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 <60 days with clinical sepsis were enrolled during 2018 to 2020 by 19 sites in 11 countries (mainly Asia and Africa). Prospective daily observational data was collected on clinical signs, supportive care, antibiotic treatment, microbiology, and 28-day mortality. Two prediction models were developed for (1) 28-day mortality from baseline variables (baseline NeoSep Severity Score); and (2) daily risk of death on IV antibiotics from daily updated assessments (NeoSep Recovery Score). Multivariable Cox regression models included a randomly selected 85% of infants, with 15% for validation. A total of 3,204 infants were enrolled, with median birth weight of 2,500 g (IQR 1,400 to 3,000) and postnatal age of 5 days (IQR 1 to 15). 206 different empiric antibiotic combinations were started in 3,141 infants, which were structured into 5 groups based on the World Health Organization (WHO) AWaRe classification. Approximately 25.9% (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).

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. 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. 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). 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.

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. 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. 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. 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.

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.

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. 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.

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.