The Association Between Breast Milk Group B Streptococcal Capsular Antibody Levels and Late-onset Disease in Young Infants.

BACKGROUND: Animal-model studies have demonstrated less group B streptococcal (GBS) invasive disease and gastrointestinal colonization after enteral administration of serotype-specific capsular antibodies. There is, however, a paucity of information on the association of breast milk GBS serotype-specific capsular antibodies and risks for invasive disease in infants. The aim of this study was to explore the association between natural secretory immunoglobulin A (sIgA) capsular antibodies in breast milk and the occurrence of late-onset disease (LOD) in young infants. METHODS: A matched case-control study was undertaken in infants <3 months of age in Johannesburg, South Africa. Breast milk samples were collected on cases and controls matched for gestational age, maternal age, and human immunodeficiency virus status at time of enrollment. Capsular serotype Ia, Ib, III, and V sIgA antibody concentrations were measured using the fluorescence-based micro-bead immunosorbent assay. RESULTS: Breast milk samples were available for 31 LOD cases (8 serotype Ia and 23 serotype III), 21 recto-vaginally colonized matched controls (10 serotype Ia and 11 serotype III), and 84 serotype Ia and 105 serotype III noncolonized matched controls. Using a Bayesian model to estimate the probability of disease, there were 90% reductions in the risks of developing serotypes Ia and III LOD with sIgA concentrations ≥0.14 µg/mL and ≥2.52 µg/mL, respectively. CONCLUSIONS: Breast milk sIgA capsular antibodies were associated with lower risks for LOD in young infants. The ability of GBS polysaccharide-protein conjugate vaccines currently under development to induce sIgA responses warrant investigation as potential mediators of protection against LOD.

Growth of extremely low birth weight infants at a tertiary hospital in a middle-income country.

BACKGROUND: Survival of extremely low birth weight (ELBW; birth weight less than 1000 g) infants has improved significantly since the 1990s. Consequently, growth monitoring in ELBW infants has gained more relevance. METHODS: We conducted this study to describe the growth of ELBW infants at a tertiary hospital, to audit macronutrient intake and explore the association of prematurity complications with growth. This was a retrospective study on 92 ELBW infants born at Charlotte Maxeke Johannesburg Academic Hospital. The association between good growth (regaining birth weight in 21 days or less and subsequent growth velocity > 15 g/kg/day) and complications of prematurity was explored. RESULTS: Only 11infants (13%) had a discharge weight above the 10th centile when the Fenton growth chart was used compared to 20 infants (22.4%) when the Intergrowth 21st Project growth standard was used. The mean weight velocity was 13.5 g/kg/day and the mean number of days to regain birth weight was 18.2 days. Factors associated with poor growth were late-onset sepsis, persistent patent ductus arteriosus, continuous positive airway pressure for more than 2 days, invasive ventilation, oxygen on day 28 and being kept nil per os. Protein and caloric intake correlate positively with growth velocity. Unlike the Fenton Growth Charts, use of the Intergrowth 21st Project growth standards revealed the association between neonatal factors and poor growth. CONCLUSION: Growth outcome in infants is poor at 36 weeks postmenstrual age at our institution. Intergrowth 21st Project growth standards were superior to Fenton Growth Charts, however a multicentre study is required before adoption.

Neurodevelopmental outcome of late preterm infants in Johannesburg, South Africa.

BACKGROUND: Late preterm infants, previously considered low risk, have been identified to be at risk of developmental problems in infancy and early childhood. There is limited information on the outcome of these infants in low and middle income countries. METHODS: Bayley scales of infant and toddler development, version III, were done on a group of late preterm infants in Johannesburg, South Africa. The mean composite cognitive, language and motor sub-scales were compared to those obtained from a group of typically developed control infants. Infants were considered to be "at risk" if the composite subscale score was below 85 and "disabled" if the composite subscale score was below 70. Infants identified with cerebral palsy were also reported. RESULTS: 56 of 73 (76.7%) late preterm infants enrolled in the study had at least one Bayley assessment at a mean age of 16.5 months (95% CI 15.2-17.6). The mean birth weight was 1.9 kg (95%CI 1.8-2.0) and mean gestational age 33.0 weeks (95% CI 32.56-33.51). There was no difference in the mean cognitive subscales between late preterm infants and controls (95.4 9, 95% CI 91.2-99.5 vs 91.9.95% CI 87.7-96.0). There was similarly no difference in mean language subscales (94.5, 95% CI 91.3-97.7 vs 95.9, 95% CI 92.9-99.0) or motor subscales (96.2, 95% CI 91.8-100.7 vs 97.6, 95% CI 94.7-100.5). There were four late preterm infants who were classified as disabled, two of whom had cerebral palsy. None of the control group was disabled. CONCLUSIONS: This study demonstrates that overall developmental outcome, as assessed by the Bayley scales of infant and toddler development, was not different between late preterm infants and a group of normal controls. However, 7.1% of the late preterm infants, had evidence of developmental disability. Thus late preterm infants in low and middle income countries require long term follow up to monitor developmental outcome. In a resource limited setting, this may best be achieved by including a parental screening questionnaire, such as the Ages and Stages Questionnaire, in the routine well baby clinic visits.

Comparison of morbidity and mortality of very low birth weight infants in a Central Hospital in Johannesburg between 2006/2007 and 2013.

BACKGROUND: Health protocols need to be guided by current data on survival and benefits of interventions within the local context. Periodic clinical audits are required to inform and update health care protocols. This study aimed to review morbidity and mortality in very low birth weight (VLBW) infants in 2013 compared with similar data from 2006/2007. METHODS: We performed a retrospective review of patients' records from a neonatal computer database for 562 VLBW infants. These neonates weighed between 500 and 1500 g at birth, and were admitted within 48 hours after birth between 01 January 2013 and 31 December 2013. Patients' characteristics, complications of prematurity, and therapeutic interventions were compared with 2006/2007 data. Univariate analysis and multiple logistic regression were performed to establish significant associations of various factors with survival to discharge for 2013. RESULTS: Survival in 2013 was similar to that in 2006/2007 (73.4% vs 70.2%, p = 0.27). However, survival in neonates who weighed 750-900 g significantly improved from 20.4% in 2006/2007 to 52.4% in 2013 (p = 0.001). The use of nasal continuous positive airway pressure (NCPAP) increased from 20.3% to 62.9% and surfactant use increased from 19.2% to 65.5% between the two time periods (both p < 0.001). Antenatal care attendance improved from 54.4% to 70.6% (p = 0.001) and late onset sepsis (>72 hours after birth) increased from 12.5% to 19% (p = 0.006) between the two time periods. Other variables remained unchanged between 2006/2007 and 2013. The main determinants of survival to discharge in 2013 were birth weight (odds ratio 1.005, 95% confidence interval 1.003-1.0007, resuscitation at birth (2.673, 1.375-5.197), NCPAP (0.247, 0.109-0.560), necrotising enterocolitis (4.555, 1.659-12.51), and mode of delivery, including normal vaginal delivery (0.456, 0.231-0.903) and vaginal breech (0.069, 0.013-0.364). CONCLUSIONS: There was a marked improvement in the survival of neonates weighing between 750 and 900 g at birth, most likely due to provision of surfactant and NCPAP. Provision of NCPAP, prevention of necrotising enterocolitis, and control of infection need to be prioritised in VLBW infants to improve their outcome.

Neurodevelopmental Outcomes of Extremely Low Birth Weight Survivors in Johannesburg, South Africa.

Background: Improved survival in extremely low birth weight infants (ELBWI) in Sub-Saharan Africa has raised the question whether these survivors have an increased chance of adverse neurodevelopmental outcomes. Objectives: To describe neurodevelopmental outcomes of ELBWI in a neonatal unit in South Africa. Methods: This was a prospective follow-up study. All ELBWI who survived to discharge between 1 July 2013 and 31 December 2017 were invited to attend the clinic. Bayley Scales of Infant and Toddler Development (version III) were conducted at 9 to 12 months and 18 to 24 months. Results: There were 723 ELBWI admissions during the study period, 292 (40.4%) survived to hospital discharge and 85/292 (29.1%) attended the neonatal follow up clinic. The mean birth weight was 857.7 g (95% CI: 838.2-877.2) and the mean gestational age was 27.5 weeks (95% CI 27.1-27.9). None of the infants had any major complication of prematurity. A total of 76/85 (89.4%) of the infants had a Bayley-III assessment at a mean corrected age of 17.21 months (95% CI: 16.2-18.3). The mean composite scores for cognition were 98.4 (95% CI 95.1-101.7), language 89.9 (95% CI 87.3-92.5) and motor 97.6 (95% CI 94.5-100.6). All mean scores fell within the normal range, The study found 28 (36.8%) infants to be "at risk" for neurodevelopmental delay. Conclusion: Our study demonstrates good neurodevelopmental outcome in a small group of surviving ELBWI, but these results must be interpreted in the context of the high mortality in this group of infants.

A Review of Very-Low-Birth-Weight Infants Admitted to the Kangaroo Mother Care Unit in Johannesburg, South Africa.

Background Kangaroo Mother Care (KMC) is a widely implemented intervention developed as an alternative form of care in low- and middle-income countries (LMICs) for neonates. The implementation of KMC has significantly reduced morbidity and mortality in very-low-birth-weight infants (VLBWIs). Aim To describe the maternal and neonatal characteristics and clinical outcomes in VLBWIs who received KMC at a tertiary hospital. Methods This is a retrospective descriptive study of 981 VLBWIs admitted at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) over a six-year period (January 1, 2014, to December 31, 2019). Results The mean gestational age of infants admitted to the unit was 29.6 weeks (standard deviation (SD): 2.4), with a mean birth weight of 1185 g (SD: 205.6). The average duration of admission in the neonatal unit was 37 days. The mean rate of weight gain was 37.6 g/kg/day (SD: 57.6). The majority of infants were breastfed (61.4%). In our study, the prevalences of the complications of prematurity were as follows: respiratory distress syndrome (RDS), 84.2%; late-onset sepsis (LOS), 26.1%; and retinopathy of prematurity (ROP), 10.6%. The mortality rate was 3.1%. Maternal comorbidities include human immunodeficiency virus (HIV) (26.4%), syphilis (2.9%) and gestational hypertension (33.7%). The antenatal clinic attendance rate was good (84.7%). Conclusion KMC is a cost-effective alternative to conventional care for VLBWIs in limited-resource countries, with evidence of increased weight gain, less rates of complications of prematurity and low overall mortality. The provision of KMC facilities is urgently required in LMICs.

Global research priorities for COVID-19 in maternal, reproductive and child health: Results of an international survey.

BACKGROUND: The World Health Organization's "Coordinated Global Research Roadmap: 2019 Novel Coronavirus" outlined the need for research that focuses on the impact of COVID-19 on pregnant women and children. More than one year after the first reported case significant knowledge gaps remain, highlighting the need for a coordinated approach. To address this need, the Maternal, Newborn and Child Health Working Group (MNCH WG) of the COVID-19 Clinical Research Coalition conducted an international survey to identify global research priorities for COVID-19 in maternal, reproductive and child health. METHOD: This project was undertaken using a modified Delphi method. An electronic questionnaire was disseminated to clinicians and researchers in three different languages (English, French and Spanish) via MNCH WG affiliated networks. Respondents were asked to select the five most urgent research priorities among a list of 17 identified by the MNCH WG. Analysis of questionnaire data was undertaken to identify key similarities and differences among respondents according to questionnaire language, location and specialty. Following elimination of the seven lowest ranking priorities, the questionnaire was recirculated to the original pool of respondents. Thematic analysis of final questionnaire data was undertaken by the MNCH WG from which four priority research themes emerged. RESULTS: Questionnaire 1 was completed by 225 respondents from 29 countries. Questionnaire 2 was returned by 49 respondents. The four priority research themes which emerged from the analysis were 1) access to healthcare during the COVID-19 pandemic, 2) the direct and 3) indirect effects of COVID-19 on pregnant and breastfeeding women and children and 4) the transmission of COVID-19 and protection from infection. CONCLUSION: The results of these questionnaires indicated a high level of concordance among continents and specialties regarding priority research themes. This prioritized list of research uncertainties, developed to specifically highlight the most urgent clinical needs as perceived by healthcare professionals and researchers, could help funding organizations and researchers to answer the most pressing questions for clinicians and public health professionals during the pandemic. It is hoped that these identified priority research themes can help focus the discussion regarding the allocation of limited resources to enhance COVID-19 research in MNCH globally.

The Use of Therapeutic Hypothermia in Neonates with Perinatal Asphyxia at Charlotte Maxeke Johannesburg Academic Hospital: A Retrospective Review.

Therapeutic hypothermia (TH) has become the standard of care to reduce neurological damage following perinatal asphyxia. Current recommendations call for implementation of a standard, evidence-based protocol for the provision of TH. This is particularly challenging in resource-limited settings. This is a retrospective, descriptive study to determine whether neonates at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) are receiving TH according to the unit protocol in place. The study included all neonates with a birth weight greater than 1800 g admitted to the CMJAH neonatal unit from January 1, 2013, to June 30, 2017, before 24 hours of life. Neonates were assessed as to whether they met the criteria for TH according to the protocol, and reasons for not providing TH to those who qualified were investigated. The total number of neonates enrolled for the study was 485. Three hundred patients met the criteria for TH. 185/300 appropriately received TH. One hundred fifteen patients were not cooled, despite meeting TH criteria. Reasons for this included severe clinical conditions (73/115) and a lack of equipment (26/115). Of the remaining 185 patients who did not meet TH criteria, 21 patients inappropriately received TH. A total of 206 neonates received TH. TH at CMJAH is largely being practiced as per protocol. Still, more resources are needed, not only to optimize the number of patients who have access to this treatment modality but also in terms of imaging and support strategies.

An audit of mother to child HIV transmission rates and neonatal outcomes at a tertiary hospital in South Africa.

OBJECTIVE: The aim of this study was to explore the prevalence of congenital HIV infection of neonates at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) between 2015 and 2017, as well as compare the HIV PCR positive and HIV PCR negative neonates. RESULTS: A total number of 1443 HIV exposed neonates was examined for the study period out of a total of 5029 admissions (HIV exposure 28.6%) The study found that the rate of HIV transmission at birth was 2.52%. The majority of infants had low birth weight and were also born prematurely. These results show that, despite the introduction of the extended mother to child transmission programme, HIV transmission is high.

A comparison between raw and predicted mortality in a paediatric intensive care unit in South Africa.

OBJECTIVE: Paediatric intensive care resources are limited in sub-Saharan Africa. The mortality rate in a combined Paediatric/Neonatal Intensive Care Unit in Johannesburg, South Africa was almost double that in a dedicated paediatric intensive care unit in the same country. This study aimed to compare the raw mortality rate with that predicted with the Paediatric Index of Mortality (version 3), by doing a retrospective analysis of an existing database. RESULTS: A total of 530 patients admitted to the intensive care unit between 1 January 2015 and 31 December 2017 were included. The raw mortality rate was 27.1% and the predicted mortality rate was 27.0% (p = 0.971). Cardiac arrest during ICU admission (p < 0.001), non-reactive pupils (0.035), inotropic support (p < 0.001) and renal disease (p = 0.002) were all associated with an increased risk of mortality. These findings indicate that the high mortality rate is due to the severity of illness in the patients that are admitted. It also indicates that the quality of care delivered is acceptable.

Use of the Bayley Scales of Infant and Toddler Development, Third Edition, to Assess Developmental Outcome in Infants and Young Children in an Urban Setting in South Africa.

BACKGROUND: The Bayley Scales of Infant and Toddler Development (III) is a tool developed in a Western setting. AIM: To evaluate the development of a group of inner city children in South Africa with no neonatal risk factors using the Bayley Scales of Infant and Toddler Development (III), to determine an appropriate cut-off to define developmental delay, and to establish variation in scores done in the same children before and after one year of age. METHODS: Cohort follow-up study. RESULTS: 74 children had at least one Bayley III assessment at a mean age of 19.4 months (95% CI 18.4 to 20.4). The mean composite cognitive score was 92.2 (95% CI 89.4 to 95.0), the mean composite language score was 94.8 (95% CI 92.5 to 97.1), and mean composite motor score was 98.8 (95% CI 96.8 to 101.0). No child had developmental delay using a cut-off score of 70. In paired assessments above and below one year of age, the cognitive score remained unchanged, the language score decreased significantly (p = 0.001), and motor score increased significantly (p = 0.004) between the two ages. CONCLUSION: The Bayley Scales of Infant and Toddler Development (III) is a suitable tool for assessing development in urban children in southern Africa.

Assessment of developmental outcome in very low birth weight infants in Southern Africa using the Bayley Scales of Infant Development (III).

OBJECTIVES: The study aimed to compare the developmental outcome of very low birth weight infants with a group of normal-term controls in a tertiary hospital in sub-Saharan Africa. DESIGN: A group of 105 very low birth weight infants were assessed at a mean age of 17.6 months (95% CI 16.7 to 18.6) using the Bayley Scales of Infant Development, Third Edition, and compared with a group of normal-term controls at the same mean age. RESULTS: Seven of the study infants (7%) had developmental delay (a score below 70), compared with none in the control group (p=0.04). Three of the seven study infants were delayed on all three subscales, one of whom had cerebral palsy. A further 34% of the study infants were 'at risk' of developmental delay (a score below 85). There was no difference in the mean composite score between the study group and controls for the cognitive (p=0.56), motor (p=0.57) or language (p=0.66) subscales. There was no difference in mean composite scores on all subscales between infants who were appropriate for gestational age and those who were small for gestational age. Cognitive and motor scores remained stable in paired assessments of study infants before and after 1 year of age; language scores decreased significantly (p<0.001). Mechanical ventilation was the only risk factor significantly associated with a cognitive score below 85 in study infants. CONCLUSION: Very low birth weight infants in sub-Saharan Africa are at risk of developmental delay and require long-term neurodevelopmental follow-up.

A review of delivery room resuscitation in very low birth weight infants in a middle income country.

BACKGROUND: Advanced levels of delivery room resuscitation in very low birth weight infants are reported to be associated with death and complications of prematurity. In resource limited settings, the need for delivery room resuscitation is often used as a reason to limit care in these infants. METHODS: This was a review of delivery room resuscitation in very low birth weight infants born in a tertiary hospital in South Africa between 01 January 2013 and 30 June 2016. Outcomes included death and serious complications of prematurity. Advanced delivery room resuscitation was defined as the need for intubation, chest compressions or the administration of adrenaline. RESULTS: A total of 1511 very low birth weight infants were included in the study. The majority (1332/1511 (88.2%) required oxygen in the delivery room. Face mask ventilation was needed in 45.2% (683/1511). Advanced delivery room resuscitation was only required in 10.6% (160/1511). More than half the infants who required advanced delivery room resuscitation died (89/160; 55.6%). Advanced delivery room resuscitation was required in significantly more infants <1000 grams at birth than those infants >1000 grams (83/539 (15.4%) vs 77/972 (7.9%) p < 0.001). Advanced delivery room resuscitation was significantly associated with a 5 minute Apgar score < 6 (OR 13.8 (95%CI 8.6-22.0), supplemental oxygen at day 28 (OR 2.2 (95% CI 1.4-3.9), metabolic acidosis (OR 2.3 (95% CI 1.1-4.8) and death (OR 1.9 95% CI 1.1-3.3). Other serious complications of prematurity were not associated with advanced delivery room resuscitation. Mortality was increased in infants with a low admission temperature (35.1 °C (SD 0.92) vs 36.1 °C (SD 1.4) (p < 0.001). CONCLUSION: There was a high mortality rate associated with advanced delivery room resuscitation; however complications of prematurity were not increased in survivors..The need for advanced delivery room resuscitation alone should not be used as a predictor of poor outcome in very low birth weight infants. Survivors of advanced delivery room resuscitation should be afforded ventilatory support if required. Special care must be taken to avoid hypothermia in very low birth weight infants requiring resuscitation at birth.

Burden of invasive group B Streptococcus disease and early neurological sequelae in South African infants.

INTRODUCTION: Group B Streptococcus (GBS) is a leading cause of neonatal sepsis and meningitis. We aimed to evaluate the burden of invasive early-onset (0-6 days of life, EOD) and late-onset (7-89 days, LOD) GBS disease and subsequent neurological sequelae in infants from a setting with a high prevalence (29.5%) of HIV among pregnant women. METHODS: A case-control study was undertaken at three secondary-tertiary care public hospitals in Johannesburg. Invasive cases in infants <3 months age were identified by surveillance of laboratories from November 2012 to February 2014. Neurodevelopmental screening was done in surviving cases and controls at 3 and 6 months of age. RESULTS: We identified 122 cases of invasive GBS disease over a 12 month period. Although the incidence (per 1,000 live births) of EOD was similar between HIV-exposed and HIV-unexposed infants (1.13 vs. 1.46; p = 0.487), there was a 4.67-fold (95%CI: 2.24-9.74) greater risk for LOD in HIV-exposed infants (2.27 vs. 0.49; p<0.001). Overall, serotypes Ia, Ib and III constituted 75.8% and 92.5% of EOD and LOD, respectively. Risk factors for EOD included offensive draining liquor (adjusted Odds Ratio: 27.37; 95%CI: 1.94-386.50) and maternal GBS bacteriuria (aOR: 8.41; 95%CI: 1.44-49.15), which was also a risk-factor for LOD (aOR: 3.49; 95%CI: 1.17-10.40). The overall case fatality rate among cases was 18.0%. The adjusted odds for neurological sequelae at 6 months age was 13.18-fold (95%CI: 1.44-120.95) greater in cases (13.2%) than controls (0.4%). DISCUSSION: The high burden of invasive GBS disease in South Africa, which is also associated with high case fatality rates and significant neurological sequelae among survivors, is partly due to the heightened risk for LOD in infants born to HIV-infected women. An effective trivalent GBS conjugate vaccine targeted at pregnant women could prevent invasive GBS disease in this setting.