A population-based, multifaceted strategy to implement antenatal corticosteroid treatment versus standard care for the reduction of neonatal mortality due to preterm birth in low-income and middle-income countries: the ACT cluster-randomised trial.

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.

A multi-faceted intervention including antenatal corticosteroids to reduce neonatal mortality associated with preterm birth: a case study from the Guatemalan Western Highlands.

BACKGROUND: The Global Network for Women's and Children's Health Research undertook a cluster-randomized trial to assess the impact of a multi-faceted intervention to identify women at high-risk of preterm birth at all levels of care, to administer corticosteroids to women and refer for facility delivery compared with standard care. Of the seven sites that participated in the ACT trial, only two sites had statistically significant reductions in the neonatal mortality among the target group of <5th percentile infants, and of the two, Guatemala's improvement in neonatal mortality was by far the largest. METHODS: We used data available from the ACT trial as well as pretrial data in an attempt to understand why neonatal mortality may have decreased in the intervention clusters in <5(th) percentile infants in Chimaltenango, Guatemala. The intervention and control clusters were compared in regards to ACS use, the various types of medical care, outcomes in facility and community births and among births in various birth weight categories. RESULTS: Neonatal mortality decreased to a greater extent in the intervention compared to the control clusters in the <5(th) percentile infants in Guatemala during the ACT Trial. ACS use for the <5(th) percentile infants in the intervention clusters was 49.1 % compared to 13.8 % in the control clusters. Many measures of the quality of obstetric and neonatal care improved to a greater extent in the intervention compared to the control clusters during the trial. Births in facilities and births weighing 1500 to 2500 g had the greatest reduction in neonatal mortality. CONCLUSIONS: The combination of improved care and greater ACS use may potentially account for the observed difference in neonatal mortality between the intervention and control clusters. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01084096 .