Projects Details

Study Period: February 2024 to July 2025

Donor: Burnet Institute, Melbourn, Australia

Background and Rationale:

Globally, an estimated 13.4 million babies are born preterm each year. Preterm birth complications are the leading cause of death in neonates and children under 5 years of age. Compared to term born babies, preterm-born babies are more likely to develop a range of short and long-term morbidities, including respiratory complications, neurodevelopmental disorders, behavioral problems, and learning difficulties. Antenatal corticosteroids (ACS) are a critical intervention for mitigating the short-term effects of preterm birth. ACS administered to women at risk of preterm birth prior to 34 weeks’ gestation significantly reduces the risk of short-term neonatal mortality and morbidities. However, current knowledge regarding the long-term health effects of ACS is limited and somewhat conflicting. Few trials and some observational studies, nearly all from high-income countries, suggest ACS for preterm birth might prevent neurodevelopmental impairment up to 12 years of age. However, some observational studies report higher rates of adverse neurodevelopmental conditions in early childhood, when babies were exposed to ACS and born after 34 weeks.

There has been no long-term follow-up of children in low and low-middle income countries whose mothers were exposed to ACS or placebo during randomized trials. International expert bodies, including WHO, have identified the need for long-term follow-up studies to evaluate child health outcomes as a high research priority. Most early preterm efficacy trials of ACS were conducted decades ago, and the opportunity for evaluating childhood outcomes has been lost. However, the WHO ACTION-I trial was a multi-country, placebo-controlled, randomized trial that evaluated the efficacy and safety of antenatal dexamethasone in women at risk of imminent preterm birth between 26 weeks to <34 weeks of gestation. The study recruited 2,852 women in 29 hospitals in Bangladesh, India, Kenya, Nigeria and Pakistan, between December 2017 to November 2019. The trial collected outcome data until 28 days postnatal and demonstrated that antenatal dexamethasone reduced neonatal death by 28 days of life. Thus, a pilot study might inform the decision to conduct future, larger follow-up studies in the ACTION-I population.

Objective:
The general objective of this pilot study is to assess participant follow-up and to provide data to estimate the parameters required to design a definitive follow-up cohort study. The specific objectives are:

• To assess how many ACTION-I participants can be contacted and are willing to participate in a follow-up study in Sylhet, Bangladesh.
• To determine the prevalence of long-term child health outcomes of interest, to inform development of a future, definitive follow-up cohort study.
• To evaluate the effects of ACS exposure prior to 34 weeks’ gestation compared to placebo on neurodevelopmental, survival, growth, and health-related quality of life at 5 years’ corrected age in participating children in Sylhet, Bangladesh.
• To collect and synthesise data, from which the sample size of a definitive follow-up cohort study can be estimated.

Study design

Pilot follow-up cohort study of the WHO ACTION-I participants in Bangladesh.

Children whose mothers were enrolled in the ACTION-I trial in 3 hospitals in Sylhet, Bangladesh.

Sample size

In Sylhet, there were 259 live births among 259 randomized women, of which 181 infants survived to 28 completed days after birth. As this is a pilot study with a fixed number of potentially eligible participants, we aim to identify and re-enrol as many as possible of the 181 children.

Potential Impact

This pilot study will inform the decision to conduct future, larger follow-up studies in the ACTION-I population. It will also generate critical new data on the long-term effects of exposure to dexamethasone during pregnancy.