Tanusha Ramdin

: Late-onset sepsis (LOS) in neonates is defined as a bloodstream infection occurring after 72 hours of life and is primarily caused by bacterial pathogens, often associated with catheter use and prolonged hospitalization. Despite its clinical and policy relevance, limited data exist on the etiology of neonatal infections in sub-Saharan Africa. This 8-year retrospective study investigated microbial patterns and antibiotic trends of LOS in a South African neonatal unit to inform infection control and antibiotic stewardship strategies. Data from neonates weighing 500 to 2,500 g admitted to the neonatal unit of a public tertiary hospital in Johannesburg (2013–2020) were analyzed for culture-confirmed LOS. Microbial prevalence was stratified by birth weight and year, and temporal shifts were assessed using Joinpoint regression. Among 7,468 neonates, 1,454 LOS episodes occurred (194 per 1,000 live births), with males accounting for 51.1%. Gram-positive bacteria predominated (55.4%), mainly coagulase-negative staphylococci (CoNS; 37%), followed by Gram-negative bacteria (44.4%), notably extended-spectrum beta lactamase-producing Klebsiella (13.2%) and Acinetobacter baumannii (12.8%). A marked decline in CoNS incidence was observed in 2016 (annual percentage change: −17.6%). Meropenem (35%) and vancomycin (30.5%) were most frequently used, with extreme-low-birth-weight (ELBW) neonates disproportionately affected. Late-onset sepsis remains a persistent challenge, with CoNS as the leading pathogen and increasing multidrug-resistant Gram-negative infections, particularly in ELBW and very-low-birth-weight infants. The observed decline in CoNS may signal improved infection control, whereas reliance on last-line antibiotics underscores an urgent need for enhanced surveillance, prevention, and antimicrobial stewardship.

Background: There is limited data on antibiotic treatment in hospitalized neonates in low- and middle-income countries (LMICs). We aimed to describe patterns of antibiotic use, pathogens, and clinical outcomes, and to develop a severity score predicting mortality in neonatal sepsis to inform future clinical trial design. Methods and findings: Hospitalized infants n = 814) of infants started WHO first line regimens (Group 1—Access) and 13.8% (n = 432) started WHO second-line cephalosporins (cefotaxime/ceftriaxone) (Group 2—“Low” Watch). The largest group (34.0%, n = 1,068) started a regimen providing partial extended-spectrum beta-lactamase (ESBL)/pseudomonal coverage (piperacillin-tazobactam, ceftazidime, or fluoroquinolone-based) (Group 3—“Medium” Watch), 18.0% (n = 566) started a carbapenem (Group 4—“High” Watch), and 1.8% (n = 57) a Reserve antibiotic (Group 5, largely colistin-based), and 728/2,880 (25.3%) of initial regimens in Groups 1 to 4 were escalated, mainly to carbapenems, usually for clinical deterioration (n = 480; 65.9%). A total of 564/3,195 infants (17.7%) were blood culture pathogen positive, of whom 62.9% (n = 355) had a gram-negative organism, predominantly Klebsiella pneumoniae (n = 132) or Acinetobacter spp. (n = 72). Both were commonly resistant to WHO-recommended regimens and to carbapenems in 43 (32.6%) and 50 (71.4%) of cases, respectively. MRSA accounted for 33 (61.1%) of 54 Staphylococcus aureus isolates. Overall, 350/3,204 infants died (11.3%; 95% CI 10.2% to 12.5%), 17.7% if blood cultures were positive for pathogens (95% CI 14.7% to 21.1%, n = 99/564). A baseline NeoSep Severity Score had a C-index of 0.76 (0.69 to 0.82) in the validation sample, with mortality of 1.6% (3/189; 95% CI: 0.5% to 4.6%), 11.0% (27/245; 7.7% to 15.6%), and 27.3% (12/44; 16.3% to 41.8%) in low (score 0 to 4), medium (5 to 8), and high (9 to 16) risk groups, respectively, with similar performance across subgroups. A related NeoSep Recovery Score had an area under the receiver operating curve for predicting death the next day between 0.8 and 0.9 over the first week. There was significant variation in outcomes between sites and external validation would strengthen score applicability. Conclusion: Antibiotic regimens used in neonatal sepsis commonly diverge from WHO guidelines, and trials of novel empiric regimens are urgently needed in the context of increasing antimicrobial resistance (AMR). The baseline NeoSep Severity Score identifies high mortality risk criteria for trial entry, while the NeoSep Recovery Score can help guide decisions on regimen change. NeoOBS data informed the NeoSep1 antibiotic trial (ISRCTN48721236), which aims to identify novel first- and second-line empiric antibiotic regimens for neonatal sepsis. Trial registration: ClinicalTrials.gov, (NCT03721302).

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.

Patients with Gaucher disease (GD), a rare autosomal recessive lysosomal storage disease, commonly present to paediatricians with massive splenomegaly. While the diagnosis and management of patients with this chronic multisystem disorder has evolved significantly in recent years, the initial diagnosis represents a challenge. We describe the case of a 15-year-old black African male who presented with abdominal distension, delayed growth and fatigue. Initial laboratory studies revealed severe anaemia (haemoglobin concentration 8 g/dL) and moderate thrombocytopenia (platelet count 80 × 109/L). A computed tomography scan of the abdomen showed an enlarged liver of 173 mm and massive splenomegaly of 27 mm. The diagnosis of GD was confirmed by reduced beta-glucocerebrosidase activity and heterozygous mutations in the GBA1 gene. The patient was managed at a dedicated paediatric haematology unit with enzyme replacement therapy and regular clinical, biochemical and radiological monitoring.

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). To describe the maternal and neonatal characteristics and clinical outcomes in VLBWIs who received KMC at a tertiary hospital. 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). 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%). 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.

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.

Background: The global spread of the novel coronavirus 2019 (COVID-19) has been sudden shock to the world and resulted in many questions that remain unanswered. Limited data has been published in low-middle-income country settings (LMICS) Objectives: To describe the clinical characteristics and outcome of mothers and neonates delivered from COVID-19 positive mothers, and to identify the incidence of COVID-19 positive neonates.Methods: A prospective, descriptive study, from 1 August 2020 to 31 March 2021 conducted at a tertiary hospital, in JohannesburgAll neonates born to mothers that were COVID-19 positive and that required admission to the neonatal unit were included. Informed consent was obtained from mothers prior to enrolment.Results: A total of 111 COVID-19 positive pregnant women delivered neonates at the tertiary hospital. In this study, only 28 of the 111 (25%) neonates born to COVID-19 positive mothers were admitted. The majority of the COVID-19 pregnant mothers were asymptomatic or had mild symptomatic disease (80%). Two (2/111 (2%) mothers required ICU admission and three (3/111 (3%) of them demised. In relation to neonatal outcomes, the majority of the neonates were delivered at a gestational age of 35 weeks with a birth weight of 2400 grams .The most common symptom was respiratory distress (89 %). The one (3%) neonate that tested positive for COVID-19 was born moderately preterm with a low birth weight and respiratory distress syndrome. Two (2/28 (7%) neonates demised, however the cause of death was not related to COVID-19. All the remaining (26/28 (93%) neonates were discharged and were well on follow up. Conclusion: Our study has shown that the risk of neonatal transmission from pregnant COVID-19 mothers is relatively low, and the majority of neonatal disease ranged from asymptomatic to mildly symptomatic disease. Further research efforts are essential to improve neonatal care in LMICS.

Background: Improved survival in preterm infants whether due to technological progress or treatment like antenatal steroids, surfactant administration or nasal continuous positive airway pressure (NCPAP) and aggressive resuscitation have raised the question about whether the survivors would be more prone to increased morbidity and adverse neurodevelopmental disability. Methods: This was a prospective follow-up study conducted in the neonatal unit of a tertiary hospital in Johannesburg, South Africa. Bayley scales of infant and toddler development, version III, were conducted on a group of extreme low birth weight infants (ELBWI). The mean composite cognitive, language and motor sub-scales were reported. 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: The mean birth weight of the study group was 858.5grams (95% CI 839.2- 877.8) and the mean gestational age was 27.5 weeks (95% CI 27.1-27.9). The majority of ELBWI enrolled in the study had at least one Bayley at a mean corrected age of 17.09 months (CI 16.04 to 18.14). The mean composite scores for cognition were 98.4 (CI 95.1-101.7), language 90.0 (CI 87.5-92.6) and motor 97.9 (CI 94.8-101.0). All mean scores fell within the normal range, but the composite language score was the lowest. The study did not diagnose cerebral palsy in any of the infants. The study found 28 (36.3%) infants to be “at risk” for neurodevelopmental delay. Significantly more males were classified as “at risk” than females (13/25 (52%) vs. 15/52 (28.8%). Late onset sepsis (sepsis18/37 (48.6%) vs. no sepsis 10/40 (25%) p=0.031) and longer duration of ventilation (median of 12 days (IQR 46) vs. median of 4.0 days (IQR 5) p=0.048) were significantly associated with an “at risk” classification. Conclusion: Rates of early neurodevelopmental impairment have altered minimally despite significant improvements in the overall survival of ELBWI. It is of paramount importance to ensure that early neurodevelopmental outcomes are accurately assessed so as to assist doctors and families in establishing a foundation for advocacy for the immediate intensive care and post discharge follow up.

Background: The novel coronavirus disease 2019 (COVID-19) pandemic has spread to South Africa and poses an infection risk in pregnant women and their newborns, as well as health-care workers and other patients.Objective: To discuss the implementation of international and local recommendations, and any additional actions undertaken at our Neonatal Unit in order to prepare for COVID-19.Discussion: Standard precautions in order to prepare a facility and its personnel to safely care for COVID-19 patients as outlined by the World Health Organization procedures have been implemented. Further actions undertaken in our Neonatal Unit included the creation of standard operating procedures, increased communication between neonatal and obstetric teams, limiting staff exposure, the creation of disposable resuscitation boxes to attend deliveries, reallocation of a triage area in the high care ward to an isolation area for sick newborns of suspected or confirmed maternal COVID-19 cases, staff training on personal protective equipment procedures and initiation of an online resources portal for neonatal staff.Conclusion: A rational approach to suspected cases and infection control in-line with local and international guidelines as well as ongoing education should diminish anxiety amongst health-care professionals and provide the best possible care to patients. South Africa is a low-to-middle income country, and the lack of resources available means we cannot increase our capacity, staffing numbers or available equipment. Yet, we must be as prepared, adaptable and efficient as possible to maximize the resources and equipment we have available to us.