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).

1. The effects of the chemical composition of fruit juices and fruit on the absorption of iron from a rice (Oryza sativa) meal were measured in 234 parous Indian women, using the erythrocyte utilization of radioactive Fe method.2. The corrected geometric mean Fe absorptions with different juices varied between 0.040 and 0.129, with the variation correlating closely with the ascorbic acid contents of the juices (r_s 0.838, P < 0.01).3. Ascorbic acid was not the only organic acid responsible for the promoting effects of citrus fruit juices on Fe absorption. Fe absorption from laboratory ‘orange juice’ (100 ml water, 33 mg ascorbic acid and 750 mg citric acid) was significantly better than that from 100 ml water and 33 mg ascorbic acid alone (0.097 and 0.059 respectively), while Fe absorption from 100 ml orange juice (28 mg ascorbic acid) was better than that from 100 ml water containing the same amount of ascorbic acid (0.139 and 0.098 respectively). Finally, Fe absorption from laboratory ‘lemon juice’ (100 ml orange juice and 4 g citric acid) was significantly better than that from 100 ml orange juice (0.226 and 0,166 respectively).4. The corrected geometric mean Fe absorption from the rice meal was 0.025. Several fruits had little or no effect on Fe absorption from the meal (0.013–0.024). These included grape (Vitis vinifera), peach (Prunuspersica), apple (Malus sylvestris) and avocado pear (Persea americana). Fruit with a mild to moderate enhancing effect on Fe absorption (0.03 1–0.088) included strawberry (Fragaria sp.) (uncorrected values), plum (Prunus domestica), rhubarb (Rheum rhaponticum), banana (Musa cavendishii), mango (Mangifera indica), pear (Pyrus cornmunis), cantaloup (Cucumis melo) and pineapple (Ananas comosus) (uncorrected values). Guava (Psidium guajava) and pawpaw (Carica papaya) markedly increased Fe absorption (0.126–0.293).5. There was a close correlation between Fe absorption and the ascorbic acid content of the fruits tested (r_s 0.738, P < 0.0001). There was also a weaker but significant correlation with the citric acid content (r_s 0.55, P < 0.03). Although this may have reflected a direct effect of citric acid on Fe absorption, it should be noted that fruits containing citric acid also contained ascorbic acid (r_s 0.70, P < 0.002). Similarly, the negative correlation (r^s –0.62, P < 0,008) between Fe absorption and the malic acid content of fruits may have been due to the fact that fruits with a high malic acid content tended to have low levels of ascorbic acid (r^s–0.45, P < 0.06).6. These various results suggested that most fruits have only a limited effect on overall Fe nutrition. However, the presence of citrus fruit, guava or pawpaw would be expected to increase Fe absorption markedly from diets of low Fe availability.

A targeted, double-blind controlled iron fortification trial using Fe(111)-EDTA in masala (curry powder) was directed towards an Fe-deficient Indian population for 2 y. The Fe status of the fortified group improved more than that of control subjects. Improvement reached significance over control subjects for females in hemoglobin (p = 0.0005), ferritin (p = 0.0002), and body Fe stores (p = 0.001) and for males in ferritin (p = 0.04). The prevalence of Fe-deficiency anemia (IDA) decreased from 22 to 5% in fortified females. Premenopausal women, multipara women, and women with prolonged menstruation or initial IDA benefitted most from fortification. The mean increase in body Fe stores in females with initial IDA was 9.0 +/- 1.3 mmol, representing an increased absorption of 12 mumol/d. Fortified subjects with normal Fe status did not accumulate excessive body Fe and there was no alteration in serum Zn concentrations. Targeted fortification is a safe and effective means of combatting Fe deficiency.

Objective To gain an understanding of the variation in available resources and clinical practices between neonatal units (NNUs) in the low-income and middle-income country (LMIC) setting to inform the design of an observational study on the burden of unit-level antimicrobial resistance (AMR). Design A web-based survey using a REDCap database was circulated to NNUs participating in the Neonatal AMR research network. The survey included questions about NNU funding structure, size, admission rates, access to supportive therapies, empirical antimicrobial guidelines and period prevalence of neonatal blood culture isolates and their resistance patterns. Setting 39 NNUs from 12 countries. Patients Any neonate admitted to one of the participating NNUs. Interventions This was an observational cohort study. Results The number of live births per unit ranged from 513 to 27 700 over the 12-month study period, with the number of neonatal cots ranging from 12 to 110. The proportion of preterm admissions <32 weeks ranged from 0% to 19%, and the majority of units (26/39, 66%) use Essential Medicines List ‘Access’ antimicrobials as their first-line treatment in neonatal sepsis. Cephalosporin resistance rates in Gram-negative isolates ranged from 26% to 84%, and carbapenem resistance rates ranged from 0% to 81%. Glycopeptide resistance rates among Gram-positive isolates ranged from 0% to 45%. Conclusion AMR is already a significant issue in NNUs worldwide. The apparent burden of AMR in a given NNU in the LMIC setting can be influenced by a range of factors which will vary substantially between NNUs. These variations must be considered when designing interventions to improve neonatal mortality globally.

Audit of disease and mortality patterns provides essential information for health budgeting and planning, as well as a benchmark for comparison. Neonatal mortality accounts for about 1/3 of deaths < 5 years of age and very low birth weight (VLBW) mortality for approximately 1/3 of neonatal mortality. Intervention programs must be based on reliable statistics applicable to the local setting; First World data cannot be used in a Third World setting. Many neonatal units participate in the Vermont Oxford Network (VON); limited resources prevent a significant number of large neonatal units from developing countries taking part, hence data from such units is lacking. The purpose of this study was to provide reliable, recent statistics relevant to a developing African country, useful for guiding neonatal interventions in that setting.

Advances in neonatal care allow survival of extremely premature infants, who are at risk of handicap. Neurodevelopmental follow up of these infants is an essential part of ongoing evaluation of neonatal care. The neonatal care in resource limited developing countries is very different to that in first world settings. Follow up data from developing countries is essential; it is not appropriate to extrapolate data from units in developed countries. This study provides follow up data on a population of very low birth weight (VLBW) infants in Johannesburg, South Africa.