Abstract:
Background: Antenatal corticosteroids are commonly used to reduce neonatal mortality, but most research to date
has been in high-resource settings and few studies have evaluated its impact on stillbirth. In the Antenatal Corticosteroids
Trial (ACT), a multi-country trial to assess impact of a multi-faceted intervention including antenatal corticosteroids to
reduce neonatal mortality associated with preterm birth, we found an overall increase in 28-day neonatal mortality and
stillbirth associated with the intervention.
Methods: The ACT was a cluster-randomized trial conducted in 102 clusters across 7 research sites in 6 countries (India
[2 sites], Pakistan, Zambia, Kenya, Guatemala and Argentina), comparing an intervention to train birth attendants at all
levels of the health system to identify women at risk of preterm birth, administer corticosteroids and refer women at risk.
Because of inadequate gestational age dating, the <5 th percentile birth weight was used as a proxy for preterm birth. A
pre-specified secondary outcome of the trial was stillbirth.
Results: After adjusting for the pre-trial imbalance in stillbirth rates, the ACT intervention was associated with a
non-significant increased risk of stillbirth (aRR 1.08, 95 % CI, 0.99–1.17, p–0.073). Additionally, the stillbirth rate was
higher in the term births (1.20 95 % CI 1.06–1.37, 0.004) and among those with signs of maceration (RR 1.18 (1.04–1.35),
p = 0.013) in the intervention vs. control clusters. Differences in obstetric care favored the control clusters and maternal
infection was likely more common in the intervention clusters.
Conclusions: In this pragmatic trial, limited data were available to identify the causes of the increase in stillbirths in
the intervention clusters. A higher rate of stillbirth in the intervention clusters prior to the trial, differences in obstetric
care and an increase in maternal infection are potential explanations for the observed increase in stillbirths in the
intervention clusters during the trial.
