Background and rationale: Inhaled nitric oxide (iNO) is recommended for the treatment of severe persistent pulmonary hypertension of the newborn (PPHN) because it reduces the need for extracorporeal membrane oxygenation (ECMO). There is insufficient evidence that iNO reduces mortality in the absence of ECMO. Although neonates in some South African public hospitals have access to iNO, ECMO is not available. Oral sildenafil can be effective in settings where iNO is not available, but its effect on outcome and cost of treatment in this setting have not been described. The literature review in the first part of this thesis describes five studies reporting short-term outcomes of PPHN in the absence of ECMO. No studies from South Africa were identified. Only two studies described outcomes after iNO – the coadministration of Sildenafil with iNO was only reported in one small study. There were insufficient published data to guide management in settings where ECMO is not available. Aim: To describe a cohort of term and near term neonates with PPHN who were treated with iNO, with or without sildenafil, in a tertiary neonatal unit in South Africa Objectives: (i) to describe the characteristics at birth, the clinical course, and shortterm outcomes; (ii) to determine if any variables were associated with mortality; (iii) to describe the relationship between the use of sildenafil and cost of care, represented by the duration of intubation and iNO use; and (iv) to describe the frequency of sildenafil prescription. Methods. A retrospective review was carried out on folders of neonates with PPHN who were treated with iNO in Groote Schuur Hospital, Cape Town, South Africa, between January 2010 and December 2014. Results. Forty neonates were included – most were full term (85%). Meconium aspiration syndrome (MAS) was the commonest cause of PPHN (50%), followed by intrapartum hypoxia (20%), sepsis (17.5%), pulmonary hypoplasia (7.5%) and idiopathic (5%). Fourteen neonates (35%) died. Pulmonary hypoplasia and pneumothorax were associated with mortality (p=0.037 and p=0.004 respectively). An FiO2 of 1.0 and an iNO dose of ≥ 20 ppm at 24 and 48 hours respectively, both predicted death (specificity 89% vs. 100%, sensitivity 67% vs. 43% and p=0.003 vs. p=0.007 respectively). Sildenafil was prescribed more often after 2011 (83% vs. 65%) and was associated with increased survival (p=0.018) – early administration was associated with a shorter time to extubation (p=0.012) and a shorter course of iNO (p=0.044). Conclusion. The treatment of PPHN with iNO in the absence of ECMO was associated with high mortality, particularly in neonates with congenital lung abnormalities. The FiO2 and iNO requirements at 24 and 48 hours respectively could be used to identify neonates who are unlikely to benefit from continued treatment. Sildenafil was prescribed with increasing frequency during the study. The combination of iNO with sildenafil was associated with more cost-effective care and improved short term outcomes. These findings provide a potential basis for costsaving measures and resource allocation.

Background: Syphilis is a disease that was first described in the 1300s and now 700 years later, despite preventive measures and effective treatment, continues to impact on a global scale, with the burden falling largely on the developing world. We could find no recent published literature looking at predictors of outcomes in neonates born with symptomatic congenital syphilis, especially in the context of a tertiary neonatal setting. Methodology: The study design was a retrospective descriptive folder review of neonates born with symptomatic congenital syphilis at Groote Schuur Hospital (GSH) from January 2011 to December 2013. One of the primary objectives was to address outcome as well as look at modifiable preventable factors. All neonates treated at GSH (inborn and outborn) who tested serologically positive for syphilis together with clinical signs of syphilis were included. Data was obtained from the National Health Laboratory System (NHLS) database, as well as the notification and death registers at GSH nursery. All data was collected in a Microsoft excel spread sheet and analysed using Microsoft StatPlus. Results: Fifty of eighty neonates (62.5%) with positive syphilis serology as well as clinical signs of congenital syphilis were included together with their fifty mothers. The majority (98%) of mothers were inadequately untreated. Nineteen neonates demised. There were no statistically significant differences between the deaths and survivors in terms of gestational age (p = 0.15), birth weight (p = 0.08) or maternal age (p = 0.51). Two significant predictors of mortality were one minute and five minute Apgar scores of less than five ([RR], 3.5; 95% CI 1.6-7.7 and [RR], 2.9; 95% CI 1.5-5.3 respectively). Hydropic neonates, tended to be sicker at birth, requiring intubation and inotropes, which was associated with a poorer outcome (increased risk of mortality). Conclusion: Despite the introduction of a National Syphilis Screening programme more than twenty years ago together with a large proportion of pregnant women having access to antenatal care, congenital syphilis is still prevalent in South Africa. Failure to access antenatal care, poor partner tracing and a number of modifiable health worker related failures contribute to poor maternal diagnosis and treatment. Many neonates with congenital syphilis require aggressive interventions and there is a high mortality rate. This dissertation adds to the existing body of research particularly with regard to predictors of outcome in tertiary neonatal settings. Certain categories of neonates have a lower survival rate and guidelines about limitation of care may need to be considered in order to optimise resource allocation particularly in resource-constrained settings. Further research is required to elaborate how best to develop protocols in these neonates.

Children with disabling chronic illnesses are known to have complex and frequently unmet health care needs. Limited information exists in South Africa regarding the prevalence of children with disability, as well their needs and utilization of services. The purpose of the current study is twofold: (1) identify the number of children known with disability, or disabling chronic illnesses in the western health sub-district of Cape Town; (2) analyse the health services that currently exist for these children. A period prevalence survey was conducted between January 2010 and December 2011. Numerous sources of information were sought to identify as many children with disabling chronic illness as possible. These included the referral hospitals for the Western sub-district, namely Red Cross War Memorial Children's Hospital and New Somerset Hospital, as well as the institutions where children with disability are cared for or educated, and relevant non-profit organisations in the disability sector. Information was gathered between January 2011 and Sept 2012.

Introduction: HIV exposed but uninfected infants have been shown to have a higher morbidity and mortality than unexposed infants. There is almost no literature comparing the short-term outcomes of HIV exposed versus unexposed VLBW neonates who are born prematurely. Methods: A retrospective review of all VLBW neonates who were admitted at Groote Schuur Hospital nursery from 2012-2014. Data were obtained from the Vermont Oxford Database and the Prevention of Mother to Child register. Results: A total of 1593 VLBW neonates were admitted during the 3 years of which it was possible to obtain maternal HIV status in 1579 babies. Of these 1579 babies, 316 (20%)were HIV exposed. Eleven of the 230 (4.8%)infant HIV tests were positive. There was no difference in mortality, birth weight, gestational age, length of stay, sepsis and delivery room outcomes for the HIV-exposed (HIVE), maternal ARV-exposed (mARVE) and HIV-positive neonates. Differences between HIV exposed and HIV unexposed neonates were noted in an increased risk of NEC [OR 1.83 (1.2-2.8)] and an increased need for ventilation [OR 1.35 (1.01-1.8)]. Maternal antiretroviral exposed neonates developed less NEC compared with maternal antiretroviral under-exposed neonates with a birth weight under 1000grams appearing to contribute in the development and outcome of NEC. Differences in HIV-positive neonates included more chronic lung disease [OR 5.49 (1.31-23)] and more necrotising enterocolitis [OR 4.12 (1.02-17.18)]. Conclusion: This study is the first to compare the short-term outcomes of HIV exposed and HIV unexposed very low birth weight infants and consider maternal ARV exposure. It demonstrated no difference in birth weight, gestational age, mortality or sepsis. Necrotising enterocolitis is increased in the HIV exposed neonates especially if they are under-exposed to maternal antiretrovirals. Adequate maternal antiretrovirals may have a protective effect on incidence of necrotising enterocolitis and respiratory outcomes.

Background Muscular dystrophies (MD) and myopathies are a distinct group of clinically and genetically heterogeneous inherited muscle diseases. They cause muscle weakness often with cardiac, pulmonary, and musculoskeletal dysfunction, leading to reduced longevity. MDs and myopathies present across all life stages. Delineation of this condition and specifically the subgroups with additional connective tissue involvement is poorly described in subSaharan African populations. Aim To delineate the phenotypic, and where possible genotypic expression, of muscular dystrophies and myopathies with connective tissue involvement in an African setting. Methods A retrospective cohort study was undertaken of children with muscular dystrophy / myopathy and connective tissue involvement who attend a dedicated neuromuscular service. Patient demographics, diagnosis and clinical profile was collated. Patients were allocated into two groups, congenial /infantile and childhood, based on age of onset. Muscle biopsy characteristics, biochemical findings, and where available, genetic analysis were captured. Based on the combined findings children were categorised into connective tissue variant groups i.e., Collagen 6 related myopathies, Rigid Spine Syndrome (SELENON phenotype), LMNA-related, ACTA1 related myopathies, MDC1A, and a subgroup who could not be categorised. Descriptive statistics and categorical variables were compared to evaluate primary study questions. Ethical approval was obtained by the University of Cape Town Human Research Ethics Committee (HREC:549/2019). Families gave informed consent prior to enrolment. Results A total of 57 children were reviewed, 50 of whom met the inclusion criteria of connective tissue spectrum in the setting of muscle disease (female to male ratio 1.3:1). There was a predominance in children from African ancestries, followed by those of European descent. 31/50 (62%) presented in the congenital-infantile age period, the remainder presented after 2 years of age. Children with congenital/infantile onset were more likely to lose independent ambulation compared to children with childhood onset (5/8, 62% vs 3/8 38%). Scoliosis complicated the course in 29/50 (58%) children, again affecting congenital/infantile onset children more when compared to the childhood onset group (19/29, 65%, vs 10/29,35%); (p=0.003), and spinal rigidity was more prevalent in the congenital/infantile onset compared to the childhood group, (8/11 (73%) vs 3/11 (27%)). The childhood group were statistically more at risk of suffering compromising respiratory muscle dysfunction (32/45, 71%, vs 13/45,29%) ;(p=0.04 ). Genetic diagnosis was available for 9 patients. Based on this and the combined phenotypes n=17 were considered part of the Collagen 6 group, n=7 Rigid Spine Syndrome and n=14 LMNA spectrum, n=3 under the ACTA1 mutation expression, n=2 LAMA2 and the remaining 7 could not be categorized or did not fall under one of the main groupings. Conclusion This study confirmed expression of this subgroup of muscular diseases with connective tissue involvement within the SSA population. The burden of disease from these conditions is across multiple systems and significant, requiring specialized care. Early recognition and referral to neuromuscular centre, would improve the potential outcomes for these children with collaborative multidisciplinary team. Serum creatine kinase (CK) levels and clinical markers such as rigid spine, dropped head, and skin laxity could be used in resource limited settings for probable and possible phenotype.

Background and aim: The Groote Schuur Hospital (GSH) Neonatal Nursery provides Level 3 care for the Metro West Health District in the Western Cape. Worldwide, VLBW neonates have improved outcomes when delivered in Level 3 neonatal units, compared with those who are transported from other facilities. This study aims to identify the characteristics and clinical outcomes of our VLBW patients, with emphasis on differences between inborns and outborns. Methodology: A retrospective cohort study. VLBW neonates admitted to the GSH Neonatal Nursery between 1 January 2012 and 31 December 2013 were enrolled on the Vermont Oxford Network database and reviewed. Maternal and infant characteristics, and outcomes at the time of discharge from hospital were analysed. Results: A total of 1032 VLBW neonates were enrolled. 906 (87.8%) were delivered at GSH, and 126 (12.2%) were outborn. Access to antenatal care, antenatal steroids and inborn status were statistically significant predictors for mortality and survival without morbidity. The mothers of inborn patients were more likely to have received antenatal care (89.1% vs 57.9%, p <0.0001) and antenatal steroids (64.2% vs 15.2%, p <0.0001). Inborns required less ventilatory support (16.2% vs 57.9%, p <0.0001) and surfactant administration (25.3% vs 65.1%, p <0.0001). Inborns had a lower incidence of late infection (8.8% vs 23.4%, p <0.0001), severe intraventricular haemorrhage (3.7% vs 13.9%, p <0.0001) and chronic lung disease (5.3% vs 13.4%, p =0.003). The incidence of necrotising enterocolitis was similar between the two groups (5.9% vs 8.7%, p =0.227). 18.4% of inborns and 33.3% of outborns demised (p <0.0001), mostly on the first 2 days of admission. Mortality declined as birth weight increased. Of the survivors, 83.5% of inborns and 70.2% of outborns did not develop serious morbidity (p =0.003). Significant morbidity and mortality was noted in the outborn group weighing 800g and less, with only one outborn patient in the cohort surviving to discharge without major morbidity. Conclusion: VLBW neonates delivered at Groote Schuur Hospital had better outcomes than their outborn counterparts. Perinatal regionalisation is beneficial to our patients, with antenatal care, timeous in-utero transfer and antenatal steroids contributing to excellent outcomes.

Clinical profile of children with Autism Spectrum Disorder in a developmental clinic in Western Cape Abstract Introduction Autism Spectrum Disorder (ASD) is increasingly being recognised as a significant neurodevelopmental condition in African countries. There is some evidence to suggest that the children who present with ASD in Africa may be diagnosed late and have a more severe clinical picture. The purpose of this study was to describe the clinical profile of children with ASD in the neurodevelopmental clinic at Red Cross War Memorial Children's Hospital in Western Cape Province South Africa. Methods We sampled patients with a previous or new diagnosis who attended our clinic during the period January to July 2017. Consenting participants were administered a questionnaire with sociodemographic and clinical questions, clinical details of medical and developmental diagnosis were extracted from medical records and children. were further assessed using the Autism Diagnostic Observation Schedule version 2 (ADOS-2). Results A total of 32 patients were recruited into the study with 26 out of 32 (81%) being boys. On assessment as part of the study, all participants met DSM 5 criteria for the diagnosis of ASD. Most participants (94%) had not experienced general developmental regression but a substantial proportion (39%) had reported early regression of language milestones. Almost half of participants (48%) had self-injurious behaviour reported, 25% had associated motor difficulty and 10% comorbid epilepsy. More than half of participants (53%) required substantial support in day-to-day activities. Most participants (81%) were administered module 1 of the ADOS-2 reflecting the high proportion of children in the sample who were either preverbal or using only single words. Conclusions Children seen in this clinical sample reflected the more severe end of the autism spectrum with a significant proportion having associated comorbidities such as epilepsy, and motor difficulties. The phenotypic profile on the ADOS 2 in this study correlated well with clinical assessments.

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