Background Neonatal deaths now account for 47% of all deaths in children younger than 5 years globally. More than a third of newborn deaths are due to preterm birth complications, which is the leading cause of death. Understanding the causes and factors contributing to neonatal deaths is needed to identify interventions that will reduce mortality. We aimed to establish the major causes of preterm mortality in preterm infants in the first 28 days of life in Ethiopia. Methods We did a prospective, cross-sectional, observational study in five hospitals in Ethiopia. Study participants were preterm infants born in the study hospitals at younger than 37 gestational weeks. Infants whose gestational age could not be reliably estimated and those born as a result of induced abortion were excluded from the study. Data were collected on maternal and obstetric history, clinical maternal and neonatal conditions, and laboratory investigations. For neonates who died of those enrolled, consent was requested from parents for post-mortem examinations (both complete diagnostic autopsy and minimally invasive tissue sampling). An independent panel of experts established the primary and contributory causes of preterm mortality with available data. Findings Between July 1, 2016, to May 31, 2018, 4919 preterm infants were enrolled in the study and 3852 were admitted to neonatal intensive care units. By 28 days of post-natal age, 1109 (29%) of those admitted to the neonatal intensive care unit died. Complete diagnostic autopsy was done in 441 (40%) and minimally invasive tissue sampling in 126 (11%) of the neonatal intensive care unit deaths. The main primary causes of death in the 1109 infants were established as respiratory distress syndrome (502 [45%]); sepsis, pneumonia and meningitis (combined as neonatal infections; 331 [30%]), and asphyxia (151 [14%]). Hypothermia was the most common contributory cause of preterm mortality (770 [69%]). The highest mortality occurred in infants younger than 28 weeks of gestation (89 [86%] of 104), followed by infants aged 28-31 weeks (512 [54%] of 952), 32-34 weeks (349 [18%] of 1975), and 35-36 weeks (159 [8%] of 1888). Interpretation Three conditions accounted for 89% of all deaths among preterm infants in Ethiopia. Scale-up interventions are needed to prevent or treat these conditions. Further research is required to develop effective and affordable interventions to prevent and treat the major causes of preterm death. Funding Bill & Melinda Gates Foundation.

Neonatal infections are estimated to account for a quarter of the 2·8 million annual neonatal deaths, as well as approximately 3% of all DALYs. Despite this burden, data are limited on incidence, aetiology and outcomes, particularly regarding impairment. We aimed to develop guidelines for improved scientific reporting of observational and interventional neonatal infection studies, to increase comparability and to strengthen research in this area. This statement, Strengthening the Reporting of Observational Studies in Epidemiology for Newborn Infection (STROBE-NI) is an extension of the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist. STROBE-NI was developed following systematic reviews of published literature (1996)(1997)(1998)(1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015), compilation of over 130 potential reporting recommendations, and circulation of a survey to relevant professionals worldwide, eliciting responses from 147 professionals from 37 countries. An international consensus meeting of 18 participants (with expertise in infectious diseases, neonatology, microbiology, epidemiology and statistics) identified priority recommendations for reporting, additional to the STROBE statement. Implementation of these STROBE-NI recommendations, and linked checklist, aims to improve scientific reporting of neonatal infection studies, increasing data utility and allowing meta-analyses and pathogen-specific burden estimates to inform global policy and new interventions, including maternal vaccines.

BackgroundPreterm birth (PTB), low birth weight (LBW) and small for gestational age (SGA) contribute to neonatal mortality. Maternal HIV-1 infection has been associated with an increased risk of PTB, but mechanisms underlying this association are undefined. We describe correlates and outcomes of PTB, LBW, and SGA in HIV-exposed uninfected infants.MethodsThis was a retrospective analysis of cohort study. Between 1999–2002, pregnant, HIV-infected women were enrolled into an HIV-1 transmission study. Logistic regression was used to identify correlates of PTB, LBW and SGA in HIV-negative, spontaneous singleton deliveries. Associations between birth outcomes and mortality were measured using survival analyses.ResultsIn multivariable models, maternal plasma (OR = 2.1, 95% CI = 1.1-3.8) and cervical HIV-1 RNA levels (OR = 1.6, 95% CI = 1.1-2.4), and CD4 < 15% (OR = 2.4, 95% CI = 1.0-5.6) were associated with increased odds of PTB. Abnormal vaginal discharge and cervical polymorphonuclear leukocytes were also associated with PTB. Cervical HIV-1 RNA level (OR = 2.4, 95% CI = 1.5-6.7) was associated with an increased odds of LBW, while increasing parity (OR = 0.46, 95% CI = 0.24-0.88) was associated with reduced odds. Higher maternal body mass index (OR = 0.75, 95% CI = 0.61-0.92) was associated with a reduced odds of SGA, while bacterial vaginosis was associated with >3-fold increased odds (OR = 3.2, 95% CI = 1.4-7.4). PTB, LBW, and SGA were each associated with a >6-fold increased risk of neonatal death, and a >2-fold increased rate of infant mortality within the first year.ConclusionsMaternal plasma and cervical HIV-1 RNA load, and genital infections may be important risk factors for PTB in HIV-exposed uninfected infants. PTB, LBW, and SGA are associated with increased neonatal and infant mortality in HIV-exposed uninfected infants.

BackgroundIn South Asia, where most stillbirths and neonatal deaths occur, much remains unknown about the causes of these deaths. About one-third of neonatal deaths are attributed to prematurity, yet the specific conditions which cause these deaths are often unclear as is the etiology of stillbirths. In low-resource settings, most women are not routinely tested for infections and autopsy is rare.MethodsThis prospective, cohort study will be conducted in hospitals in Davengere, India and Karachi, Pakistan. All women who deliver either a stillbirth or a preterm birth at one of the hospitals will be eligible for enrollment. With consent, the participant and, when applicable, her offspring, will be followed to 28-days post-delivery. A series of research tests will be conducted to determine infection and presence of other conditions which may contribute to the death. In addition, all routine clinical investigations will be documented. For both stillbirths and preterm neonates who die ≤ 28 days, with consent, a standard autopsy as well as minimally invasive tissue sampling will be conducted. Finally, an expert panel will review all available data for stillbirths and neonatal deaths to determine the primary and contributing causes of death using pre-specified guidance.ConclusionThis will be among the first studies to prospectively obtain detailed information on causes of stillbirth and preterm neonatal death in low-resource settings in Asia. Determining the primary causes of death will be important to inform strategies most likely to reduce the high mortality rates in South Asia.Trial registrationClinicaltrials.gov (NCT03438110) Clinical Trial Registry of India (CTRI/2018/03/012281).

The scientific basis for antenatal corticosteroids (ACS) for women at risk of preterm birth has rapidly changed in recent years. Two landmark trials—the Antenatal Corticosteroid Trial and the Antenatal Late Preterm Steroids Trial—have challenged the long-held assumptions on the comparative health benefits and harms regarding the use of ACS for preterm birth across all levels of care and contexts, including resource-limited settings. Researchers, clinicians, programme managers, policymakers and donors working in low-income and middle-income countries now face challenging questions of whether, where and how ACS can be used to optimise outcomes for both women and preterm newborns.In this article, we briefly present an appraisal of the current evidence around ACS, how these findings informed WHO’s current recommendations on ACS use, and the knowledge gaps that have emerged in the light of new trial evidence. Critical considerations in the generalisability of the available evidence demonstrate that a true state of clinical equipoise exists for this treatment option in low-resource settings. An expert group convened by WHO concluded that there is a clear need for more efficacy trials of ACS in these settings to inform clinical practice.

Accurate knowledge regarding cause of death (COD) for stillbirths and neonatal deaths is crucial, especially in low-income countries, in order for public health and medical officials to choose appropriate interventions likely to reduce these deaths. To date, many of the COD studies in these areas have relied only on obstetric or neonatal clinical information and the determination of COD is likely to be inaccurate. Information related to infectious COD is especially lacking. Thus, without more sophisticated testing, data as currently collected only provide a very weak approximation of the COD and may well lead to adoption of interventions of limited usefulness. In this commentary, we propose recommendations regarding the type of data needed to determine with reasonable accuracy the COD for stillbirths and neonatal deaths in low-resource settings. Using these data, and a method to determine the degree of certainty, we then propose definitions for the most common COD. Our goal is to reduce subjectivity and provide more specificity for the tests used in existing classification systems so that the methodology of COD determination is transparent and able to be replicated over time and from location to location.

BackgroundAs efforts to scale up the delivery of Kangaroo Mother Care (KMC) in facilities are increasing, a standardized approach to measure implementation and progress towards effective coverage is needed. Here, we describe a consensus–based approach to develop a measurement framework and identify a core set of indicators for monitoring facility–based KMC that would be feasible to measure within existing systems.MethodsThe KMC measurement framework and core list of indicators were developed through: 1) scoping exercise to identify potential indicators through literature review and requests from researchers and program implementers; and 2) face–to–face consultations with KMC and measurement experts working at country and global levels to review candidate indicators and finalize selection and definitions.ResultsThe KMC measurement framework includes two main components: 1) service readiness, based on the WHO building blocks framework; and 2) service delivery action sequence covering identification, service initiation, continuation to discharge, and follow–up to graduation. Consensus was reached on 10 core indicators for KMC, which were organized according to the measurement framework. We identified 4 service readiness indicators, capturing national level policy for KMC, availability of KMC indicators in HMIS, costed operational plans for KMC and availability of KMC services at health facilities with inpatient maternity services. Six indicators were defined for service delivery, including weighing of babies at birth, identification of those ≤2000 g, initiation of facility–based KMC, monitoring the quality of KMC, status of babies at discharge from the facility and levels of follow–up (according to country–specific protocol).ConclusionsThese core KMC indicators, identified with input from a wide range of global and country–level KMC and measurement experts, can aid efforts to strengthen monitoring systems and facilitate global tracking of KMC implementation. As data collection systems advance, we encourage program managers and evaluators to document their experiences using this framework to measure progress and allow indicator refinement, with the overall aim of working towards sustainable, country–led data systems.

BackgroundWith nearly 15 million annual preterm births globally, preterm birth is the most common cause of neonatal death. Forty to 60 % of neonatal deaths are directly or indirectly associated with preterm mortality. As countries aim to meet the Sustainable Development Goals to reduce neonatal mortality, significant reductions in preterm mortality are needed. This study aims to identify the common causes of preterm illness and their contribution to preterm mortality in low-resource settings. This article will describe the methods used to undertake the study.MethodsThis is a prospective, multi-centre, descriptive clinical study. Socio-demographic, obstetric, and maternal factors, and clinical and laboratory findings will be documented. The major causes of preterm mortality will be identified using clinical, laboratory, imaging, and autopsy methods and use the national Ethiopian guidelines on management of preterm infants including required investigations to reach final diagnoses. The study will document the clinical and management protocols followed in these settings. The approach consists of clinical examinations and monitoring, laboratory investigations, and determination of primary and contributory causes of mortality through both clinical means and by post-mortem examinations. An independent panel of experts will validate the primary and contributory causes of mortality.To obtain the estimated sample size of 5000 preterm births, the study will be undertaken in five hospitals in three regions of Ethiopia, which are geographically distributed across the country. All preterm infants who are either born or transferred to these hospitals will be eligible for the study. Three methods (last menstrual period, physical examination using the New Ballard Score, and ultrasound) will be used to determine gestational age.All clinical procedures will be conducted per hospital protocol and informed consent will be taken from parents or caretakers prior to their participation in the study as well as for autopsy if the infant dies.DiscussionThis study will determine the major causes of death and illness among hospitalized preterm infants in a low-resource setting. The result will inform policy makers and implementers of areas that can be prioritized in order to contribute to a significant reduction in neonatal mortality.