Characteristics and outcomes of neonates with intrapartum asphyxia managed with therapeutic hypothermia in a public tertiary hospital in South Africa.

BACKGROUND: In randomized clinical trials, therapeutic hypothermia (TH) has been shown to reduce death and/or moderate-to-severe disability in neonates with hypoxic ischemic encephalopathy (HIE) in high-income countries, while this has not consistently been the case in low-and middle-income countries (LMICs). Many studies reporting on outcomes of neonates with HIE managed with TH are those conducted under controlled study conditions, and few reporting in settings where this intervention is offered as part of standard of care, especially from LMICs. In this study we report on short-term outcomes of neonates with moderate-to-severe HIE where TH was offered as part of standard of care. OBJECTIVE: To determine characteristics and mortality rate at hospital discharge in neonates with moderate-to-severe HIE. METHODS: Hospital records of neonates with intrapartum asphyxia were reviewed for clinical findings, management with TH (cooled or non-cooled) and mortality at hospital discharge. Inclusion criteria were birthweight ≥ 1800 g, gestational age ≥ 36 weeks and moderate-to-severe HIE. Comparisons were made between survivors and non-survivors in cooled and/or non-cooled neonates. RESULTS: Intrapartum asphyxia was diagnosed in 856 neonates, with three having no recorded HIE status; 30% (258/853) had mild HIE, and 595/853 (69%) with moderate-to-severe HIE. The overall incidence of intrapartum asphyxia was 8.8/1000 live births. Of the 595 with moderate-to-severe HIE, three had no records on cooling and 67% (399/592) were cooled. Amongst 193 non-cooled neonates, 126 (67%) had documented reasons for not being cooled with common reasons being a moribund neonate (54.0%), equipment unavailability (11.1%), pulmonary hypertension (9.5%), postnatal age > 6 h on admission (8.7%), and improvement in severity of encephalopathy (8.7%). Overall mortality was 29.0%, being 17.0% and 53.4% in cooled and non-cooled infants respectively. On multivariate analysis, the only factor associated with mortality was severe encephalopathy. CONCLUSION: Overall mortality in neonates with moderate-to-severe HIE was 29.0% and 17.0% in those who were cooled. Cooling was not offered to all neonates mainly because of severe clinical illness, equipment unavailability and delayed presentation, making it difficult to assess overall impact of this intervention. Prospective clinical studies need to be conducted in LMIC to further assess effect of TH in short and long-term outcomes.

A randomized, double-blind trial investigating the efficacy of caspofungin versus amphotericin B deoxycholate in the treatment of invasive candidiasis in neonates and infants younger than 3 months of age.

OBJECTIVES: Investigate the efficacy of caspofungin in participants <3 months of age with invasive Candida infection (ICI). METHODS: This multicentre, randomized, double-blind, comparator-controlled, Phase 2 study (protocol MK0991-064; NCT01945281) enrolled participants <3 months of age with culture-confirmed ICI within 96 h of study entry. Participants were randomly assigned 2:1 to once-daily intravenous 2 mg/kg caspofungin or intravenous 1 mg/kg amphotericin B deoxycholate (dAMB). The primary endpoint was fungal-free survival (FFS) 2 weeks after treatment in the full-analysis-set (FAS) population, defined as participants with culture-confirmed ICI who received ≥1 dose of therapy. Planned enrolment was 90 participants. RESULTS: Fifty-one participants were enrolled; 49 received treatment (caspofungin, n=33; dAMB, n=16); 2 additional participants did not have confirmed infections at study entry. The study was terminated after ∼ 3.5 years because of low enrolment. Forty-seven participants were included in the FAS population (caspofungin, n=31; dAMB, n=16). FFS rate at 2 weeks after treatment was 71.0% (22/31) in the caspofungin arm and 68.8% (11/16) in the dAMB arm [difference, stratified by weight, - 0.9% (95% CI, - 24.3%-27.7%)]. Adverse events developed in 84.8% (28/33) of participants in the caspofungin arm and 100% (16/16) in the dAMB arm. CONCLUSIONS: Among neonates and infants with confirmed ICI, FFS at 2 weeks was similar in the caspofungin and dAMB treatment arms. A smaller proportion of participants who received caspofungin experienced adverse events.

Single surgeon case series of myelomeningocele repairs in a developing world setting: Challenges and lessons.

Purpose: Neural Tube Defects are the second most common group of birth malformations following congenital heart anomalies, with myelomeningoceles being the most severe manifestation (MMC). They require expedited surgical repair, preferably within 72 â€‹h of birth. In low- and middle-income countries (LMIC) where resources are limited, timing to MMC repair is not optimal and leads to undesirable outcomes. The purpose of this study was to determine whether a proactive approach in a setting from a LMIC could achieve repair within 72 â€‹h. Methods: A concerted effort to expedite repair of all neonates referred with a MMC was undertaken from 01 January 2014 to 1 August 2015. A consensus was reached between neonatologists and neurosurgeons that neonates born or admitted with a MMC are referred immediately to surgeons and that repair will be performed within 72 â€‹h of birth. Hospital records of neonates who had MMC repaired during this period were reviewed for infant characteristics and hospital outcomes. Results: 24 patients with a MMC were operated upon by the senior author (CP) during the study period. Only 13 of these patients were born at the treating institution and 11 were referred from outside hospitals. Most MMCs were in the lumbosacral region and mean MMC surface area was 19.4 â€‹cm2. Mean time to repair for the entire series was 13.6 days. Patients born at the treating institution has a mean time to repair of 10.5 days and patients referred from outside had a mean time to repair of 17.3 days. Series wide, only 21% of neonates were operated upon in less than 72 â€‹h. Conclusion: Despite a pro-active commitment to repairing MMCs within 72 â€‹h for the duration of this series, satisfactory time to repair was not achieved. Late referral, referral from outside hospitals and operating theatre availability were the predominant factors leading to delay in MMC repair. Nevertheless, time to repair in our series was significantly shorter than that reported in MMC repair series based in similar environments. This suggests that even if the gold-standard of a 72-h window cannot be achieved, neonates benefit from much quicker repair when a concerted effort to minimise repair time is employed. This study also highlights the urgent need to address health care constraints in LMIC to improve outcomes for this vulnerable group.

Healthcare-associated Infections Drive Antimicrobial Prescribing in Pediatric Departments at Three Academic Hospitals in South Africa.

BACKGROUND: The prevalence of antimicrobial prescriptions for healthcare-associated infections (HAI) in South Africa is largely unknown. This study aimed to estimate the point prevalence of pediatric antibiotic and antifungal usage in 3 South African academic hospitals. METHODS: This cross-sectional study included hospitalized neonates and children (0-15 years). We used the World Health Organization methodology for antimicrobial point prevalence studies, with weekly surveys to achieve a sample size of ~400 at each site. RESULTS: Overall, 1,946 antimicrobials were prescribed to 1,191 patients. At least 1 antimicrobial was prescribed for 22.9% [95% confidence interval (CI): 15.5-32.5%] of patients. The prevalence of antimicrobial prescribing for HAI was 45.6%. In the multivariable analysis, relative to children 6-12 years, neonates [adjusted relative risk (aRR): 1.64; 95% CI: 1.06-2.53], infants (aRR: 1.57; 95% CI: 1.12-2.21) and adolescents (aRR: 2.18; 95% CI: 1.45-3.29) had significantly increased risk of prescriptions for HAI. Being preterm (aRR: 1.33; 95% CI: 1.04-1.70) and underweight (aRR: 1.25; 95% CI: 1.01-1.54) was predictive of antimicrobial usage for HAI. Having an indwelling device, surgery since admission, blood transfusions and classification as rapidly fatal on McCabe score also increased the risk of prescriptions for HAI. CONCLUSIONS: The high prevalence of antimicrobial prescribing for HAI to treat children with recognized risk factors in academic hospitals in South Africa is concerning. Concerted efforts need to be made to strengthen hospital-level infection prevention and control measures, with a critical review of antimicrobial usage through functional antibiotic stewardship programs to preserve the available antimicrobial armamentarium at the hospital level.

Challenges in the Implementation of the NeoOBS Study, a Global Pragmatic Observational Cohort Study, to Investigate the Aetiology and Management of Neonatal Sepsis in the Hospital Setting.

Neonatal sepsis is a significant cause of mortality and morbidity in low- and middle-income countries. To deliver high-quality data studies and inform future trials, it is crucial to understand the challenges encountered when managing global multi-centre research studies and to identify solutions that can feasibly be implemented in these settings. This paper provides an overview of the complexities faced by diverse research teams in different countries and regions, together with actions implemented to achieve pragmatic study management of a large multi-centre observational study of neonatal sepsis. We discuss specific considerations for enrolling sites with different approval processes and varied research experience, structures, and training. Implementing a flexible recruitment strategy and providing ongoing training were necessary to overcome these challenges. We emphasize the attention that must be given to designing the database and monitoring plans. Extensive data collection tools, complex databases, tight timelines, and stringent monitoring arrangements can be problematic and might put the study at risk. Finally, we discuss the complexities added when collecting and shipping isolates and the importance of having a robust central management team and interdisciplinary collaborators able to adapt easily and make swift decisions to deliver the study on time and to target. With pragmatic approaches, appropriate training, and good communication, these challenges can be overcome to deliver high-quality data from a complex study in challenging settings through a collaborative research network.

Prediction of Retinopathy of Prematurity Using the WINROP (Weight, IGF-1, Neonatal Retinopathy of Prematurity) Algorithm in a South African Population.

Aim: This study aimed to assess the efficacy of the WINROP (Weight, IGF-1, Neonatal Retinopathy of Prematurity) screening algorithm in a South African population. Methods: A retrospective record review included infants born between 1 January 2013 and 1 December 2014 who underwent ROP (retinopathy of prematurity) screening. Outcomes of ophthalmology examinations were compared to alarms triggered on WINROP after gestational age, date of birth, and weekly weights were entered. Sensitivity, specificity, positive predictive, and negative predictive values and mean time of alarm were calculated. Results: Rates of ROP were 5.9% for all stages of ROP and 2.3% for severe ROP in the 220 infants included. Mean gestation age was 29.1 ± 1.3 weeks and mean birth weight 1,115.5 ± 201 g. WINROP triggered high-risk alarms in 70.5% of infants at a mean of 30.7 weeks of gestational age. Sensitivity for severe ROP was 100 and 76.9% for all stages of ROP. Specificity was low for both severe ROP and all stages of ROP at 30.2 and 30.0%, respectively. Conclusion: Rates of ROP are low in this population. The high number of alarms with a low negative predictive value would reduce the number of screens by 29.5%. Alarms were triggered before scheduled screening, possibly helpful in planning discharges and follow-up visits.

A comparison of weight gain between HIV exposed uninfected and HIV unexposed uninfected infants who received KMC at Chris Hani Baragwanath Academic Hospital.

Introduction: Kangaroo Mother Care (KMC) has been associated with improved growth in low birthweight infants and reduction in hypothermia, hypoglycaemia, apnoeas, sepsis, hospital stay, and mortality. The growth of HIV-infected children is poorer than those who are HIV-uninfected. There is paucity of data on weight gain in the HIV-exposed uninfected (HEU) infants compared to HIV-unexposed uninfected (HUU) infants receiving KMC. Aim: This study compared the weight gain of HEU and infants HUU from admission to the KMC ward until 12 months corrected age (CA) follow-up visit. Methods: Retrospective record review of the neonates admitted in KMC at Chris Hani Baragwanath Hospital over a 2-year period (2012-2013). The weight gain was assessed via weight velocity using the formula; weight/kg/day from admission to KMC to discharge, and g/ week at term, 3, 6 and 9- and 12-months (CA). The demographics were collected and analyzed using Statistica. Results: Seventy-seven (129/166) percent of the mothers were HIV negative. HIV negative mothers were younger (25.9 vs. 31.6 years; p = 0.000) and had fewer pregnancies (p = 0.02). There was no difference between the gestational age (30.3 ± 2.53 vs. 30.8 ± 2.88 weeks; p = 0.35) and birthweight (1,345 g ± 234 vs. 1,314 g ± 209; p = 0.47) between HEU and HUU. There were no differences in the weight gain (23.83 g ± 12.2 vs. 23.22 g ± 15.2; p = 0.83) in KMC. There was no differences in weight gain at the different follow-up time points between the two groups. Conclusion: Both HEU and HUU groups of infants showed reasonable weight gain despite maternal HIV status.

Hypothermia in neonates born by caesarean section at a tertiary hospital in South Africa.

Introduction: neonatal hypothermia has previously been noted in a large proportion of neonates born through Caesarean section at Chris Hani Baragwanath Hospital (CHBAH), yet no study in South Africa specifically explores the extent and severity of the threat of hypothermia to this population of neonates. Objectives: to describe the proportion and severity of neonatal hypothermia in infants born via Caesarean section at CHBAH as well as to document and describe possible contributing factors to neonatal hypothermia in this population. Methods: A neonatal unit's database records were reviewed for demographic information of patients and their mothers, clinical characteristics, body temperature and outcomes. Comparisons between normothermic and hypothermic neonates were performed. Results: Forty-one percent of neonates born via Caesarean section had hypothermia at birth, of whom 71%, 27% and 2% had mild, moderate and severe hypothermia, respectively. Prevalence of admission hypothermia was 42%. On average, neonates were born at term and were of normal birth weight. No maternal factors were found to be statistically significant. Bag-mask ventilation (BMV) and cardiopulmonary resuscitation (CPR) [3.4% vs. 0.7%, p-0.033; OR 2.67 (95% CI: 1.06-6.77)] and an elevated lactate [13.25 vs. 3.2 mmol/l, p-0.032; OR 1.13 (95% CI: 1.01-1.26)] were associated with hypothermia. In the multivariable logistic regression analysis hypothermia in neonates was associated with an elevated lactate. Conclusions: Prevalence of hypothermia in neonates born by Caesarean section is high and further prospective studies are required to elucidate the factors contributing to this.

An outbreak of infection due to severe acute respiratory corona virus-2 in a neonatal unit from a low and middle income setting.

Introduction: The provision of kangaroo mother care (KMC) involving continuous skin-to-skin care (SSC) is an important intervention in neonatal care, which is recommended even when women are infected with severe acute respiratory syndrome coronavirus (SARS-CoV-2). We report on a nosocomial outbreak of SARS-CoV-2 infections in a KMC ward. Methods: Contact tracing was conducted following the diagnosis of SARS-CoV-2 in a mother lodging in the KMC ward. All mother-newborn dyads in the KMC and healthcare workers (HCW) were tested for SARS-CoV-2 within 24-72 h of diagnosing the index case. Nasopharyngeal swab samples were obtained and tested from contacts, with a nucleic acid amplification test (NAAT) assay. Next-generation sequencing was done on positive samples. The secondary attack rate (SAR) was calculated assuming that the mother who presented with symptoms was the source of infection. Results: Twelve (70.6%) of 17 mothers and 8 (42.1%) of 19 neonates who were in the KMC ward with the index case were found to be positive with SARS-CoV-2. Seven (87.5%) of the 8 neonates who tested positive had mothers who also tested positive. Seventy-five percent (9/12) of the mothers and 62.5% (5/8) of the neonates who tested positive were asymptomatic. Eight (27.6%) of 29 HCW were found to be positive and were all asymptomatic. One neonate died from Acinetobacter baumannii sepsis, and his post-mortem lung histopathology showed features compatible with SARS-CoV-2 pneumonia. The sequencing of 13 specimens, which included 1 mother-newborn dyad, indicated clustering to the same phylogenetic lineage with identical mutations. In assessing for factors contributing to this outbreak, it was found that spaces between beds were less than 1 m and mothers had their meals around the same table at the same time. Conclusion: We report on a nosocomial outbreak of SARS-CoV-2 in a KMC ward, affecting a high number of mothers and neonates, and to a lesser extent HCWs. Although it is difficult to point to the index case as the source of this outbreak, as asymptomatic individuals can spread infection, the inadequate adherence to non-pharmaceutical interventions was assessed to have contributed to the spread of infection. This highlights the need for awareness and adherence to mitigation strategies to avoid SARS-CoV-2 outbreaks.