Rough indication of pulmonary septum blood pressure Rounded: PAP <50% of systemic pressure Flattened: PAP is 50 - 100% of systemic pressure Bows into the left ventricle: PAP exceeds systemic pressure TR = tricuspid regurgitation; RV= right ventricle; PAP = pulmonary artery pressure.

PH can occur in premature infants, with one-third of patients with bronchopulmonary dysplasia (BPD) having an underlying diagnosis of PH. The combination of BPD and PH is associated with a poor outcome.[3,6,8] Congenital cardiac disease, such as total anomalous pulmonary venous return and hypoplastic left heart syndrome, may also present with PPHN.[4] SAJCH

Labile hypoxaemia[3]

Marked change in oxygen saturation with minimal or no changes in ventilator settings

Disproportionate hypoxaemia[3,6]

Hypoxaemia not correlating with the amount of parenchymal disease seen on CXR

CXR[4,10]

Identify underlying parenchymal disease

Complete blood count[4]

Diagnose infection and/or polycythaemia

Serum glucose and calcium[4]

Underlying metabolic causes

BNP[3-6]

Correlates with TR jet Monitor response to treatment Not routinely used

CXR = chest X-ray; BNP = brain natriuretic peptide.

Table 3. Echocardiographic diagnosis of PPHN[3-5,9,10]

195

Pre-ductal saturation 5 - 10% higher than post-ductal

Risk factors

Several risk factors have been identified, including an unfavourable perinatal fetal environment which, in combination with certain epigenetic factors, may play a role in the expression of genes involved in the regulation of perinatal pulmonary circulation (Table 2).[2]

Diagnosis

PPHN presents in the first 24 hours of life. The classic clinical presentation includes respiratory distress, cyanosis, hypoxaemia and acidosis.[5] The echocardiogram is the gold standard for the diagnosis of PPHN (Table 3).[3-5,9] Although the echocardiogram is the gold standard for the diagnosis of PPHN, it is often not available in resource-limited settings, therefore other special investigations are of critical importance (Table 4).[13] The traditional comprehensive structural and functional echocardiogram performed by cardiologists can be supplemented by training neonatologists to perform a targeted neonatal echocardiogram (TnEcho) to expedite diagnosis of PPHN and to monitor the response to therapy.[14]

Severity of PPHN

The severity of PPHN can be calculated using the oxygenation index (Table 5).[3]

DECEMBER 2016 Vol. 10 No. 4

REVIEW Table 5. Classification of PPHN severity[3] Severity

OI*†

Mild

≤15

Moderate

>15 - 25

Severe

25 - 40

Very severe

>40

OI = oxygenation index; MAP = mean airway pressure in cmH2O; FiO2 = fraction of inspired oxygen; PaO2 = partial pressure of oxygen in mmHg; OSI = oxygenation saturation index. *OI = MAP × FiO2 × 100/PaO2. † OI = OSI × 2; OSI = MAP × FiO2 × 100/pre-ductal saturation (no intravenous access required).

Table 6. Recommendations for use of iNO[3,4,6] Starting dose

20 ppm

Consider FiO2 <60% weaning when PaO2 >60 mmHg (>8 kPa) Preductal saturation >90% Above maintained for >60 minutes Weaning procedure

Wean by 5 ppm every 2 - 4 hours till 5 ppm is reached Then wean by 1 ppm every 2 - 4 hours

Contraindications

Hypoplastic left heart Interrupted aortic arch

but does not reduce the duration of ventilation, length of the hospital stay or incidence of complications.[4,5] Prior to giving the surfactant, adequate recruitment of lung volume should be prioritised. [4,5] The greatest benefit was seen when administered at an OI of 15 - 25.[3,6] Dosages of 50 – 200 mg/kg may be used up to four times in the first 24 hours.[16] The use of a surfactant in CDH is not recommended, unless there is clear evidence of surfactant deficiency, and then only 50% of the dose should be given because of the underlying pulmonary hypoplasia.[3]

Management of systemic hypotension

Systemic hypotension should be managed with fluids, vasopressors and inotropes. The optimal blood pressure (BP) has not been determined in a randomised controlled trial (RCT), and should therefore be maintained at the normal value for the gestational age.[5,6] Supraphysiologic BP ought to be avoided, as it may add to ventricular strain and increase endothelial dysfunction by increasing shear stress in the constricted pulmonary circuit.[3] Inotropic support should be considered early, as decreased systemic BP exacerbates right-to-left shunting and worsens hypox­ aemia.[3,10] Dopamine is commonly used, but at doses >10 µg/kg/ min it is not selective to systemic vasculature and may increase the PVR.[17] Dobutamine increases cardiac output and has limited effects on systemic pressure.[17] Norepinephrine is effective in improving oxygenation and improving systemic BP, and in newborn lambs was associated with improved postnatal adaptation and significantly decreased oxygen requirement.[17] Vasopressin and hydrocortisone may also be considered.[17]

Pulmonary vasodilators

ppm = parts per million.

Inhaled NO

Management

General management

The first-line management includes ventilation, oxygenation, maintaining systemic blood pressure and maintaining homeostasis.[10] Stabilisation, establishing venous access and treating the underlying cause are critically important.

Supportive care

Hypothermia, acidosis, polycythaemia, hypoglycaemia, hypocalcaemia and hypomagnesaemia should be corrected appro-priately.[3,10] Correction of acidosis with controlled alkalosis using an alkali infusion and hyperventilation is no longer advocated due to the association with sensorineural hearing loss and impaired cerebral perfusion.[3,10] Minimal handling and judicious sedation is advised to avoid labile hypoxaemia. Antimicrobial therapy should be initiated if underlying infection is suspected.[6]

Mechanical ventilation and oxygenation

Oxygen is a pulmonary vasodilator; however, hyperoxia and ventilation with 100% oxygen has been associated with a reduced response to NO in experimental lamb models.[3,4] The aim of mechanical ventilation should be to maintain a PaCO2 of 40 - 60 mmHg (5.3 – 8.0 kPa) and PaO2 of 60 – 90 mmHg (8 - 12 kPa) by using gentle ventilation to optimise lung volume.[4,5] High-frequency oscillatory ventilation (HFOV) can minimise lung injury, but has not been proven to have a clear benefit over conventional ventilation, except when used in combination with inhaled NO (iNO) in the treatment of MAS.[4,5,15] HFOV is recommended if peak inspiratory pressures (PIP) of >28 cmH2O or tidal volumes > 6 mL/kg are required to maintain PaCO2 <60 mmHg (<8 kPa).[3]

Surfactant

In patients with MAS or pneumonia, surfactant may reduce the need for extracorporeal membrane oxygenation (ECMO), 196

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iNO is a potent and selective pulmonary vasodilator that leads to improved oxygenation and reduced need for ECMO by stimulating sGC activity to increase cGMP, a second messenger in the vasodilation pathway.[4,8,15] The use of iNO was FDA approved in 1999 for term and near-term infants with PPHN, especially when the OI is greater than 25.[3,6] The Neonatal Inhaled Nitric Oxide Study (NINOS) determined that the most effective starting dose of iNO is 20 ppm, and response should be seen within 30 - 60 minutes with an increase in PaO2 of 53 mmHg (8.6 kPa) or a decrease in OI of 15.[4,5,18,19] The use of iNO has significantly reduced the mortality of PPHN; however, ~40% of patients will not respond to iNO.[2,6,10] Failure to respond to 20 ppm is rarely followed by a response at a higher dosage.[8,18] The American Academy of Pediatrics (AAP) recommends the use of ECMO in non-responders.[20] Methaemoglobinaemia and increased nitrogen dioxide are known side-effects that occur more frequently at dosages greater than 20 ppm.[3,4] In patients with CDH, iNO can be attempted early with optimal ventilation and recruitment, but should be discontinued if no improvements are seen.[21] iNO requires gradual weaning to avoid rebound PH (Table 6). The rebound phenomenon may appear even in patients who did not show any improvement on iNO initially.

In patients with PPHN refractory to iNO, ensure adequate lung recruitment, repeat echocardiogram and consider alternative treatments.[2]

Sildenafil

Sildenafil is a PDE5 inhibitor, which results in increased availability of cGMP, and subsequent selective reduction in PVR.[3-5,8,22] Increased PDE5 activity was documented in animal models with PPHN.[2] Enteral sildenafil, dose range 1 - 3 mg/kg every 6 hours, reduced mortality in resource-limited settings where iNO is not available and reduced rebound PH after the withdrawal of iNO.[4-6,13,22-24] A Cochrane review recommended this as a significant alternative for PPHN treatment when iNO is not available.[25]

DECEMBER 2016 Vol. 10 No. 4

REVIEW Outcome

Table 7. Alternative drug treatments for PPHN Drug

Effects/mechanism of action

Evidence/recommendation

Inhaled PGI2, e.g. iloprost, treprostinil[4,6,8,23,29]

Activates adenylyl cyclase Increases cAMP

Cannot be recommended for routine use

Magnesium sulphate[4,5,30]

Reduce PAP Systemic hypotension

Observational data only More studies recommended

Bosentan[3-5,23]

Non-selective endothelin receptor antagonist

Efficacy in RCT where iNO not available

Sitaxentan[4] Ambrisentan[4]

Selective ETA receptor antagonists

More studies needed

Thromboxane synthase inhibitor 34% reduction in PVR

Animal studies only

eNOS agonist

Case series only

Improved pulmonary artery relaxation Reduced oxidative stress

Animal studies

[5]

Furegulate sodium

Adenosine[2,5] [3,6]

Antenatal betamethasone

Postnatal systemic steroids[3,6,23] Reduced hospital stay and oxygen dependence in MAS

Not routinely recommended More research needed, especially in limited-resource settings

Postnatal hydrocortisone[3,6,23] Improved oxygenation Increased cGMP Reduced ROS Increased SOD

Animal studies Case reports*

Recombinant human SOD[6]

Animal studies only

[31]

Apocynin

-

NADPH oxidase inhibitor Animal studies only Improved oxygenation Reduced vascular dysfunction

PAP = pulmonary artery pressure; ETA = endothelin-A; ROS = reactive oxygen species; SOD = superoxide dismutase; NADPH = nicotinamide adenine dinucleotide phosphate. *Case reports of improved oxygenation when stress doses used for systemic hypotension.

In the treatment of PH secondary to BPD, sildenafil at doses of 0.5 mg/kg every 8 hours to 2 mg/kg every 6 hours is considered safe and effective, and contributes to improved survival at 12 months.[23,26]

Milrinone

Milrinone is a PDE3 inhibitor that leads to increased availability of cAMP, with resultant positive inotropic effects, peripheral vasodilatation, left ventricular afterload reduction and increased myocardial contract­ ility.[3,5,8,23] There are case reports of improved oxygenation in cases of PPHN refractory to iNO,[3,23] but there are also reports of an increased incidence of intracranial hae­ morrhages.[27] Safety and efficacy is unknown, and therefore it is recommended for use only within randomised controlled trials (RCTs).[28]

Other drug therapies

Other promising treatment modalities in­ clude PGI2, magnesium sulphate, bosentan, adenosine, steroids and apocynin, but there is insufficient evidence to recommend any for routine or combination use (Table 7).

197

Extracorporeal membrane oxygenation

Although ECMO is viewed as the ultimate rescue therapy in developed countries, it is not freely available in lowresource countries, therefore rendering its usefulness in developing countries questionable.[3,6]

Special categories

Special consideration should be given when treating a patient with PPHN and perinatal asphyxia, as the treatment of PPHN may affect cerebral blood flow.[3,32] Inhaled NO does not significantly alter neurodevelopmental outcome.[3,32] The effects of moderate therapeutic hypothermia at 33.5oC for 72 hours does not result in a significant increase in PPHN.[3] There are case reports that preceding hypoxia requiring FiO2 >50% and/or iNO may be associated with exacerbation of PPHN with hypothermia and/or rewarming.[3] Fluid boluses are not recommended in these patients, unless there is hypovolaemia, as it may increase cerebral oedema.[3,32] SAJCH

The long-term neurological outcome is largely determined by the underlying condition. Neurodevelopmental impairment has been reported in up to 25% at 2 years of age and hearing impairment in 23%.[3,5] At school age, there were 24% persistent respiratory problems, 60% abnormal chest X-rays, 6% sensorineural hearing loss, 9% IQ <90, and 7% IQ 70 - 84.[3] These infants require long-term multidisciplinary follow-up.

Conclusion

PPHN is an acute neonatal disorder with complex underlying pathophysiology, which has a high mortality rate despite several advances in the management thereof.

Inhaled NO is a safe and effective clinical strategy in the majority of patients, but is not always available in resource-limited settings.

Oral sildenafil is a relatively safe alternative option in these settings. Newer drugs need to be studied before any recommendations can be made for routine use.

References

1. Gersony WM, Duc GV, Sinclair JC. “PFC” syndrome (persistence of fetal circulation).

Circulation 1969;40(suppl 1):3-87.

2. Distefano G, Sciacca P. Molecular physiopathogenetic mechanisms and development of new potential therapeutic strategies in persistent pulmonary hypertension of the newborn. Ital J Pediatr 2015;41(1):6. http:// dx.doi.org/10.1186/s13052-015-0111-0 3. Sharma V, Berkelhamer S, Lakshminrusimha S. Persistent pulmonary hypertension of the newborn. Matern Health Neonatol Perinatol 2015;1:14. http://dx.doi.org/10.1186/s40748-0150015-4 4. Puthiyachirakkal M, Mhanna MJ. Pathophysiology, management, and outcome of persistent pulmonary hypertension of the newborn: A clinical review. Front Pediatr 2013;1:23. http:// dx.doi.org/10.3389/fped.2013.00023 5. Bendapudi P, Rao GG, Greenough A. Diagnosis and management of persistent pulmonary hypertension of the newborn. Paediatr Respir Rev 2015;16(3):157-161. http://dx.doi.org/10.1016/j. prrv.2015.02.001 6. Nair J, Lakshminrusimha S. Update on PPHN: Mechanisms and treatment. Semin Perinatol 2014;38(2):78-91. http://dx.doi.org/10.1053/j. semperi.2013.11.004 7. Jain A, McNamara PJ. Persistent pulmonary hypertension of the newborn: Advances in diagnosis and treatment. Semin Fetal Neonatal Med 2015:20(4):262-271. http://dx.doi. org/10.1016/j.siny.2015.03.001 8. Porta NFM, Steinhorn RH. Pulmonary vasodilator therapy in the NICU: Inhaled nitric oxide, sildenafil, and other pulmonary vasodilating agents. Clin Perinatol 2012;39(1):149-164. http:// dx.doi.org/10.1016/j.clp.2011.12.006 9. Aggarwal S, Natarajan G. Echocardiographic correlates of persistent pulmonary hypertension of the newborn. Early Hum Dev 2015;91(4):285-289. http://dx.doi.org/10.1016/j. earlhumdev.2015.02.008 10. Bendapudi P, Barr S. Diagnosis and management of pulmonary hypertension of the newborn.

Paediatr Child Health 2014;24(1):12-16. http:// dx.doi.org/10.1016/j.paed.2013.05.021 11. Hillman NH, Kallapur SG, Jobe AH. Physiology of transition from intrauterine to extrauterine life.

Clin Perinatol 2012;39(4):769-783. http://dx.doi. org/10.1016/j.clp.2012.09.009

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REVIEW 12. Huybrechts KF, Bateman BT, Palmsten K, et al. Antidepressant use late in pregnancy and risk of persistent pulmonary hypertension of the newborn. JAMA 2015;313(21):2142-2151. http://dx.doi.org/10.1097/01.ogx.0000472158.66771.3e 13. Engelbrecht AL. Sildenafil in the management of neonates with PPHN: A rural regional hospital experience. S Afr J Child Health 2008;2(4):166-169.

14. El-Khuffash A, Herbozo C, Jain A, Lapointe A, McNamara PJ. Targeted neonatal echocardiography (TnECHO) service in a Canadian neonatal intensive care unit: A 4-year experience. J Perinatol 2013;33(9):687-690. http:// dx.doi.org/10.1038/jp.2013.42 15. Kinsella JP, Abman SH. Inhaled nitric oxide and high frequency oscillatory ventilation in persistent pulmonary hypertension of the newborn. Eur J Pediatr 1998;157(Suppl 1):S28-30. http://dx.doi.org/10.1378/chest.114.1_supplement.100s 16. Ullah A. Surfactant therapy in meconium aspiration syndrome (MAS). New Indian J OBGYN 2014;1(1):24-29. http://journal.barpetaogs.co.in/pdfs/1124.pdf 17. Tourneux P, Rakza T, Bouissou A, Krim G, Storme L. Pulmonary circulatory effects of norepinephrine in newborn infants with persistent pulmonary hypertension. J Pediatr 2008;153(3):345-349. http://dx.doi.org/10.1016/j. jpeds.2008.03.007 18. The Neonatal Inhaled Nitric Oxide Study Group. Inhaled nitric oxide in fullterm and nearly full-term infants with hypoxic respiratory failure. N Engl J Med 1997;336(9):597-604. http://dx.doi.org/10.1056/nejm199702273360901 19. Finer NN, Barrington KJ. Nitric oxide for respiratory failure in infants born at or near term. Cochrane Database Syst Rev 2001;Issue 4:Art. no. CD000399. http://dx.doi.org/10.1002/14651858.cd000399 20. Lakshminrusimha S, Keszler M. Persistent pulmonary hypertension of the newborn. Neoreviews 2015;16(12):e680-692. http://dx.doi.org/10.1542/neo.1612-e680 21. Pierro M, ThĂŠbaud B. Understanding and treating pulmonary hypertension in congenital diaphragmatic hernia. Semin Fetal Neonatal Med 2014;19(6):357363. http://dx.doi.org/10.1016/j.siny.2014.09.008 22. Michelakis ED, Tymchak W, Noga M, et al. Long-term treatment with oral sildenafil is safe and improves functional capacity and hemodynamics in patients with pulmonary arterial hypertension. Circulation 2003;108(17):20662069. http://dx.doi.org/10.1161/01.cir.0000099502.17776.c2 23. Lakshminrusimha S, Mathew B, Leach CL. Pharmacologic strategies in neonatal pulmonary hypertension other than nitric oxide. Semin Perinatol 2016;40(3):160-173. http://dx.doi.org/10.1053/j.semperi.2015.12.004

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24. Baquero H, Soliz A, Neira F, Venegas ME, Sola A. Oral sildenafil in infants with persistent pulmonary hypertension of the newborn: A pilot randomised blinded study. Pediatrics 2006;117(4):1077-1083. http://dx.doi.org/10.1542/ peds.2005-0523 25. Shah PS, Ohlsson A. Sildenafil for pulmonary hypertension in neonates. In: Shah PS, ed. Reviews. Chichester, UK: Wiley-Blackwell, 2011. http://dx.doi. org/10.1002/14651858.cd005494.pub3 26. Wardle AJ, Wardle R, Luyt K, Tulloh R. The utility of sildenafil in pulmonary hypertension: A focus on bronchopulmonary dysplasia. Arch Dis Child 2013;98(8):613-617. http://dx.doi.org/10.1136/archdischild-2012-303333 27. James AT, Corcoran JD, McNamara PJ, Franklin O, El-Khuffash AF. The effect of milrinone on right and left ventricular function when used as a rescue therapy for term infants with pulmonary hypertension. Cardiol Young 2016;35(11):913918. http://dx.doi.org/10.1017/s1047951114002698 28. Bassler D, Kreutzer K, McNamara P, Kirpalani H. Milrinone for persistent pulmonary hypertension of the newborn. Cochrane Database Syst Rev 2010;(11):CD007802. http://dx.doi.org/10.1002/14651858.CD007802.pub2 29. Kelly LK, Porta NFM, Goodman DM, Carroll CL, Steinhorn RH. Inhaled prostacyclin for term infants with persistent pulmonary hypertension refractory to inhaled nitric oxide. J Pediatr 2002;141(6):830-832. http://dx.doi. org/10.1067/mpd.2002.129849 30. Ho JJ, Rasa G. Magnesium sulfate for persistent pulmonary hypertension of the newborn. Cochrane Database Syst Rev 2007;(3):CD005588. http://dx.doi. org/10.1002/14651858. CD005588.pub2 31. Wedgwood S, Lakshminrusimha S, Farrow KN, et al. Apocynin improves oxygenation and increases eNOS in persistent pulmonary hypertension of the newborn. Am J Lung Cell Mol Physiol 2012;302(6):L616-626. http://dx.doi. org/10.1152/ajplung.00064.2011 32. Lapointe A, Barrington KJ. Pulmonary hypertension and the asphyxiated newborn. J Pediatr 2011;158(2 Suppl):e19-24. http://dx.doi.org/10.1016/j. jpeds.2010.11.008

Accepted 20 July 2016.

DECEMBER 2016 Vol. 10 No. 4

RESEARCH

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

Outcome of very-low-birth-weight babies managed with nasal continuous positive airway pressure, with or without surfactant, in a high-care nursery T Bopape-Chinyanga, MB ChB; R Thomas, MB ChB, FC Paed; S Velaphi, MB ChB, FC Paed, MMed Department of Paediatrics, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa Corresponding author: S Velaphi (sithembiso.velaphi@wits.ac.za) Background. Very-low-birth-weight (VLBW) infants who require nasal continuous positive airway pressure (NCPAP) are managed in neonatal intensive care units (NICUs) in developed countries, while in low-resource settings this is not always possible. The failure rate of NCPAP provided outside NICUs is not well known.

Objectives. To determine the failure rate, assessed as the need for invasive medical ventilation (iMV) and mortality on NCPAP in VLBW infants managed in a high-care nursery (HCN) within the first 72 hours of life.

Methods. Records of VLBW infants managed with NCPAP, at Chris Hani Baragwanath Hospital, were reviewed for infant characteristics, need for iMV and mortality on NCPAP. Clinical risk index for babies (CRIB) was calculated for each infant. Comparisons were made between those who needed iMV and those who did not, and between survivors and non-survivors on NCPAP. Results. A total of 325 VLBW infants were managed with NCPAP in the HCN. Mean (standard deviation) birth weight was 1 120 (184)g, 98.5% were of gestational age (GA) <34 weeks and 14.9% were small for GA (SGA). Thirteen percent died while on NCPAP and 33% of survivors required iMV â&#x20AC;&#x201C; an overall failure rate of 43%. Factors associated with iMV were high CRIB score (p<0.001), lower Apgar score (p=0.013), lower PaO2 (p=0.022) and high base deficit (p=0.034). Those who died were more likely to have extremely low birth weight (p<0.001), lower GA (p<0.001), high CRIB score (p<0.001) and base deficit (p<0.001). On multivariate analysis, the predictors for need of iMV were low Apgar score (p=0.033), SGA (p=0.042) and CRIB score (p=0.005), while that of mortality on NCPAP was birth weight.

Conclusion. Although failure rate of NCPAP in VLBW infants managed in HCN is high, a significant proportion of VLBW infants benefit from this intervention.

S Afr J Child Health 2016;10(4):199-206. DOI:10.7196/SAJCH.2016.v10i4.1096

Respiratory distress is a common clinical presentation in newborn infants shortly after birth. Respiratory distress in preterm infants or very-low-birth-weight (VLBW) infants is often due to respiratory distress syndrome (RDS), resulting from insufficient production of surfactant leading to atelectasis. It can also result from chest wall weakness and immature alveoli. One of the management strategies for respiratory distress in VLBW infants is non-invasive mechanical ventilation (MV) using continuous positive airway pressure (CPAP). CPAP was first used as a method of supporting the breathing of preterm infants in 1971.[1] It is considered to be one of the interventions that has contributed significantly to the reduction of neonatal mortality globally.[2] The physiological effects of CPAP include increasing functional residual capacity, hence improving oxygenation and maintaining lung volume, reducing work of breathing, conserving surfactant and reducing obstructive apnoea. Nasal CPAP (NCPAP) is the commonly used form of administering CPAP.[3] Nasal prongs are used as they offer less resistance than an endotracheal tube. NCPAP is widely used for a range of neonatal respiratory conditions and is considered the firstline intervention in the management of preterm or VLBW infants with RDS.[4] In developed countries this intervention is applied in the neonatal intensive care unit (NICU), but in developing or lowresource settings this is not always possible.

The proportion of preterm infants at gestation of 25 - 28 weeks who are managed successfully with NCPAP soon after birth ranges from 45 to 68%, and the proportion of those at gestation 29 - 32 weeks has been reported to be 64 - 76%.[5-7] The use of NCPAP in preterm infants with respiratory distress is associated with lower risk for death or use of assisted ventilation.[8] A number of studies in preterm infants 199

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reported that the use of NCPAP soon after birth with or without prior administration of exogenous surfactant was associated with similar or better outcomes than invasive MV (iMV).[9] Although a large number of patients managed with NCPAP do well, a significant proportion of infants managed on NCPAP fail and go on to be intubated for MV. The proportion of preterm or VLBW infants who are initially managed with NCPAP only and subsequently require intubation for iMV is reported to be 45 - 51%.[7] Even with the addition of exogenous surfactant to NCPAP, there is still a failure rate of 25 38%.[10] The criteria used to define failure of NCPAP varies from study to study, most likely explaining the variations in proportion of infants reported to have failed on NCPAP. Studies have used different parameters and values to define criteria for NCPAP failure.

The criteria have included fraction of inspired oxygen (FiO2) ranging from 30 to 60% PaCO2 >60 or 65 mmHg, pH <7.20 or 7.25, pressure on NCPAP and persistent apnoeas.[10,11] Factors that have been found to be associated with CPAP failure have included lower gestational age (GA) and birth weight, amount of supplemental oxygen, male gender, FiO2/PaO2 ratio, PaCO2, pH and presence of apnoeas.[11,12] These factors indirectly reflect on the maturity of the infant and on the severity of the lung disease. A composite parameter that has been used to assess severity of illness in neonates is the clinical risk index for babies (CRIB) score.[13] Factors that are reported to be associated with NCPAP failure are similar to the parameters used in the CRIB score, therefore making it appropriate to use the CRIB score to predict neonates who may fail on NCPAP. The variables used in calculating the CRIB score are GA, birth weight, maximum base excess, congenital abnormalities, and minimum and maximum FiO2 requirements. These variables are assessed in the first 12 hours

DECEMBER 2016 Vol. 10 No. 4

RESEARCH Table 1. Baseline characteristics of VLBW infants managed with NCPAP Characteristic

n (%)

Maternal age (years)*

28 (7)†

<20

35 (11.3)

20 - 35

233 (75.2)

>35

42 (13.5)

Place of birth CHBH

283 (87.1)

Clinic

22 (6.8)

Outside healthcare facility

20 (6.1)

Mode of delivery Vaginal

136 (41.8)

Caesarean section

189 (58.2)

HIV status* Positive

107 (33.4)

Negative

213 (66.6)

Booked Yes

255 (78.5)

No

70 (21.5)

Antenatal steroids Yes

118 (36.3)

No

42 (12.9)

Not recorded

165 (50.8) 29 (2)†

Gestation (weeks) <28

76 (23.4)

28 - <30

128 (39.4)

30 - <34

116 (35.7)

≥34

5 (1.5) 1 120 (184)†

Weight (g) <1 000 g

95 (29.2)

≥1 000 g

230 (70.8)

Small GA Yes

48 (14.9)

No

274 (85.1)

Gender Male

161 (49.5)

Female

164 (50.5)

APGAR score at 5 minutes <7

53 (16.3)

Resuscitation required Yes

157 (48.3)

No

168 (51.7)

Extent of resuscitation required Bag mask ventilation (BMV) only

153 (97.4)

BMV and adrenaline

4 (2.6)

*Missing data: 15 for maternal age, and 5 for HIV status. †

Mean (SD).

200

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of life, making them less susceptible to treatment effects. A score of <5 has a smaller risk for mortality when compared with a score of >10.[13] Most of the studies that have looked at NCPAP failure rate were conducted in developed countries; therefore none of the babies was reported to have died on NCPAP as anyone who failed NCPAP was intubated and put on MV. In developing countries or settings where resources are limited, a number of preterm infants might die while receiving NCPAP. A study on outcomes of extremely-low-birth-weight (ELBW) infants managed with CPAP in a developing country, where NICU facilities are limited, reported a mortality rate of 8% on NCPAP.[10] Factors associated with deaths in VLBW infants managed with CPAP in a setting with limited resources are not known. In this study we sought to determine the proportion of VLBW infants managed with NCPAP outside NICU, their outcome as determined by the need for intubation for ventilation or death while on NCPAP and factors associated with these poor outcomes.

This study was conducted after approval from the University of the Witwatersrand Human Research Ethics Committee.

Methods

This was a retrospective, descriptive study of VLBW infants weighing 800 - 1 499 g admitted to the high-care nursery (HCN) at Chris Hani Baragwanath Hospital (CHBH) in January to December 2012, managed with NCPAP within first 72 hours of life with or without surfactant. Medical records of VLBW infants weighing 800 g - 1 499 g were retrieved and reviewed for maternal and infant data. Data collection sheets were used to capture all the information required. A CRIB score was calculated for each neonate.

CHBH is the referral hospital for all clinics in Soweto and surrounding areas. The protocol on the management of VLBW infants stipulated that those weighing ≥800 g with respiratory distress are started on NCPAP using flow drivers. Infants are only given surfactant using the intubation, surfactant and extubation (InSurE) technique if they require >40% FiO2 on NCPAP. The NCPAP is started with pressures of 4 - 6 cm H2O, and gradually increased up to a pressure of 8 cm H2O if there is no improvement in saturations on >60% supplemental oxygen. A second dose of surfactant is given 6 hours after the first dose if the FiO2 cannot be weaned below 40%. All patients with respiratory distress had arterial blood gas done by the time they were started on NCPAP. Because of limited resources, infants weighing <800 g were not offered NCPAP during the period of this record review. Patients admitted with respiratory distress had a full blood count and blood cultures done on admission, and a

DECEMBER 2016 Vol. 10 No. 4

RESEARCH C-reactive protein (CRP) was obtained after 24 - 48 hours of birth. Patients who weighed >900 g were offered MV and transferred to NICU if they failed to maintain saturations above 88% despite NCPAP, a second dose of surfactant and required FiO2 >0.60, or if the arterial blood gas revealed a PaO2 <50 mmHg on an FiO2 >0.60, or a PaCO2 >55 mmHg with pH<7.25 or a PaCO2 >60 mmHg. The protocol on weaning patients off NCPAP was to gradually wean FiO2 to below 40% and then wean pressure on NCPAP to levels of 4 - 6 cm H2O, after which the patient was taken off NCPAP if saturations were maintained above 90%, and the patient was not distressed and had no apnoeas.

Data collected included maternal and infant characteristics, antenatal management, clinical diagnosis, laboratory findings, use of exogenous surfactant and outcome on NCPAP. Outcomes assessed were weaning off NCPAP in high care, need for MV, or death irrespective of cause while on NCPAP. Data were captured onto an Excel 2010 (Microsoft, USA) spreadsheet. The Excel spreadsheet was imported into Statistica version 12.0 (Statsoft Inc., USA) for statistical analysis.

Means with standard deviations (SDs) and medians with ranges were used to describe the parametric and non-parametric data, respectively. Frequencies and percentages were used to describe categorical variables.

In comparing those who failed on NCPAP and those who weaned off NCPAP, χ2 and Fisher’s exact test were used to assess for statistically significant differences between categorical variables, and Student’s t-test and Mann-Whitney U-test for parametric and non-parametric continuous variables, respectively. Differences with p-values <0.05 were considered to be statistically significant.

In order to determine predictors of need for MV or death on NCPAP, variables where p<0.1 on univariate analysis were included in the logistic regression model.

antenatal steroids were given in 50.8% of cases. Only 29% weighed between 800 and 1 000 g. The GA of most (98.5%) patients was <34 weeks, as determined by Ballard score. Among the 322 patients who had GA recorded, 48 (14.9%) were small for

GA (SGA). Numbers of male and female babies were equally distributed. Forty-seven percent required resuscitation, with most of them only requiring bag mask ventilation and 16.3% having an Apgar score <7 at 5 minutes. The common diagnosis on ad-

Table 2. Clinical diagnosis, severity of illness (CRIB score), and laboratory findings Characteristics Clinical diagnosis Respiratory distress syndrome

307 (94.5)

Asphyxia

11 (3.4)

Congenital pneumonia

5 (0.5)

Apnoea

2 (0.6)

CRIB score* <4

18 (5.5)

4 - 10

215 (66.2)

>10

77 (23.7)

Postnatal age (hours)*

There were 21 601 live births at CHBH in 2012, of whom 806 were VLBW infants, accounting for 3.7% of all live births. Among these 806 VLBW infants, medical records of 635 (78.8%) were retrieved; the rest could not be found. Of these 635 VLBW infants with medical records, 325 (51.2%) patients were managed with NCPAP in the HCN. The majority of mothers (75.2%) were in the age group 20 - 35 years, and a third (33.4%) of VLBW infants were born to HIV-positive mothers. Only 78.5% of mothers attended antenatal care, defined as the mother having attended antenatal care at least once before delivery (Table 1). Antenatal steroids during labour were recorded as being given in only 36.3% of patients and not given in 12.9%, and there were no records of whether or not 201

3.6 (2.0, 6.4; 4.42)†

≤2 hours

65 (23.0)

2-6

143 (50.5)

>6 - 12

48 (17.0)

>12

27 (9.5)

Blood gases‡ (n=282) pH

7.24 (0.12)

PaCO2

46 (26)

PaO2

149 (76)

Base excess

8.7 (4.7)

White cell count (× 109/L)* <5

57 (18.3)

5 - 25

241 (77.2)

>25

14 (4.5)

Haemoglobin (Hb) (g/dL)* <12

16 (5.1)

12 - 18

267 (85.6)

>18

Results

n (%)

29 (9.3) 9

Platelets (× 10 /L)* <100

42 (13.5)

100 - 150

67 (21.5)

>150

203 (65.0)

C-reactive protein (CRP) (mg/dL)* ≤10

256 (87.1)

>10

38 (12.9)

Blood culture* Positive

18 (5.8)

Negative

295 (94.2)

*Missing data: 15 for CRIB score; 42 for postnatal age; 13 for white cell count, Hb and platelets; 31 for CRP; 12 for blood culture. † Median (25th, 75th percentile; IQR). ‡ Mean (SD).

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RESEARCH Table 3. Outcome of patients of VLBW infants managed with NCPAP in high care Management and outcome

n (%)

Requiring surfactant on NCPAP

156 (48.0)

Type of surfactant* Survanta

91 (61.5)

Curosurf

57 (38.5)

Death on NCPAP (n=324) Yes

44 (13.6)

No

280 (86.3)

Required intubation for MV among survivors Yes

96 (34.2)

No

184 (65.8)

Weaned off NCPAP in high-care nursery (n=324) No

140 (43.2)

Yes

184 (56.6)

*Missing data for 8 patients.

mission was RDS. About two-thirds of patients (66.2%) had a CRIB score of 4 - 10, and 23.7% a CRIB score of >10. Arterial blood gases done before administration of NCPAP showed a mean (SD) pH of 7.24 (0.12), PaCO2 46 (26) mmHg, PaO2 149 (76) mmHg, and base deficit of 8.70 (4.7) mmol/L (Table 2). The full blood count on admission showed that 22.8% had an abnormal white cell count (18.3% with leukopenia and 4.5% with leukocytosis), 5% had anaemia (haemoglobin <12 g/dL) and 25% had thrombocytopenia (platelet count <150 × 109/L). Only 12.9% had CRP >10 mg/L and 5% had positive blood cultures. The median age when NCPAP was started was 3.6 hours.

Out of the 325 VLBW infants who received NCPAP, 156 (48%) required surfactants in addition to NCPAP, 44 (13.5%) died while on NCPAP and 96 (34.2%) survivors required intubation for MV (Table 3). Among the 156 who received surfactant, 20 (12.8%) required a second dose. The median postnatal age at time of death among those who died on CPAP was 64 hours (range 3 - 420 hours).

Overall, 56.6% of VLBW infants managed with NCPAP were weaned off NCPAP while in HCN, and 43.4% either required intubation for MV or died while on NCPAP, therefore were not weaned off NCPAP within the HCN. There were more patients who needed resuscitation (64.9 v. 52.7%, p=0.003), and who had a CRIB score >10 (28.9 v.

20.2%, p=0.001) in the VLBW, and who required surfactant in addition to NCPAP compared with those who did not require surfactant (Table 4). There were no statistical significant differences in other variables.

Among the survivors on NCPAP, 96 needed intubation for MV. There were 202

more patients who were SGA (22.1 v. 12.0%, p=0.027), had lower Apgar score at 5 minutes (median 8 v. 9, p=0.013) and a CRIB score >10 (37.4 v. 12.0%, p<0.001) among those who needed MV (Table 5). They also had a lower PaO2 (137 (67) v. 161 (81) mmHg, p=0.022) and higher base deficit (9.0 (4.4) v.

7.8 (4.0) mmol/L, p=0.034) compared with those who did not need ventilation. There were no statistical significant differences in other variables between those who required MV and those who did not require ventilation among the survivors. On multivariate logistic regression analysis, the predictors of need for intubation for MV were SGA (p=0.033), Apgar score at 5 minutes (p=0.042) and CRIB score (p=0.005).

Among all the patients who were managed with NCPAP within the first 72 hours of life, 44 died while on NCPAP and 280 survived, either weaning off NCPAP or requiring intubation for MV (Table 6). There were more patients with a CRIB score >10 among those who died than among those who survived (51.2 v. 20.9%, p<0.001). Patients who died had lower birth weight (944 (142) v. 16 147 (175) g, p<0.001), were of lower GA (27 (2) v. 29 (2) weeks, p<0.001), had a lower pH (7.165 (0.16) v. 7.25 (0.11)), lower PaO2 (120 (62) v. 153 (77), p=0.011) and higher base deficit (11.9 (6.0) v. 8.2 (4.2) mmol/L, p<0.001) than those who survived. There were no statistically significant differences in other variables between those who died and those who survived. On multivariate logistic regression analysis, the only predictor of death on NCPAP was birth weight (p<0.001).

Discussion

VLBW infants account for a significant number of infants who require respiratory SAJCH

support soon after delivery. Providing NCPAP has been reported to reduce mortality and the need for intubation for MV in this group of infants.[14] Success or failure rates of NCPAP are often reported from developed countries, where it is often initiated soon after delivery and offered in a setting where resources are not restricted, typically administered in an NICU setting.

In developing countries where resources are limited, NCPAP is often offered outside the NICU setting. Some of the infants may not get access to NICU and therefore die on NCPAP. It is important to assess the success or failure rate of NCPAP in a setting where intubation for MV might not always be accessible to those who fail NCPAP. This study looked at the short-term outcomes of babies who were treated with NCPAP with or without surfactant outside a NICU setting. The short-term outcomes assessed were death on NCPAP or need for intubation for MV, and these were labelled as NCPAP failures.

The main findings in this study were that 51% of VLBW infants weighing between 800 and 1 499 g inclusive required NCPAP within the first 72 hours of life and were managed in a HCN. The median age of starting NCPAP was about 3.5 hours of life. Forty-eight percent of VLBW infants required exogenous surfactant despite NCPAP. Thirteen percent of VLBW infants managed with NCPAP died while receiving NCPAP, and 34% of the survivors required iMV, with an overall CPAP failure rate of 43%. The patients who required iMV had lower median Apgar score at 5 minutes, higher CRIB score, lower PaO2 and higher base deficit, and those who died on NCPAP had a CRIB score >10, were ELBW and lower gestation, had lower pH and PaO2, and had a higher base deficit than survivors.

Among the VLBW infants managed with NCPAP in whom use of antenatal steroids was recorded, <50% had received antenatal steroids. This most likely contributed to these infants having severe disease as shown by high CRIB score, requiring NCPAP and having poor outcomes, as it has been shown that use of antenatal steroids reduces the incidence of RDS and mortality in preterm infants.[15] In the settings where NICU facilities are limited, management of VLBW infants outside NICU is feasible. While 13% died on NCPAP, 66% of survivors weaned off NCPAP without the need for intubation for MV. There are not many studies that have reported on use of NCPAP in VLBW infants outside NICU. One of the studies from a developing country reported on use of NCPAP outside the NICU and showed that 92% of ELBW infants were managed with NCPAP outside NICU set-up with good outcomes.[10] Recently

DECEMBER 2016 Vol. 10 No. 4

RESEARCH a report from a district hospital showed that managing patients outside a NICU is possible, improves outcomes and gives an opportunity to offer support while waiting for transport for transfer to a facility with NICU.[16] This suggests that CPAP can be safely used in resource-limited settings as the first line of therapy, with great benefits.

Forty-eight percent of patients who were managed with NCPAP in this report also required exogenous surfactant. This is sim­ ilar to the 46% reported by Dunn et al.[9] Patients who required exogenous surfactant were smaller and sicker, as reflected by higher CRIB score, and had factors that might have inhibited the production or function of surfactant, namely acidosis, resulting in greater need for surfactant. Randomised trials point towards using early NCPAP as an alternative to surfactant administration in preterm infants with RDS,[17] but in smaller VLBW infants elective administration of surfactant may decrease the need for MV. One-third of patients required intubation for MV despite NCPAP. Other studies have reported higher numbers of 40 - 48% of patients managed with NCPAP requiring intubation for MV.[18,19] The reasons for the lower rates MV need in this study are most likely due to those neonates weighing <1 000 g not being considered for ventilation because of limited NICU beds. Other factors associated with need for intubation for MV in infants managed with NCPAP have been reported to be a high FiO2 (≥0.3) requirement in the first hours of life, and moderate-tosevere respiratory distress syndrome.[20] This is similar to the findings in this study that showed that the need for iMV was associated with high CRIB score, which represents severity of illness.

Thirteen percent of patients died on NCPAP. Most of these deaths were babies who were of lower gestation and birth weight. In areas where resources are limited, infants at borders of viability are often not offered iMV in the NICU. Where this study was conducted, the majority (those weighing <900 g) of ELBW infants were not offered iMV. The highest ventilator support they could get was NCPAP. The mortality rate of 13% on NCPAP reported in this study is higher than that reported by Kirsten et al.,[10] who reported a mortality rate of 8%. The explanation for this difference could be due to differences in severity of illness and GA, which are reflected in a CRIB score, but the study by Kirsten et al. did not report on the CRIB score of babies they studied.

There are some limitations in the data collection in this study. The retrospective design of the study meant that not all the files could be retrieved. Some files were missing from the filing room and from the files that were retrieved, and some data were missing or incomplete. This is unlikely to

have affected the results, as a significant number (79%) of files of all VLBW infants were retrieved. It is unlikely that the missing data would have affected the findings in this study as the missing data was <20% for most variables except for antenatal steroids.

203

Conclusion

Use of NCPAP in VLBW infants can be applied outside a NICU setting with reasonable short-term outcomes. It is effective in the management of respiratory distress, as about 87% of patients survive on

Table 4. Comparison between those who needed surfactant and those who required NCPAP only NCPAP and surfactant (N=156), n (%)

NCPAP only (N=169), n (%) p-value

n=156

n=169

Vaginal

63 (40.4)

73 (43.2)

Caesarean section

93 (59.6)

96 (56.8)

n=82

n=78

Yes

56 (68.3)

62 (79.4)

No

26 (31.7)

16 (20.6)

Gestation (weeks)*

29.0 (2.1)

28.9 (2.3)

0.754

Birth weight (g)*

1 112 (185)

1 124 (184)

0.554

SGA

24 (15.4)

24 (14.2)

0.814 0.265

Mode of delivery

Maternal steroids

0.587

0.142

n=156

n=169

Male

83 (53.2)

78 (46.2)

Female

73 (46.8)

91 (53.8)

8 (7; 9)

9 (7; 10)

0.777 0.003

Sex

Apgar score at 5 minutes†

n=131

n=151

None

46 (35.1)

71 (47.0)

Yes

85 (64.9)

80 (53.0)

n=138

n=145

<2

39 (28.3)

36 (24.8)

2-6

64 (46.4)

70 (48.3)

>6 - 12

23 (16.7)

25 (17.2)

>12

12 (8.70)

14 (9.7)

n=149

n=161

<4

6 (4.03)

12 (7.5)

4 - 10

100 (67.1)

115 (71.4)

>10

43 (28.9)

34 (21.1)

n=134

n=148

pH

7.24 (0.10)

7.23 (0.13)

0.360

Resuscitation required

Postnatal age at starting NCPAP (hours)

CRIB score

Blood gases, mean (SD)*

0.959

0.001

PaCO2 (mmHg)

45.0 (32.8)

45.6 (14.5)

0.437

PaO2 (mmHg)

145 (72.8)

154 (79.4)

0.896

Base deficit (mmol/L)

8.79 (3.89)

8.51 (5.17)

0.610

n=142

n=152

0.469

≤10

126 (88.7)

130 (85.5)

>10

16 (11.3)

22 (14.5)

CRP (mg/L)

n=147

n=155

Positive

17 (11.6)

20 (12.9)

Negative

130 (88.4)

134 (87.1)

Blood culture on admission

*Mean (SD). † Median (IQR).

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DECEMBER 2016 Vol. 10 No. 4

0.804

RESEARCH Table 5. Comparison of those who needed intubation and those who did not among survivors Needed MV despite NCPAP (N=96), n (%)

MV not required (N=184), n (%)

Univariate analysis, p-value

Multivariate analysis, p-value

n=96

n=184

0.780

N/A

Vaginal

38 (39.6)

76 (41.3)

Caesarean section

58 (60.4)

108 (58.7)

n=55

n=81

0.698

N/A

Yes

43 (79.2)

61 (75.3)

No

12 (21.8)

20 (24.7)

Gestation (weeks)*

29 (2.2)

29 (2.1)

0.678

N/A

Weight (g)*

1 143 (151)

1 149 (187)

0.778

N/A

SGA

21 (22.1)

22 (12.0)

0.027

0.033

Female infants

43 (44.8)

96 (52.2)

0.241

N/A

Apgar at 5 minutes, median (25th, 75th percentile; IQR)

8 (7, 10; 3)

9 (7, 10; 3.5)

0.013

0.042

Resuscitation required

n=84

n=161

0.056

NS

No

52 (61.9)

79 (49.1)

Yes

32 (38.1)

82 (50.9)

n=85

n=159

0.789

N/A

<2

23 (27.1)

46 (28.9)

2-6

38 (44.7)

77 (48.4)

>6 - 12

15 (17.6)

24 (15.1)

>12

9 (10.6)

12 (7.55) <0.001

0.005

Mode of delivery

Maternal steroids

Postnatal age at initiation of NCPAP (hours)

n=91

n=175

â&#x2030;¤10

57 (62.6)

154 (88.0)

>10

34 (37.4)

21 (12.0)

n=81

n=159

pH

7.233 (0.115)

7.256 (0.099)

0.119

N/A

PaCO2 (mmHg)

44.3 (18.9)

46.0 (29.3)

0.658

N/A

PaO2 (mmHg)

137.3 (67.3)

161 (81)

0.022

NS

Base deficit (mmol/L)

9.0 (4.4)

7.8 (4.1)

0.034

NS

0.644

N/A

0.601

N/A

CRIB score

Blood gases*

n=87

n=178

â&#x2030;¤10

75 (86.2)

157 (88.2)

>10

12 (13.8)

21 (11.8)

CRP (mg/L)

n=97

n=183

Positive

9 (10.1)

15 (8.2)

Negative

88 (89.9)

168 (91.8)

Blood culture

N/A = not applicable; NS = not significant. *Mean (SD).

NCPAP, although about one-third of those who survive on NCPAP end up requiring iMV. The patients who died on NCPAP were those of lower GA and those with severe illness. The ones who died with lower GA were most likely not offered iMV because of limited NICU beds. The high failure rate on NCPAP, which included deaths, is therefore partly related to inadequate resources. There is therefore a need to improve access to iMV to fully appreciate the impact of providing NCPAP, especially to those who are of lower GA and who are critically ill.

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References 1. Gregory GA, Kitterman JA, Phibbs RH, Tooley WH, Hamilton WK. Treatment of the idiopathic respiratory-distress syndrome with continuous positive airway pressure. N Engl J Med 1971;284(24):1333-1340. http://dx.doi.org/10.1056/ NEJM197106172842401 2. Verder H. Nasal CPAP has become an indispensable part of the primary treatment of newborns with respiratory distress syndrome. Acta Paediatr 2007;96(4):482-484. http://dx.doi.org/10.1111/j.1651-2227.2007.00263.x 3. De Paoli AG, Morley C, Davis PG. Nasal CPAP for neonates: What we know in 2003? Arch Dis Child Fetal Neonatal Ed 2003;3(88):F168-F172. http://dx.doi. org/10.1136/fn.88.3.F168

DECEMBER 2016 Vol. 10 No. 4

RESEARCH Table 6. Comparison of deaths and survivors on NCPAP, with or without need for surfactant or intubation*

Mode of delivery Vaginal Caesarean section Maternal steroids† Yes No

Died on NCPAP (N=44), n (%)

Did not die on NCPAP (N=280), n (%)

Univariate analysis, p-value

Multivariate analysis, p-value

n=44

n=277

0.338

N/A

21 (47.7)

111 (40.1) 0.063

NS

23 (52.3)

166 (59.9)

n=24

n=136

14 (58.3)

104 (76.5)

10 (41.7)

32 (23.5)

27 (2

29 (2

<0.001

NS

Weight (g)

944 (142

1 147 (175

<0.001

<0.001

SGA

4 (9.1)

43 (15.5)

0.265

N/A

Females

25 (56.8)

139 (49.6)

0.376

N/A

Resuscitation required

0.055

NS

0.501

N/A

<0.001

NS

Gestation (weeks)‡ ‡

n=38

n=245

None

11 (29.7)

114 (46.5)

Yes

26 (70.7)

131 (53.5)

n=44

n=225

11 (25.0)

77 (27.5)

Postnatal age at start of NCPAP (hours) <2 2-6

19 (43.2)

143 (51.1)

>6 - 12

9 (20.4)

3 (13.9)

>12

5 (11.4)

21 (7.50)

n=41

n=250

19 (48.8)

195 (79.3)

CRIB score ≤10 >10

22 (51.2)

55 (20.7)

n=41

n=240

pH

7.165 (0.163)

7.248 (0.105)

<0.001

NS

PaCO2

49.9 (21.4)

45.4 (26.2)

0.305

N/A

PaO2

120 (62)

153 (77)

0.011

NS

Base deficit

11.9 (6.0)

8.2 (4.2)

<0.001

NS

n=28

n=267

0.418

N/A

≤10

23 (82.1)

234 (87.5)

>10

5 (17.9)

33 (12.4)

n=29

n=272

0.733

N/A

Blood gases‡

CRP

Blood culture Positive

3 (10.3)

33 (12.1)

Negative

26 (89.7)

239 (87.9)

N/A = not applicable; NS = not significant. *One patient outcome not recorded as the last page was missing. † Data missing for 165 patients. ‡ Mean (SD).

4. De Winter JP, de Vries MA, Zimmermann LJ. Clinical practice: Noninvasive respiratory support in newborns. Eur J Pediatr 2010;169(7):777-782. http:// dx.doi.org/10.1007/s00431-010-1159-x 5. Aly H, Massaro AN, Patel K, El-Mohandes AA. Is it safer to intubate premature infants in the delivery room? Pediatrics 2005;115(6):1660-1665. http://dx.doi. org/10.1542/peds.2004-2493 6. Ammari A, Suri M, Milisavljevic V, et al. Variables associated with the early failure of nasal CPAP in very low birth weight infants. J Pediatr 2005;147(3):341-347. http://dx.doi.org/10.1016/j.jpeds.2005.04.062 7. Fuchs H, Lindner W, Leiprecht A, Mendler MR, Hummler HD. Predictors of early nasal CPAP failure and effects of various intubation criteria on the rate of mechanical ventilation in preterm infants of <29 weeks’ gestational age. Arch Dis Child Fetal Neonatal Ed 2011;96(5):F343-347. http://dx.doi. org/10.1136/adc.2010.205898

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8. Ho JJ, Subramaniam P, Davis PG. Continuous distending pressure for respiratory distress in preterm infants. Cochrane Database Syst Rev 2015;4(7):CD002271. http://dx.doi.org/10.1002/14651858.CD002271.pub2 9. Dunn MS, Kaempf J, de Klerk A, et al. Randomized trial comparing 3 approaches to the initial respiratory management of preterm neonates.

Pediatrics 2011;128(5):e1069-1076. http://dx.doi.org/10.1542/peds.20103848 10. Kirsten GF, Kirsten CL, Henning PA, et al. The outcome of ELBW infants treated with NCPAP and InSurE in a resource-limited institution. Pediatrics 2012;129(4):e952-959. http://dx.doi.org/10.1542/peds.2011-1365 11. Świetliński J, Bachman T, Gajewska E, et al. Factors affecting outcomes in very low birth weight infants treated electively with nasal continuous positive airway pressure. J Perinatol 2010;30(2):112-117. http://dx.doi.org/10.1038/ jp.2009.135

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RESEARCH 12. Rocha G, Flor-de-Lima F, Proenca E, et al. Failure of early nasal continuous positive airway pressure in preterm infants of 26 to 30 weeks' gestation. J Perinatol 2013;33(4):297-301. http://dx.doi.org/10.1038/jp.2012.110 13. Sarquis AL, Miyaki M, Cat MN. [The use of CRIB score for predicting neonatal mortality risk]. J Pediatr (Rio J) 2002;78(3):225-229.

14. Kambarami R, Chidede O, Chirisa M. Neonatal intensive care in a developing country: Outcome and factors associated with mortality. Cent Afr J Med 2000;46(8):205-207.

15. Mwansa-Kambafwile J, Cousens S, Hansen T, Lawn JE. Antenatal steroids in preterm labour for the prevention of neonatal deaths due to complications of preterm birth. Int J Epidemiol 2010;39(Suppl 1):i122-i133. http://dx.doi. org/10.1093/ije/dyq029 16. Hendriks H, Kirsten GF, Voss M, Conradie H. Is continuous positive airway pressure a feasible treatment modality for neonates with respiratory distress syndrome in a rural district hospital? J Trop Pediatr 2014;60(5):348-351. http:// dx.doi.org/10.1093/tropej/fmu025

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17. Polin RA, Carlo WA, Committee on Fetus and Newborn, American Academy of Pediatrics. 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 18. Morley CJ, Davis PG, Doyle LW, et al. Nasal CPAP or intubation at birth for very preterm infants. N Engl J Med 2008;358(7):700-708. http://dx.doi.org/10.1056/ NEJMoa072788 19. Schmolzer GM, Kumar M, Pichler G, Aziz K, Oâ&#x20AC;&#x2122;Reilly M, Cheung PY. Non-invasive versus invasive respiratory support in preterm infants at birth: Systematic review and meta-analysis. BMJ 2013;347:f5980. http://dx.doi.org/10.1136/bmj.f5980 20. Dargaville PA, Aiyappan A, de Paoli AG, et al. Continuous positive airway pressure failure in preterm infants: Incidence, predictors and consequences.

Neonatology 2013;104(1):8-14. http://dx.doi.org/159/000346460 Accepted 29 November 2015.

DECEMBER 2016 Vol. 10 No. 4

RESEARCH

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

Upper gastrointestinal endoscopy in children: The Lagos University Teaching Hospital experience O F Adeniyi,1 MBBS, FMC (Paed), MSc (Child Health); O A Lesi,2 MBBS, FWACP; E A Odeghe,2 MBBS, FWACP; O Adekola,3 MBBS, FMC (Anaesth); O A Oduwole,4 MBBS, FWACP Department of Paediatrics, College of Medicine, University of Lagos/Lagos University Teaching Hospital, Nigeria Department of Medicine, College of Medicine, University of Lagos/Lagos University Teaching Hospital, Nigeria 3 Department of Anaesthesia, College of Medicine, University of Lagos/Lagos University Teaching Hospital, Nigeria 4 Department of Paediatrics, College of Medicine, University of Lagos/Lagos University Teaching Hospital, Nigeria

1

2

Corresponding author: O F Adeniyi (layo_funke@yahoo.co.uk) Background. Paediatric endoscopy is now standard care in the developed world for the management of gastrointestinal (GI) disorders.

However, in developing countries endoscopy remains an underutilised tool.

Objective. To determine the indications and the spectrum of endoscopic findings in children seen at the Lagos University Teaching Hospital, Nigeria.

Methods. The indications for upper GI endoscopy and endoscopic findings in children ≤16 years old, referred for the procedure from June 2013 to June 2016, were documented. The endoscopic yield in these children was also determined.

Results. In total 71 children were referred for upper GI endoscopy during the study period. There were 35 boys and 36 girls aged 3 months to 16 years. The indications for upper endoscopy were recurrent abdominal pain in 37 (52.1%), upper GI bleeding in 17 (23.9%), recurrent vomiting in 7 (9.9%), dyspepsia in 5 (7.0), heartburn in 2 (2.8%), dysphagia in 1 (1.4), portal hypertension in 1 (1.4) and ingestion of corrosives in 1 (1.4%) of the subjects. Endoscopic findings were as follows: gastritis 19 (26.8%), hiatus hernia in 13 (18.3%), gastric erosions in 12 (16.9%), oesophageal varices 6 (8.4%), duodenitis in 4 (5.6%), gastric ulcer in 3 (4.2%), gastric polyp in 2 (2.8%). The overall endoscopic yield was 60.2%.

Conclusion. There is a need to increase the awareness of the role of paediatric endoscopy in the diagnosis and treatment of GI disorders in developing countries. Recurrent abdominal pain still remains a relevant indication for the procedure. The need to develop training programmes for paediatric endoscopy and paediatric gastroenterology in general in developing countries cannot be overemphasised.

S Afr J Child Health 2016;10(4):207-210. DOI:10.7196/SAJCH.2016.v10i4.1116

With the introduction of flexible upper gastrointestinal (GI) endoscopic procedures in the 1970s and development of more instruments in the 1990s, paediatric endoscopic procedures have now become standard care in the developed world for the management of GI disorders.[1] In developing countries upper GI endoscopy remains an underutilised tool in the care and management of these paediatric disorders. This is more so in sub-Saharan countries, where accessibility and affordability are still very limited.

Previous studies documenting the indications and endoscopic findings in children have been mainly from developed countries,[2-5] and few reports are available from developing countries, especially from sub-Saharan Africa. In Sudan, the most common indication for upper GI endoscopy was haematemesis (24%) and portal hypertension (PHT) (21%), while the most common endoscopic findings were oesophageal varices (16%) and gastritis (7%).[6] In Uganda, gastritis and duodenal ulcers were found to be the most common endoscopic findings.[7] There is a dearth of information on the utility of the procedure in children, especially in the West African sub-region. Therefore, this study was carried out to outline the indications and the spectrum of endoscopic diagnosis in children seen at the Lagos University Teaching Hospital (LUTH).

Methods

We conducted a prospective, descriptive study at the endoscopy centre of LUTH in Nigeria, from June 2013 to June 2016. All consecutive children referred to the endoscopy unit for the procedure were enrolled into the study. LUTH is a tertiary referral hospital in Lagos, Nigeria, and its endoscopy centre, which offers both training 207

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and service facilities, is one of the centres in the Nigeria providing both diagnostic and therapeutic upper GI endoscopy services to both adult and paediatric populations from all over the country.

All children ≤16 years old referred for upper endoscopy, both from the outpatient clinics and inpatient wards during the study period, were enrolled into the study. Children who were referred for endoscopy included those with recurrent abdominal pain (usually children who had experienced abdominal pain for ≥3 months) and patients with abdominal pain for whom the attending physician requested the procedure. Subjects with other appropriate symptoms, namely upper GI bleeding, recurrent and intractable vomiting, ingestion of corrosives, unexplained anorexia, unexplained weight loss or failure to thrive, unexplained anaemia and evidence of PHT, were also referred for the procedure.

Definition of terms

• Dyspepsia: Presence of troublesome pain or discomfort located in the upper part of the abdomen (epigastrium) and/or nausea, early satiety or uncomfortable feeling of fullness after meals.[8,9] • Epigastric pain: Troublesome pain or discomfort located in the epigastric region of the abdomen.[8,9] • Abdominal pain: Troublesome pain or discomfort indicated anywhere in the abdomen.[8,9] • Heartburn: Burning pain in the chest and possibly retrosternal pain, which is often worse when lying down or bending over.[8,9] These symptom definitions were adapted from the validated Abdominal Symptom Questionnaire (ASQ),[8,9] which describes the abdominal symptoms from the upper and lower part of the abdomen.

DECEMBER 2016 Vol. 10 No. 4

RESEARCH The ASQ is a validated document describing the presence or absence (yes/no) of 27 troublesome GI symptoms over the preceding 3 months, and also includes the abdominal pain location. This document has been validated to ascertain pain and found to have a high sensitivity and specificity. The document was adapted for this study in order to describe the GI symptoms in the subjects accurately.

The basic demographic data and indications for the procedure and endoscopic findings were entered into a standardised proforma.

The basic work-up for each subject referred on account of abdominal pain included stool examination done for ova, parasites, occult blood and faecal antigen for Helicobacter pylori. An abdominal scan was also carried out. Other investigations carried out for each patient were based on the clinical suspicion of the underlying condition.

Prior to the procedure, each child was requested to undergo an overnight fast – the procedure was performed the next morning. The Karlz Storz video endoscope (model 13821 PKS/NKS, Germany) was used to perform the procedures, and endoscopic diagnosis was based on visual evaluation in collaboration with experienced endoscopists. Each procedure was carried out after a venous access was established for the child and the vital signs and oxygen saturation were monitored. Two endoscopy nurses assisted with the procedure.

Sedation

For children >5 years old sedation was performed using 1% local lignocaine spray to anaesthetise the oropharynx. Subsequently, each child was given intravenous (IV) midazolam at 0.5 mg/kg, IV pentazocine at 0.5 mg/kg and IV Buscopan 0.5 mg/kg for conscious sedation. For children <5 years similar drugs were administered and intravenous ketamine 1 mg/kg was added to achieve adequate sedation.

IV ketamine was added to the above medications in 35 subjects with ages between 3 months and 14 years (21 males and 14 females) to achieve adequate sedation for carrying out the procedure successfully.

Sedation was performed with the assistance of the anaesthetists, especially for children <6 years old. None of the patients had general anaesthesia and no adverse reaction to the sedative agents was recorded in the subjects.

Statistical analysis

Data were entered and analysed using SPSS version 21 (SPSS Statistics for Windows, version 21.0, IBM Corp., USA). Basic Table 1. Clinical characteristics of the subjects in the study Parameter

n (%)

Age (yr)

71 (100)

<5

18 (25.4)

5-9

28 (39.4)

10 - 15

21 (29.6)

>15

4 (5.6) 35 (49.3)

Female

36 (50.7)

Religion Christian

54 (76.0)

Muslim

17 (24.0)

Ethnicity Yoruba

46 (64.8)

Igbo

35 (35.2)

208

Ethical considerations

The study was approved by the Health Research and Ethical Committee of LUTH. A brief discussion was held with the parents and the child prior to the procedure, during which details of the procedure were explained. Thereafter, written informed consent was obtained from the parents, and consent was also obtained from the child where appropriate, before he or she was enrolled in the study.

Results

General characteristics

A total of 71 children had upper GI endoscopy during the study period.

The patients were aged 3 months to 16 years. The mean (standard deviation (SD)) age was 7.8 (3.8) years. There were 35 (49.3%) males and 36 (50.7%) females.

The largest group of subjects was aged 5 - 9 years (28.0%). Most were Christian (76%) and belonged to the Yoruba tribe (64.8%) (Table 1). The means (SDs) for the weights and heights of the subjects were 23.8 (12.2) kg and 117 (32.6) cm, respectively. All the subjects were retroviral-disease-negative. Two of the subjects had haemoglobinopathy (HbSC and HbSS).

Indications for endoscopy

The most common indication for upper endoscopy was recurrent abdominal pain, present in 37 (52.1%), followed by upper GI bleeding in 17 (23.9%) and recurrent vomiting in 7 (9.9%). Heartburn in 2 (2.8%), dysphagia in 1 (1.4%) and ingestion of corrosive substance 1 (1.4%) were the least common indications for the procedure (Table 2).

Four of the subjects with abdominal pain had dyspepsia and three of these localised the pain as being epigastric. One of the subjects, a patient with known HbSS, was referred for screening endoscopy following an abdominal computed tomography (CT) scan diagnosis of PHT. Six of the subjects who presented with upper GI bleeding had ingested herbal preparations while three of them had been on non-steroidal anti-inflammatory drugs (NSAIDs) prior to presentation.

Endoscopic findings

The most common endoscopic finding in this study was gastritis, seen in 19 (26.8%) of the subjects. Hiatus hernia was seen in 16 (18.3%).

Twelve (16.9%) had gastric erosions, 11 (15.5%) had normal studies while 6 (8.4%) had oesophageal varices. Gastric ulcers and gastric polyps were found in 3 (4.2%) and 2 (2.8%) subjects, respectively (Table 3).

Table 2. Indications for endoscopy in children

Sex Male

descriptive statistics were performed and displayed as frequency tables. Continuous data and categorical data were compared using Student’s t-test, χ2 test and Fischer’s exact test, where appropriate.

Indication

n (%)

Recurrent abdominal pain*

37 (52.1)

Upper GI bleeding

17 (23.9)

Dyspepsia

5 (7.0)

Recurrent vomiting

7 (9.9)

Heartburn

2 (2.8)

Dysphagia

1 (1.4)

PHT

1 (1.4)

Ingestion of corrosive substance

1 (1.4)

Total

71 (100)

*Three patients with recurrent abdominal pain also had epigastric pain.

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RESEARCH Discussion

Table 4 shows the endoscopic findings in relation to the indications in the subjects. The biggest group of subjects with recurrent abdominal pain had gastritis (33.3%) while 21.4% of them had hiatus hernia. Similarly, a significant group of the subjects (35.3%) with upper GI bleeding had gastric erosions. Oesophageal varices occurred in 23.5% of the subjects, while 57.1% of the subjects with recurrent vomiting had hiatus hernia.

The indication for endoscopy was significantly associated with the endoscopic findings (p=0.000) while gender, ethnicity and the nutritional status were not significantly related to the endoscopic findings (p>0.05).

In this study, the most common indication for endoscopy was recurrent abdominal pain, which was seen in just over half the subjects. This finding is higher than in some reports from other developing countries where recurrent abdominal pain constitutes 8 - 43% of the endoscopic indications.[6,10-12] Okello et al.[13] in Uganda observed that 67.4% of the 135 children undergoing the procedure in a tertiary hospital had recurrent abdominal pain. Recurrent abdominal pain is a common presentation in children and is a frequent reason for referral to the paediatric gastroenterologist with a request for upper GI endoscopy.[14-16] Upper GI bleeding was another important indication for endoscopy observed in our study, and was seen in 23.9% of the subjects. In Sudan, upper GI bleeding, especially secondary to PHT, is the most common reason for paediatric upper GI endoscopy.[6] This is believed to be related to the endemicity of schistosomiasis in the country.

Dysphagia and heartburn were the least common reasons for performing endoscopy in the present study; these indications

Endoscopic yield

Table 5 shows the endoscopic yield in relation to the major indications and significantly abnormal endoscopic findings. The overall endoscopic yield obtained in this study was 60.2%. The highest yield was obtained for upper GI bleeding (82.4%) while the lowest yield was for heartburn/dyspepsia (42.8%). Just over 40% of children with recurrent abdominal pain had endoscopic evidence of pathology.

Table 3. Endoscopic findings in children Endoscopic diagnosis n (%)

Outcome in subjects post endoscopy

Twelve (66.7%) of the 18 subjects with gastritis were H. pyloripositive and had triple therapy with amoxicillin, clarithromycin and omeprazole.

Four of the six subjects with oesophageal varices had underlying chronic liver disease from biliary atresia, hepatitis B infection or idiopathic causes.

All the subjects with varices were on propranolol therapy post endoscopy and two of them have had variceal banding done. However, the HbSS patient died during admission. Six (35%) and 2 (11.8%) of the subjects with gastric erosions who presented with GI bleeding used herbal preparations and NSAIDs, respectively, prior to presentation.

They were counselled against the use of these agents subsequently.

All subjects with gastric erosions/ulcers, duodenitis and hiatus hernia were also treated with proton pump inhibitors.

All the subjects are being followed up in the paediatric outpatient clinic of LUTH.

Gastritis

19 (26.8)

Hiatus hernia*

13 (18.3)

Gastric erosions

12 (16.9)

Normal

11 (15.5)

Oesophageal varices†

6 (8.4)

Duodenitis

4 (5.6)

Gastric ulcer

3 (4.2) ‡

Gastric polyp

2 (2.8)

Achalasia

1 (1.4)

Total

71 (100)

*Three patients with recurrent abdominal pain had epigastric pain. †One subject with oesophageal varices also had gastric varices and evidence of portal hypertensive gastropathy. ‡One subject with a gastric polyp also had a duodenal polyp.

Table 4. Indications for endoscopy and endoscopic findings in the subjects Endoscopic finding, n (%) Indication Total (n) Normal

Gastritis

Hiatus hernia

Oesophageal varices

Gastric polyp

Gastric erosions

Gastric ulcer

Duodenitis

Achalasia

Recurrent abdominal pain

37

6 (16.2)

11 (29.7)

8 (21.6)

1 (2.7)

2 (5.4)

5 (13.5)

-

4 (10.8)

-

Upper GI bleeding

17

3 (17.6)

4 (23.5)

-

3 (17.6)

-

6 (35.3)

1 (5.9)

-

-

Recurrent vomiting

7

1 (14.3)

1 (14.3)

4 (57.1)

-

-

-

1 (14.3)

-

-

Dyspepsia

5

-

3 (60.0)

1 (20.0)

-

-

-

1 (20.0)

-

-

Heartburn

2

-

-

1 (50.0)

-

1 (50.0)

-

-

-

Dysphagia

1

-

-

-

-

-

-

-

-

1 (100.0)

PHT

1

-

-

-

1 (100.0)

-

-

-

-

Ingestion of corrosive substance

1

1 (100.0)

-

-

-

-

-

-

-

Total

71

11 (15.5)

19 (26.8)

13 (18.3)

6 (8.5)

2 (2.8)

12 (16.9)

3 (4.2)

4 (5.6)

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1 (1.4)

RESEARCH Study limitations

Table 5. Endoscopic yield in children Major indications

N

Children with significant abnormal endoscopic findings, endoscopic yield, n (%)

Conclusion

Recurrent abdominal pain 37 20 (42.9) Upper GI bleeding

17 14 (82.4)

Recurrent vomiting

7

4 (57.1)

Heartburn and dyspepsia

7

3 (42.8)

Total

68 41 (60.2)

The main limitation of the study was the small number of subjects studied. The histopathological results were not available for inclusion in the study because of logistical reasons.

do not appear to be documented in many paediatric endoscopic studies.[2,5-7,10-13] In terms of endoscopic findings, 15.5% of our subjects had normal studies while the most common finding was gastritis (25.3%). Studies done in Pakistan, Saudi Arabia and Colombia have also reported similar findings.[6,12,14-16] In the Colombian study, the reason was linked to a high prevalence of H. pylori in the subjects, where up to 70% of the subjects had H. pylori colonisation.[14] Other authors have corroborated this finding,[15-17] and in our study two-thirds of the subjects with gastritis were positive for H. pylori.

The majority of these subjects also presented with abdominal pain.

Therefore, it appears that in children with recurrent abdominal pain, there is the need to screen for this organism and to have a high index of suspicion for gastritis when the screening test is positive.

Other significant findings in our study were hiatus hernia, which was seen in 18.3%. One-fifth (21.3%) of the subjects with hiatus hernia also presented with abdominal pain. Half of the subjects with gastric erosions had ingested herbal preparations, a common phenomenon in developing countries. Therefore there is a need to evaluate for the use of herbal preparations and even the use of NSAIDs in children who present with upper GI bleeding, especially when there is no evidence of underlying liver disease. In our cohort, very few subjects had duodenal lesions compared with other studies.[18,19] The reason for this finding is not clear.

The overall endoscopic yield obtained in this study was 60.2%, which is higher than reports by El-Mouzan et al.[18] in Saudi Arabia (43%) and Sheiko[20] in the USA (34%). It must be noted that endoscopic yield remains a function of the indication for the procedure and possibly the expertise of the endoscopist. The high yield obtained in this study may be related to the small number of subjects studied. The best diagnostic yield was for upper GI bleeding (81.8%) in this study. Other authors have also reported a high diagnostic yield for this symptom.[17-20] Upper GI bleeding has been reported to be an important indication for endoscopy and constitutes one of the alarm symptoms that warrant urgent endoscopy.

Upper GI endoscopy remains a very useful diagnostic and therapeutic tool in the management of GI disorders. The overall symptomatology of the patients and the anticipated endoscopic yield should be taken into consideration before the procedure is performed on any child, however.

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There is a need to increase the awareness of the role that paediatric endoscopy plays in the diagnosis and therapy of GI disorders in developing countries. Recurrent abdominal pain remains a relevant indication for the procedure. Every child with upper GI bleeding should certainly have upper GI endoscopy. The need to develop training programmes in developing countries on paediatric endoscopy and paediatric gastroenterology in general cannot be overemphasised.

References 1. Eisen GM, Chuntkan R, Goldstein JL, et al. Modification of endoscopic practice for pediatric patients. Gastrointest Endosc 2000;52(6):838-842.

2. Jantchou P, Schirrer J, Bocquet A. Appropriateness of upper gastrointestinal endoscopy in children: A retrospective study. J Pediatr Gastroenterol Nutr 2007;44(4):440-445. http://dx.doi.org/10.1097/MPG.0b013e31802c6847 3. Bishop PR, Nowicki MJ, May WL, et al. Unsedated upper endoscopy in children. Gastrointest Endosc 2002;55(6):624-630.

4. Gilger MA, Gold BD. Pediatric endoscopy: New information from the PEDSCORI project. Curr Gastroenterol Rep 2005;7(3):234-239.

5. Franciosi JP, Fiorino K, Ruchelli E, et al. Changing indications for upper endoscopy in children during a 20-year period. J Pediatr Gastroenterol Nutr 2010;51(4):443-447. http://dx.doi.org/10.1097/MPG.0b013e3181d67bee 6. Mudawi HMY, El Tahir MA, Suleiman SH, et al. Paediatric gastrointestinal endoscopy: Experience in a Sudanese university hospital. East Mediterr Health J 2009;15(4):1027-1031.

7. Khan MR, Ahmed S, Ali SR, Maheshwari PK, Jamal MS. Spectrum of upper GI endoscopy in paediatric population at a tertiary care centre in Pakistan. Open J Pediatr 2014;4(3):180-184. http://dx.doi.org/10.4236/ojped.2014.43025 8. Aro P, Ronkainen J, Talley NJ, Storskrubb T, Bolling-Sternevald E, Agréus L. Body mass index and chronic unexplained gastrointestinal symptoms: An adult endoscopic population based study. Gut 2005;54(10):1377-1383. http://dx.doi. org/10.1136/gut.2004.057497 9. Agréus L, Svardsudd K, Nyren O, Tibblin G. Reproducibility and validity of a postal questionnaire. The abdominal symptom study. Scand J Prim Health Care 1993;11(4):252-262.

10. Rawashdeh MO, Abu-Farkash N, Al-Jaberi TM. Paediatric upper gastro-intestinal endoscopy in developing countries. Ann Trop Paediatr 1996;16(4):314-316.

11. Joshi MR, Sharma SK, Baral MR. Upper GI endoscopy in children in an adult suite. Kathmandu Univ Med J 2005;3(2):111-114.

12. Hafeez A, Ali S, Hassan M. An audit of paediatric upper gastrointestinal endoscopies. J Coll Physicians Surg Pak 2000;10:13-15.

13. Okello TR. Upper gastrointestinal endoscopic findings in adolescents at Lacor Hospital, Uganda. Afr Health Sci 2006;6(1):39-42.

14. Zuleta MAG, Morales OFR, Riveros J. Diagnostic usefulness of upper gastrointestinal endoscopy for patients under 18 years of age. Rev Col Gastroenterol 2014;29(2):111-115.

15. Kawakami E, Machado RS, Fonseca JA, Patricio FRS. Clinical and histological features of duodenal ulcer in children and adolescents. J Pediatr (Rio J) 2004;80(4):321-325. http://dx.doi.org/10.2223/1207 16. Lubetzky R, Mandel D, Reif S, Bujanover Y. Special clinical manifestations of Helicobacter pylori infection in children and adolescents. Harefuah 2004;143(8):554-556.

17. Vithayasai N. Childhood Helicobacter pylori infection, clinical presentations, endoscopic, histologic features and results of treatment. J Med Assoc Thai 2003;86(3):S600-S604.

18. El-Mouzan MI, Al-Mofleh IA, Abdullah AM, Al-Rasheed R. Indications and yield of upper gastrointestinal endoscopy in children. Saudi Med J 2004;25(9):1223-1225.

19. Ferreira CT, Berti MR, Pires AL, Wieczorek C, Alves J. Endoscopia digestiva alta em pediatria: Indicações e resultados [Upper gastrointestinal endoscopy in children: Indications and results]. J Pediatr (Rio J) 1998;s74(1):39-44.

20. Sheiko MA, Feinstein JA, Capocelli KE, Kramer RE. Diagnostic yield of EGD in children: A retrospective single centre study of 1000 cases. Gastrointest Endosc 2013;78(1):47-51. http://dx.doi.org/10.1016/j.gie.2013.03.168 Accepted 20 July 2016.

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RESEARCH

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

Omphalocoeles: A decade in review S Singh, MB ChB, FC Plast Surg (SA); A Madaree, FRCS (Eng), FCS (Plast), MMed Department of Plastic Surgery, Inkosi Albert Luthuli Central Hospital and School of Clinical Medicine, College of Health Sciences, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa Corresponding author: S Singh (simmi19@icloud.com) Background. Omphalocoeles are associated with significant morbidity and mortality. The presentation varies greatly and management options differ accordingly. Limited literature exists regarding the varied presentation, associated congenital abnormalities and survival from a South African, or even an African perspective.

Objective. To describe the presentation of omphalocoeles, associated abnormalities and survival rates.

Methods. A retrospective epidemiological chart review of patients referred to the paediatric surgical service with newly diagnosed omphalocoeles, between January 2002 and December 2012. Data retrieved included patient demographics, perinatal history, HIV status, associated abnormalities, size of the omphalocoele, management and outcome.

Results. One hundred and fifty-four patients were diagnosed with an omphalocoele during the study period. There were 117 (75.9%) associated congenital abnormalities, 64 (41.5%) minor omphalocoeles (defined as <5 cm) and 66 (42.8%) major omphalocoeles (defined as >5 cm). Eleven patients (7.1%) had ruptured omphalocoeles. Beckwith-Wiedemann syndrome was the most commonly associated abnormality (37.6%), followed by cardiac defects (34.4%).

Conclusion. Omphalocoeles are associated with high numbers of congenital abnormalities. This further complicates management in a resource-poor environment. There is an increased association with Beckwith-Wiedemann syndrome compared with previous studies. This highlights the need to be vigilant with glucose monitoring and to prevent secondary, avoidable complications.

S Afr J Child Health 2016;10(4):211-214. DOI:10.7196/SAJCH.2016.v10i4.1149

Omphalocoele is one of the most dramatic presentations in medicine.

An omphalocoele is a congenital abnormality characterised by the protrusion of abdominal contents through a full thickness defect, with a thin membrane or sac covering the contents. The condition encompasses variably sized ‘simple’ abdominal wall defects with no associated abnormalities, to those associated with a spectrum of congenitally acquired abnormalities that include BeckwithWiedemann syndrome, ‘omphalocoele, extrophy, imperforate anus, spinal’ (OEIS) complex and the pentalogy of Cantrell. Advances in neonatal care have improved the survival of these neonates over the decades; however, their management is not yet standardised to reduce complications and provide a best outcome. The reported incidence is approximately 1 in 3 000 to 1 in 10 000 live births.[1,2] The incidence of omphalocoeles in South Africa (SA) is unknown owing to the lack of a national database. Omphalocoele is a common presentation to the surgical services at Inkosi Albert Luthuli Central Hospital (IALCH) since it is one of only two facilities in KwaZulu-Natal (KZN) Province with specialised paediatric surgical services capable of managing this condition. IALCH is a tertiary healthcare facility that manages specialist paediatric surgical cases in the public health sector in KZN and the eastern part of Eastern Cape Province. There is currently limited literature from an SA perspective regarding the associated abnormalities, size, management or survival. Survival and outcome are directly linked to the nature of these abnormalities, with complex cardiac defects the leading cause of mortality. It is therefore necessary to define the presentation of these neonates and the challenges that are unique to our environment.

Methods

A descriptive, retrospective epidemiological chart review of all patients referred to the IALCH department of paediatric surgery was conducted. Patients with a newly diagnosed omphalocoele between January 2002 and December 2012 were included.

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Ethical approval was granted by the management of IALCH, the Biomedical Research and Ethics Committee of the University of KZN (BE234/15) and the KZN Department of Health (DoH) (KZ_2016RP3_572) prior to the commencement of this study.

Study participants were identified by subject numbers linked to their hospital numbers by means of a password-protected file. All data collected were de-identified for maintenance of confidentiality. Records of all patients with omphalocoele admitted and managed at IALCH between 2002 and 2012 were retrieved from the hospital computer database and analysed. The data included patient demographics, perinatal history, the size of the omphalocoele, any associated congenital anomalies/syndromes, any associated infection (e.g. HIV positivity), as well as overall management and survival. A minor omphalocoele was defined as an abdominal wall defect <5 cm in diameter, while a major omphalocoele was defined as one >5 cm in diameter. BeckwithWiedemann syndrome was diagnosed clinically with the presence of an omphalocoele, macroglossia and neonatal hypoglycaemia (i.e. two major and one minor criteria).[3] The data were entered on a Microsoft Office Excel 2010 (USA, South Africa) spreadsheet and analysed. Simple descriptive statistics were determined using means, standard deviations (SDs) and modes.

Results

One hundred and fifty-four patients with omphalocoeles were included in the study series, with an average of 15 patients a year.

Ten (6%) of the mothers were <18 years old. Maternal age of 57 (37.1%) mothers ranged between 18 and 29 years, 21 (13.6%) ranged between 30 and 39 years, only 4 (2.5%) patients were in the 40 - 49-year category, while there were none >50 years. The maternal age was not documented in 62 (40%) of the patients.

Seventy-five (48.7%) patients had a vaginal delivery, whereas 67 (43.5%) had a caesarean section. The mode of delivery was not documented in 12 (7.7%) patients. Forty-nine (31.8%) of the

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RESEARCH 70 60

Number, n

Number, n

80 70 60 50 40 30 20 10 0

50 40 30 20

Male

Female

Ambiguous genitalia

10 0

Fig. 1. Gender distribution.

Minor

Major

90

Unknown

Fig. 4. Size and type of omphalocoele.

80

Number, n

Ruptured

Size of omphalocoele

100

70 60

Yes

50

No

40

25%

30 20 10

75%

0 <28

28 - 32

33- 36

>37

Gestational age (wk) Fig. 2. Gestational age at delivery.

Fig. 5. Distribution of associated congenital anomalies.

80

70

70

60

60

50

Number, n

30 10

10

0

om

ck w

ith

Birth weight (g)

Pe nt ol

>3 000

os

2 000 - 2 999

ro m

1 000 - 1 999

-W ie d

<1 000

em

0

al

an n

20

Be

Fig. 3. Birthweight at delivery.

babies were HIV exposed, and for 38 (24.6%) patients the results were unknown or undocumented. Regarding the patients, there were 73 (47.4%) females, 72 (46.7%) males and 9 (5.8%) with ambiguous genitalia (Fig. 1). No patients had a gestational age <28 weeks. Sixteen (10.3%) patients had a gestational age of between 28 and 32 weeks, 35 (22.7%) were between 33 and 36 weeks, while the majority were delivered at term, 88 (57.1%) patients (Fig. 2).

Three (1.94%) babies had a birth weight <1 000 g, 19 (12.3%) were between 1 000 and 1 999 g, 84 (54.5%) between 2 000 and 2 999Â g and 43 (27.9%) were >3 000 g (Fig. 3). One hundred and thirty (84.4%) patients had the size of the omphalocoele documented.

In this series, the size of the omphalocoele was documented as 212

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IS

20

OE

30

40

ll

40

og yo fC an tre

50

Ch

Number, n

90

Associated syndromes Fig. 6. Types of associated syndromes.

minor, major or with dimensions. Sixty-four (41.5%) were minor while 66 (42.8%) were major; overall, 11 (7.14%) were ruptured.

The size in 13 (8.44%) patients was not documented (Fig. 4). The size of the omphalocoele in patients with associated congenital abnormalities was minor in 45 (38.4%) patients and major in 50 (42.7%) patients. In isolated omphalocoeles, 19 (61.2%) patients had a minor omphalocoele, while 16 (41%) had a major omphalocoele. There were 117 (75.9%) patients with associated congenital abnormalities, while only 39 (24.1%) had isolated

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RESEARCH both methods were utilised similarly, with 5% more vaginal deliveries noted. It is difficult to ascertain why some of the mothers had caesarean section deliveries, as their medical records were kept in the peripheral hospitals.

Sub-Saharan Africa has the largest number of HIV-infected people. Thirty-one percent of patients were exposed to the virus.

These patients routinely receive antenatal prophylaxis in the third trimester and undergo polymerase chain reaction testing postnatally.

The short- and long-term implications of HIV association with omphalocoeles are yet to be determined.

60

Number, n

50 40 30 20 10

Neonatal factors

he r Ot

Ca rd i

ac Ur og en ita l Sk el Ga et st al ro in te st He in al ad an d ne ck Re sp ira to ry

0

Associated non-syndromic abnormalities Fig. 7. Non-syndromic congential anomalies identified by organ system.

omphalocoeles (Fig. 5). Beckwith-Wiedemann syndrome had the largest association in this series, with 58 (37.6%) patients. Other syndromes included chromosomal abnormalities, viz. trisomy 18, 13 and 21 in 12 (7.79%) patients, pentalogy of Cantrell in 7 (4.54%) and OEIS complex in 4 (2.59%) (Fig. 6). The associated systemic abnormalies in decreasing frequency were cardiac abnormalies in 53 (34.4%), urogenital 49 (31.8%), skeletal 32 (20.7%), gastrointestinal tract 20 (12.9%); head and neck 10 (6.49%); respiratory 6 (3.89%) and 5 (3.24%) other non-specific abnormalities (Fig. 7). Thirty-nine (25.3%) were described as dysmorphic, which included low-set ears, pre-auricular pits or coarse facial features. The management entailed primary closure in 99 (64.2%) patients, while conservative management with topical silver sulphadiazide (Flamazine, Smith and Nephew SA, SA) applied in 45 (29.2%) patients. The placement of a Gortex patch (Flagstaff, USA) occurred in 6 (3.89%) patients, while amnioinversion was used in 4 (2.59%) and a silo-bag closure in only 2 (1.29%) patients. There were 27 (17.5%) deaths in this series.

Two-thirds of the deaths (n=18) were attributed to the associated congenital abnormality. Six patients (22.2%) succumbed to sepsis, 2 (7.4%) died as a result of aspiration pneumonia and 1 (3.7%) had an abdominal compartment syndrome.

Discussion

Omphalocoele is a congenital, central abdominal wall defect that results in the herniation of the abdominal contents through an umbilical defect with an overlying membrane covering the contents.

This study focused on the different presentations of omphalocoeles and the associated congenital abnormalities.

Maternal factors

McNair et al.[1] reported an association of omphalocoeles with advanced maternal age. In this series, however, 43% of mothers were <30 years and 16% were ≥30 years. Interestingly, it is known that advanced maternal age (>35 years) is associated with increased chromosomal abnormalities. The presence of chromosomal abnor­ malities in this study was <10%. Mann et al. [4] also showed that maternal age >35 years is a risk factor for some of the trisomies asso­ ciated with omphalocoele; maternal age per se does not appear to be an independent risk factor for omphalocoele. Mode of delivery is still controversial. Islam[5] found that there is no study that advocates one method over the other, and numerous reports of safe delivery vaginally. The mode of delivery in this series appears irrelevant as 213

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A study by McNair et al.[1] reported that omphalocoeles occur more frequently in males than in females, at a ratio of 1.5 - 3:1. Mortellaro et al.[2] also reported a male preponderance. In this series, an almost equal number of males and females were found, with 5.8% of patients having ambiguous genitalia. More than half of the babies were born at term, with only 10% born before 32 gestational weeks. Hence it follows that most of the babies were ≥2 kg in weight and only 13% were <2 kg in weight. In a study done in Germany, the average birth weight was 2 432 g and gestational age 35.5 weeks.[6] A UK study showed that outcomes have been influenced negatively by birth weight and gestational age, if the birth weight is < 2 kg or gestational age <35 weeks.[7]

Omphalocoele size: Minor v. major

The literature arbitrarily defines a major omphalocoele as >5 cm and containing liver or small bowel, and minor as <5 cm.[2,5,8] This definition is flawed as it does not consider the size of the baby or the visceroabdominal disproportion. It is, however, the only working definition that helps stratify omphalocoeles. The size of the omphalocoele was fairly equally distributed between the two groups in this study. Groves et al.[9] found that congenital abnormalities were commonly associated with a minor omphalocoele. In his series, he found 39% of chromosomal abnormalities associated with a minor omphalocoele. In this study, with 75% associated congenital abnormalities, 42.7% had a major omphalocoele and 38.4% had a minor omphalocoele associated with a congenital abnormality. The associated abnormalities did not correlate with the defect size as shown by Groves et al. A minor omphalocoele was more commonly associated with an isolated omphalocoele (61%). Mann et al.[4] reported that several studies have shown no correlation between defect size and neonatal outcome.

Associated congenital abnormalities

In this review of one decade, 75% of patients had other associated abnormalities. This is often associated with increased morbidity and mortality. The literature reports 50 - 80% of associated abnormalities. [5,10- 12] A UK study found 75% of exomphalos have associated anomalies, 29% chromosomal, 30% non-syndromic multiple congenital anomalies, and recognisable malformation syn­ drome or pattern in 44%.[7] Although the associated abnormalities are contributing factors to mortality, the mortality rate in this series was 18% despite the constraints of a resource-poor environment. The survival rate of isolated omphalocoele is as high as 96%, but this drops significantly in the presence of associated abnormalities.[8] Yazbeck et al.[10] found the overall mortality rate to be 37%, while a Canadian study found a mortality rate of 31%.

An interesting finding was the high association of BeckwithWiedemann syndrome. Although this is a known association, the literature reports an incidence of 1 - 14%.[1,8,10,11,13] In this series, there were 37.6% of patients with Beckwith-Wiedemann syndrome. This is often a clinical diagnosis that is easily missed, hence the low reports in the literature. Other syndromes associated with omphalocoele include pentalogy of Cantrell (4.5%) and

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RESEARCH OEIS complex (2.5%). The OEIS complex is rare, occurring in ~1 in 250 000 to 1 in 200 000.[14] These syndromes are often incompatible with life. Survival is fraught with morbidities and eventual mortalities. Chromosomal abnormalities, viz. trisomy 13, 18 and 21, were found in 7.7% of patients. Trisomy 13 was the most common (54.5%). Chromosomal abnormalities are generally associated with advanced maternal age; in this series, only 2.5% of patients were >40 years. In a Canadian study, 11% had chromosomal abnormalities.[10] In a New York study, 8% had chromosomal anomalies with trisomy 13 the most common.[15] Chromosomal abnormalities range from 8 to 40% in the literature, with trisomy 13 and 18 the most common.[1,11,15] In the nonsyndromic associated abnormalities, cardiac defects were most frequently found (34.4%). This is a similar finding to that in the literature (20 - 50%).[1,2,5,10,11] Tetralogy of Fallot and atrial septal defects were most common,[1] with 50% having an abnormal cardiac axis.[4] In this series, patent ductus arteriosus was the most common defect (n=29), followed by atrial septal defect (n=9) and ventricular septal defect (n=7). There were three patients with tetralogy of Fallot, two patients with dextrocardia, two patients with coarctation of aorta and one patient with a hypoplastic left heart syndrome. Genitourinary abnormalities were also common in this series (31.8%), while it is reported as less common in other series where genitourinary, skeletal and facial defects are found in 10 - 20% of cases.[1] These include undescended testes, ambiguous genitalia, hydronephrosis, bladder extrophy, cloacal extrophy, patent urachus, polycystic kidneys, hypospadias, bifid scrotum, posterior urethral valves, absent kidney, horseshoe kidney, renal cyst and epispadias.

Skeletal abnormalities were found in 20.7% of patients. These included, in decreasing order of frequency, club feet, polydactyly, scoliosis, sacral agenesis, hemivertebrae, myelomeningocoele, spina bifida, clinodactyly, syndactyly and absent clavicle. Respiratory abnormalities were only detected in 3.8% of cases, with pulmonary hypoplasia, pulmonary hypertension, congenital diaphragmatic hernia and bronchomalacia being implicated, as found in the literature.[4]

Study limitations

The study is limited by the unknown number of pregnancy terminations due to antenatally diagnosed omphalocoele and the incidence in spontaneous abortions with this anomaly. Additionally, this was a single-centre study conducted in the public sector, albeit in one of the largest SA provinces and in one of only two referral centres for paediatric surgery in the province.

Conclusion

Omphalocoele is a congenital, midline abdominal defect carrying a high association with other congenital abnormalities. BeckwithWiedemann syndrome has a much higher association with omphalocoele than has previously been described in the literature. Strict glucose monitoring is vital to prevent secondary

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complications. Cardiac and genitourinary anomalies are also frequently found. The associated congenital abnormalities prompt a thorough pre-anaesthetic work-up to prevent morbidities and mortalities. Advanced maternal age is not a risk factor for omphalocoele in the local population and there is an equal gender distribution in this series. The size of the omphalocoele does not appear to affect the neonatal outcome. Despite the constraints of a resource-poor environment, the mortality is much lower than quoted in the literature, at only 18%.

Acknowledgement. Thanks to Dr T C Hardcastle for layout and grammar review prior to finalisation of the submission version.

References

1. McNair C, Hawes J, Urquhart H. Caring for the newborn with an omphalocoele.

Neonatal Netw 2006;25(5):319-332. http://dx.doi.org/10.1891/07300832.25.5.319 2. Mortellaro VE, St Peter SD, Fike FB, Islam S. Review of the evidence on closure of abdominal wall defects. Pediatr Surg Int 2011;27(4):391-397. http://dx.doi. org/10.1007/s00383-010-2803 3. Weksberg R, Shuman C, Beckwith JB. Beckwith-Wiedemann syndrome. Eur J Hum Genet 2010;18(1):8-14. http://dx.doi.org/10.1038/ejhg.2009.106 4. Mann S, Blinman TA, Wilson R. Prenatal and postnatal management of omphalocele. Prenat Diagn 2008;28(7):626-632. http://dx.doi.org/10.1002/ pd.2008 5. Islam S. Advances in surgery for abdominal wall defects: Gastroschisis and omphalocele. Clin Perinatol 2012;39(2):375-386. http://dx.doi.org/10.1016/J. CLP.2012.04.008 6. Axt R, Quijano F, Boos A, et al. Omphalocele and gastroschisis: Prenatal diagnosis and peripartal management. A case analysis of the years 1989-1997 at the Department of Obstetrics and Gynecology, University of Homburg/Saar.

Eur J Obstet Gynecol Reprod Biol 1999;87(1):47-54. http://dx.doi.org/10.1016/ S0301-2115(99)00078-0 7. Marven S, Owen A. Contemporary postnatal surgical management strategies for congenital abdominal wall defects. Semin Pediatr Surg 2008;17(4):222-235. http://dx.doi.org/10.1053/j.sempedsurg.2008.07.002 8. Cohen-Overbeek TE, Tong WH, Hatzmann TR, et al. Omphalocele: Comparison of outcome following prenatal or postnatal diagnosis. Ultrasound Obstet Gynecol 2010;36(6):687-692. http://dx.doi.org/10.1002/uog.7698 9. Groves R, Sunderajan L, Khan AR, et al. Congenital anomalies are commonly associated with exomphalos minor. J Pediatr Surg 41(2):358-361. http://dx.doi. org/10.1016/j.jpedsurg.2005.11.013 10. St-Vil D, Shaw KS, Lallier M, et al. Chromosomal abnormalities in newborns with omphalocoele. J Paediatr Surg 1996;31(6):831-834. http://dx.doi. org/10.1016/S0022-3468(96)90146-3 11. Ledbetter DJ. Congenital abdominal wall defects and reconstruction in pediatric surgery: Gastroschisis and omphalocele. Surg Clin North Am 2012;92(3):713727. http://dx.doi.org/10.1016/j.suc.2012.03.010 12. Islam S. Clinical care outcomes in abdominal wall defects. Curr Opin Pediatr 2008;20(3):305-310. http://dx.doi.org/10.1097/MOP.0b013e3282ffdc1e 13. Kilby MD, Lander A, Usher-Somers. Invited commentary: Current issues in obstetrics and genetics exomphalos (omphalocele). Prenatal Diag 1998;18:12831288.

14. Brantberg A, Blaas HG, Haugen SE, Eik-Nes SH. Characteristics and outcome of 90 cases of fetal omphalocele. Ultrasound Obstet Gynecol 2005;26(5):527537. http://dx.doi.org/10.1002/uog.1978 15. Salihu HM, Pierre-Louis BJ, Druschel CM, Kirby RS. Omphalocele and gastroschisis in the State of New York, 1992-1999. Birth Defects Res A Clin Mol Teratol 2003;67(9):630-636. http://dx.doi.org/10.1002/bdra.10113

Accepted 8 March 2016.

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

Management of acute diarrhoeal disease at Edendale Hospital: Are standard treatment guidelines followed?

K Reddy,1 MB BCh, B Pharm, FCPaed (SA); M E Patrick,1,2 MB ChB, DCH (SA), FCPaed (SA); C R Stephen,3,4 MB ChB, DCH (SA) epartment of Paediatrics and Child Health, Nelson R Mandela School of Medicine, Faculty of Health Sciences, University of KwaZulu-Natal, D Durban, South Africa 2 Greys Hospital, Pietermaritzburg Metropolitan Hospitals Complex, South Africa 3 Department of Paediatrics and Child Health, University of Cape Town, South Africa 4 Red Cross War Memorial Children’s Hospital, Cape Town, South Africa 1

Corresponding author: K Reddy (kershinee@yahoo.com) Background. Diarrhoeal disease (DD) is a major cause of childhood mortality in developing countries. In South Africa (SA), it ranks as one of the top five causes of under-5 mortality. Local and global guidelines on the management of acute DD are readily available. The Standard Treatment Guidelines (STGs) and Essential Drugs List for Hospital Level Paediatrics are a recognised standard of care for children in SA hospitals. However, children still die from this preventable disease.

Objective. To determine whether doctors adhered to standard treatment guidelines when treating children under 5 years of age presenting to Edendale Hospital in Pietermaritzburg, KwaZulu-Natal Province, with acute DD. Methods. The study was a retrospective clinical audit of individual patient records.

Results. One hundred and thirty-five patient records were reviewed. Forty-seven percent had a correct nutritional assessment, 41% were correctly assessed for shock and 27% for dehydration. Appropriate investigations were undertaken in 12%. Ninety-seven percent of patients had appropriate fluid plans prescribed. Zinc was prescribed in only 39% of patients, whereas 84% were appropriately not prescribed antibiotics and no patients received anti-diarrhoeal medication. In 90% of patients, the correct post-care patient referral was made, and 47% of caregivers were adequately advised about ongoing care of their children.

Conclusion. This study identifies substantial non-adherence to the SA STGs for the management of young children with acute DD. S Afr J Child Health 2016;10(3):215-220. DOI:10.7196/SAJCH.2016.v106i4.1177

The fourth Millennium Development Goal (MDG 4) committed participating countries to reduce the under-5 mortality rate (U5 MR) by two-thirds between 1990 and 2015.[1] South Africa (SA) made insufficient progress of achieving the MDG 4 U5 MR target of 21 per 1 000 live births by 2015.[2] From 1990 to 2005, SA’s rate of progress was lower than conflict-ridden countries such as Somalia, Iraq and the Democratic Republic of Congo. However, from the middle of the last decade, SA’s U5 MR has declined significantly, and between 2006 and 2011, the annual rate of decline was the fourth fastest globally.[2] Causes of death in children vary according to age. Globally, in 2011, the top five causes were preterm birth complications, diarrhoeal disease (DD), birth asphyxia, malaria and ‘other’ causes. [1] In SA, during the neonatal period, preterm birth, birth asphyxia and infections contributed to the majority of early deaths.

Outside the neonatal period, HIV/AIDS and childhood infections (especially diarrhoea and pneumonia) are the major causes of death and are also responsible for the majority of childhood morbidity in SA.[3] According to the SA Child Healthcare Problem Identification Programme (PIP), for the period 2005 - 2009, DD was the second most important direct cause of death after acute respiratory infections.[4] In SA, the incidence of DD decreased in the under-5 age group from 286.4 cases per 1 000 population in 1998 to 95.9 cases per 1 000 population in 2011.[5] There was a decrease in DD incidence in all provinces. However, KwaZuluNatal (KZN) has shown a much smaller decrease when compared with other provinces. KZN’s DD incidence was above the national average with 139.1 cases per 1 000 population in 2011.[5] Child PIP statistics from Edendale Hospital (EDH), a regional hospital in 215

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KZN, between 2005 and 2013 showed that DD was the third most frequent cause of death in children under 5 years, but a decrease was noted in the overall under-5 in-hospital mortality rate (U5 IHMR). From January 2005 to July 2013, the U5 IHMR decreased from 8.4 to 2.5 deaths per 100 admissions.

In the 1978 declaration of Alma Ata, the availability of essential medicines was listed as one of the eight minimum requirements of primary healthcare.[6] The concept of essential medicines is that the availability of a limited and select range of medicines would lead to better healthcare, better drug management, better use of financial resources, and therefore improved healthcare. Twenty-five years after the declaration, over 100 countries had national drug policies, 156 countries had national or provincial essential medicines lists and over 130 countries had developed national treatment guidelines to provide objective and unbiased guidance on rational use of medicines.[7] National STGs were introduced in SA during 1996.[8] At EDH, an orientation programme is provided for all new doctors working in the paediatric department, irrespective of rank. This 2-week comprehensive training programme includes the assessment and management of DD and emphasises the overall importance of using guidelines in paediatrics. The objective of this study was to determine whether doctors in the EDH Paediatric Outpatient Department (POPD) followed the 2006 Standard Treatment Guidelines (STGs) and Essential Drugs List (EDL) for HospitalLevel Paediatrics when managing children with DD – the STGs and EDL for Hospital-Level Paediatrics 2006 were in use at the time of the study. A secondary objective was to assess differences in STG adherence between different ranks of attending doctor.

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This was a descriptive cross-sectional study, using a retrospective review of patient records to perform a clinical audit.

The setting was the POPD at EDH in Pietermaritzburg, KZN, during two summer (January, February) and two winter (June, July) months in 2013. Patients aged 2 months to 5 years attending the Edendale POPD with acute DD were included in the study. Patients were identified using the POPD register for the respective study months. Relevant patient records were then obtained from the hospital’s records department. The following were excluded: children with chronic DD, children with another coincident serious illness and children with dysentery. It was postulated that a review of 150 - 200 patient records would provide sufficient data to describe doctors’ adherence to the STGs. The first 100 patient records over the summer months and the first 100 patient records over the winter months were evaluated.

Two hundred patient records were retrieved, and 135 records met inclusion criteria. Sixtyfive were excluded (Fig. 1). Ten key actions in the management of children with DD were evaluated by the principal investigator. Apart from the nutritional assessment (which included the evaluation of moderate and severe malnutrition as current best practice according to the National Department of Health), all the actions were based on the 2006 STGs and EDL for Hospital-Level Paediatrics, namely: 1. Correct nutritional assessment 2. Correct assessment for shock 3. Correct assessment for dehydration 4. Appropriate investigations 5.

Appropriate fluid management plans according to the child’s dehydration severity assessment 6. Appropriate prescriptions, specifically: a) prescription of zinc b) non-prescription of antibiotics c) non-prescription of anti-diarrhoeal mediation 7. Appropriate referral to the next place of care (home, oral rehydration corner or ward admission) 8. Adequate advice to caregivers regarding the diagnosis, severity of illness and ongoing care of their children.

For each of the ten actions, a compliance score was given, whereby compliant = 2, partially compliant =1 or non-compliant = 0.

A data collection tool was developed using a compliance scale (Appendix A). The tool also included demographic data (age, nutritional status, HIV status and rotavirus immunisation), the assessment of the child’s fluid deficit (shock and dehydration) and the rank of attending doctor (intern, medical officer, registrar and paediatric specialist).

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Data were analysed in Microsoft Excel (Microsoft Corp., USA). Simple descriptive statistics were used to assess adherence to STGs.

Results

Patient demographics

The median age of patients was 22 (range 2 - 60) months. The nutritional status was unknown in 53%. Retrospective analysis of nutritional status in the unknown group showed that 89% had no acute malnutrition, 9% were classified as having moderate acute malnutrition and 3% were classified as having severe acute malnutrition. Seventy-eight percent were

HIV uninfected, and in 13% the HIV status was unknown. In 70% rotavirus vaccine had been given but in 22% this information was unknown. Over 40% of children were assessed as dehydrated and only 3% were assessed as shocked. Sixty-two percent of the patients were seen by interns and in 8% the doctor’s rank was unknown (Table 1).

Adherence to STGs

Forty-seven percent of patients had a correct nutritional assessment. Forty-one percent of patients had a correct assessment for shock and 27% of patients had a correct assessment for dehydration. Twelve per cent had appropriate

Table 1. Demographic profile of patients with diarrhoeal disease (N=135) n (%)* Age (months) Range

2 - 60

Median

22

Nutrition No acute malnutrition

51 (38)

Moderate acute malnutrition

7 (5)

Severe acute malnutrition

6 (4)

Unknown

71 (53)

HIV status Infected

4 (3)

Uninfected

105 (78)

Uninfected and breastfed

8 (6)

Unknown

18 (13)

Rotavirus vaccine Yes

94 (70)

No

11 (8)

Unknown

30 (22)

Patient condition Shocked Yes

4 (3)

No

121 (90)

Unknown

10 (7)

Dehydrated Yes

57 (42)

No

67 (50)

Unknown

11 (8)

Rank of attending doctor Intern

84 (62)

Medical officer

21 (16)

Registrar

19 (14)

Paediatric specialist

0 (0)

Unknown

11 (8)

*Unless otherwise indicated.

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RESEARCH investigations undertaken. The most commonly omitted investigations were urine dipsticks and blood sugar finger prick. Ninety-seven percent of patients had fluid plans appropriate to their dehydration severity assessment. Thirty-nine percent of patients had zinc correctly prescribed. The correct non-prescription of antibiotics occurred in 84% of patients and no patients were prescribed anti-diarrhoeal medication, as outlined in the STGs. Ninety percent of patients received appropriate post-care referral. Patient records indicated that almost half of caregivers (47%) were adequately advised on the diagnosis, severity of the illness and ongoing care of their children (Table 2).

Discussion

DD is a major cause of childhood mortality in developing countries.

The annual mortality report released by Statistics SA for deaths occurring in 2013 listed intestinal infectious diseases as the leading cause of death in children under 5 years of age.[9] At EDH, where DD is ranked as the third most frequent cause of death in children under 5 years, this study found significant non-adherence to STGs for the management of DD by doctors in a setting of high DD prevalence.

There was poor adherence in six of ten key actions for managing children with DD, which is cause for concern. For these six steps, the average compliance by rank of doctor was 38% for interns, 36% for medical officers and 24% for registrars. It appears that the more senior the doctor, the lower the adherence.

Nutrition

Of the 135 patients, only 47% had a correct nutritional assessment, with low adherence rates by all ranks of doctor (Table 2). All children accessing healthcare should have a correct nutritional assessment, both because of the high prevalence of malnutrition in the population served, and because a childâ&#x20AC;&#x2122;s nutrition status informs correct fluid management in DD.

Shock and dehydration

Fluid management

Ninety-seven percent of patients appeared to have correct fluid management plans. However, this may have been an overestimate as doctors showed poor STG adherence for the assessment of shock and dehydration, making it difficult to match fluid plans with the actual clinical condition of the patient.

Prescribing

Zinc While it is accepted that the use of zinc is beneficial in DD,[10] only 39% of patients received zinc. In contrast to the overall trend by rank, registrars (53%) prescribed zinc more often than interns (36%).

Antibiotics Sixteen percent of children had antibiotics prescribed, with no clear indication documented in the patient records, i.e. a condition other than DD. Antibiotic use is advocated in certain diarrhoeal conditions, e.g. dysentery, and also in some common medical conditions that may co-exist at the time of the diarrhoeal presentation. However, these patient records were specifically excluded from the study.

Anti-diarrhoeal medication It was encouraging to find that no children were prescribed antidiarrhoeal medication. This may be because the use of anti-diarrhoeal medication is generally strongly discouraged in the management of DD, by medical schools, in the clinical setting and in clinical guidelines.

Place of further care

Ninety percent of children were assigned to the correct place of further care. There was greater adherence among the medical officers (100%) and interns (93%), compared with the registrars (79%).

Caregiver advice/education

Only 41% of children had a correct assessment for shock and only 27% were correctly assessed for dehydration. This could reflect poor quality of care, poor quality of guidelines or poor documentation, or a combination of all three. Proper assessment of shock and dehydration is an important part of providing proper emergency care for children.

Forty-seven percent of caregivers were adequately counselled. A possible reason for this low adherence is that attending doctors may not have recorded their counselling of the caregivers in the patient record. Nevertheless it cannot be assumed that the caregivers were counselled about danger signs on discharge or the use of ORS in DD if this was not documented.

Investigations

Rank of attending doctor

Adherence to requesting appropriate investigations was low (12%) for all ranks of doctor, mostly due to inadequate investigation.

The results showed non-adherence to treatment guidelines ir­ respective of the rank of attending doctor. Registrar adherence to

Table 2. Analysis of primary and secondary objectives: Adherence to STGs Compliant, n (%) Patients

Rank of attending doctor

Total (N=135)

Intern (N=84)

Medical officer (N=21)

Registrar (N=19)

Unknown (N=11)

Correct nutritional classification

63 (47)

39 (46)

12 (57)

5 (26)

7 (63)

Correct shock assessment

56 (41)

38 (45)

10 (48)

4 (21)

4 (36)

Correct dehydration assessment

36 (27)

27 (32)

2 (10)

2 (11)

5 (45)

Appropriate investigations

16 (12)

9 (11)

4 (19)

2 (11)

1 (9)

Appropriate fluid plan

131 (97)

81 (96)

21 (100)

19 (100)

10 (91)

Appropriate zinc prescription

52 (39)

30 (36)

9 (43)

10 (53)

3 (27)

Non-prescription of antibiotics

113 (84)

72 (86)

15 (71)

17 (89)

9 (82)

Non-prescription of anti-diarrhoeals

135 (100)

84 (100)

21 (100)

19 (100)

11 (100)

Appropriate referral to next place of care

122 (90)

78 (93)

21 (100)

15 (79)

8 (73)

Adequate counselling provided

64 (47)

48 (57)

8 (38)

4 (21)

4 (36)

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RESEARCH STGs was lower than interns for six of the ten actions, i.e. nutritional classification, shock assessment, dehydration assessment, use of investigations, further place of care and counselling of caregivers.

Furthermore, registrars also scored lower than medical officers for five of the ten actions. This is a major concern as registrars are specialists-in-training and have an important role to play in supervising and teaching their junior colleagues, and in role modelling.

The study showed that guidelines were not being properly followed by doctors at EDH POPD. This may adversely affect the quality of care received by patients, the utilisation of resources, costs to the hospital and income for parents who may have to stay in hospital with their children.

It is not known from this study whether or not substantial nonadherence to DD guidelines directly impacts mortality. However, this possibility is also a cause for concern.

The study findings are surprising for a number of reasons. At medical schools, the pathophysiology and management of DD is taught in great detail through lectures and the use of prescribed texts. But focus on the management of DD according to the STGs in particular is often not included. Instead the focus is more on the use of Integrated Management of Childhood Illness (IMCI) guidelines for management of DD and other common conditions. In the IMCI guidelines, assessment of dehydration and fluid management is similar to that described in the STGs. In the authors’ experience, the use of the STGs was first emphasised during internship and subsequent training years.

EDH is a typical KZN regional hospital providing primary and regional levels of care. It is possible that studies in other KZN hospitals may reveal similar findings of non-adherence to STGs. Reasons given for non-adherence include lack of time due to high patient load, staff shortages, lack of supervision of junior doctors, increased pressure on senior doctors, poor documentation of findings in patient records and/or poor interpretation of clinical signs, all of which may have serious implications for the patient.

Staff indifference to the use of guidelines is another possible factor.

The actual reasons for non-adherence to the STGs need to be further elucidated.

Recommendations

The findings of this study suggest a few easily implementable actions: 1. Teaching on the importance of standard guideline usage (as opposed to teaching guideline content) during orientation training for staff, to ensure that all doctors irrespective of rank receive training in the use of STGs and understand the importance of STGs in disease management and prevention in children.

2. The introduction of a standardised clerking sheet to be used by doctors for patients presenting with DD, where all the information required for a successful consultation, as described in the STGs, is presented.

3. Regular record and clinical audit of patients presenting with DD to assess if guidelines are being adhered to and, if not, to assess the impact of this on morbidity and mortality.

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4. Action plans based on audit results can lead to further strategies for improving quality of care for children with DD. The global target set for MDG 4 was to reduce U5 MR by twothirds between 1990 and 2015. According to the MDG Report 2015, the global U5 MR has declined by more than half, with the rate of reduction of U5 MR more than tripling since the early 1990s.[10] In sub-Saharan Africa, the annual rate of reduction of U5 MR was over five times faster during 2005 - 2013 than during 1990 - 1995.

Despite impressive improvements in most regions, current trends are not yet sufficient to meet the MDG 4 target. At today’s rate of progress, it would take about 10 more years to reach the target.[11] DD is a significant cause of childhood mortality in SA and more work needs to be done to limit unnecessary loss of life caused by this preventable illness. This study focused on one aspect of care by assessing if doctors adhered to STGs for the management of DD.

Conclusion

This study has identified that the majority of doctors at EDH POPD did not follow STGs in the management of children with acute DD. Solutions to the problem are broader than simply issuing instructions on guideline usage to junior doctors. As described in a recent article in The Lancet ‘… if a health system is weak, guidelines cannot compensate for it. Addressing issues in quality of care and supporting health systems is necessary to tackle the challenges of paediatric care in resource limited settings.’[11] References 1. World Health Organization. Children: Reducing Mortality Factsheet No. 178.

Geneva: WHO, 2012. http://www.who.int>factsheets>fs178 (accessed 14 April 2016).

2. Kerber KJ, Lawn JE, Johnson LF, et al. South African child deaths 1990 - 2011: Have HIV services reversed the trend enough to meet Millennium Development Goal 4? AIDS 2013;27(16):2637-2648. http://dx.doi.org/10.1097/01. aids.0000432987.53271.40 3. Sanders D, Bradshaw D, Ngongo N. The status of child health in South Africa.

In: Kibel M, Lake L, Pendelbury S, Smith C, eds. South African Child Gauge 2009/2010. Cape Town: Children’s Institute, University of Cape Town; 2010:31.

4. Westwood A. Diarrhoeal Disease. In: Stephen CR, Bamford LJ, Patrick ME, Wittenberg DF, eds. Saving Children 2009: Five Years of Data. A Sixth Survey of Child Healthcare in South Africa. Pretoria: Tshepesa Press, Medical Research Council, Centers for Disease Control, 2011:61-75.

5. Health statistic indicators. http://indicators.hst.org.za/healthstats/132/data (accessed 2013).

6. World Health Organization (WHO). Declaration of Alma-Ata. International Conference on Primary Health Care, Alma Ata, USSR, 6 - 12 September 1978. http:// www.who.int/publications/almaata_declaration_en.pdf (accessed 14 April 2016).

7. Quick JD. Essential medicines twenty-five years on: Closing the access gap.

Health Policy Plan 2003;15(1):1-3. http://dx.doi.org/10.1093/heapol/18.1.1 8. Sooruth UR, Sibiya MN, Sokhela DG. The use of Standard Treatment Guidelines and Essential Medicines List by professional nurses at primary healthcare clinics in the uMgungundlovu District in South Africa. Int J Afr Nurs Sciences 2015;(3):50-55. http://dx.doi.org/10.1016/j.ijans.2015.08.001 9. Statistics South Africa. Mortality and Causes of Death in South Africa, 2013: Findings from Death Notification. Pretoria: Statistics South Africa, 2014:33.

10. United Nations. The Millennium Development Goals Report. New York: United Nations, 2015:32-35.

11. Duke T. New WHO guidelines on emergency triage assessment and treatment. Lancet 2016;387(10020):721-724. http://dx.doi.org/10.1016/S01406736(16)00148-3 Accepted 13 July 2016.

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

An audit of primary medical conditions in children admitted to the paediatric intensive care unit of Charlotte Maxeke Johannesburg Academic Hospital R K Mopeli, MB BCh, FCPaed (SA); D E Ballot, MB ChB, FCPaed (SA), PhD; D A White, MB BCh, FCPaed (SA), MMed (Paed), Dip Allerg (SA), Cert Pulm (SA) Paed Department of Paediatrics, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa Corresponding author: R K Mopeli (kmopeli@yahoo.com) Background. There is approximately one paediatric intensive care unit (PICU) bed per 22 800 children in SA, making PICU beds a very limited resource.

Objectives. To determine the spectrum of medical conditions in children admitted to a PICU, their outcomes, and to compare the number and outcomes of HIV-exposed/infected children v. HIV-unexposed children.

Methods. This was a retrospective chart review of children older than 28 days, admitted to Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) PICU for medical conditions from 1 January 2013 to 31 July 2014.

Results. There were 883 admissions; 518 (59%) were neonates and 234 (26.5%) were surgical patients, leaving a final sample of 131 (14.8%) children with medical conditions. The median age of children admitted was 3.8 months. Out of 131 children, 44 (34%) were HIV-exposed and 16 (12.2%) had a positive HIV polymerase chain reaction (PCR) result. Lower respiratory tract infections (LRTIs) accounted for two-thirds of all admissions at 84 (64.1%) and were significantly more common in HIV-exposed children (p=0.0005); 32 (24.4%) patients died. HIV-exposed children stayed 3 days longer (p=0.015), were ventilated for 4 more days (p=0.012) and were three times more likely to require high-frequency oscillatory ventilation (p=0.0005) than HIV-unexposed children. Mortality was similar between these two groups.

Children confirmed HIV PCR-positive had a significantly longer duration of ICU stay (p=0.03) and ventilation (p=0.006) than those who were exposed but uninfected.

Conclusion. There were 883 children admitted in 19 months to CMJAH PICU. A total of 15% of admissions were for medical conditions, two-thirds of which were for LRTIs. One-third of the children were HIV-exposed and had similar outcomes to their unaffected counterparts, although their duration of ventilation and length of stay were longer.

S Afr J Child Health 2016;10(4):221-226. DOI:10.7196/SAJCH.2016.v10i4.1187

South Africa (SA) is a low- to middle-income country with an estimated population of 18.6 million children.[1] The mortality rate in <5-year-olds was estimated to be 41 per 1 000 live births in 2015, with lower respiratory tract infections (LRTIs) causing 16.9% of those deaths.[2] Many of these children may have benefitted from admission into a paediatric intensive care unit (PICU) where mechanical ventilation could have been offered to them. However, there are not enough PICU beds in SA to cater for the needs of the most seriously ill children.

An SA national audit of critical care resources done in 2005 found that only 815 of 4 618 ICU beds were assigned to paediatric and neonatal patients, and these are often shared. There is a paucity of data on the breakdown of allocated paediatric v. neonatal beds. Most hospitals were found to be admitting children to combined medical and surgical units.[3] There is therefore approximately one paediatric ICU bed per 22 800 (815/18.6 million) children.

In this SA setting with limited resources, decisions have to be made as to how best to allocate these resources. Some PICUs have developed and implemented explicit policies for the use of PICU resources, thus providing a ‘reasonable’ process for equitable utilisation of limited resources; however, SA does not have national or provincial guidelines for admitting patients to an ICU.[4,5] Various scoring systems have been developed to allow for assessment of the quality of care in PICUs, e.g. PRISM III, PIM2, PEMOD, PELOD, TISS and SOFA scores.[6] Wells et al.[7] found the PRISM score to have a poor discriminatory function over a 6-year period (1989 - 1994) in a SA ICU. Subsequent to that a study done at the Red Cross War Memorial Children’s Hospital in 2007 found that 221

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the PIM and PIM2 scores demonstrated good overall discrimination, therefore validating their use in SA.[8] Data on admission trends and outcomes in SA PICUs, which could be used to develop our own scoring systems, are scarce.

Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) is a tertiary teaching and referral centre that provides healthcare services to the people of Gauteng Province, SA, as well as to neighbouring provinces. The 220-bed paediatric service caters for all paediatric medical and paediatric surgical subspecialties. There are 15 beds in the PICU, which are in high demand. The consultant staff in the PICU consist of four neonatologists and one paediatric pulmonologist. There are no dedicated paediatric intensivists. A retrospective review was done from 1993 to 1994 by Ballot et al.,[9] which included all patients >3 months of age admitted to the PICU. They found that patients with the highest mortality rates were those with complicated infectious illnesses, near-drowning, gastroenteritis and cardiomyopathy. An audit of this nature at CMJAH PICU has not been done for several years.

Impact of HIV on PICU admissions

SA is faced with one of the highest rates of HIV infection worldwide.

The Joint United Nations Programme on HIV/AIDS estimated that in 2013 there were 360 000 children from 0 to 14 years of age living with HIV in SA.[10] In the era before highly active antiretroviral therapy (HAART), HIV-infected children with co-infections such as Pneumocystis jirovecii pneumonia (PCP) had worse outcomes than other patients admitted to PICU and were therefore not routinely ventilated. Admitting HIV-infected children with severe pneumonia

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RESEARCH to a PICU in a setting of scarce resources created several ethical dilemmas for paediatricians.[11] Often, the first suspicion of HIV in infected children is after they have been admitted to the PICU.[12] More information is needed as to whether there are differences in comorbidities and outcomes of HIV-exposed and HIV-infected children admitted to PICU and if these differences should be considered when making decisions for PICU bed allocations. A retrospective chart review by Rabie et al.[5] at Tygerberg Children’s Hospital, to determine the prevalence and outcome of HIV-infected patients in PICU, showed a median length of stay for HIV-infected children of 6 days, which was significantly longer than for the non HIV-infected children (3 days), p=0.0001). Cost differentials for HIV-infected and HIV-uninfected children admitted for the management of pneumonia in a public setting were determined

by Kitchin et al.,[13] who found that the length of stay for HIVinfected children was 5.7 days longer among admissions to the PICU, and that the cost of admission for HIV-infected children was significantly higher. They also found that the number of deaths of HIV-infected children were 28.1% higher than uninfected children.

However, it has been shown that early initiation of antiretroviral (ARV) therapy can improve outcomes of HIV-infected children in a PICU.[11] Acute respiratory failure as a result of LRTI is a major cause for admission in HIV-exposed and HIV-infected children. Rabie et al.[5] found that 76% of HIV-infected children admitted to the PICU were admitted for acute respiratory failure and 33% of admissions had a confirmed diagnosis of PCP. Another review found that cytomegalovirus (CMV) infection had affected nearly 90% of HIVexposed children.[14]

Objectives

To describe the disease spectrum and outcome of children admitted for medical conditions to PICU at CMJAH, and to determine the spectrum of medical conditions among children admitted to the PICU, the short-term outcomes of children admitted to the PICU and the number and outcomes of HIV-exposed or HIV-infected children admitted compared with HIV-unexposed children.

Methods

This study was a retrospective review conducted in the PICU of CMJAH, a referral hospital in Gauteng, SA. The records of children admitted to the PICU from 1 January 2013 to 31 July 2014 were reviewed. Admission to the PICU at the time of the study was primarily based on the need for ventilation, but occasionally patients requiring intensive observation were admitted. The study included children >28 days old admitted to PICU for medical conditions. All surgical and trauma ad-missions were excluded. If a child had had a medical condition but subsequently required surgery, they were excluded. Children with a confirmed HIV infection would not be routinely readmitted to the PICU. The records were reviewed for demographics, admission diagnosis, HIV status, duration of ICU stay and ventilation, and survival to discharge from the PICU. Some children had multiple diagnoses; each one was counted.

The definitions used for the conditions have been listed in Table 1.

All children admitted with a medical condition were routinely tested for HIV with an enzyme-linked immunosorbent assay test. Blood specimens were taken under sterile conditions for bacterial culture in all patients. Children with acute LRTIs were only screened for respiratory pathogens if clinically indicated, at the discretion of the attending physician, including any of the following: tracheal aspirates for multiplex real-time reverse transcription polymerase chain reaction (RT-PCR) assay for respiratory viruses, microscopy and culture, pertussis PCR, gene Xpert for tuberculosis and/or Pneumocystis carinii pneumonia (PCP) immunofluorescence.

Children were managed according to standard treatment protocols 222

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at the discretion of the attending physician. Empirical antibiotics for bacterial pneumonia were intravenous ampicillin and gentamicin.

Children with suspected PCP and cytomegalovirus (CMV) pneumonia were treated as a syndrome as the two are not easy to differentiate clinically; therefore, children were treated empirically with trimethoprim-sulphamethoxazole plus corticosteroids and ganciclovir, while awaiting confirmatory results.

After reviewing the records for conditions and outcomes, the children were then divided into two groups: HIV-exposed and HIVunexposed. Comparisons were made between the two groups to find statistically significant differences in all the variables. The group of HIV-exposed children was further divided into those who were HIV PCR-positive and those who were HIV PCR-negative. These two groups were also compared for any significant differences.

Data were managed using Research Electronic Data Capture tools (REDCap) (Vanderbilt University, USA), hosted by the University of the Witwatersrand.[15] Information was captured for each patient on discharge from the PICU. De-identified data were then entered into Microsoft Excel (USA). Cases were allocated a study number.

Statistical analysis

Categorical variables were described using percentages and frequencies. Continuous variables were described using median and range as the data were skewed. Comparisons were made using the χ2 test for categorical variables and the Mann-Whitney U-test for continuous variables. A p-value <0.05 was used as the level of significance.

Ethical considerations

Ethical approval was obtained from the University of the Witwatersrand Human Research Ethics Committee (Ethics Clearance no.: M140363). Permission to review the patients’ records Table 1. Definitions Medical condition

A life-threatening disease not requiring surgical intervention

Duration

Period of time calculated in days and not hours

Upper respiratory tract infections (URTIs)

An infection affecting the respiratory tract above the level of the larynx, including croup and retropharyngeal abscess

LRTI

An infection affecting the respiratory tract from below the larynx, leading to cough, difficulty breathing, tachypnoea or chest wall indrawing

Clinical diagnosis of PCP

An LRTI accompanied by severe hypoxia, a clear chest on auscultation and a ground-glass interstitial infiltrate on chest radiograph findings

Neonates

Children <28 days old, including those who had been discharged and admitted from home

Bacterial infection

Diagnosis made on the basis of a positive blood culture

Cardiovascular conditions

Includes congenital cardiac lesions, myocarditis, shock, cardiac failure and arrhythmia

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RESEARCH was obtained from the clinical manager of CMJAH.

70

Results

60

40 30 19

20 15.3 10

3.8 2.3

0

4.6

8.4

4.6 5.3

9.2

4.5 4.6

6.9 0

ns

Ot Co Oth L he ng er r c en LR A RTIs ar ita T c sth di l c o ov a nd ma as rdi iti cu ac on la di s r c se on as di e tio Ot E pi ns he le rC NS Ap psy c n Ot Ga on oea he st dit r G roe ion IT nt s co er Ot he R nd itis r r en itio en a n al l fa s co ilu nd re Dr ition ow s n Ba Poi ing c t so er ni Vi ial ng r s Fu al in eps ng fe is al cti in on fe ct io n

re s UR t TI s

ar tc ar di ac

o Tc

6.8 7.6

tio

i nd

UR

3.8

16.7 18.3

13

Fig. 1. Admission diagnoses for children admitted with medical conditions to the PICU from 1 January 2013 to 31 July 2014. Some children had multiple admission diagnoses.

Table 2. Infections of children admitted confirmed on blood culture

Conditions of children admitted

The spectrum of medical conditions was wide, with 84/131 (64.1%) having LRTIs, accounting for the majority of admissions (Fig. 1).

Of the 131 children, 122 were intubated and ventilated, 1 received continuous positive airway pressure, and 8 were not ventilated. Of those 122 who were on intermittent positive pressure ventilation (IPPV), 14 (11.4%) were switched to high-frequency oscillatory ventilation (HFOV). Inotropic support was needed by 12 children.

Pathogens

There were 22/131 (16.7%) positive bacterial cultures on blood specimens from the child­ ren. Coagulase-negative Staphylococcus was the bacterial pathogen most frequently iden­ tified, in 6/131 (4.6%) children (Table 2).

Viral pathogens were identified in 16/131 (12.2%) children. No fungi were isolated, and PCP was identified in only 3/131 (2.3%) tracheal aspirates by direct immunofluorescence assay (Tables 2 and 3).

Eight children had a clinical diagnosis of CMV made by the admitting doctors. These 8 patients were also found to be HIV-positive on DNA PCR. The patients had their CMV viral loads quantified from a blood specimen by DNA PCR to support the diagnosis, and were empirically treated with ganciclovir while awaiting viral load results. Only 2 patients had viral loads >6 000 IU/mL, while 5 were below the level of quantification and 1 was indeterminate. At the CMJAH PICU a viral load of greater than 4.0 log copies is considered indicative of active CMV

50

Po s

There were 883 PICU admissions during the 19-month study period. Of these, 518 (59%) were neonates and 234 (26.5%) were surgical patients. The remaining sample therefore included 131 children (14.8%). The male:female ratio was 1:0.66. The median age of the patients admitted was 3.8 months with an interquartile range (IQR) of 14.3 months.

The median (IQR) duration of ventilation was 4 (6) days, while the duration of stay was 5 (7) days. There were 32/131 (24.4%) deaths in the PICU, and a further 8 (6%) children died in the hospital wards after discharge from the PICU. There were 129/131 children tested for HIV. Of these, 44/131 (33.5%) were HIVexposed, 85/131 (65.9%) were unexposed, and HIV exposure was unknown for 2. The 2 children whose status was unknown were excluded from further analysis. Of the 131 children, 16 (12.2%) were HIV-infected with a positive HIV PCR.

Percentage, %

Demographics

64.1

Infections

n (%)

Bacterial sepsis

22/131 (16.7)

Klebsiella pneumoniae

1 (0.8)

ESBL Klebsiella

2 (1.5)

Staphylococcus aureus

1 (0.8)

Coagulase-negative Staphylococcus

6 (4.6)

Streptococcus viridans

4 (3.1)

Streptococcus pneumoniae

1 (0.8)

Acinetobacter baumannii

1 (0.8)

Escherichia coli

5 (3.8)

Enterococcus faecalis

2 (1.5)

Enterobacter cloacae

1 (0.8)

infection and disease, and infection was therefore not proven in the eight children.

Comparison between HIVunexposed and HIV-exposed children

Table 4 compares the demographics, medical conditions and outcomes of HIV-exposed and unexposed children. A total of 44/131 (34.1%) were HIV-exposed. The median duration of stay for HIV-exposed children of 8 days was significantly longer than the 5 days for HIV-unexposed children (p=0.015). Duration of ventilation was also 4 days longer for HIV-exposed children (p=0.012). More HIV-exposed children (11/44 (25%)) transitioned to HFOV than HIV-unexposed children (3/85 (3.5%), p=0.0005).

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LRTIs accounted for more than half of all admissions, regardless of HIV status, but HIV-exposed children were much more likely to be admitted with LRTI (90.9%) than HIVunexposed children (51.8%) (p=0.0005).

There was no significant difference in the number of deaths between the two groups.

Some of the diagnoses of bacterial or viral pneumonia were made clinically by the admitting doctor before blood or tracheal aspirate samples could be collected, and the children were therefore treated empirically for those conditions. Taking a closer look at the LRTIs it was found that HIV-exposed children were significantly more likely to present with bacterial pneumonia (45.5%) compared with HIV-unexposed children (20.3%) (p=0.002).

All 10 children who had a clinical diagnosis of PCP were HIV-exposed (p=0.0005). Eight

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RESEARCH of these children had β-D glucan assays done.

Five children had a β-D glucan level greater than 500 pg/mL, and the others were below that level. This supports but does not confirm the diagnosis made by the doctors clinically.

Table 3. Infections of children admitted confirmed on tracheal aspirate Infections

n (%)

Viral infection

16/131 (12.2)

Adenovirus

4 (3.1)

Respiratory syncytial virus (RSV)

9 (6.9)

Other viruses

3 (2.3)

P. jirovecii

3 (2.3)

Fungal infection

Comparison of HIV PCR-positive and PCR-negative children

Of the 44 children who were HIV-exposed, 1 child did not undergo a PCR test. A total of 16/43 (37.2%) children were found to be HIV PCR-positive. The mortality between the groups was not significantly different.

Of significance was that HIV PCR-positive children required more days of ventilation (p=0.006), were more likely to require HFOV (p=0.0005) and stayed longer in PICU (p=0.03) than HIV-exposed PCR-negative children (Table 5).

There were no significant differences with regard to the number and type of medical conditions found.

Discussion

0 (0)

This audit showed that the majority of admissions to the PICU at CMJAH are

Table 4. Comparison of HIV-unexposed children with HIV-exposed children HIV-unexposed, n (%)*

HIV-exposed, n (%)*

p-value

Total admissions (2 unknown)

85 (65.9)

44 (34.1)

-

Age (months), median

6.3

2.7

0.0005

Died in the PICU

19 (22.4)

11 (25)

0.730

PICU stay (days), median

5

8

0.015

Duration ventilated (days), median

4

8

0.012

Readmission

11 (12.9)

0

0.013

IPPV

77 (90.6)

42 (95.5)

0.320

HFOV

3 (3.5)

11 (25.0)

0.0005

Inotropes

6 (7.1)

5 (11.4)

0.400

Respiratory tract conditions Upper respiratory tract (URT) conditions URTIs

4 (4.7)

1 (2.3)

0.394

Other URT conditions

1 (1.2)

2 (4.5)

0.210

LRT infections

44 (51.8)

40 (90.9)

0.0005

Asthma

5 (5.9)

0

0.100

Pleural effusion

2 (2.4)

0

0.300

Other LRT conditions

4 (4.7)

0

0.250

Cardiovascular conditions

25 (29.4)

9 (20.5)

0.270

Central nervous system (CNS) conditions

23 (27.1)

9 (20.5)

0.410

Gastrointestinal tract (GIT) conditions

9 (10.6)

3 (6.8)

0.485

Renal conditions

16 (18.8)

2 (4.5)

0.027

Bacterial sepsis

12 (14.1)

10 (22.7)

0.218

Viral infections

10 (11.8)

6 (13.6)

0.780

RSV

5 (5.9)

4 (9.1)

0.490

PCP infection

1 (1.2)

2 (4.5)

0.229

Other systems

Infections

*Unless otherwise shown.

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neonates, followed by post-surgical and trauma patients. Medical admissions comprised 15% of the total, with the majority being infants of ≤3.7 months of age. More male than female children were admitted, which was a similar finding to other studies.

[16] There were 34.1% HIV-exposed children, while 12.2% were HIV PCR-positive. We were unable to calculate how many children were denied beds owing to their positive HIV status, as this information was unavailable.

It’s possible that there may have been a selection bias. All the children admitted were severely ill, as 92% required conventional ventilation and 10% requiring transition to HFOV. The median duration of stay was 5 days, and 24.4% of children died in the PICU. The spectrum of conditions was wide, but the predominance of acute LRTI was not surprising, as up to 40% of hospital admissions in SA are accounted for by communityacquired pneumonia.[17] Respiratory viral pathogens were identified in 12.2% of admissions, with RSV accounting for the highest number. RSV is known to be the most common cause of moderate or severe bronchiolitis.[18] Only three children had confirmed PCP infection on tracheal aspirate analysis. Two of the 3 were HIV-exposed and 1 was HIVunexposed. PCP has been found in HIVunexposed children who have compromised immune systems for other reasons such as malnutrition.

Comparison between HIV-exposed and HIV-unexposed children

There was no significant difference in mortality rates between HIV-exposed and HIV-unexposed patients. This is possibly because of the ventilation strategies and choice of antibiotics used in the PICU. HIVexposed children stayed 3 days longer in the PICU and were ventilated for 4 more days than HIV-unexposed children. Length of stay may be linked to increased expense.

In the CMJAH PICU, HFOV is used as a second-line ventilation strategy for children who remain in respiratory fail-ure, or whose condition deteriorates on con­ ventional mechanical ventilation. A total of 25% of HIV-exposed children were converted to HFOV compared with only 3.5% of unexposed children (p=0.0005).

This is another indicator that HIV-exposed children were generally more seriously ill and required more support.

Almost all HIV-exposed children suffered from a LRTI. A birth cohort study done in Paarl, SA, showed that exposure to HIV was a significant independent risk factor for severe pneumonia. This could be because of limited protection owing to lower maternal antibodies.[19]

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RESEARCH Conclusion

Table 5. Comparison of HIV PCR-negative and HIV PCR-positive children HIV PCRnegative, n (%)*

HIV PCRpositive, n (%)*

p-value

Total admissions

27 (62.7)

16 (37.2)

-

Age (months), median (IQR)

2.5 (1.9)

3.1 (1.2)

0.030

Died in the PICU

5 (18.5)

5 (31.3)

0.330

PICU stay (days), median

5

11.5

0.030

Time ventilated (days), median

4

11

0.006

IPPV

26 (96.3)

15 (93.8)

-

HFOV

2 (7.4)

9 (56.3)

0.0005

Inotropes

2 (7.4)

2 (12.5)

0.580

URTIs

1 (3.7)

0

-

Other URT conditions

1 (3.7)

1 (6.3)

-

LRT infections

23 (85.2)

16 (100)

0.100

PCP

3 (11.1)

7 (43.8)

0.140

Cardiovascular conditions

6 (22.2)

3 (18.8)

0.780

CNS conditions

8 (29.6)

1 (6.3)

0.069

GIT conditions

3 (11.1)

0

-

Renal conditions

2 (7.4)

0

-

Bacterial sepsis

6 (22.2)

4 (25)

0.660

Viral infection

5 (18.5)

1 (0.06)

0.390

Respiratory tract conditions URT conditions

LRT conditions

Other systems

Infections

*Unless otherwise indicated.

It was clear that bacterial pneumonia and PCP pneumonia were the predominant LRTIs affecting HIV-exposed children.

Kitchin[11] suggested that the immune dysregulation that increases the risk for PCP in HIV-infected children is also present in HIV-exposed but uninfected children.

Comparison between HIV PCRpositive and PCR-negative children

HIV-infected children had a higher mortality compared with those who were exposed but uninfected, but this difference was not statistically significant. HIV-infected children had a significantly longer duration of ICU stay and duration of ventilation than exposed but uninfected patients. This finding is similar to that in other studies in which it was found that HIV-infected children had a longer length of hospital stay because of the increased severity of their LRTI.[20,21] A study done at the Steve Biko Academic Hospital PICU showed better survival to 1 year of age compared with previous studies when HAART was initiated early in the course of the disease.[11] This highlights the importance of early testing and initiation

of ARVs for children, as well as an effective prevention of mother-to-child transmission programme in decreasing the burden of HIV. It has been said that PCP occurs most frequently in HIV-infected children, and can be the first clinical presentation of HIV infection.[22] We found 7 HIVinfected children clinically diagnosed with PCP compared with 3 HIV-exposed but uninfected children (p=0.14). Only 2 children were proven sputum-positive for PCP in this group; however, this is not a sensitive method of diagnosis, even though microscopic visualisation is the gold standard.[23]

Study limitations

This was a retrospective study. Different clinicians may have used different criteria for the clinical diagnosis of some conditions.

Some data were missing and there was no routine screening of patients for respiratory pathogens. It is difficult to know whether some of the positive cultures were contaminants. The exclusion of all neonates may have led to those with medical, and not purely neonatal conditions, being missed.

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The PICU admitted slightly fewer than 900 children in 19 months. The mortality rate of the children with medical conditions was 24.4%. The most frequent cause for admission was LRTI, which is reflective of the high rates of pneumonia affecting SA children.

Overall, 34% of children were HIV-exposed while 12.2% were HIV PCR-positive. These children were mostly admitted for LRTIs with bacterial pneumonia and PCP being prominent causes.

Although the HIV-exposed patients were more seriously ill, as proven by increased need for HFOV and longer duration of ventilation and PICU stay, they did not have a higher mortality. Their exclusion from admission to the PICU is no longer justified, especially in the era of HAART. References 1. South Africa’s Children: A review of equity and child rights. South African Human Rights Commission/UNICEF, March 2011, Pretoria, SA. 2. World Health Organization. Global Health Observatory Data. 2015. http://www.who.int/ gho/child_health/mortality/causes/en (accessed 2 August 2016).

3. Bhagwanjee S, Scribante J. National audit of critical care resources in South Africa - unit and bed distribution. S Afr Med J 2007;97(12 Pt 3):1311-1314.

4. Argent AC, Ahrens J, Morrow BM, et al. Pediatric intensive care in South Africa: An account of making optimum use of limited resources at the Red Cross War Memorial Children’s Hospital.

Pediatr Crit Care Med 2014;15(1):7-14. http:// dx.doi.org/10.1097/PCC.0000000000000029 5. Rabie H, de Boer A, van den Bos S, Cotton MF, Kling S, Goussard P. Children with human immunodeficiency virus infection admitted to a paediatric intensive care unit in South Africa.

J Trop Pediatr 2007;53(4):270-273. http://dx.doi. org/10.1093/tropej/fmm036 6. Rady HI, Mohamed SA, Mohssen NA, ElBaz M. Application of different scoring systems and their value in pediatric intensive care. Gaz Egypt Pediatr Assoc 2014;62(3):59-64. http://dx.doi. org/10.1016/j.epag.2014.10.003 7. Wells M, Riera-Fanego JF, Luyt DK, Dance M, Lipman J. Poor discriminatory performance of the pediatric risk of mortality (PRISM) score in a South African intensive care unit. Crit Care Med 1996;24(9):1507-1513. http://dx.doi. org/10.1097/00003246-199609000-00013 8. Solomon LJ, Morrow BM, Argent AC. Paediatric index of mortality scores: An evaluation of function in the paediatric intensive care unit of the Red Cross War Memorial Children’s Hospital.

S Afr J Crit Care 2014;30(1):8-13. http://dx.doi. org/10.7196/sajcc.166 9. Ballot DE, Davies VA, Rothberg AD, Ginsberg N. Selection of paediatric patients for intensive care. S Afr Med J 1995;85(11 Suppl):1221-1223, 1226.

10. Joint United Nations Programme on HIV and AIDS. HIV and AIDS Estimates 2014. http:// www.unaids.org/en/regionscountries/countries/ southafrica (accessed 24 March 2016).

11. Kitchin OP, Masekela R, Becker P, Moodley T, Risenga SM, Green RJ. Outcome of human immunodeficiency virus-exposed and -infected children admitted to a pediatric intensive care unit for respiratory failure. Pediatr Crit Care Med 2012;13(5):516-519. http://dx.doi.org/10.1097/ pcc.0b013e31824ea143

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RESEARCH 12. Jeena PM, McNally LM, Stobie M, Coovadia HM, Adhikari MA, Petros AJ. Challenges in the provision of ICU services to HIV-infected children in resource poor settings: A South African case study. J Med Ethics 2005;31(4):226-230. http://dx.doi.org/10.1136/jme.2003.004010 13. Kitchin OP, Wessels F, Masekela R, Becker P, Green RJ. Costs of admission for paediatric pneumonia in a setting of human immunodeficiency virus infection. Int J Tuberc Lung Dis 2011;15(12):1702-1707. http://dx.doi.org/10.5588/ijtld.11.0167 14. Slyker JA, Lohman-Payne BL, John-Stewart GC, et al. Acute cytomegalovirus infection in Kenyan HIV-infected infants. AIDS 2009;23(16):2173-2181. http:// dx.doi.org/10.1097/QAD.0b013e32833016e8 15. 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. JÂ Biomed Inform 2009;42(2):377-381. http://dx.doi.org/10.1016/j. jbi.2008.08.010 16. Haque A, Bano S. Clinical profile and outcome in a paediatric intensive care unit in Pakistan. J Coll Physicians Surg Pak 2009;19(8):534-535. http://dx.doi. org/08.2009/JCPSP.534535 17. Zar HJ, Jeena P, Argent A, Gie R, et al. Diagnosis and management of community-acquired pneumonia in childhood - South African Thoracic Society guidelines. S Afr Med J 2005;95(12 Pt 2):977-981,984-990.

18. Green RJ, Zar HJ, Jeena PM, Madhi SA, Lewis H. South African guideline for the diagnosis, management and prevention of acute viral bronchiolitis in children. S Afr Med J 2010;100(5):320,322-325. http://dx.doi.org/10.7196/samj.4016

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19. Le Roux DM, Myer L, Nicol MP, Zar HJ. Incidence and severity of childhood pneumonia in the first year of life in a South African birth cohort: The Drakenstein Child Health Study. Lancet 2015;3(2):95-103. http://dx.doi. org/10.1016/S2214-109X(14)70360-2 20. Zar HJ, Hanslo D, Tannenbaum E, et al. Aetiology and outcome of pneumonia in human immunodeficiency virus-infected children hospitalized in South Africa. Acta Paediatr 2001;90(2):119-125. http://dx.doi. org/10.1080/080352501300049163 21. 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 22. Zar HJ. Pneumonia in HIV-infected and HIV-uninfected children in developing countries: Epidemiology, clinical features, and management. Curr Opin Pulm Med 2004;10(3):176-182. http://dx.doi.org/10.1097/00063198-20040500000006 23. Onishi A, Sugiyama D, Kogata Y, et al. Diagnostic accuracy of serum 1,3-betaD-glucan for Pneumocystis jiroveci (sic) pneumonia, invasive candidiasis, and invasive aspergillosis: Systematic review and meta-analysis. J Clin Microbiol 2012;50(1):7-15. http://dx.doi.org/10.1128/JCM.05267-11

Accepted 29 August 2016.

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RESEARCH

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

Mothers’ perception of neonatal jaundice in Lagos, Nigeria: An urgent need for greater awareness V C Ezeaka, MBBS, MPH, FWACP (Paed); E N Ekure, MB BCh, FWACP (Paed); I B Fajolu, MBBS, FMCPaed; B N Ezenwa, MBBS, MPH, FMCPaed; P E Akintan, MBBS, FMCPaed Department of Paediatrics, Lagos University Teaching Hospital, Nigeria Corresponding author: V C Ezeaka (ezeakac@yahoo.com) Background. Neonatal jaundice remains a leading cause of preventable brain damage, mental handicap, physical disabilities and early death among infants. The high mortality and morbidity from neonatal jaundice is exacerbated by the poor understanding and mismanagement of this common neonatal problem by the general populace, leading to dangerous delays and complications.

Objective. To assess the knowledge of pregnant women on the causative factors, treatment modalities and sequelae of neonatal jaundice.

Methods. Data were obtained from all consecutive women who attended the antenatal clinic of the Lagos University Teaching Hospital, Nigeria, from January 2013 to April 2013, using a pretested questionnaire focusing on knowledge of neonatal jaundice and its causes, treatment and complications.

Results. The study participants numbered 395, of whom 213 (53.9%) were within the age range of 30 - 39 years. Only 101 (25.6%) participants gave a correct definition of neonatal jaundice. The highest proportion of those who did not give a correct definition were from the lower socioeconomic groups V and IV (χ2=12.08, p=0.017). Participants who did not know the causes numbered 313 (79.2%), while 325 (82.2%) participants chose ineffective treatment options. Furthermore, 296 (74.9%) respondents, especially those with a low level of education, did not identify the complications correctly (χ2=12.61, p=0.006).

Conclusion. Women in the study showed inadequate knowledge of and misconceptions regarding neonatal jaundice, which must be addressed in order to reduce significantly the devastating consequences of this common condition. We advocate for improved female literacy and mass health enlightenment programmes.

S Afr J Child Health 2016;10(4):227-230. DOI:10.7196/SAJCH.2016.v10i4.1190

Neonatal jaundice remains a leading cause of preventable brain damage, mental handicap, physical disabilities and early death among infants.[1-7] This hyperbilirubinaemia results from a predisposition to bilirubin production in the newborn and their limited ability to excrete it. Infants, especially preterms, have higher rates of bilirubin production than adults because they have red cells with a shorter life span, a higher rate of haemolysis, inadequate caloric intake with increased enterohepatic circulation, and an underdeveloped conjugating system.[1,4,8] Apart from causing neonatal deaths and chronic handicapping conditions such as cerebral palsy, severe unconjugated hyperbilirubinaemia usually causes deafness, speech disorders, learning disabilities and mental retardation.[1-4,6-8] Several studies in Nigeria have shown neonatal jaundice to be one of the most common neonatal emergencies in the referral centres,[3,9-11] and some reports have shown that severe neonatal jaundice and kernicterus contributed to about a half of all cases of cerebral palsy.[2,12-14] Furthermore, it has been reported that even moderate neonatal hyperbilirubinaemia may lead to mild neurological damage, which may not be obvious during the neonatal period, but manifests only in later life.[15] The high mortality and morbidity from neonatal jaundice is exacerbated by the poor understanding, and mismanagement, of this common neonatal problem by the general populace, leading to dangerous delays and complications.[11,16-18] The experience has been that the caregivers do not usually detect this potentially serious condition early, and in many situations the healthcare providers and the mothers are misguided about the conventional modalities of management, such that these infants consequently develop kernicterus. In view of the high two-thirds prevalence of home deliveries in our environment, the widespread practice of early hospital discharge for the approximately one-third of the mothers who deliver in the health facilities[19] and the lack of effective 227

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postnatal follow-up health visits, there is a crucial need for mothers to be duly educated on the early detection of neonatal jaundice and the avoidance of precipitating factors. Mothers, who are usually the primary caregivers of the newborns, must possess basic knowledge pertaining to the aetiology and complications of neonatal jaundice, and must be given skills in its early diagnosis and management.

Most studies on neonatal jaundice in Nigeria have dwelt mainly on clinical research concentrating on the medical aetiological factors[2-4,7,8] and on the management of neonatal jaundice by healthcare staff.[16,17] In view of the real need for early detection and prompt institution of appropriate therapy, the present study aims to assess the perception of caregivers on the causative factors, treatment modalities and complications of neonatal jaundice. To our knowledge, this is the first study on the assessment of mothers’ knowledge of neonatal jaundice in Lagos, Nigeria, and it will help to provide baseline data for the formulation of effective interventional measures.

Methods

This cross-sectional study was carried out at the Lagos University Teaching Hospital (LUTH), Nigeria, from January 2013 to April 2013. LUTH is a 750-bed tertiary hospital offering maternal and child health services to all ethnic, religious and socioeconomic populations of Nigerians within and outside Lagos State. The hospital is a referral centre for general hospitals, maternity facilities and private hospitals, within Lagos and its neighbouring states.

Data were obtained from all consecutive women who attended the antenatal clinic of the institution during the study period using a pretested questionnaire. Questionnaires were administered after obtaining informed consent from the mothers. Ethical approval was obtained from the Ethical Committee of the institution. The first section of the questionnaire included personal data, sociodemographic data, educational level attained and obstetric data of respondents.

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RESEARCH The next section of the survey instrument aimed to assess the knowledge of the mothers regarding the definition of neonatal jaundice and what it entails, possible causes, treatment modalities, complications and how to detect neonatal jaundice in the newborn, using closed- and open-ended questions of multiple choice types. The mothers were encouraged to seek clarification on any of the questions from the attending interviewer but discussion among them was discouraged while they were filling in the questionnaires. To avoid bias the interviewer only interpreted the question into the local language if mothers sought clarification, and then without further explanations.

Social classification criteria designed by Olusanya et al.[20] were used. These comprise five social classes (I - V) according to a scoring system based on the mother’s education and her husband’s occupation.

Social classes I and II represent the elites, class III is the middle class while class Table 1. Sociodemographic characteristics of respondents Variables

Frequency, n (%)

Total

395 (100.0)

IV and V occupy the lowest rungs of the socioeconomic ladder.

The SPSS version 17.0 (IBM Corp., USA) statistical software was used for data entry, validation and analysis. Pearson’s χ2 statistic was used to examine the association between categorical variables. Differences, associations and relationships were said to be statistically significant when p≤0.05.

Results

The number of respondents who participated in the study was 395. Most of them were within the age range of 30 - 39 years (Table 1).

Of the 395 participants interviewed, 101 (25.6%) correctly defined neonatal jaundice as a yellowish discoloration of the eyes and skin owing to accumulation of bilirubin, while 294 (74.4%) mothers did not know the correct definition of neonatal jaundice.

Table 2 shows the participants’ definition of neonatal jaundice based on social classification. The results are statistically significant (χ2=12.08, p=0.017).

Regarding the question on knowledge of the causes of jaundice in the newborn, 313 (79.2%) participants answered that they did not know the causes, 43 (10.9%) gave varied incorrect answers in different combinations, 27 (6.8%) respondents attri-buted the newborn jaundice

to mosquito bites while 3 (0.8%) participants attributed the cause to yellow fever. However, only 39 (9.9%) participants correctly identified the causes as blood incompatibility between mother and baby, infection in baby and prematurity. Of these, 13 (33.3%) correctly identified one cause, while 20 (51.3%) and 6 (15.4%) correctly identified two and three causes, respectively.

Fig. 1 shows that in answer to the question on how neonatal jaundice should be effectively treated, 70 (17.8%) of the participants said they had no knowledge. Of the 325 (82.2%) participants who mentioned treatment options, 114 (35.1%) incorrectly chose the use of ampiclox syrup, 87 (26.8%) chose exposure to natural sunlight, while only 31 (9.5%) correctly identified the use of a specific phototherapy machine, and 20 (6.2%) chose exchange blood transfusion (EBT) as modalities of treatment. A combination of both phototherapy and exchange blood transfusion was chosen by 18 (5.5%). Other treatment options reported by the subjects were the use of unripe pawpaw water (28 (8.6%)), use of herbal medications (11 (3.4%)), glucose water (7 (2.2%)) and varied combinations (9 (3.1%)).

Furthermore, to the question about knowledge of complications of neonatal

6 (1.5)

Primary

22 (5.6)

Secondary

170 (43.0)

Tertiary

197 (49.9)

Na tu

No formal education

126 (31.9)

II

145 (36.7)

III

62 (15.7)

IV V

he rs Ot

ra py

Fig. 1. Treatment options chosen by respondents.

Social class I

he

Am

pi

Education level

EB T

52 (13.2)

ot ot

Others

ph

12 (3.0)

aw

161 (40.8)

Hausa

EB T+

Yoruba

Pa wp

170 (43.0)

ra py

Ibo

clo x

Ethnicity

he

12 (3.0)

ht

213 (53.9)

≥40

to t

30 - 39

40 35 30 25 20 15 10 5 0

lig

167 (42.3)

Ph o

3 (0.8)

20 - 29

ra ls un

15 - 19

Percentage, %

Age range (years)

Table 2. Participants’ definition of neonatal jaundice by social classification Social class

Correct definition, n (%)

Incorrect definition, n (%) Total, n (%)

43 (10.9)

Total

101 (100.0)

294 (100.0)

395 (100.0)

19 (4.8)

I

46 (36.5)

80 (63.5)

126 (100.0)

II

30 (20.7)

115 (79.3)

145 (100.0)

0

153 (38.7)

III

14 (22.6)

48 (77.4)

62 (100.0)

1 - 5

228 (57.7)

IV

8 (18.6)

35 (81.4)

43 (100.0)

≥6

14 (3.5)

V

3 (15.8)

16 (84.2)

9 (100.0)

Parity

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RESEARCH jaundice, 99 (25.1%) respondents correctly identified brain damage, mental retardation, hearing impairment, delayed development and convulsions in the baby as complications singly and in combinations, while 296 (74.9%) participants did not correctly identify the complications. Of these 296 respondents, 263 (88.9%) did not think they knew the complications, while 33 (10.9%) respondents gave incorrect answers such as sickle cell anaemia, blindness and damage to the blood. These results are shown in Table 3 and are statistically significant (χ2=12.61; p=0.006).

Regarding information received about neonatal jaundice, 185 (46.8%) had never received any such information, 89 (22.5%) admitted they had some information from health workers (either nurse or doctor), 68 (17.2%) were informed by friends and relatives and only 16 (4.05%) received information from the mass media (television and radio). Various combinations of the above options were given by 37 (9.4%) of the respondents.

Discussion

Neonatal jaundice is the most common neonatal emergency and a significant contributor to neonatal morbidity and mortality in developing countries. However, in spite of its high prevalence, it is apparent from the present study that the mothers, who are the primary caregivers, have a poor understanding of this common, potentially lethal condition.

The finding that as many as 75% of the respondents could not describe correctly what neonatal jaundice entails is rather disheartening, since this translates to undue delays in identification and seeking appropriate care. The end result may be the development of severe brain damage in the affected baby. This corroborates studies

by Ekanem et al.[16] and Ogunfowora et al.,[17] although their studies centred on primary healthcare workers. The result that many of the mothers described newborn jaundice as malaria in the newborn is further evidence of this poor knowledge. Furthermore, the result that this knowledge gap is significantly wider in mothers from the lower socioeconomic group, who have poorer educational status, underscores the urgent need for improved female education and mass health enlightenment programmes on newborn jaundice.

In the same light, >75% of the participants did not correctly identify the causes of neonatal jaundice despite the fact that blood group incompatibility, prematurity, infections and glucose-6-phosphate dehydrogenase deficiency have been reported by several authors in Nigeria as common aetiological factors.[3,7,8] Furthermore, certain agents commonly used by the mothers in their homes, such as naphthalene balls, herbal drinks and drugs, have been documented to be icterogenic, causing an increase in the prevalence and severity of neonatal jaundice.[7,8] Some respondents attributed the cause to yellow fever in the newborn. Therefore, while continuous research on clinical patterns and technologically advanced therapeutic options remain very relevant, there should be a major focus on formulating appropriate preventive and interventional strategies in the community.

More than half of the respondents incorrectly chose the use of ampiclox syrup (a combination of ampicillin and cloxacillin antibiotic), glucose drinks, unripe pawpaw water and exposure to sunlight, which have all been shown to be totally unreliable. Sadly, these same therapeutic options are among those chosen by primary healthcare workers from previous studies in Nigeria >2 decades ago.[16] It is imperative that the healthcare system be strengthened, and better provision made for improved health education programmes in the community, as a matter of urgency. The ineffective treatment options widely practised by the mothers tend to create a false confidence, thus delaying institution of appropriate care and leading to devastating consequences for the infant.

Regarding the complications, it was not surprising that most of the mothers were not well-informed since most were not aware of what the disease entailed or the possible causative agents. The knowledge gap is significantly more evident in mothers with lower educational 229

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Table 3. Respondents’ knowledge of the complications of neonatal jaundice by education level Educational Correct Incorrect Total, level knowledge, n (%) knowledge, n (%) n (%) Total

99 (25.1)

296 (74.9)

395 (100.0)

No formal education

0 (0.0)

6 (100.0)

6 (100.0)

Primary

1 (4.5)

21 (95.5)

22 (100.0)

Secondary

36 (21.2)

134 (78.8)

170 (100.0)

Tertiary

62 (31.5)

135 (68.5)

197 (100.0)

status, while overall a quarter of the respondents correctly identified brain damage, mental retardation and delayed development as complications. This poor understanding of the dangers of jaundice on the brain of the newborn infant further trivialises the mother’s management of this silent crippling condition.

Neonatal jaundice occurs in most newborns and the hallmark of effective treatment is early identification and appropriate therapy.

In developed countries, the menace of newborn jaundice has received better priority and attention. In the USA, the national healthcare organisations including the Centers for Disease Control, the Joint Commission for the Accreditation of Healthcare Organizations and the American Academy of Pediatrics issued alerts to all accredited hospitals and public health professionals that all healthy infants are at potential risk of kernicterus if their newborn jaundice is unmonitored and inadequately treated.[6] However, in many developing countries, compared with many conditions that require advanced pharmacological strategies, newborn jaundice seems to be overshadowed, and has lost the attention that it deserves as a condition that has potentially deleterious consequences.

Intensive health education campaigns on neonatal jaundice should be instituted at antenatal clinics, immunisation clinics, paediatric clinics, well-baby clinics and in all health centres in the community. This is to ensure that mothers are duly educated at every opportunity about the causes of neonatal jaundice. Areas in which to concentrate in jaundice education should include the possible triggers of haemolysis that are commonly used in the homes, such as menthol and naphthalene balls, how newborn jaundice can be identified early and effective treatment options for neonatal jaundice.

This is especially pertinent as many newborns are usually discharged home <48 hours after birth, when the jaundice is not yet evident.

These new mothers are left at the mercy of grandmothers and neighbours who recommend local remedies such as pawpaw water and herbal medications. The mass media should be involved in mass mobilisation campaigns to help avert this apparent lack of awareness as the present study has shown that only a negligible proportion of the respondents received information about neonatal jaundice from that source. Increased knowledge about the predispositions and consequences of severe hyperbilirubinaemia by the mothers is imperative for the institution of early appropriate care, thereby reducing significantly the menaces from the devastating disabilities of this condition in our communities.

References

1. Stoll BJ, Kliegman RM. Jaundice and hyperbilirubinaemia in the newborn. In: Behrman RE, Kliegman RM, Jenson HB, eds. Nelson Textbook of Paediatrics.

Philadelphia: WB Saunders Company, 2005:513-519.

2. Belonwu RO, Gwarzo GD, Adeleke SI. Cerebral palsy in Kano, Nigeria - a review.

Niger J Med 2009;18(2):186-189. http://dx.doi.org/10.4314/njm.v18i2.45062 3. Owa JA, Osinaike AI. Neonatal morbidity and mortality in Nigeria. Indian J Pediatr 1998;65(3):441-449. http://dx.doi.org/10.1007/bf02761140 4. American Academy of Pediatrics Subcommittee on Hyperbilirubinemia.

Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics 2004;114(1):297-316. http://dx.doi.org/10.1542/peds.114.1.297

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RESEARCH 5. Watson RL. Hyperbilirubinemia. Crit Care Nurs Clin North Am 2009;21(1):97120. http://dx.doi.org/10.1016/j.ccell.2008.11.001 6. Bhutani VK, Johnson LH. Newborn jaundice and kernicterus - health and societal perspectives. Indian J Pediatr 2003;70(5):407-416. http://dx.doi. org/10.1007/bf02723615 7. Ogunlesi TA. Managing neonatal jaundice at the general practice and primary health care level: An overview. Nig J Paed 2004;31(2):33-38. http://dx.doi. org/10.4314/njp.v31i2.12086 8. Olusanya BO, Emokpae AA, Zamora TG, Slusher TM. Addressing the burden of neonatal hyperbilirubinaemia in countries with significant glucose-6phosphate dehydrogenase deficiency. Acta Paediatr 2014;103(11):1102-1109. http://dx.doi.org/10.1111/apa.12735 9. Ransome-Kuti O. Problems of paediatric emergencies in Nigeria. Nig J Med 1972;2:62-70.

10. Lesi FEA, Temiye EO, Epelle TGS. The changing pattern of childhood mortality in the childrenâ&#x20AC;&#x2122;s emergency room of the Lagos University Teaching Hospital after 20 years. Niger Med J 2000;38(2):38-41.

11. Ezeaka C, Ogunbase AO, Awogbemi OT, Grange AO. Why our children die: A review of paediatric mortality in a tertiary centre in Lagos, Nigeria. Nig Qt J Hosp Med 2003;13(1-2):17-21. http://dx.doi.org/10.4314/nqjhm.v13i1.12502 12. Animashaun A. Aetiology of cerebral palsy in African children. Afr J Med Sci 1971;2(2):165-171.

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13. Duggan MB, Ogala W. Cerebral palsy in Nigeria: A report from Zaria. Ann Trop Paediatr 1982;2(1):7-11.

14. Asindi AA. The pattern of neurological disabilities in children seen at the University of Calabar Teaching Hospital. Nig J Paediatr 1988;13:127-132.

15. Naeye RL. Amniotic fluid infections, neonatal hyperbiliubinaemia and psychomotor impairment. Paediatrics 1978;62(4):497-503.

16. Ekanem EE, Young MU. Knowledge of the causes and management of neonatal jaundice by primary health care staff. Niger J Paed 1994;21(2):37-42.

17. Ogunfowora OB, Daniel OJ. Neonatal jaundice and its management: Knowledge, attitude and practice of community health workers in Nigeria.

BMC Public Health 2006;6:19. http://dx.doi.org/10.1186/1471-2458-6-19 18. Owa JA, Ogunlesi TA. Why we are still doing so many exchange blood transfusion for neonatal jaundice in Nigeria. World J Pediatr 2009;5(1):51-55. http://dx.doi.org/10.1007/s12519-009-0009-2 19. National Demographic and Health Survey 2008. National Population Commission and ORC Macro, Calverton, MD, 2004.

20. Olusanya O, Okpere E, Ezimokhai M. The importance of social class in voluntary fertility control in a developing country. W Afr J Med 1985;4:205-212.

Accepted 12 August 2016.

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CASE REPORT

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

Fatal Lemierre’s syndrome as a complication of chronic otitis media with cholesteatoma M Roos,1,2 MB ChB; T Harris,1,3 MB ChB, FCORL(SA), MMed (Otol); R Seedat,2 MB ChB, MMed (ORL), FCORL(SA) Department of Otolaryngology, Kimberley Hospital Complex, South Africa Department of Otorhinolaryngology, Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa 3 Division of Otolaryngology, Department of Surgery, Faculty of Health Sciences, University of Cape Town, South Africa 1 2

Corresponding author: M Roos (visagieme@gmail.com) Background. Lemierre’s syndrome is septic thrombophlebitis of the internal jugular vein, initiated by an infection of the head and neck region. This septic thrombophlebitis gives rise to septic microemboli that can disseminate throughout the body to form septic infarctions and abscesses, with the most frequent site being pulmonary.

Methods. We discuss the case of a 14-year-old male with Lemierre’s syndrome as a complication of chronic middle ear infection.

Results. The patient developed septic shock and microemboli, and subsequently died.

Conclusion. This case report illustrates that untreated chronic middle ear infection can lead to potentially fatal complications such as Lemierre’s syndrome, and emphasises the importance of timeous treatment of chronic middle ear pathology.

S Afr J Child Health 2016; 10(4):231-232. DOI:10.7196/SAJCH.2016.v10i4.1074

Lemierre’s syndrome is septic thrombophlebitis of the internal jugular vein (IJV) occurring secondary to infection in the head and neck region of otherwise healthy young patients.[1] The thrombophlebitis is often followed by pulmonary emboli and distal septic embolisation.[2,3] The syndrome was first described in 1936 as sepsis secondary to Fuscobacterium necrophorum, although other organisms, for example Streptococcus, Staphylococcus, Lactobacillus, Bacteroides, Peptostreptococcus and Eikenella, are also described as being involved in the aetiology of this syndrome.[1,2] Although it is an uncommon syndrome (it is also referred to as the ‘forgotten disease’), a high index of suspicion should be maintained, as it remains a potentially life-threatening disease with a reported mortality rate of up to 10%.[3] A few cases of Lemierre’s syndrome have been reported with the primary event being otological in nature.[1,3,4] The following report describes the fatal outcome of a 14-year-old boy who developed Lemierre’s syndrome secondary to untreated chronic otitis media with cholesteatoma.

Case report

A previously healthy 14-year-old boy was admitted to hospital with a 1-week history of worsening headaches, photophobia and malaise.

The patient had been seen in casualty 3 days prior to admission, diagnosed with an acute otitis media and treated with oral antibiotics.

There was a history of right-sided otorrhoea for many years and, despite multiple visits to his local clinic, the patient was never referred to an otolaryngologist. There was no other relevant past medical or surgical history.

On admission, the patient was pyrexial with a temperature of 38.2°C and had rigors. His blood pressure was 114/44 mmHg and his pulse 62 bpm. The respiratory and cardiovascular examinations were normal. The patient was noted to have a discharging right ear and tenderness of his neck. There were no signs of meningeal irritation. The results of the laboratory investigations were as follows: white cell count of 28.8 × 109/L, haemoglobin of 9.5 g/dL, platelets of 120 × 109/L and a C-reactive protein level of 190.8 mg/L. A lumbar puncture was performed to exclude meningitis and this was normal.

The chest X-ray (CXR) on admission revealed no abnormalities.

Empirical treatment was started with intravenous ceftriaxone 2 g

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twice daily. Aerobic and anaerobic cultures were taken, with negative results.

After 1 week, there was no clinical improvement and the signs of sepsis persisted. The intravenous antibiotics were changed to gentamicin 240 mg once daily and ertapenem 1 g daily. The patient then complained of central chest pain and shortness of breath. His blood pressure was 118/69 mmHg and his respiratory rate was 28 breaths/min. An electrocardiogram was done, showing a sinus tachycardia. A repeat lumbar puncture revealed no abnormalities and blood cultures remained negative. Intravenous vancomycin 1 g daily was added to the treatment.

A repeat CXR showed small focal opacities in both lung fields consistent with septic emboli. An abdominal ultrasound was done, revealing hepatosplenomegaly and a solitary cystic lesion of 3 cm × 3 cm in the liver. An urgent computed tomography (CT) scan of the brain and temporal bones was requested, revealing an opacified middle ear and epitympanum. An extensive thrombus was seen in the right transverse dural sinus (Fig. 1), extending inferiorly into the sigmoid sinus and IJV. Dehiscence of the posterior cerebellar plate was seen, but there was no intracranial collection.

The patient was referred to the ear, nose and throat (ENT) department for further assessment and management. On ENT examination, the presence of keratin and a granuloma was noted in the right ear and the diagnosis of a right-sided cholesteatoma was made. A pus swab taken from the right ear cultured Proteus vulgaris and Pseudomonas aeruginosa. Audiological testing revealed a mild conductive hearing loss of the right ear, but normal hearing in the left.

The patient developed haemoptysis and deteriorated clinically, secondary to a suspected pulmonary embolism and septic shock. He was resuscitated and transferred to the intensive care unit. A repeat heart sonar revealed a normal right heart, tachycardia of 141 beats/ min and no signs of a pulmonary embolism. A repeat CXR showed worsening of the opacification, consistent with pneumonia.

He was started on enoxaparin 40 mg 12-hourly subcutaneously. He developed a right-sided pneumothorax and an intercostal chest drain was inserted. His sepsis continued and he required inotropic support.

He also developed generalised tonic-clonic seizures and was started on intravenous phenytoin. He had repeated cardiac arrests, and

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CASE REPORT

Fig. 1. Post-contrast CT brain showing filling defect in the right transverse and sigmoid sinus with the appearance of a thrombus.

after 2 days in intensive care it was noted that he had no brainstem reflexes. After 4 days in intensive care all active resuscitative efforts were stopped and the patient died shortly thereafter.

Discussion

The clinical presentation of Lemierre’s syndrome includes fever, neck swelling, respiratory symptoms, oropharyngeal pain, hepatosplenomegaly, jaundice, haematuria, diffuse encephalopathy, myalgia and arthralgia.[1,2] Owing to the wide range of presenting symptoms and signs, the diagnosis could easily be missed if not actively sought. Findings on CXR may include infiltrates, embolic phenomena, pleural effusion, pneumothorax and empyema, but a normal CXR does not exclude the diagnosis.[2,3] The incidence ranges from 0.6 to 2.3 cases per million per year,[4] although progressively more cases have been reported, possibly because of the development of antibiotic resistance.[1] Complications of Lemierre’s syndrome include extension of the thrombophlebitis to involve other vessels such as the pharyngeal venous plexus and cavernous sinus, meningitis, brain abscesses, descending necrotising mediastinitis, necrosis of infected blood vessels, suppurative arthritis and endocarditis.[1] With otogenic infection the close proximity of the middle ear and mastoid to the dural venous sinuses predispose these regions to lateral sinus thrombophlebitis. Formation may be either a direct dissemination through neighbouring eroded bone or from thrombophlebitis of small veins of the mastoid communicating with the lateral sinus.[3] Extension of the thrombus may be significant, reaching the superior petrosal sinus superior, or as low as the subclavian vein.[3] Another complication is intravascular coagulation secondary to platelet aggregation, possibly contributing to the thrombophlebitis, by creating

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a favourable environment for growth of anaerobic bacteria.[4] This was seen in our patient, who developed sepsis-related thrombocytopenia with a platelet count of 45 × 109/L. The septic thrombophlebitis of the IJV may lead to metastatic septic emboli with pulmonary involvement in up to 85% of cases.[1] Distal complications may be present in about 90% of cases at the time of diagnosis.[4] We suspected that the probable cause of the patient’s ongoing sepsis was septic microemboli to the lungs, although the heart sonar ruled out a large pulmonary embolus. He was therefore started on enoxaparin. The use of anticoagulation is controversial, as there are no randomised control trials and septis-related thrombocytopenia is often an associated complication, possibly increasing the risk of bleeding.[2,3] Antibiotics are the mainstay of treatment of Lemierre’s syndrome[1,2] and should be continued for at least 6 weeks.[2] Combined treatment with penicillin and metronidazole are recommended.[3] It is crucial to take blood cultures early to allow initiation of the appropriate therapy. The patient’s blood cultures remained negative, possibly because antibiotics were initiated at the time the first cultures were requested. In children with chronic suppurative otitis media, Gramnegative bacteria are the most common pathogens cultured, with a high sensitivity to quinolones.[5] Surgical excision and ligation of the IJV is reserved for cases with continued sepsis and septic embolisation.[3] Further management includes surgical drainage of any purulent collections.[3] Contrastenhanced CT is the imaging modality of choice for accurate diagnosis of Lemierre’s syndrome. Ultrasonography has been used as an initial investigation; however, it can miss a fresh thrombus.

Magnetic resonance imaging has also been suggested as the study of choice and has the added advantage of avoiding an intravenous contrast agent and exposure to radiation.[3] The delay in diagnosis of chronic suppurative otitis media is a significant problem. Tiedt et al.[5] noted a long delay in seeking treatment for chronic middle ear infection, with the mean duration of otorrhoea being >3 years. It is important to have a high index of suspicion as patients who are diagnosed and treated early are reported to have a favourable outcome.[2] Patients with chronic middle ear infection often have associated comorbidities such as anaemia, malnutrition and HIV infection.[6]

Conclusion

Lemierre’s syndrome is a rare but life-threatening complication of untreated middle ear infections. This case study demonstrates the importance of treating any middle ear infection timeously as it could be fatal if left untreated.

References

1. Gilbert JD, Warner MS, Byard RW. Lemierre syndrome and unexpected death in childhood. J Forensic Leg Med 2009;16(8):478-481. http://dx.doi. org/10.1016/j.jflm.2009.07.005 2. Chen CH, Lin CH, Chin CH, Chiu MH, Chen PH. Lemierre’s syndrome. J Med Ultrasound 2005;13(3):149-152.

3. Adhikari P, Guragain RP, Bhusal, CL, Pradhananga RB. Lemierre’s syndrome after modified radical mastoidectomy: An unusual variant caused by Citrobacter freneli. Int J Pediatr Otorhinolaryngol Extra 2010;5(4):152-154. http://dx.doi. org/10.1016/j.ijporl.2004.07.023 4. Masterson T, El-Hakim H, Magnus K, Robinson J. A case of the otogenic variant of Lemierre’s syndrome with atypical sequelae and review of pediatric literature.

Int J Pediatr Otorhinolaryngol 2005;69(1):117-122. http://dx.doi.org/10.1016/j. ijporl.2004.07.023 5. Tiedt NJ, Butler IR, Hallbauer UM, et al. Paediatric chronic suppurative otitis media in the Free State Province: Clinical and audiological features. S Afr Med J 2013;103(7):467-470. http://dx.doi.org/10.7196/samj.6636 6. Hallbauer UM, Atkins MD, Tiedt NJ, et al. Co-morbidities in children presenting with chronic suppurative otitis media – A South African study.

J Trop Pediatr 2014;60(3):198-202. http://dx.doi.org/10.1093/tropej/fmt107

Accepted 20 July 2016.

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CASE REPORT

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

Intracardiac and intracerebral thrombosis associated with methylenetetrahydrofolate reductase A1298C homozygote mutation in paediatric steroidresistant nephrotic syndrome R Renda,1 MD; Ö Aydoğ,2 MD; M Bülbül,2 MD; E K Çakıcı,2 MD 1 2

Pediatric Nephrology Department, Antalya Education and Research Hospital, Antalya, Turkey Pediatric Nephrology Department, Dr Sami Ulus Maternity and Children’s Research and Education Hospital, Ankara, Turkey

Corresponding author: R Renda (rahimeg@yahoo.com) Thromboembolic complications are a significant cause of morbidity and mortality in cases of nephrotic syndrome. Hereditary thrombophilias are also known to increase vascular thrombosis. We present a case that has been followed up for steroid-resistant nephrotic syndrome (NS) in which intracardiac and intracranial thrombosis subsequently developed. The patient was found to have a homozygote mutation in the methylenetetrahydrofolate reductase (MTHFR) gene as an additional risk factor for recurrent thrombosis. MTHFR mutation with NS was considered to have an important effect on the development of life-threatening thrombosis.

S Afr J Child Health 2016;10(4):233-236. DOI:10.7196/SAJCH.2016.v10i4.1189

Although thromboembolic events in nephrotic syndrome (NS) are seen less often in children (2 - 5%) than in adults (20 - 30%), these are life-threatening complications.[1] An increase in clotting factors, a decrease in anticoagulant proteins, thrombocytosis and thrombocyte hyperaggregation, abnormal fibrinolysis, an increase in plasma lipids, corticosteroid and diuretic treatment and immobilisation all cause an increased tendency to thrombosis in NS.[2] Although venous thrombosis is more commonly observed, arterial thrombosis may also develop. Despite the rare occurrence of renal vein, sagittal sinus and intracardiac thrombosis, and pulmonary embolism, they are seriously life-threatening when they develop.[3] Early diagnosis, appropriate fibrinolytic treatment and long-term use of protective anticoagulants are extremely important.[4] Using folic acid as a cofactor, methylenetetrahydrofolate reductase (MTHFR) enzyme converts homocysteine to methionine. In the absence or impairment of this enzyme, hyperhomocysteinaemia occurs, causing atherosclerosis and vascular thrombosis. Mutations most often seen in the MTHFR gene, in particular C677T and A1298C missense mutations, have been found to have a relationship with cerebrovascular diseases.[5] In the case presented here the patient was diagnosed as having steroid-resistant NS (SRNS) at the age of 2 years. During the followup period he first developed intracardiac thrombosis and 5 years later intracranial thrombosis appeared. The patient was determined to have MTHFR A1298C homozygote mutation as an additional risk factor for recurrent thrombosis in NS.

Case report

The patient had previously experienced two NS attacks that responded to steroids, then, as no response was obtained with 8 weeks of steroid treatment in the 3rd attack, he was referred to Dr Sami Ulus Maternity and Children’s Research and Education Hospital. There was no consanguinity or familial nephropathy history. The physical examination determined a body temperature of 39°C, tachypnoea, subcostal retraction, crepitant rales on auscultation of the lungs and anasarca-type oedema. The laboratory findings showed leukocytosis, thrombocytosis (831 000/mm3), hypoalbuminemia (13 g/L), massive

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proteinuria and hyperlipidaemia (cholesterol 280 mg/dL, triglyceride 196 mg/dL). The kidney and liver function tests, and C3 and C4, were normal. Antinuclear antibody, anti-dsDNA, hepatitis serology and Purified Protein Derivative Test were found to be negative. On the abdominal ultrasound there was massive acites. On the pulmonary radiograph the bilateral costophrenic angles were obscured and there was bilateral paracardiac infiltration.

With a diagnosis of pulmonary infection and thrombocytosis, the patient was started on antibiotic therapy and acetylsalicylic acid as antiplatelet treatment. The level of infection reduced within 1 week. However, after 2 weeks, there was a sudden development of tachycardia, tachypnoea, gallop rhythm, 2/6 systolic murmur on the left of the sternum and hepatomegaly. Echocardiograph showed mitral and tricuspid insufficiency and thrombus, located below the anterior wall and tricuspid valve, extending to the apex within the right ventricle (Fig. 1A). Of the coagulation parameters, while prothrombin and partial thromboplastin times, protein S and factors 2, 5, 8, 9, 10 and 11, were determined as normal, antithrombin III (15.8%; normal 75 - 125%) and protein C (62%; normal 70 - 140%) were found to be low. Anticardiolipin and antiphospholipid antibodies and factor 5 Leiden and prothrombin 20210A gene mutations were found to be negative. MTHFR gene mutations could not be assayed at our hospital at that time.

The patient was started on a treatment of low-molecular-weight heparin as an anticoagulant and oral prednisolone 60 mg/m2/day.

Antiplatelet treatment was continued. After 2 weeks the thrombus had started to diminish and complete remission in NS was obtained.

The patient was discharged with prednisolone in tapering doses and anticoagulant and antiplatelet treatments, and 2 months later, the thrombus had disappeared completely on echocardiograph (Fig. 1b).

Antithrombin III and protein C levels returned to normal; therefore, anticoagulant treatment could be stopped.

In the follow-up of the patient, because of the development of secondary steroid resistance, a renal biopsy was obtained. Focal segmental glomerulosclerosis was determined and cyclosporine was added to the treatment. Complete remission was achieved with cyclosporine and low-dose prednisolone (0.25 mg/kg/day) for

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CASE REPORT A

A

B

B

Fig. 1. (A) Echocardiograph showing thrombus (red arrow) located below the anterior wall and tricuspid valve, extending to the apex within the right ventricle.

(B) Echocardiogram showing resolution of thrombosis.

2 years and immunosuppressive treatment was stopped 2 years later.

In the 5th year of follow-up, owing to an increase in gastrointestinal complaints and with measurable thrombophilic gene mutations being negative, antiplatelet treatment was also terminated.

In the 6th year of follow-up, the patient again presented with frequently relapsing NS. Intravenous pulse methylprednisolone (30 mg/kg/day, max. 1 g/day; 3 days) was administered and mycophenolate-mofetil treatment was begun. After 20 days the patient developed severe headache, vomiting and loss of sight in his left eye, and bilateral papillary oedema was observed. Cranial diffusion magnetic resonance (MR) and MR angiography showed brain oedema, the slowing of the blood flow in the left sagittal-transverse sinus and left jugular vein, as well as intravascular thrombus (Fig. 2).

Coagulation parameters (factor 2, 5, 8, 9, 10, 11, protein C and S, antithrombin III, active protein C resistance and homocysteine levels (2.38 mmol/L and 12 mmol/L, N 4 - 15)) were found to be normal.

Anticardiolipin and antiphospholipid antibodies were also negative.

From the MTHFR gene mutations examined, while no mutation was found in C677T, homozygote mutation in A1298C was determined.

A diminishing of the thrombus was achieved with low-molecularweight heparin (Fig. 3), and the patient’s headache diminished and his sight also recovered.

The patient was discharged with low-dose oral steroid, myco­ phenolate mofetil, low-molecular-weight heparin prophylaxis and antiplatelet treatment. Prophylactic anticoagulant therapy was discontinued after 6 months. The patient is still being followed-up 234

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Fig. 2. Diffusion cranial MR and MR angiography showing brain oedema, the slowing of the blood flow in the left sagittal-transverse sinus and left jugular vein (red arrows), and intravascular thrombus.

by the paediatric nephrology and haematology departments. During the last 4-year follow-up period, with only antiplatelet treatment, no recurrence of thrombus has been observed in spite of a few relapse NS attacks.

Discussion

SRNS patients are at a higher risk of developing thromboembolic complications compared with steroid-sensitive NS patients.[6] Recurrent thrombotic events are seen more often in NS patients if there are additional risk factors for hypercoagulability such as infection, dehydration or hereditary thrombophilic conditions (congenital deficiencies of anticoagulant proteins such as ATIII, protein C and S, or thrombophilic gene mutations such as FV Leiden mutation, prothrombin 20210A mutation, MTHFR mutations or

DECEMBER 2016 Vol. 10 No. 4

CASE REPORT In particular, MTHFR A1298C homozygote mutation has been shown to lead to cerebrovascular thrombosis and stroke in children.

[7,10] Compound MTHFR heterozygosity (677C→T and 1298A→C) has also been reported to be a risk factor for thrombosis.[11] Although SRNS patients are at a higher risk of developing thromboembolic complications, sagittal sinus and intracardiac thrombosis are rarely observed. A large intracardiac thrombus in a child with SRNS was previously reported in the Turkish literature.[3] Divekar et al.[12] found only one case with cerebral sinus thrombosis among 700 children with NS. Clinical presentation of cerebral sinus thrombosis is variable, from headaches and vomiting to seizures, vision loss, hemiparesis and coma.[13] Although prophylactic treatment of thrombosis in NS is uncertain, some authors suggest anticoagulant treatment in patients with low albumin levels and antiplatelet drugs in patients with severe thrombocytosis.[14] There are also limited unproven data concerning the treatment of thromboembolic complications in children with NS. Lowmolecular-weight heparin is preferred in paediatric patients and the recommended treatment duration is usually between 3 and 6 months. In the literature different anticoagulants have been used in NS patients with intracardiac or intracerebral thrombosis, ensuring full recovery. It is suggested that the positive outcome in these patients is based on the early diagnosis of thrombosis and administration of anticoagulation therapy along with control of NS.[3,13-16]

A

B

Conclusion

In our case, the MTHFR mutation, in addition to NS, was considered to have an important effect on the development of cerebral and intracardiac thromboses. Complete recovery of the thrombosis was achieved with early anticoagulant therapy and folic acid support.

The patient is still being followed-up by the paediatric nephrology and haematology departments. During the last 4-year follow-up period, with only antiplatelet treatment, no recurrence of thrombus has been observed in spite of occasional relapse NS attacks.

References

Fig 3. A diminishing of the thrombus (red arrow) on control diffusion cranial MR angiography.

platelet glycoprotein polymorphisms).[7] The potential risk factors for thrombosis in our case were thrombocytosis, hypoalbuminemia, hyperlipidemia and long-term steroid use owing to NS as well as the presence of MTHFR A1298C homozygote mutation.

The MTHFR gene is located on chromosome 1p36.3 locus. Aided by folic acid and vitamin B12, homocysteine is transformed to methionine by remethylation.[5] Hyperhomocysteinemia, forming as a result of a molecular defect in this gene, leads to vascular endothelial damage, venous thrombosis, atherosclerosis, stroke, coronary artery disease, neural tube defects and migraine, owing to vasodilatator nitric oxide deficiency and superoxide formation.

[8] Weisberg et al.[9] found that the MTHFR gene mutation has the effect of reducing enzyme activity rather than causing low enzyme levels or hyperhomocysteinemia. Our patient’s homocysteine levels were found to be normal, which is consistent with his findings.

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1. Lilova MI, Velkovski IG, Topalov IB. Thromboembolic complications in children with nephrotic syndrome in Bulgaria (1974-1996). Pediatr Nephrol 2000;15(1-2):74-78. http://dx.doi.org/10.1007/s004679900253 2. Niaudet P, Boyer O. Idiopathic nephrotic syndrome in children: Clinical aspects. In: Ellis DA, Harmon WE, Niaudet P, Yoshikawa N, eds. Pediatric Nephrology (6th ed.). Berlin: Springer-Verlag, 2009:667-703.

3. Ekici F, Çakar N. A large intracardiac thrombus in a child with steroid-resistant nephrotic syndrome. Cardiol Young 2013;23(3):440-442. http://dx.doi. org/10.1017/S1047951112000923 4. Lin CC, Lui CC, Tain YL. Thalamic stroke secondary to straight sinus thrombosis in a nephrotic child. Pediatr Nephrol 2002;17(3):184-186.

5. Fodinger M, Horl WH, Sunder-Plassmann G. Molecular biology of 5,10-methylenetetrahydrofolate reductase. J Nephrol 2000;13(1):20-33.

6. Hoyer PF, Gonda S, Barthels M, Krohn HP, Brodehl J. Thromboembolic complications in children with nephrotic syndrome. Risk and incidence. Acta Paediatr Scand 1986;75(5):804-810.

7. Suri D, Ahluwalia J, Saxena AK, et al. Thromboembolic complications in childhood nephrotic syndrome: A clinical profile. Clin Exp Nephrol 2014;18(5):803-813. http://dx.doi.org/10.1007/s10157-013-0917-2 8. Boers GH. Hyperhomocysteinemia as a risk factor for arterial and venous disease.

A review of evidence and relevance. Thromb Haemost 1997;78(1):520-522.

9. Weisberg I, Tran P, Christensen B, Sibani S, Rozen R. A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity. Mol Genet Metab 1998;64(3):169-172. http:// dx.doi.org/10.1006/mgme.1998.2714 10. Rook JL, Nugent DJ, Young G. Pediatric stroke and methylenetetrahydrofolate reductase polymorphisms: An examination of C677T and A1298C mutations.

J Pediatr Hematol Oncol 2005;27(11):590-593. http://dx.doi.org/10.1097/01. mph.0000188119.33452.fd 11. Simsek E, Yesilyurt A, Pinarli F, Eyerci N, Ulus A. Combined genetic mutations have remarkable effect on deep venous thrombosis and/or pulmonary embolism occurrence. Gene 2014:536(1):171-176. http://dx.doi.org/10.1016/j. gene.2013.11.019

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CASE REPORT 12. Divekar AA, Ali US, Ronghe MD, Singh AR, Dalvi RB. Superior sagittal sinus thrombosis in a child with nephrotic syndrome. Pediatr Nephrol 1996;10(2):206-267. http://dx.doi.org/10.1007/bf00862081 13. Palcoux JB, Gaspard F, Campagne D. Cerebral sinus thrombosis in a child with steroid-resistant nephrotic syndrome. Pediatr Nephrol 2003;18(6):610-611. http://dx.doi.org/10.1007/s00467-003-1100-x 14. Papachristou FT, Petridou SH, Printza NG, Zafeiriou DI, Gompakis NP. Superior sagittal sinus thrombosis in steroid-resistant nephrotic syndrome. Pediatr Neurol 2005;32(4):282-284. http://dx.doi.org/10.1016/j.pediatrneurol.2004.11.004

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15. Skalova S, Lukes A, Vanicek H, et al. Intracardiac thrombus â&#x20AC;&#x201C; a rare complication of the steroid resistant nephrotic syndrome. Bratisl Lek Listy 2008;109(12):573575.

16. Ueno K, Nagasako H, Ueno M, et al. Large intracardiac thrombus in a child with refractory nephrotic syndrome. Pediatr Int 2010;52(1):e51-e53. http:// dx.doi.org/10.1111/j.1442-200X.2009.02991.x Accepted 29 August 2016.

DECEMBER 2016 Vol. 10 No. 4

CASE REPORT

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

Rosai-Dorfman disease in a 12-year-old Nigerian male J C Elo-Ilo,1 MBBS, FWACP; K K Odinaka,1 MBBS, FWACP; C O Ukah,2 MBBS, FMC Path 1 2

Department of Paediatrics, Federal Medical Centre, Owerri, Nigeria Department of Histopathology, Federal Medical Centre, Owerri, Nigeria

Corresponding author: K K Odinaka (kellymed112@yahoo.com) Rosai-Dorfman disease is a rare disorder of systemic histioproliferation, first described in 1969 by Juan Rosai and Ronald Dorfman. It is characterised by massive lymphadenopathy, particularly of the head and neck region, and it is sometimes associated with extranodal involvement. This is the first case to be reported from our centre. We report a case of Rosai-Dorfman disease in a 12-year-old Nigerian boy who presented at the children’s outpatient clinic of the Federal Medical Centre, Owerri, Imo State, Nigeria, with a 5-year history of bilateral neck swelling, a 2-year history of groin swelling and a recurrent fever of over a year’s duration. An initial diagnosis of Hodgkin’s lymphoma was made. An excisional biopsy of the cervical lymph node was undertaken and the histology showed massive histiocytosis with emperipolesis, which confirmed the diagnosis of Rosai-Dorfman disease.Rosai-Dorfman disease, although a rare clinical entity, should be suspected in patients presenting with massive lymphadenopathy located especially in the neck and groin regions.

S Afr J Child Health 2016;10(4):237-238. DOI:10.7196/SAJCH.2016.v10i4.1197

Rosai-Dorfman disease (RDD), otherwise known as sinus histiocytosis with massive lymphadenopathy (SHML), is a rare and benign histiocytic proliferative disorder of unknown aetiology.[1] It was previously classified as histiocytosis X. Patients with the disease usually present with massive painless cervical lymphadenopathy and fever. About 25 - 40% of affected individuals present with extranodal manifestations, typically in the head and neck regions. The skin, soft tissue, upper respiratory tract, bone, eyelids, retro-orbital tissue and the kidneys may also be involved.[1,2] RDD is most frequently seen in children and young adults, although it can occur in any age group.

The disease is more common in males, with a male:female ratio of 2:1. It is also common in individuals of African descent and usually occurs in the first two decades of life.[3] The clinical course of RDD is unpredictable, with episodes of exacerbation and remissions that can last many years.[2] The disease is often self-limiting and therefore requires no treatment, with a very good outcome in the majority of cases.[2] However, treatment may be required for patients with extranodal RDD involving vital organs such as orbits, or those with nodal disease, causing life-threatening complications.[2] Various treatment options have been recommended if required and they include the use of corticosteroids, interferon, radiation, chemotherapy and surgery.[4,5] We are reporting the case of RDD in a 12-year-old Nigerian male to highlight the need for physicians to evaluate children with massive lymphadenopathy for the likelihood of this rare disease entity.

Case presentation

A 12-year-old Nigerian male presented at the children’s outpatient clinic of the Federal Medical Centre, Owerri, Nigeria, with a 5-year history of bilateral neck swelling, 2-year history of groin swelling and a 1-year recurrent fever. There was no history of cough, weight loss or drenching night sweats. At the onset of the illness, he was taken to a private hospital where he was placed on anti-tuberculosis (TB) drugs for 6 months, with no improvement. He also received a course of herbal concoctions, again with no improvement. The neck swelling continued to increase, necessitating self-referral to our facility for expert medical care. His past medical history was not significant except that he had been transfused once in a private hospital because of febrile illness when he was 6 years old. He is the third child in a family of seven children. There was no history of similar illness among his siblings. Physical examination revealed 237

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mild pallor, bilateral cervical lymphadenopathy measuring 8 × 6 cm on the left and 6 × 4 cm on the right. The nodes were multiple, firm and attached to neither superficial or deep tissues. He also had left inguinal lymphadenopathy measuring 8 × 8 cm, and 2 × 2 cm on the right. There was no positive cough impulse. His weight was 70% of the expected weight without oedema, and his height was appropriate for his age. Other aspects on examination were essentially normal.

A working diagnosis of Hodgkin’s lymphoma with tuberculous lymphadenopathy as a differential diagnosis was made. The laboratory investigations showed a white blood cell count of 13.8 × 109 L, neutrophils 70%, lymphocytes 30%, platelet count 188 × 109 L, left shift of neutrophils, normocytic normochromic red blood cells and elevated erythrocyte sedimentation rate (ESR) (100 mm/hr).

Haemoglobin was 9.8 g/dL, HIV I and II screenings were negative and haemoglobin electrophoresis had a normal AA pattern. A Mantoux test was non-reactive (0 mm). A chest X-ray showed no evidence of enlarged lymph nodes and no focal lung lesions were seen. Blood films for detecting malaria parasites showed a ring form of Plasmodium falciparum. An abdominal ultrasound scan, random blood glucose tests, urinalysis and direct Coombs tests were all normal. The patient was commenced on oral antibiotics (cefuroxime) and antimalarial therpay (Coartem) based on local sensitivity patterns and malarial tests, pending the result of the excision biopsy of the lymph node.

The histology report showed a benign, non-neoplastic lesion characterised by expanded sinuses that were filled with enlarged histiocytes containing abundant cytoplasm and plasma cells.

Within some of the enlarged histiocytes were intact lymphocytes (emperipolesis). A histological diagnosis of RDD was made. The parents were counselled on the benign nature of the disease and were scheduled for monthly follow-up visits. The size of the cervical lymph node was observed to be regressing by the third monthly visit.

However, the parents defaulted on further follow-up visits despite numerous telephonic requests.

Discussion

The term RDD was first introduced into scientific literature in 1969 when Juan Rosai and Ronald Dorfman described four cases of a rare, idiopathic, non-neoplastic lymphoproliferative disorder.[6] They described its clinico-pathological features in 1972. Typically, it is characterised by bilateral cervical lymphadenopathy with fever, leukocytosis, elevated ESR and hypergammaglobunaemia.[7] Our

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CASE REPORT patient had all the typical features of the disease except that we could not ascertain if he had hypergammaglobunaemia because we lacked the facilities to test for gammaglobunin. The extranodal manifestation of the disease has been documented in about 25 - 40% of affected individuals, with the most frequent sites being the head and neck regions.[1,2] The urogenital tract, breast, gastrointestinal tract, liver, pancreas and lungs have also been reported to be affected by the disease.[2] Our patient did not have any extranodal disease.

Histologically, lymph nodes in this disease show pericapsular fibrosis and dilated sinuses, heavily infiltrated with large histiocytes, lymphocytes and plasma cells. The presence of emperipolesis, or the engulfment of lymphocytes and erythrocytes by histiocytes that express S-100, is considered diagnostic of RDD.[2] In this case, the authors lacked the facilities for testing an immunohistochemical stain for S-100 positivity in histiocytes, and therefore it was not done on this patient’s biopsy.

Although the aetiology of RDD is unknown, it is presumed to be due to an immune regulation disorder. Patients with clinically apparent immunological disorders have a higher mortality. There also appears to be a familial relationship with regard to RDD: two sets of twins, two other sets of siblings and four individuals of blood relatives were documented by Foucar[8] in 1984. RDD has also been presumed to be triggered by infections caused by viruses such as various herpes viruses, the Epstein-Barr virus, cytomegalovirus, Brucella and Klebsiella.[9,10] However, there is presently no strong evidence for this.[2] Stebbing et al.[11] reported a possible association with sickle cell disease. The haemoglobin electrophoresis of our patient was AA. This implies that a person’s genotype may not play a contributory role. However, our patient and the patient of Stebbing et al.[11] had been transfused in the past. Could there be a possible association of RDD with blood transfusion? More research will be required to address this question. It is noteworthy that RDD has been reported following bone marrow transplants for precursor-B acute lymphoblastic leukaemia.[12] As previously mentioned, the patient was lost to follow-up, probably because of emotional burn-out from repeated hospital visits and perceived slow response to treatment. Similar observations have been documented in parents of children with incurable chronic diseases in Nigeria.[13]

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Conclusion

This case report highlights this rare disease entity in order to raise a high index of suspicion on diagnosis. Patients who present with lymphadenopathy and who do not respond to treatment with antibiotics or anti-TB treatment must be followed up. These patients may need a biopsy to exclude malignant diseases or other diseases such as RDD. 1. References Santra G, Das BK, Mandal B, Kundu SS, Bandopadhyay A. RosaiDorfman disease. Singapore Med J 2010;51(10):e173-e175.

2. Histiocyte Society. Rosai-Dorfman Disease. 2011. http://www.histiocytesociety. org.http://histiocytesociety.org/document.doc?id=54 (accessed 20 March 2016).

3. Lauwers GY, Perez-Atayde A, Dorfman RF, Rosai J. The digestive system manifestations of Rosai-Dorfman disease (sinus histiocytosis with massive lymphadenopathy): Review of 11 cases. Hum Pathol 2000;31(3):380-385. http:// dx.doi.org/10.1016/s0046-8177(00)80254-3 4. Horneff G, Jürgens H, Hort W, Karitzky D, GÖbel U. Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease): Response to methotrexate and mercaptopurine. Med Pediatr Oncol 1996;27(3):187-192. http://dx.doi. org/10.1002/(sici)1096-911x(199609)27:3<187::aid-mpo10>3.0.co;2-d 5. LÖhr HF, Gödderz W, Wölfe T, et al. Long-term survival in a patient with RosaiDorfman disease treated with interferon-alpha. Eur J Cancer 1995;31A(1314):2427-2428. http://dx.doi.org/10.1016/0959-8049(95)00375-4 6. Rosai J, Dorfman RF. Sinus histiocytosis with massive lymphadenopathy. A newly recognized benign clinicopathological entity. Arch Path 1969;87(1):6370.

7. Foucar E, Rosai J, Dorfman RF. Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease): Review of the entity. Semin Diagn Pathol 1990;7(1):19-73.

8. Foucar E, Rosai J, Dorfman RF, Eyman JM. Immunologic abnormalities and their significance in sinus histiocytosis with massive lymphadenopathy. Am J Clin Pathol 1984;82(5):515-525.

9. Kare M, Dang S, Dang A. Rosai-Dorfman syndrome with sinonasal mucosa and intraocular involvement. J Assoc Physicians India 2007;55:448-450.

10. Fudenberg HH, Good RA, Hitzig W, et al. Classification of the primary immune deficiencies: WHO recommendation. N Engl J Med 1970;283(12): 656-657. http://dx.doi.org/10.1056/NEJM197009172831211 11. Stebbing C, van der Walt J, Ramadan G, Inusa B. Rosai-Dorfman disease: A previously unreported association with sickle cell disease. BMC Clin Pathol 2007;7:3. http://dx.doi.org/10.1186/1472-6890-7-3 12. Ambati S, Chamyan G, Restrepo R, et al. Rosai-Dorfman disease following bone marrow transplantation for pre-B cell acute lymphoblastic leukemia.

Pediatr Blood Cancer 2008;51(3):433-435. http://dx.doi.org/10.1002/pbc.21606 13. Odinaka KK, Nwolisa EC. Challenges in the management of the child with Duchenne muscular dystrophy in a resource poor setting: A case report. Pan Afr Med J 2014;19:227. http://dx.doi.org/10.11604/pamj.2014.19.227.3137

Accepted 12 August 2016.

DECEMBER 2016 Vol. 10 No. 4

CPD December 2016 CPD questionnaires must be completed online at www.mpconsulting.co.za

True (T) or false (F): Regarding the management of persistent pulmonary hypertension of the newborn (PPHN) 1. During fetal life, only ~20% of blood ejected from the ventricles will reach the pulmonary circulation.

2. Nitric oxide released from the endothelium during delivery facilitates smooth-muscle relaxation.

3. The incidence of PPHN is an estimated ~5% in developed countries.

Regarding very low birth weight (VLBW) babies treated with nasal continuous positive airway pressure (nCPAP) 4. nCPAP should be reserved for VLBW infants who have failed mechanical ventilation.

5. The failure rate of nCPAP in the first 72 hours of life in VLBW neonates is nearly 50%.

6. Surfactant administration in nCPAP-treated VLBW infants is <20%.

Regarding upper gastrointestinal tract (GIT) endoscopy in children 7. In a referral hospital in West Africa, the most common reason for upper GIT endoscopy is intestinal bleeding.

8. Forty percent of children with recurrent abdominal pain had endoscopic evidence of pathology.

Regarding the management of acute diarrhoeal disease in KwaZulu-Natal 9. According to standard treatment guidelines, >50% of children with diarrhoea are appropriately investigated.

10. Over two-thirds of children with diarrhoea have had rotavirus immunisation.

Regarding children admitted to a paediatric intensive care unit (ICU) 11. It is estimated that there is ~1 paediatric intensive care bed per 23 000 children in South Africa.

12. Over 50% of children (excluding neonates) admitted to ICU have medical rather than surgical conditions.

Regarding mothers’ perceptions of neonatal jaundice in Nigeria 13. Two-thirds of pregnant mothers were able to describe the clinical presentation of neonatal jaundice.

14. Twenty-five percent of pregnant mothers were aware of the neurological complications associated with neonatal jaundice.

Regarding Lemierre’s syndrome 15. Lemierre’s syndrome is associated with septic thrombophlebitis of the internal jugular vein.

16. Lemierre’s syndrome may be caused by septic chronic middle-ear disease.

Regarding thrombosis in paediatric steroid-resistant nephrotic syndrome 17. Thromboembolic disease is not an uncommon severe complication in nephrotic syndrome.

18. Arterial thrombosis is more common than venous thrombosis.

Regarding Rosai-Dorfman disease 19. Rosai-Dorfman disease is a benign histiocytic proliferative dis­ order.

20. Extranodal involvement is rare in this condition.

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: MDB015/177/02/2016 (Clinical)

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