Summary Background Antenatal corticosteroids for pregnant women at risk of preterm birth are among the most effective hospital-based interventions to reduce neonatal mortality. We aimed to assess the feasibility, effectiveness, and safety of a multifaceted intervention designed to increase the use of antenatal corticosteroids at all levels of health care in low-income and middle-income countries. Methods In this 18-month, cluster-randomised trial, we randomly assigned (1:1) rural and semi-urban clusters within six countries (Argentina, Guatemala, India, Kenya, Pakistan, and Zambia) to standard care or a multifaceted intervention including components to improve identification of women at risk of preterm birth and to facilitate appropriate use of antenatal corticosteroids. The primary outcome was 28-day neonatal mortality among infants less than the 5th percentile for birthweight (a proxy for preterm birth) across the clusters. Use of antenatal corticosteroids and suspected maternal infection were additional main outcomes. This trial is registered with ClinicalTrials.gov, number NCT01084096. Findings The ACT trial took place between October, 2011, and March, 2014 (start dates varied by site). 51 intervention clusters with 47 394 livebirths (2520 [5%] less than 5th percentile for birthweight) and 50 control clusters with 50 743 livebirths (2258 [4%] less than 5th percentile) completed follow-up. 1052 (45%) of 2327 women in intervention clusters who delivered less-than-5th-percentile infants received antenatal corticosteroids, compared with 215 (10%) of 2062 in control clusters (p<0·0001). Among the less-than-5th-percentile infants, 28-day neonatal mortality was 225 per 1000 livebirths for the intervention group and 232 per 1000 livebirths for the control group (relative risk [RR] 0·96, 95% CI 0·87–1·06, p=0·65) and suspected maternal infection was reported in 236 (10%) of 2361 women in the intervention group and 133 (6%) of 2094 in the control group (odds ratio [OR] 1·67, 1·33–2·09, p<0·0001). Among the whole population, 28-day neonatal mortality was 27·4 per 1000 livebirths for the intervention group and 23·9 per 1000 livebirths for the control group (RR 1·12, 1·02–1·22, p=0·0127) and suspected maternal infection was reported in 1207 (3%) of 48 219 women in the intervention group and 867 (2%) of 51 523 in the control group (OR 1·45, 1·33–1·58, p<0·0001). Interpretation Despite increased use of antenatal corticosteroids in low-birthweight infants in the intervention groups, neonatal mortality did not decrease in this group, and increased in the population overall. For every 1000 women exposed to this strategy, an excess of 3·5 neonatal deaths occurred, and the risk of maternal infection seems to have been increased. Funding Eunice Kennedy Shriver National Institute of Child Health and Human Development.

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.

BackgroundReported benefits of maternal nutrition supplements commenced during pregnancy in low-resource populations have typically been quite limited.ObjectivesThis study tested the effects on newborn size, especially length, of commencing nutrition supplements for women in low-resource populations ≥3 mo before conception (Arm 1), compared with the same supplement commenced late in the first trimester of pregnancy (Arm 2) or not at all (control Arm 3).MethodsWomen First was a 3-arm individualized randomized controlled trial (RCT). The intervention was a lipid-based micronutrient supplement; a protein-energy supplement was also provided if maternal body mass index (kg/m2) was <20 or gestational weight gain was less than recommendations. Study sites were in rural locations of the Democratic Republic of the Congo (DRC), Guatemala, India, and Pakistan. The primary outcome was length-for-age z score (LAZ), with all anthropometry obtained <48 h post delivery. Because gestational ages were unavailable in DRC, outcomes were determined for all 4 sites from WHO newborn standards (non-gestational-age-adjusted, NGAA) as well as INTERGROWTH-21st fetal standards (3 sites, gestational age-adjusted, GAA).ResultsA total of 7387 nonpregnant women were randomly assigned, yielding 2451 births with NGAA primary outcomes and 1465 with GAA outcomes. Mean LAZ and other outcomes did not differ between Arm 1 and Arm 2 using either NGAA or GAA. Mean LAZ (NGAA) for Arm 1 was greater than for Arm 3 (effect size: +0.19; 95% CI: 0.08, 0.30, P = 0.0008). For GAA outcomes, rates of stunting and small-for-gestational-age were lower in Arm 1 than in Arm 3 (RR: 0.69; 95% CI: 0.49, 0.98, P = 0.0361 and RR: 0.78; 95% CI: 0.70, 0.88, P < 0.001, respectively). Rates of preterm birth did not differ among arms.ConclusionsIn low-resource populations, benefits on fetal growth–related birth outcomes were derived from nutrition supplements commenced before conception or late in the first trimester.This trial was registered at clinicaltrials.gov as NCT01883193.

BackgroundThe first minutes after birth are critical to reducing neonatal mortality. Helping Babies Breathe (HBB) is a simulation-based neonatal resuscitation program for low resource settings. We studied the impact of initial HBB training followed by refresher training on the knowledge and skills of the birth attendants in facilities.MethodsWe conducted HBB trainings in 71 facilities in the NICHD Global Network research sites (Nagpur and Belgaum, India and Eldoret, Kenya), with a 6:1 ratio of facility trainees to Master Trainers (MT). Because of staff turnover, some birth attendants (BA) were trained as they joined the delivery room staff, after the initial training was completed (catch-up initial training). We compared pass rates for skills and knowledge pre- and post- initial HBB training and following refresher training among active BAs. An Objective Structured Clinical Examination (OSCE) B tested resuscitation skill retention by comparing post-initial training performance with pre-refresher training performance. We identified factors associated with loss of skills in pre-refresher training performance using multivariable logistic regression analysis. Daily bag and mask ventilation practice, equipment checks and supportive supervision were stressed as part of training.ResultsOne hundred five MT (1.6 MT per facility) conducted initial and refresher HBB trainings for 835 BAs; 76% had no prior resuscitation training. Initial training improved knowledge and skills: the pass percentage for knowledge tests improved from 74 to 99% (p < 0.001). Only 5% could ventilate a newborn mannequin correctly before initial training but 97% passed the post-initial ventilation training test (p < 0.0001) and 99% passed the OSCE B resuscitation evaluation. During pre-refresher training evaluation, a mean of 6.7 (SD 2.49) months after the initial training, 99% passed the knowledge test, but the successful completion rate fell to 81% for the OSCE B resuscitation skills test. Characteristics associated with deterioration of resuscitation skills were BAs from tertiary care facilities, no prior resuscitation training, and the timing of training (initial vs. catch-up training).ConclusionsHBB training significantly improved neonatal resuscitation knowledge and skills. However, skills declined more than knowledge over time. Ongoing skills practice and monitoring, more frequent retesting, and refresher trainings are needed to maintain neonatal resuscitation skills.Trial registrationClinicalTrials.gov Identifier: NCT01681017; 04 September 2012, retrospectively registered.Electronic supplementary materialThe online version of this article (doi:10.1186/s12884-016-1141-3) contains supplementary material, which is available to authorized users.