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Background: Retinopathy of prematurity (ROP) screening in Nigeria is at a nascent stage and at the moment there are no National guidelines for ROP screening in Nigeria. Thus it is desirable for screening programs to report findings amongst screened preterm infants in order to facilitate the development of national ROP screening criteria and guidelines. The aim of this report is to describe the frequency, severity and risk factors for retinopathy of prematurity (ROP) among preterm and very low-birth-weight babies screened within the first year of initiating an ROP screening program at a Nigerian tertiary facility. Methods: A cross-sectional study of infants born at less than 34 weeks gestational age; or with birth weight less than 1500g between May 2016 and May 2017. ROP screening examinations were performed by ophthalmologists with the use of an indirect ophthalmoscope, after pupillary dilation, in collaboration with the neonatology team. Information on gestational age at birth, birth weight, oxygen therapy and presence of other risk factors were recorded and analyzed. Results: A total of 74 infants were screened during the period. There were 36 (48.6%) males. Mean gestational age at birth was 29.6 (±2.35) weeks. Mean birth weight was 1.26 (±0.27) kg with a range of 800 to 1950g. ROP was detected in 9 (12.2%) infants. Two (22.2%) of these had Threshold ROP. There was no significant difference between the mean birth weight and mean gestational age of the infants who had ROP compared to those without ROP. The two infants with Threshold ROP were treated with intravitreal Bevazicumab and had regression of ROP. Conclusion: Retinopathy of prematurity was diagnosed in at risk infants in this facility. There is, therefore, a need to establish ROP screening programs in all neonatal units across the country. In addition, established programs need to evaluate their screening criteria with a view towards developing country-specific screening guidelines.

The 10th Annual General and Scientific Meeting (AGSM) of the Nigerian Society of Neonatal Medicine (NISONM) took place in Ibadan, South-West Nigeria. The theme of the conference was: Imperatives in neonatal survival initiatives in Nigeria: The current state. The conference addressed a variety of topics relevant to newborn health from eminent speakers from across the globe. The four-day conference included preconference workshops and community mobilization/ health outreach in Lagelu local government area.

Competing Interests: CDP holds leadership roles with the Philippine Society for Orphan Disorders, Asia Pacific Alliance of Rare Disease Organisations, Global Commission to End the Diagnostic Odyssey for Children with a Rare Disease, and Down Syndrome Association of the Philippines, and has received support, materials, or both from Takeda Thailand, Biorad, Revvity, Sanofi, and Mead Johnson. PI is a consultant for WHO. All other authors declare no competing interests. The authors alone are responsible for the views expressed in this Comment and they do not necessarily represent the views, decisions, or policies of the institutions with which they are affiliated.

Background: In early 2023, when Omicron was the variant of concern, we showed that vaccinating pregnant women decreased the risk for severe COVID-19-related complications and maternal morbidity and mortality., Objective: This study aimed to analyze the impact of COVID-19 during pregnancy on newborns and the effects of maternal COVID-19 vaccination on neonatal outcomes when Omicron was the variant of concern., Study Design: INTERCOVID-2022 was a large, prospective, observational study, conducted in 40 hospitals across 18 countries, from November 27, 2021 (the day after the World Health Organization declared Omicron the variant of concern) to June 30, 2022, to assess the effect of COVID-19 in pregnancy on maternal and neonatal outcomes and to assess vaccine effectiveness. Women diagnosed with laboratory-confirmed COVID-19 during pregnancy were compared with 2 nondiagnosed, unmatched women recruited concomitantly and consecutively during pregnancy or at delivery. Mother-newborn dyads were followed until hospital discharge. The primary outcomes were a neonatal positive test for COVID-19, severe neonatal morbidity index, severe perinatal morbidity and mortality index, preterm birth, neonatal death, referral to neonatal intensive care unit, and diseases during the neonatal period. Vaccine effectiveness was estimated with adjustment for maternal risk profile., Results: We enrolled 4707 neonates born to 1577 (33.5%) mothers diagnosed with COVID-19 and 3130 (66.5%) nondiagnosed mothers. Among the diagnosed mothers, 642 (40.7%) were not vaccinated, 147 (9.3%) were partially vaccinated, 551 (34.9%) were completely vaccinated, and 237 (15.0%) also had a booster vaccine. Neonates of booster-vaccinated mothers had less than half (relative risk, 0.46; 95% confidence interval, 0.23-0.91) the risk of being diagnosed with COVID-19 when compared with those of unvaccinated mothers; they also had the lowest rates of preterm birth, medically indicated preterm birth, respiratory distress syndrome, and number of days in the neonatal intensive care unit. Newborns of unvaccinated mothers had double the risk for neonatal death (relative risk, 2.06; 95% confidence interval, 1.06-4.00) when compared with those of nondiagnosed mothers. Vaccination was not associated with any congenital malformations. Although all vaccines provided protection against neonatal test positivity, newborns of booster-vaccinated mothers had the highest vaccine effectiveness (64%; 95% confidence interval, 10%-86%). Vaccine effectiveness was not as high for messenger RNA vaccines only. Vaccine effectiveness against moderate or severe neonatal outcomes was much lower, namely 13% in the booster-vaccinated group (all vaccines) and 25% and 28% in the completely and booster-vaccinated groups, respectively (messenger RNA vaccines only). Vaccines were fairly effective in protecting neonates when given to pregnant women ≤100 days (14 weeks) before birth; thereafter, the risk increased and was much higher after 200 days (29 weeks). Finally, none of the neonatal practices studied, including skin-to-skin contact and direct breastfeeding, increased the risk for infecting newborns., Conclusion: When Omicron was the variant of concern, newborns of unvaccinated mothers had an increased risk for neonatal death. Neonates of vaccinated mothers had a decreased risk for preterm birth and adverse neonatal outcomes. Because the protective effect of COVID-19 vaccination decreases with time, to ensure that newborns are maximally protected against COVID-19, mothers should receive a vaccine or booster dose no more than 14 weeks before the expected date of delivery., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Neonatal infections are a major public health concern worldwide, particularly in low- and middle-income countries, where most of the infection-related deaths in under-five children occur. Sub-Saharan Africa has the highest mortality rates, but there is a lack of data on the incidence of sepsis from this region, hindering efforts to improve child survival. We aimed to determine the incidence of possible serious bacterial infection (PSBI) in young infants in three high-burden countries in Africa., Methods: This is a secondary analysis of data from the African Neonatal Sepsis (AFRINEST) trial, conducted in the Democratic Republic of the Congo (DRC), Kenya, and Nigeria between 15 March 2012 and 15 July 2013. We recorded baseline characteristics, the incidence of PSBI (as defined by the World Health Organization), and the incidence of local infections among infants from 0-59 days after birth. We report descriptive statistics., Results: The incidence of PSBI among 0-59-day-old infants across all three countries was 11.2% (95% confidence interval (CI) = 11.0-11.4). The DRC had the highest incidence of PSBI (19.0%; 95% CI = 18.2-19.8). Likewise, PSBI rates were higher in low birth weight infants (24.5%; 95% CI = 23.1-26.0) and infants born to mothers aged <20 years (14.1%; 95% CI = 13.4-14.8). The incidence of PSBI was higher among infants delivered at home (11.7%; 95% CI = 11.4-12.0)., Conclusions: The high burden of PSBI among young infants in DRC, Kenya, and Nigeria demonstrates the importance of addressing PSBI in improving child survival in sub-Saharan Africa to reach the Sustainable Development Goals (SDGs). These data can support government authorities, policymakers, programme implementers, non-governmental organisations, and international partners in reducing preventable under-five deaths., Registration: Australian New Zealand Clinical Trials Registry: ACTRN12610000286044., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclosed the following activities and/or relationships: YBN is a staff member of the World Health Organization. The expressed views and opinions do not necessarily express the policies of the World Health Organization., (Copyright © 2024 by the Journal of Global Health. All rights reserved.)

Pneumococcal conjugate vaccine ten valent (PCV 10) was introduced into Nigeria in three phases. Phase 3 introduction started in August 2016. However, its impact on pneumonia admissions and mortality among vaccinated Nigerian children has not been determined. Data in the period before PCV-10 introduction (3 August 2013-2 August 2016), and after (3 August 2017-2 August 2020) were retrospectively extracted from the medical charts of eligible patients aged 3-24 months with hospitalized radiological pneumonia at the University College Hospital (UCH), Ibadan; National Hospital (NH), Abuja; and Federal Teaching Hospital (FTH), Gombe, allowing for an intervening period of 1 year. Proportions of the patients with hospitalized pneumonia and case fatality rates were determined during both periods. The results were compared using z-test, multiple logistic regression analysis and p  < .05 was considered significant. Adjusted pneumonia hospitalization rates between the two periods increased at the NH Abuja (10.7% vs 14.6%); decreased at the UCH, Ibadan (8.7% vs 6.9%); and decreased at the FTH, Gombe (28.5% vs 18.9%). Case fatality rates decreased across all the sites during the post-PCV introduction period: NH Abuja, from 6.6% to 4.4% ( p  = .106); FTH, Gombe, 11.7% to 7.7% ( p  = .477); and UCH, Ibadan, 2.0% to 0% ( p  = .045); but only significant at Ibadan. Overall, proportion of hospitalized pneumonia cases decreased after 3 years of PCV 10 introduction into the National Immunization Programme in Nigeria. The case fatality rate during post-PCV 10 introduction decreased at all the three sites, but this difference was significant at the UCH, Ibadan.

Managing a newborn with lethal congenital anomalies is challenging but handling a parent's request for doctors under oath to terminate the baby's life is another major ethical dilemma requiring cautious evaluation. We present a term male neonate who presented on the 7 th day of life, with a dark-blue sclera, multiple limb deformities, long bone fractures, beaded ribs, a flattened forehead, a narrow chest, and respiratory distress. A Diagnosis of Type II Osteogenesis imperfecta was made and he was managed by a multidisciplinary team including neonatologists, geneticists/endocrinologists, orthopaedic surgeons, nurses, and medical social workers. Supplemental oxygen, intravenous fluids and antibiotics, analgesia, and bisphosphonates were offered as supportive care. The main concern was the challenges of managing a newborn with lethal OI and balancing the demand for euthanasia by the parents to end the baby's misery. In providing care, the rights of the child to life, the morals of the physician, the best interests of the baby, and the family's role in decision-making in a setting of out-of-pocket expenditures must be weighed. Following extensive multidisciplinary team meetings, it was ultimately decided to allow nature to take her course. Baby subsequently had progressive respiratory distress from pulmonary hypoplasia and died of respiratory failure on the twelfth day of life. In Conclusion, Osteogenesis imperfecta of the perinatal type is usually a lethal disease, with death often occurring within the perinatal period. The physician must, therefore, balance the parental rights, the oath of office, and the existing legal framework to avoid charges of murder or manslaughter., (Copyright © 2023 Nigerian Medical Association.)

The pathway to a thriving newborn begins before conception and continues in utero with a healthy placenta and the right balance of nutrients and growth factors that are timed and sequenced alongside hormonal suppression of labour until a mature infant is ready for birth. Optimal nutrition that includes adequate quantities of quality protein, energy, essential fats, and an extensive range of vitamins and minerals not only supports fetal growth but could also prevent preterm birth by supporting the immune system and alleviating oxidative stress. Infection, illness, undernourishment, and harmful environmental exposures can alter this trajectory leading to an infant who is too small due to either poor growth during pregnancy or preterm birth. Systemic inflammation suppresses fetal growth by interfering with growth hormone and its regulation of insulin-like growth factors. Evidence supports the prevention and treatment of several maternal infections during pregnancy to improve newborn health. However, microbes, such as Ureaplasma species, which are able to ascend the cervix and cause membrane rupture and chorioamnionitis, require new strategies for detection and treatment. The surge in fetal cortisol late in pregnancy is essential to parturition at the right time, but acute or chronically high maternal cortisol levels caused by psychological or physical stress could also trigger labour onset prematurely. In every pathway to the small vulnerable newborn, there is a possibility to modify the course of pregnancy by supporting improved nutrition, protection against infection, holistic maternal wellness, and healthy environments., Competing Interests: Declaration of interests PA reports a grant from the Children's Investment Fund Foundation in support of the preparation of this manuscript (grant number 2004-04635). ALD is an unpaid Scientific Trustee of Tommy's Charity. CPD reports grant support from WHO, the US Agency for International Development, and National Institutes of Health (NIH; P30 DK040561); royalties from UpToDate; and grant support on behalf of his institution from Takeda and the American Society for Nutrition in work unrelated to this paper. UR receives honoraria from NIH for educational activities and her institution receives funding from NIH. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Preterm birth (PTB) is the leading cause of infant mortality worldwide. Changes in PTB rates, ranging from -90% to +30%, were reported in many countries following early COVID-19 pandemic response measures ('lockdowns'). It is unclear whether this variation reflects real differences in lockdown impacts, or perhaps differences in stillbirth rates and/or study designs. Here we present interrupted time series and meta-analyses using harmonized data from 52 million births in 26 countries, 18 of which had representative population-based data, with overall PTB rates ranging from 6% to 12% and stillbirth ranging from 2.5 to 10.5 per 1,000 births. We show small reductions in PTB in the first (odds ratio 0.96, 95% confidence interval 0.95-0.98, P value <0.0001), second (0.96, 0.92-0.99, 0.03) and third (0.97, 0.94-1.00, 0.09) months of lockdown, but not in the fourth month of lockdown (0.99, 0.96-1.01, 0.34), although there were some between-country differences after the first month. For high-income countries in this study, we did not observe an association between lockdown and stillbirths in the second (1.00, 0.88-1.14, 0.98), third (0.99, 0.88-1.12, 0.89) and fourth (1.01, 0.87-1.18, 0.86) months of lockdown, although we have imprecise estimates due to stillbirths being a relatively rare event. We did, however, find evidence of increased risk of stillbirth in the first month of lockdown in high-income countries (1.14, 1.02-1.29, 0.02) and, in Brazil, we found evidence for an association between lockdown and stillbirth in the second (1.09, 1.03-1.15, 0.002), third (1.10, 1.03-1.17, 0.003) and fourth (1.12, 1.05-1.19, <0.001) months of lockdown. With an estimated 14.8 million PTB annually worldwide, the modest reductions observed during early pandemic lockdowns translate into large numbers of PTB averted globally and warrant further research into causal pathways., (© 2023. The Author(s).)

Background: In 2021, we showed an increased risk associated with COVID-19 in pregnancy. Since then, the SARS-CoV-2 virus has undergone genetic mutations. We aimed to examine the effects on maternal and perinatal outcomes of COVID-19 during pregnancy, and evaluate vaccine effectiveness, when omicron (B.1.1.529) was the variant of concern., Methods: INTERCOVID-2022 is a large, prospective, observational study, involving 41 hospitals across 18 countries. Each woman with real-time PCR or rapid test, laboratory-confirmed COVID-19 in pregnancy was compared with two unmatched women without a COVID-19 diagnosis who were recruited concomitantly and consecutively in pregnancy or at delivery. Mother and neonate dyads were followed until hospital discharge. Primary outcomes were maternal morbidity and mortality index (MMMI), severe neonatal morbidity index (SNMI), and severe perinatal morbidity and mortality index (SPMMI). Vaccine effectiveness was estimated, adjusted by maternal risk profile., Findings: We enrolled 4618 pregnant women from Nov 27, 2021 (the day after WHO declared omicron a variant of concern), to June 30, 2022: 1545 (33%) women had a COVID-19 diagnosis (median gestation 36·7 weeks [IQR 29·0-38·9]) and 3073 (67%) women, with similar demographic characteristics, did not have a COVID-19 diagnosis. Overall, women with a diagnosis had an increased risk for MMMI (relative risk [RR] 1·16 [95% CI 1·03-1·31]) and SPMMI (RR 1·21 [95% CI 1·00-1·46]). Women with a diagnosis, compared with those without a diagnosis, also had increased risks of SNMI (RR 1·23 [95% CI 0·88-1·71]), although the lower bounds of the 95% CI crossed unity. Unvaccinated women with a COVID-19 diagnosis had a greater risk of MMMI (RR 1·36 [95% CI 1·12-1·65]). Severe COVID-19 symptoms in the total sample increased the risk of severe maternal complications (RR 2·51 [95% CI 1·84-3·43]), perinatal complications (RR 1·84 [95% CI 1·02-3·34]), and referral, intensive care unit (ICU) admission, or death (RR 11·83 [95% CI 6·67-20·97]). Severe COVID-19 symptoms in unvaccinated women increased the risk of MMMI (RR 2·88 [95% CI 2·02-4·12]) and referral, ICU admission, or death (RR 20·82 [95% CI 10·44-41·54]). 2886 (63%) of 4618 total participants had at least a single dose of any vaccine, and 2476 (54%) of 4618 had either complete or booster doses. Vaccine effectiveness (all vaccines combined) for severe complications of COVID-19 for all women with a complete regimen was 48% (95% CI 22-65) and 76% (47-89) after a booster dose. For women with a COVID-19 diagnosis, vaccine effectiveness of all vaccines combined for women with a complete regimen was 74% (95% CI 48-87) and 91% (65-98) after a booster dose., Interpretation: COVID-19 in pregnancy, during the first 6 months of omicron as the variant of concern, was associated with increased risk of severe maternal morbidity and mortality, especially among symptomatic and unvaccinated women. Women with complete or boosted vaccine doses had reduced risk for severe symptoms, complications, and death. Vaccination coverage among pregnant women remains a priority., Funding: None., Competing Interests: Declaration of interests LS has been a consultant for Dilafor and Ferring Pharmaceuticals and has received payment in the past for presentations and educational events from Bayer, GlaxoSmithKline, Ferring Pharmaceuticals, and Sigvaris. BMdT received a research grant from the General Health Direction of Geneva, has participated on an advisory board of Effik and Pierre Favre, and has received medical equipment from Pregnolia, Hologic, and PeriLynx. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Hospital referral and admission in many- low and middle-income countries are not feasible for many young infants with sepsis/possible serious bacterial infection (PSBI). The effectiveness of simplified antibiotic regimens when referral to a hospital was not feasible has been shown before. We analysed the pooled data from the previous trials to compare the risk of poor clinical outcome for young infants with PSBI with the two regimens containing injectable procaine penicillin and gentamicin with the oral amoxicillin plus gentamicin regimen currently recommended by the World Health Organization (WHO) when referral is not feasible., Methods: Infant records from three individually randomised trials conducted in Africa and Asia were collated in a standard format. All trials enrolled young infants aged 0-59 days with any sign of PSBI (fever, hypothermia, stopped feeding well, movement only when stimulated, or severe chest indrawing). Eligible young infants whose caretakers refused hospital admission and consented were enrolled and randomised to a trial reference arm (arm A: procaine benzylpenicillin and gentamicin) or two experimental arms (arm B: oral amoxicillin and gentamicin or arm C: procaine benzylpenicillin and gentamicin initially, followed by oral amoxicillin). We compared the rate of poor clinical outcomes by day 15 (deaths till day 15, treatment failure by day 8, and relapse between day 9 and 15) in reference arm A with experimental arms and present risk differences with 95% confidence interval (CI), adjusted for trial., Results: A total of 7617 young infants, randomised to arm A, arm B, or arm C in the three trials, were included in this analysis. Most were 7-59 days old (71%) and predominately males (56%). Slightly over one-fifth of young infants had more than one sign of PSBI at the time of enrolment. Severe chest indrawing (45%), fever (43%), and feeding problems (25%) were the most common signs. Overall, those who received arm B had a lower risk of poor clinical outcome compared to arm A for both per-protocol (risk difference = -2.1%, 95% CI = -3.8%, -0.4%; P = 0.016) and intention-to-treat (risk difference = -1.8%, 95% CI = -3.5%, -0.2%; P = 0.031) analyses. Those who received arm C did not have an increased risk of poor clinical outcome compared to arm A for both per-protocol (risk difference = -1.1%, 95% CI = -2.8%, 0.6%) and intention-to-treat (risk difference = -0.8%, 95% CI = -2.5%, 0.9%) analyses. Overall, those who received arm B had a lower risk of poor clinical outcome compared to the combined arms A and C for both per-protocol (risk difference = -1.6%, 95% CI = -3.5%, -0.1%; P = 0.035) and intention-to-treat (risk difference = -1.4%, 95% CI = -2.8%, -0.1%; P = 0.049) analyses., Conclusions: Analysis of pooled individual patient-level data from three large trials in Africa and Asia showed that the WHO-recommended simplified antibiotic regimen B (oral amoxicillin and injection gentamicin) was superior to regimen A (injection procaine penicillin and injection gentamicin) and combined arms A and C (injection procaine penicillin and injection gentamicin, followed by oral amoxicillin) in terms of poor clinical outcome for the outpatient treatment of young infants with PSBI when inpatient treatment was not feasible., Registration: AFRINEST study [9] is registered with the Australian New Zealand Clinical Trials Registry: ACTRN12610000286044. SATT Bangladesh study [10] is registered with ClinicalTrials.gov: NCT00844337. SATT Pakistan study [11] is registered at ClinicalTrials.gov: NCT01027429., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and declare the following activities and relationships: AKZ is now employed by the Bill and Melinda Gates Foundation, Seattle USA. She also maintains an adjunct teaching appointment at the Aga Khan University. She approved the final manuscript but did not influence these analyses., (Copyright © 2022 by the Journal of Global Health. All rights reserved.)

Background: The effect of COVID-19 in pregnancy on maternal outcomes and its association with preeclampsia and gestational diabetes mellitus have been reported; however, a detailed understanding of the effects of maternal positivity, delivery mode, and perinatal practices on fetal and neonatal outcomes is urgently needed., Objective: To evaluate the impact of COVID-19 on fetal and neonatal outcomes and the role of mode of delivery, breastfeeding, and early neonatal care practices on the risk of mother-to-child transmission., Study Design: In this cohort study that took place from March 2020 to March 2021, involving 43 institutions in 18 countries, 2 unmatched, consecutive, unexposed women were concomitantly enrolled immediately after each infected woman was identified, at any stage of pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed up until hospital discharge. COVID-19 in pregnancy was determined by laboratory confirmation and/or radiological pulmonary findings or ≥2 predefined COVID-19 symptoms. The outcome measures were indices of neonatal and perinatal morbidity and mortality, neonatal positivity and its correlation with mode of delivery, breastfeeding, and hospital neonatal care practices., Results: A total of 586 neonates born to women with COVID-19 diagnosis and 1535 neonates born to women without COVID-19 diagnosis were enrolled. Women with COVID-19 diagnosis had a higher rate of cesarean delivery (52.8% vs 38.5% for those without COVID-19 diagnosis, P<.01) and pregnancy-related complications, such as hypertensive disorders of pregnancy and fetal distress (all with P<.001), than women without COVID-19 diagnosis. Maternal diagnosis of COVID-19 carried an increased rate of preterm birth (P≤.001) and lower neonatal weight (P≤.001), length, and head circumference at birth. In mothers with COVID-19 diagnosis, the length of in utero exposure was significantly correlated to the risk of the neonate testing positive (odds ratio, 4.5; 95% confidence interval, 2.2-9.4 for length of in utero exposure >14 days). Among neonates born to mothers with COVID-19 diagnosis, birth via cesarean delivery was a risk factor for testing positive for COVID-19 (odds ratio, 2.4; 95% confidence interval, 1.2-4.7), even when severity of maternal conditions was considered and after multivariable logistic analysis. In the subgroup of neonates born to women with COVID-19 diagnosis, the outcomes worsened when the neonate also tested positive, with higher rates of neonatal intensive care unit admission, fever, gastrointestinal and respiratory symptoms, and death, even after adjusting for prematurity. Breastfeeding by mothers with COVID-19 diagnosis and hospital neonatal care practices, including immediate skin-to-skin contact and rooming-in, were not associated with an increased risk of newborn positivity., Conclusion: In this multinational cohort study, COVID-19 in pregnancy was associated with increased maternal and neonatal complications. Cesarean delivery was significantly associated with newborn COVID-19 diagnosis. Vaginal delivery should be considered the safest mode of delivery if obstetrical and health conditions allow it. Mother-to-child skin-to-skin contact, rooming-in, and direct breastfeeding were not risk factors for newborn COVID-19 diagnosis, thus well-established best practices can be continued among women with COVID-19 diagnosis., (Copyright © 2022. Published by Elsevier Inc.)

Introduction: Improving hospital oxygen systems can improve quality of care and reduce mortality for children, but we lack data on cost-effectiveness or sustainability. This study evaluated medium-term sustainability and cost-effectiveness of the Nigeria Oxygen Implementation programme., Methods: Prospective follow-up of a stepped-wedge trial involving 12 secondary-level hospitals. Cross-sectional facility assessment, clinical audit (January-March 2021), summary admission data (January 2018-December 2020), programme cost data., Intervention: pulse oximetry introduction followed by solar-powered oxygen system installation with clinical and technical training and support., Primary Outcomes: (i) proportion of children screened with pulse oximetry; (ii) proportion of hypoxaemic (SpO 2 <90%) children who received oxygen. Comparison across three time periods: preintervention (2014-2015), intervention (2016-2017) and follow-up (2018-2020) using mixed-effects logistic regression. Calculated cost-effectiveness of the intervention on child pneumonia mortality using programme costs, recorded deaths and estimated counterfactual deaths using effectiveness estimates from our effectiveness study. Reported cost-effectiveness over the original 2-year intervention period (2016-2017) and extrapolated over 5 years (2016-2020)., Results: Pulse oximetry coverage for neonates and children remained high during follow-up (83% and 81%) compared with full oxygen system period (94% and 92%) and preintervention (3.9% and 2.9%). Oxygen coverage for hypoxaemic neonates/children was similarly high (94%/88%) compared with full oxygen system period (90%/82%). Functional oxygen sources were present in 11/12 (92%) paediatric areas and all (8/8) neonatal areas; three-quarters (15/20) of wards had a functional oximeter. Of 32 concentrators deployed, 23/32 (72%) passed technical testing and usage was high (median 10 797 hours). Estimated 5-year cost-effectiveness US$86 per patient treated, $2694-4382 per life saved and $82-125 per disability-adjusted life year-averted. We identified practical issues for hospitals and Ministries of Health wishing to adapt and scale up pulse oximetry and oxygen., Conclusion: Hospital-level improvements to oxygen and pulse oximetry systems in Nigerian hospitals have been sustained over the medium-term and are a highly cost-effective child pneumonia intervention., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Aim: To gain insight into nutritional practices and expected growth outcomes of infants born between 34 and 36 gestational weeks defined as late preterm infants (LPT)., Methods: An anonymous online survey among paediatricians and neonatologists from Bangladesh, Indonesia, Mexico, Nigeria, Malaysia, Singapore and Taiwan was conducted from March until October 2020. The questionnaire consisted of 40 questions on the nutritional management and expected growth outcomes of LPT in and after-hospital care., Results: Healthcare professionals from low to high Human Development (HDI) countries (n = 322) and very high HDI countries (n = 169) participated in the survey. Human milk was the preferred feeding, resulting in an adequate growth of LPT (weight, length and occipitofrontal circumference), according to a majority of respondents (low to high HDI, 179/265, 68% vs. very high HDI, 73/143, 51%; p = 0.002). The expected growth outcome was higher after-hospital discharge. Less than half of healthcare professionals started enteral feeding during the 1st hour of life. Lactation difficulties, limited access to human milk fortifiers and donor human milk, especially among low to high HDI countries, were reported as major hurdles., Conclusion: Human milk is the first feeding choice for LPT. The diverse opinions on nutritional practices and expected growth outcomes among healthcare professionals indicate the necessity to develop general nutritional guidelines for LPT., (© 2022 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Introduction: Research on simplified antibiotic regimens for outpatient treatment of 'Possible Serious Bacterial Infection' (PSBI) and the subsequent World Health Organization (WHO) guidelines provide an opportunity to increase treatment coverage. This multi-country implementation research initiative aimed to learn how to implement the WHO guideline in diverse contexts. These experiences have been individually published; this overview paper provides a summary of results and lessons learned across sites., Methods Summary: A common mixed qualitative and quantitative methods protocol for implementation research was used in eleven sites in the Democratic Republic of Congo (Equateur province), Ethiopia (Tigray and Oromia regions), India (Haryana, Himachal Pradesh, Maharashtra, and Uttar Pradesh states), Malawi (Central Region), Nigeria (Kaduna and Oyo states), and Pakistan (Sindh province). Key steps in implementation research were: i) policy dialogue with the national government and key stakeholders, ii) the establishment of a 'Technical Support Unit' with the research team and district level managers, and iii) development of an implementation strategy and its refinement using an iterative process of implementation, programme learning and evaluation., Results Summary: All sites successfully developed and evaluated an implementation strategy to increase coverage of PSBI treatment. During the study period, a total of 6677 young infants from the study catchment area were identified and treated at health facilities in the study area as inpatients or outpatients among 88179 live births identified. The estimated coverage of PSBI treatment was 75.7% (95% CI 74.8% to 78.6%), assuming a 10% incidence of PSBI among all live births. The treatment coverage was variable, ranging from 53.3% in Lucknow, India to 97.3% in Ibadan, Nigeria. The coverage of inpatient treatment ranged from 1.9% in Zaria, Nigeria, to 33.9% in Tigray, Ethiopia. The outpatient treatment coverage ranged from 30.6% in Pune, India, to 93.6% in Zaria, Nigeria. Overall, the case fatality rate (CFR) was 14.6% (95% CI 11.5% to 18.2%) for 0-59-day old infants with critical illness, 1.9% (95% CI 1.5% to 2.4%) for 0-59-day old infants with clinical severe infection and 0.1% for fast breathing in 7-59 days old. Among infants treated as outpatients, CFR was 13.7% (95% CI 8.7% to 20.2%) for 0-59-day old infants with critical illness, 0.9% (95% CI 0.6% to 1.2%) for 0-59-day old infants with clinical severe infection, and 0.1% for infants 7-59 days old with fast breathing., Conclusion: Important lessons on how to conduct each step of implementation research, and the challenges and facilitators for implementation of PSBI management guideline in routine health systems are summarised and discussed. These lessons will be used to introduce and scale-up implementation in relevant Low- and middle-income countries., Competing Interests: The authors declare that no competing interests exist. Some of the authors are currently and/or were previously employed by not-for-profit organizations including: Save the Children, World Health Organization, BMGF, USAID, UNICEF, and ActionAid. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Importance: Detailed information about the association of COVID-19 with outcomes in pregnant individuals compared with not-infected pregnant individuals is much needed., Objective: To evaluate the risks associated with COVID-19 in pregnancy on maternal and neonatal outcomes compared with not-infected, concomitant pregnant individuals., Design, Setting, and Participants: In this cohort study that took place from March to October 2020, involving 43 institutions in 18 countries, 2 unmatched, consecutive, not-infected women were concomitantly enrolled immediately after each infected woman was identified, at any stage of pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed up until hospital discharge., Exposures: COVID-19 in pregnancy determined by laboratory confirmation of COVID-19 and/or radiological pulmonary findings or 2 or more predefined COVID-19 symptoms., Main Outcomes and Measures: The primary outcome measures were indices of (maternal and severe neonatal/perinatal) morbidity and mortality; the individual components of these indices were secondary outcomes. Models for these outcomes were adjusted for country, month entering study, maternal age, and history of morbidity., Results: A total of 706 pregnant women with COVID-19 diagnosis and 1424 pregnant women without COVID-19 diagnosis were enrolled, all with broadly similar demographic characteristics (mean [SD] age, 30.2 [6.1] years). Overweight early in pregnancy occurred in 323 women (48.6%) with COVID-19 diagnosis and 554 women (40.2%) without. Women with COVID-19 diagnosis were at higher risk for preeclampsia/eclampsia (relative risk [RR], 1.76; 95% CI, 1.27-2.43), severe infections (RR, 3.38; 95% CI, 1.63-7.01), intensive care unit admission (RR, 5.04; 95% CI, 3.13-8.10), maternal mortality (RR, 22.3; 95% CI, 2.88-172), preterm birth (RR, 1.59; 95% CI, 1.30-1.94), medically indicated preterm birth (RR, 1.97; 95% CI, 1.56-2.51), severe neonatal morbidity index (RR, 2.66; 95% CI, 1.69-4.18), and severe perinatal morbidity and mortality index (RR, 2.14; 95% CI, 1.66-2.75). Fever and shortness of breath for any duration was associated with increased risk of severe maternal complications (RR, 2.56; 95% CI, 1.92-3.40) and neonatal complications (RR, 4.97; 95% CI, 2.11-11.69). Asymptomatic women with COVID-19 diagnosis remained at higher risk only for maternal morbidity (RR, 1.24; 95% CI, 1.00-1.54) and preeclampsia (RR, 1.63; 95% CI, 1.01-2.63). Among women who tested positive (98.1% by real-time polymerase chain reaction), 54 (13%) of their neonates tested positive. Cesarean delivery (RR, 2.15; 95% CI, 1.18-3.91) but not breastfeeding (RR, 1.10; 95% CI, 0.66-1.85) was associated with increased risk for neonatal test positivity., Conclusions and Relevance: In this multinational cohort study, COVID-19 in pregnancy was associated with consistent and substantial increases in severe maternal morbidity and mortality and neonatal complications when pregnant women with and without COVID-19 diagnosis were compared. The findings should alert pregnant individuals and clinicians to implement strictly all the recommended COVID-19 preventive measures.

Objectives: To evaluate the effect of improved hospital oxygen systems on quality of care (QOC) for children with severe pneumonia, severe malaria, and diarrhoea with severe dehydration., Design: Stepped-wedge cluster randomised trial (unblinded), randomised at hospital-level., Setting: 12 hospitals in south-west Nigeria., Participants: 7,141 children (aged 28 days to 14 years) admitted with severe pneumonia, severe malaria or diarrhoea with severe dehydration between January 2014 and October 2017., Interventions: Phase 1 (pulse oximetry) introduced pulse oximetry for all admitted children. Phase 2 (full oxygen system) (i) standardised oxygen equipment package, (ii) clinical education and support, (iii) technical training and support, and (iv) infrastructure and systems support., Outcome Measures: We used quantitative QOC scores evaluating assessment, diagnosis, treatment, and monitoring practices against World Health Organization and Nigerian standards. We evaluated mean differences in QOC scores between study periods (baseline, oximetry, full oxygen system), using mixed-effects linear regression., Results: 7,141 eligible participants; 6,893 (96.5%) had adequate data for analysis. Mean paediatric QOC score (maximum 6) increased from 1.64 to 3.00 (adjusted mean difference 1.39; 95% CI 1.08-1.69, p<0.001) for severe pneumonia and 2.81 to 4.04 (aMD 1.53; 95% CI 1.23-1.83, p<0.001) for severe malaria, comparing the full intervention to baseline, but did not change for diarrhoea with severe dehydration (aMD -0.12; 95% CI -0.46-0.23, p = 0.501). After excluding practices directly related to pulse oximetry and oxygen, we found aMD 0.23 for severe pneumonia (95% CI -0.02-0.48, p = 0.072) and 0.65 for severe malaria (95% CI 0.41-0.89, p<0.001) comparing full intervention to baseline. Sub-analysis showed some improvements (and no deterioration) in care processes not directly related to oxygen or pulse oximetry., Conclusion: Improvements in hospital oxygen systems were associated with higher QOC scores, attributable to better use of pulse oximetry and oxygen as well as broader improvements in clinical care, with no negative distortions in care practices., Trial Registration: ACTRN12617000341325., Competing Interests: None declared.

Background: The World Health Organization recommends inpatient hospital treatment of young infants up to two months old with any sign of possible serious infection. However, each sign may have a different risk of death. The current study aims to calculate the case fatality ratio for infants with individual or combined signs of possible serious infection, stratified by inpatient or outpatient treatment., Methods: We analysed data from the African Neonatal Sepsis Trial conducted in five sites in the Democratic Republic of the Congo, Kenya and Nigeria. Trained study nurses classified sick infants as pneumonia (fast breathing in 7-59 days old), severe pneumonia (fast breathing in 0-6 days old), clinical severe infection [severe chest indrawing, high (> = 38°C) or low body temperature (<35.5°C), stopped feeding well, or movement only when stimulated] or critical illness (convulsions, not able to feed at all, or no movement at all), and referred them to a hospital for inpatient treatment. Infants whose caregivers refused referral received outpatient treatment. The case fatality ratio by day 15 was calculated for individual and combined clinical signs and stratified by place of treatment. An infant with signs of clinical severe infection or severe pneumonia was recategorised as having low- (case fatality ratio ≤2%) or moderate- (case fatality ratio >2%) mortality risk., Results: Of 7129 young infants with a possible serious infection, fast breathing (in 7-59 days old) was the most prevalent sign (26%), followed by high body temperature (20%) and severe chest indrawing (19%). Infants with pneumonia had the lowest case fatality ratio (0.2%), followed by severe pneumonia (2.0%), clinical severe infection (2.3%) and critical illness (16.9%). Infants with clinical severe infection had a wide range of case fatality ratios for individual signs (from 0.8% to 11.0%). Infants with pneumonia had similar case fatality ratio for outpatient and inpatient treatment (0.2% vs. 0.3%, p = 0.74). Infants with clinical severe infection or severe pneumonia had a lower case fatality ratio among those who received outpatient treatment compared to inpatient treatment (1.9% vs. 6.5%, p<0.0001). We recategorised infants into low-mortality risk signs (case fatality ratio ≤2%) of clinical severe infection (high body temperature, or severe chest indrawing) or severe pneumonia and moderate-mortality risk signs (case fatality ratio >2%) (stopped feeding well, movement only when stimulated, low body temperature or multiple signs of clinical severe infection). We found that both categories had four times lower case fatality ratio when treated as outpatient than inpatient treatment, i.e., 1.0% vs. 4.0% (p<0.0001) and 5.3% vs. 22.4% (p<0.0001), respectively. In contrast, infants with signs of critical illness had nearly two times higher case fatality ratio when treated as outpatient versus inpatient treatment (21.7% vs. 12.1%, p = 0.097)., Conclusions: The mortality risk differs with clinical signs. Young infants with a possible serious infection can be grouped into those with low-mortality risk signs (high body temperature, or severe chest indrawing or severe pneumonia); moderate-mortality risk signs (stopped feeding well, movement only when stimulated, low body temperature or multiple signs of clinical severe infection), or high-mortality risk signs (signs of critical illness). New treatment strategies that consider differential mortality risks for the place of treatment and duration of inpatient treatment could be developed and evaluated based on these findings., Clinical Trial Registration: This trial was registered with the Australian New Zealand Clinical Trials Registry under ID ACTRN 12610000286044., Competing Interests: All other authors declare no competing interests. YBN and RB are WHO employees. The expressed views and opinions do not necessarily express the policies of the World Health Organization. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objective: To assess the effect of a supportive educational intervention on the psychological wellbeing of mothers whose babies were admitted to Neonatal Care Unit (NCU) in Nigeria., Methods: Controlled trial involving 41 mothers whose babies were consecutively admitted into two NCUs (21 in the intervention group and 19 controls). The intervention group received two group-based sessions which included psychological coping strategies, and familiarity with NCU environment, equipment, personnel and procedures. The control group received usual care. Outcome measures were depressive symptoms (Edinburg Postnatal Depression Scale-EPDS), stress-related to NCU (Parental Stressor Scale: Neonatal Intensive Care Unit-PSS: NICU) and post-traumatic symptoms (Impact Event Scale-Revised-IES-R)., Results: Difference-in-Differences (DiD) analysis showed a difference of -4.70 in PSS: NICU score in favour of the intervention group which was statistically significant [F(3, 75) = 9.47, p < 0.0001, R2 = 0.28]. The differences in EPDS (0.91) and IES-R (2.55) were not statistically significant [F(3, 75) = 10.10, p = 0.74] and [F(3, 75) = 10.13, p = 0.73], respectively. All the mothers in the treatment group expressed satisfaction with the intervention., Conclusion: This brief group-based supportive educational intervention for mothers with babies in NCU was feasible, acceptable and helpful in reducing stress related to NCU. Larger controlled trials are recommended to establish the generalizability of these findings in this region., Lay Summary: Babies born too early and or with complications require admission to special hospital called Neonatal Care Unit (NCU) to help them to survive. However, parents whose babies are admitted to NCU can find the experience frightening. We examined how to reduce the fear and stress mothers in Nigeria experience when their babies are admitted to NCU.We had two groups of mothers. The first group made up of 21 mothers was taught how to cope with the stress of having a baby in NCU. They were also shown how the various equipment in the NCU work, what the staff in NCU do and what types of things need to be done to help their babies. The second group of 19 mothers received usual care but did not have the extra teaching the first group received. After 2 weeks, we checked the level of depression and stress the mothers in both groups had compared with the level before the first group received the extra teaching.We found that mothers in the first group who received the extra teaching were less stressed about having their babies in the NCU compared with the mothers that did not receive the teaching., (© The Author(s) [2021]. Published by Oxford University Press.)

Introduction: Neonatal infections contribute substantially to infant mortality in Nigeria and globally. Management requires hospitalization, which is not accessible to many in low resource settings. World Health Organization developed a guideline to manage possible serious bacterial infection (PSBI) in young infants up to two months of age when a referral is not feasible. We evaluated the feasibility of implementing this guideline to achieve high coverage of treatment., Methods: This implementation research was conducted in out-patient settings of eight primary health care centres (PHC) in Lagelu Local Government Area (LGA) of Ibadan, Oyo State, Nigeria. We conducted policy dialogue with the Federal and State officials to adopt the WHO guideline within the existing programme setting and held orientation and sensitization meetings with communities. We established a Technical Support Unit (TSU), built the capacity of health care providers, supervised and mentored them, monitored the quality of services and collected data for management and outcomes of sick young infants with PSBI signs. The Primary Health Care Directorate of the state ministry and the local government led the implementation and provided technical support. The enablers and barriers to implementation were documented., Results: From 1 April 2016 to 31 July 2017 we identified 5278 live births and of these, 1214 had a sign of PSBI. Assuming 30% of births were missed due to temporary migration to maternal homes for delivery care and approximately 45% cases came from outside the catchment area due to free availability of medicines, the treatment coverage was 97.3% (668 cases/6861 expected births) with an expected 10% PSBI prevalence within the first 2 months of life. Of 1214 infants with PSBI, 392 (32%) infants 7-59 days had only fast breathing (pneumonia), 338 (27.8%) infants 0-6 days had only fast breathing (severe pneumonia), 462 (38%) presented with signs of clinical severe infection (CSI) and 22 (1.8%) with signs of critical illness. All but two, 7-59 days old infants with pneumonia were treated with oral amoxicillin without a referral; 80% (312/390) adhered to full treatment; 97.7% (381/390) were cured, and no deaths were reported. Referral to the hospital was not accepted by 87.7% (721/822) families of infants presenting with signs of PSBI needing hospitalization (critical illness 5/22; clinical severe infection; 399/462 and severe pneumonia 317/338). They were treated on an outpatient basis with two days of injectable gentamicin and seven days of oral amoxicillin. Among these 81% (584/721) completed treatment; 97% (700/721) were cured, and three deaths were reported (two with critical illness and one with clinical severe infection). We identified health system gaps including lack of staff motivation and work strikes, medicines stockouts, sub-optimal home visits that affected implementation., Conclusions: When a referral is not feasible, outpatient treatment for young infants with signs of PSBI is possible within existing programme structures in Nigeria with high coverage and low case fatality. To scale up this intervention successfully, government commitment is needed to strengthen the health system, motivate and train health workers, provide necessary commodities, establish technical support for implementation and strengthen linkages with communities., Registration: Trial is registered on Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12617001373369., Competing Interests: No competing interest.

Introduction: Serious bacterial neonatal infections are a major cause of global neonatal mortality. While hospitalized treatment is recommended, families cannot access inpatient treatment in low resource settings. Two parallel randomized control trials were conducted at five sites in three countries (Democratic Republic of Congo, Kenya, and Nigeria) to compare the effectiveness of treatment with experimental regimens requiring fewer injections with a reference regimen A (injection gentamicin plus injection procaine penicillin both once daily for 7 days) on the outpatient basis provided to young infants (0-59 days) with signs of possible serious bacterial infection (PSBI) when the referral was not feasible. Costs were estimated to quantify the financial implications of scaleup, and cost-effectiveness of these regimens., Methods: Direct economic costs (including personnel, drugs and consumable costs) were estimated for identification, prenatal and postnatal visits, assessment, classification, treatment and follow-up. Data on time spent by providers on each activity was collected from 83% of providers. Indirect marginal financial costs were estimated for non-consumables/capital, training, transport, communication, administration and supervision by considering only a share of the total research and health system costs considered important for the program. Total economic costs (direct plus indirect) per young infant treated were estimated based on 39% of young infants enrolled in the trial during 2012 and the number of days each treated during one year. The incremental cost-effectiveness ratio was calculated using treatment failure after one week as the outcome indicator. Experimental regimens were compared to the reference regimen and pairwise comparisons were also made., Results: The average costs of treating a young infant with clinical severe infection (a sub-category of PSBI) in 2012 was lowest with regimen D (injection gentamicin once daily for 2 days plus oral amoxicillin twice daily for 7 days) at US$ 20.9 (95% CI US$ 16.4-25.3) or US$ 32.5 (2018 prices). While all experimental regimens B (injection gentamicin once daily plus oral amoxicillin twice daily, both for 7 days), regimen C (once daily of injection gentamicin injection plus injection procaine penicillin for 2 days, thereafter oral amoxicillin twice daily for 5 days) and regimen D were found to be more cost-effective as compared with the reference regimen A; pairwise comparison showed regimen D was more cost-effective than B or C. For fast breathing, the average cost of treatment with regimen E (oral amoxicillin twice daily for 7 days) at US$ 18.3 (95% CI US$ 13.4-23.3) or US$ 29.0 (2018 prices) was more cost-effective than regimen A. Indirect costs were 32% of the total treatment costs., Conclusion: Scaling up of outpatient treatment for PSBI when the referral is not feasible with fewer injections and oral antibiotics is cost-effective for young infants and can lead to increased access to treatment resulting in potential reductions in neonatal mortality., Clinical Trial Registration: The trial was registered with Australian New Zealand Clinical Trials Registry under ID ACTRN 12610000286044., Competing Interests: SY, YBN, and RB are WHO employees. All other authors declare no competing interests. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Community-based data on the prevalence of clinical signs of possible serious bacterial infection (PSBI) and the mortality associated with them are scarce. The aim was to examine the prevalence for each sign of infection and mortality associated with infants in the first two months of life, using community surveillance through community health workers (CHW)., Methods: We used population-based surveillance data of infants up to two months of age from the African Neonatal Sepsis Trial (AFRINEST). In this study, CHWs visited infants up to 10 times during the first two months of life at five sites in three sub-Saharan African countries. CHW assessed the infant for signs of infection (local or systemic) and referred infants who presented with any sign of infection to a health facility. We used a longitudinal analysis to calculate the risk of death associated with the presence of a sign of infection at the time of the visit until the subsequent visit., Results: During the first two months of their life, CHWs visited 84,759 live-born infants at least twice. In 11,089 infants (13.1%), one or more signs of infection were identified, of which 237 (2.1%) died. A sign of infection was detected at 2.1% of total visits. In 52% of visits, infants had one or more sign of systemic infection, while 25% had fast breathing in 7-59 days period and 23% had a local infection. All signs of infection, including multiple signs, were more frequently seen in the first week of life. The risk of mortality was very low (0.2%) for local infections and fast breathing in 7-59 days old, it was low for fast breathing 0-6 days old (0.6%), high body temperature (0.7%) and severe chest indrawing (1.0%), moderate for low body temperature (4.9%) and stopped feeding well/not able to feed at all (5.0%) and high for movement only when stimulated or no movement at all (10%) and multiple signs of systemic infection (15.5%). The risk of death associated with most clinical signs was higher (1.5 to 9 times) in the first week of life than at later age, except for low body temperature (4 times lower) as well as high body temperature (2 times lower)., Conclusion: Signs of infections are common in the first two months of life. The mortality risk differs with clinical signs and can be grouped as very low (local infections, fast breathing 7-59 days), low (fever, severe chest indrawing and fast breathing 0-6 days), moderate (low body temperature and stopped feeding well/not able to feed at all) and high (for movements only on stimulation or no movements at all and multiple signs of infection). New treatment strategies that consider differential mortality risk could be developed and evaluated based on these findings., Clinical Trial Registration: The trial was registered with Australian New Zealand Clinical Trials Registry under ID ACTRN 12610000286044., Competing Interests: YBN and RB are WHO employees. All other authors declare no competing interests.

Background: The safety and efficacy of antenatal glucocorticoids in women in low-resource countries who are at risk for preterm birth are uncertain., Methods: We conducted a multicountry, randomized trial involving pregnant women between 26 weeks 0 days and 33 weeks 6 days of gestation who were at risk for preterm birth. The participants were assigned to intramuscular dexamethasone or identical placebo. The primary outcomes were neonatal death alone, stillbirth or neonatal death, and possible maternal bacterial infection; neonatal death alone and stillbirth or neonatal death were evaluated with superiority analyses, and possible maternal bacterial infection was evaluated with a noninferiority analysis with the use of a prespecified margin of 1.25 on the relative scale., Results: A total of 2852 women (and their 3070 fetuses) from 29 secondary- and tertiary-level hospitals across Bangladesh, India, Kenya, Nigeria, and Pakistan underwent randomization. The trial was stopped for benefit at the second interim analysis. Neonatal death occurred in 278 of 1417 infants (19.6%) in the dexamethasone group and in 331 of 1406 infants (23.5%) in the placebo group (relative risk, 0.84; 95% confidence interval [CI], 0.72 to 0.97; P = 0.03). Stillbirth or neonatal death occurred in 393 of 1532 fetuses and infants (25.7%) and in 444 of 1519 fetuses and infants (29.2%), respectively (relative risk, 0.88; 95% CI, 0.78 to 0.99; P = 0.04); the incidence of possible maternal bacterial infection was 4.8% and 6.3%, respectively (relative risk, 0.76; 95% CI, 0.56 to 1.03). There was no significant between-group difference in the incidence of adverse events., Conclusions: Among women in low-resource countries who were at risk for early preterm birth, the use of dexamethasone resulted in significantly lower risks of neonatal death alone and stillbirth or neonatal death than the use of placebo, without an increase in the incidence of possible maternal bacterial infection. (Funded by the Bill and Melinda Gates Foundation and the World Health Organization; Australian and New Zealand Clinical Trials Registry number, ACTRN12617000476336; Clinical Trials Registry-India number, CTRI/2017/04/008326.)., (Copyright © 2020 Massachusetts Medical Society.)

Objective: To determine whether commencement of antibiotics within 3 postnatal days in preterm, very low birth weight (VLBW; ≤1500 g) infants is associated with the development of necrotizing enterocolitis (NEC)., Study Design: Preplanned statistical analyses were done to study the association between early antibiotic treatment and later NEC development, using the NEOMUNE-NeoNutriNet cohort of VLBW infants from 13 neonatal intensive care units (NICUs) in 5 continents (n = 2831). NEC incidence was compared between infants who received early antibiotics and those who did not, with statistical adjustments for NICU, gestational age, birth weight, sex, delivery mode, antenatal steroid use, Apgar score, and type and initiation of enteral nutrition., Results: The incidence of NEC was 9.0% in the group of infants who did not receive early antibiotics (n = 269), compared with 3.9% in those who did receive early antibiotics (n = 2562). The incidence remained lower in the early antibiotic group after stepwise statistical adjustments for NICU (OR, 0.57; 95% CI, 0.35-0.94, P < .05) and other potential confounders (OR, 0.25; 95% CI, 0.12-0.47; P < .0001)., Conclusions: In this large international cohort of preterm VLBW infants, a small proportion of infants did not receive antibiotics just after birth, and these infants had a higher incidence of NEC. It is important to better understand the role of such variables as time, type, and duration of antibiotic treatment on NEC incidence, immune development, gut colonization, and antibiotic resistance in the NICU., (Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.)

Caffeine is the preferred pharmacologic treatment for apnea of prematurity. Little is known about the availability and affordability of caffeine in the low and middle-income countries of sub-Saharan Africa (SSA). We conducted an online survey in 2020 of newborn physicians in SSA to determine their access to caffeine. Of 90 invited participants, 55 responded (61%). They worked in 13 SSA countries and 48 hospitals. Caffeine was used in 6 countries. In 5 of these countries, the price of caffeine was reported and ranged from US $1.73 in Ghana to US $73.63 in Kenya per 3 mL vial. High drug prices and lack of drug availability for purchase were identified most frequently as primary barriers. Some respondents believed that other methylxanthines are adequate substitutes for caffeine. Only 31 of 53 (58%) respondents knew that caffeine is included in the essential drug list of the World Health Organization (WHO)., (© 2020 Published by Elsevier Ltd.)

Background: Pneumonia and malaria are the leading causes of global childhood mortality. We describe the clinical presentation of children diagnosed with pneumonia and/or malaria, and identify possible missed cases and diagnostic predictors., Methods: Prospective cohort study involving children (aged 28 days to 15 years) admitted to 12 secondary-level hospitals in south-west Nigeria, from November 2015 to October 2017. We described children diagnosed with malaria and/or pneumonia on admission and identified potential missed cases using WHO criteria. We used logistic regression models to identify associations between clinical features and severe pneumonia and malaria diagnoses., Results: Of 16 432 admitted children, 16 184 (98.5%) had adequate data for analysis. Two-thirds (10 561, 65.4%) of children were diagnosed with malaria and/or pneumonia by the admitting doctor; 31.5% (567/1799) of those with pneumonia were also diagnosed with malaria. Of 1345 (8.3%) children who met WHO severe pneumonia criteria, 557 (41.4%) lacked a pneumonia diagnosis. Compared with "potential missed" diagnoses of severe pneumonia, children with "detected" severe pneumonia were more likely to receive antibiotics (odds ratio [OR], 4.03; 2.63-6.16, P < .001), and less likely to die (OR, 0.72; 0.51-1.02, P = .067). Of 2299 (14.2%) children who met WHO severe malaria criteria, 365 (15.9%) lacked a malaria diagnosis. Compared with "potential missed" diagnoses of severe malaria, children with "detected" severe malaria were less likely to die (OR, 0.59; 0.38-0.91, P = 0.017), with no observed difference in antimalarial administration (OR, 0.29; 0.87-1.93, P = .374). We identified predictors of severe pneumonia and malaria diagnosis., Conclusion: Pneumonia should be considered in all severely unwell children with respiratory signs, regardless of treatment for malaria or other conditions., (© 2020 The Authors. Pediatric Pulmonology published by Wiley Periodicals, Inc.)

Objective: To evaluate the effectiveness of intermittent pulse oximetry in guiding oxygen therapy in neonates in a low-resource setting., Design and Setting: Prospective validation study at three hospitals in southwest Nigeria. We performed concealed continuous pulse oximetry on participants to evaluate intermittent SpO 2 monitoring., Patients: We recruited all preterm or low birthweight neonates, and all term neonates who required oxygen therapy, who were admitted to the neonatal ward(s) of the study hospitals during the study period., Main Outcome Measures: Proportion of time preterm/low birthweight neonates on oxygen spent within, above and below the target SpO 2 range of 90%-95%; and the proportion of time term neonates and neonates not on oxygen spent within and below the target range of 90%-100%., Results: Preterm/low birthweight neonates receiving oxygen therapy (group A) spent 15.7% (95% CI 13.3 to 18.9) of time in the target SpO 2 range of 90%-95%. They spent 75.0% (63.6-81.1) of time above 95%, and 2.7% (1.7-5.6) of time below 85%. Term neonates and all neonates not receiving oxygen (group B) spent 97.3% (95% CI 96.4 to 98.6) of time within the target range of 90%-100%, and 0.9% (0.3-1.4) of time below 85%. Guidelines recommended SpO 2 monitoring 3 times per day for all patients, however neonates in groups A and B were monitored an average of 4.7 and 5.3 times per day, respectively., Conclusions: To better maintain SpO 2 within the target range, preterm/low birthweight neonates on oxygen should have their SpO 2 monitored more frequently than the current 4.7 times per day. In all other neonates, however, monitoring SpO 2 5.3 times per day appears suitable., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Background: Oxygen is an essential medical therapy that is poorly available globally. We evaluated the quality of oxygen therapy in 12 secondary-level Nigerian hospitals, including access to oxygen equipment, equipment functionality, healthcare worker knowledge and appropriateness of use., Methods: We conducted a three-part evaluation of oxygen access and use involving: (1) facility assessment (including technical evaluation of oxygen equipment), (2) clinical audit (children and neonates admitted January 2014-December 2015) and (3) survey of healthcare worker training and experience on the clinical use of oxygen (November 2015)., Results: Oxygen access for children and newborns is compromised by faulty equipment, lack of pulse oximetry and inadequate care practices. One hospital used pulse oximetry for paediatric care. Eleven hospitals had some access to oxygen supplies. Testing of 57 oxygen concentrators revealed two (3.5%) that were 'fit for use'. Overall, 14.4% (3708/25 677) of children and neonates received oxygen some time during their admission; 19.4% (1944/10 000) of hypoxaemic children received oxygen; 38.5% (1217/3161) of children who received oxygen therapy were not hypoxaemic., Conclusions: Oxygen access for children in Nigerian hospitals is poor, and likely results in substantial excess mortality. To improve oxygen access for children globally we must focus on actual provision of oxygen to patients-not simply the presence of oxygen equipment at the facility level. This requires a systematic approach to improve both oxygen (access [including equipment, maintenance and affordability]) and oxygen use (including pulse oximetry, guidelines and continuing education)., (© The Author(s) 2019. Published by Oxford University Press.)

Background: Malaria complicates up to 58.1% of pregnancies in Nigeria. Preventive measures include intermittent preventive treatment and consistent use of insecticide-treated nets. However, uptake of these interventions can often be sub-optimal., Objective: This study aimed to assess the prevalence of malaria in pregnancy in peri-urban and rural communities of Ibadan, Nigeria and its association with the use of preventive measures., Methods: In this cross-sectional study, pregnant women were recruited from selected primary health centres and blood films were taken for malaria parasites. Explanatory variables were the use of bed nets and chemoprophylaxis; the primary outcome was presence of peripheral malaria parasitaemia., Results: Malaria prevalence was 4.3% (67 of 1570 participants); two-thirds of women with parasitaemia had malaria symptoms. Four hundred and thirty-eight (27.9%) used prescribed sulphadoxine-pyrimethamine prophylaxis, 784 (49.9%) women reported that they consistently slept under insecticide-treated nets, and 236 (15%) complied with both interventions. Bed net use appeared more protective than chemoprophylaxis. However, the protection from malaria in those who used preventive measures was not statistically significant (p=0.075)., Conclusion: Malaria prevalence was low. No association was determined between malaria and the use of preventive measures; the lack of association may be due to the low prevalence., (© Association of Resident Doctors, UCH, Ibadan.)

Background: Improving oxygen systems may improve clinical outcomes for hospitalised children with acute lower respiratory infection (ALRI). This paper reports the effects of an improved oxygen system on mortality and clinical practices in 12 general, paediatric, and maternity hospitals in southwest Nigeria., Methods and Findings: We conducted an unblinded stepped-wedge cluster-randomised trial comparing three study periods: baseline (usual care), pulse oximetry introduction, and stepped introduction of a multifaceted oxygen system. We collected data from clinical records of all admitted neonates (<28 days old) and children (28 days to 14 years old). Primary analysis compared the full oxygen system period to the pulse oximetry period and evaluated odds of death for children, children with ALRI, neonates, and preterm neonates using mixed-effects logistic regression. Secondary analyses included the baseline period (enabling evaluation of pulse oximetry introduction) and evaluated mortality and practice outcomes on additional subgroups. Three hospitals received the oxygen system intervention at 4-month intervals. Primary analysis included 7,716 neonates and 17,143 children admitted during the 2-year stepped crossover period (November 2015 to October 2017). Compared to the pulse oximetry period, the full oxygen system had no association with death for children (adjusted odds ratio [aOR] 1.06; 95% confidence interval [CI] 0.77-1.46; p = 0.721) or children with ALRI (aOR 1.09; 95% CI 0.50-2.41; p = 0.824) and was associated with an increased risk of death for neonates overall (aOR 1.45; 95% CI 1.04-2.00; p = 0.026) but not preterm/low-birth-weight neonates (aOR 1.30; 95% CI 0.76-2.23; p = 0.366). Secondary analyses suggested that the introduction of pulse oximetry improved oxygen practices prior to implementation of the full oxygen system and was associated with lower odds of death for children with ALRI (aOR 0.33; 95% CI 0.12-0.92; p = 0.035) but not for children, preterm neonates, or neonates overall (aOR 0.97, 95% CI 0.60-1.58, p = 0.913; aOR 1.12, 95% CI 0.56-2.26, p = 0.762; aOR 0.90, 95% CI 0.57-1.43, p = 0.651). Limitations of our study are a lower-than-anticipated power to detect change in mortality outcomes (low event rates, low participant numbers, high intracluster correlation) and major contextual changes related to the 2016-2017 Nigerian economic recession that influenced care-seeking and hospital function during the study period, potentially confounding mortality outcomes., Conclusions: We observed no mortality benefit for children and a possible higher risk of neonatal death following the introduction of a multifaceted oxygen system compared to introducing pulse oximetry alone. Where some oxygen is available, pulse oximetry may improve oxygen usage and clinical outcomes for children with ALRI., Trial Registration: Australian New Zealand Clinical Trials Registry: ACTRN12617000341325., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: HRG reports consultancy grants from WHO for unrelated work during the conduct of the study. CDN has previously received project funding from Pfizer for a vaccine impact study. All other authors declare no competing interests.

Background: Hypoxaemia is a common complication of pneumonia and a major risk factor for death, but less is known about hypoxaemia in other common conditions. We evaluated the epidemiology of hypoxaemia and oxygen use in hospitalised neonates and children in Nigeria., Methods: We conducted a prospective cohort study among neonates and children (<15 years of age) admitted to 12 secondary-level hospitals in southwest Nigeria (November 2015-November 2017) using data extracted from clinical records (documented during routine care). We report summary statistics on hypoxaemia prevalence, oxygen use, and clinical predictors of hypoxaemia. We used generalised linear mixed-models to calculate relative odds of death (hypoxaemia vs not)., Findings: Participating hospitals admitted 23,926 neonates and children during the study period. Pooled hypoxaemia prevalence was 22.2% (95%CI 21.2-23.2) for neonates and 10.2% (9.7-10.8) for children. Hypoxaemia was common among children with acute lower respiratory infection (28.0%), asthma (20.4%), meningitis/encephalitis (17.4%), malnutrition (16.3%), acute febrile encephalopathy (15.4%), sepsis (8.7%) and malaria (8.5%), and neonates with neonatal encephalopathy (33.4%), prematurity (26.6%), and sepsis (21.0%). Hypoxaemia increased the adjusted odds of death 6-fold in neonates and 7-fold in children. Clinical signs predicted hypoxaemia poorly, and their predictive ability varied across ages and conditions. Hypoxaemic children received oxygen for a median of 2-3 days, consuming ∼3500 L of oxygen per admission., Interpretation: Hypoxaemia is common in respiratory and non-respiratory acute childhood illness and increases the risk of death substantially. Given the limitations of clinical signs, pulse oximetry is an essential tool for detecting hypoxaemia, and should be part of the routine assessment of all hospitalised neonates and children., Competing Interests: HG, AAB, AIA, OBO, DP, EN, TD, and AGF received payment for services on this project from the funder (Bill and Melinda Gates Foundation) and RI is an employee of the funder. HG reports consultancy grants from WHO for unrelated work during the conduct of the study. All other authors declare no competing interests., (© 2019 Published by Elsevier Ltd.)