Effects of antenatal corticosteroids in twin neonates with late preterm birth (ACTWIN [Antenatal Corticosteroids in TWIN late preterm neonates] trial): study protocol for a randomized controlled trial

Abstract

Background Antenatal corticosteroids have been proven to prevent adverse outcomes including respiratory morbidities in preterm neonates before 34 weeks of gestation. Recently, it has been suggested that antenatal corticosteroids may also be effective in singleton late preterm pregnancies, and guidelines recommend the use of corticosteroids in singleton pregnant women who are at risk for late preterm birth. On the contrary, there is a paucity of information regarding the effectiveness of corticosteroids in twin neonates with late preterm birth. This study aims to determine the effectiveness of antenatal corticosteroids in late preterm twin neonates. Methods In this multicentre randomized controlled trial, women who are at risk for late preterm birth will be enrolled at 34 0/7 to 36 5/7 weeks of gestation. The participants will be randomly assigned to receive antenatal corticosteroids (betamethasone 12 mg, 3 mL intramuscularly [IM]) or placebo (normal saline 3 mL IM). The perinatal outcomes will be compared between the two groups of cases. The primary outcome is severe respiratory complications (the use of continuous positive airway pressure or high-flow nasal cannula for at least 12 h, supplemental oxygen administration with a fraction of oxygen 0.3 or more for at least 24 h, mechanical ventilation, or extracorporeal membranes oxygenation) or perinatal death within the first 72 h of delivery. The secondary outcomes are neonatal mortality and/or other neonatal morbidities. Discussion This study will be the first randomized controlled trial that evaluates the effectiveness of antenatal corticosteroids in late preterm twin neonates. Trial registration NCT03547791 (ClinicalTrials.gov), first submitted date: March 29, 2018, first posted date: June 6, 2018 (retrospectively registered).

Association of antenatal corticosteroids with morbidity and mortality among preterm multiple gestations: meta-analysis of observational studies

“…Higher levels of evidence on the efficacy of ACS among preterm twins are of great need. 39 Second, the high heterogeneity may weaken the validity of current results. Even though subgroup analyses were performed, the high heterogeneity remained in some subgroups, suggesting the presence of unexplained heterogeneity.…”

“…No evidence of randomised trials on the efficacy of ACS in multiple pregnancies is currently available. We retrieved only one RCT protocol by Hong et al, 39 despite no restriction on study design in the literature search. Among these observational studies, the quality of evidence for outcomes of interest was categorised as very low or low, mainly due to huge inconsistency across studies, according to the GRADE criteria.…”

Controversies in the management of twin pregnancy

“…Data on the benefit of corticosteroids in twins at this later gestational age, however, are scarce, and the use of corticosteroids at or near term therefore remains under debate. The Effects of Antenatal Corticosteroids in Twin Neonates with Late Preterm Birth (ACTWIN) trial is an RCT that is currently underway to compare the benefit of corticosteroids vs placebo in twins with late preterm labor at 34 + 0 to 36 + 5 weeks (https://www .clinicaltrials.gov/ct2/show/NCT03547791) 134 .…”

Society for Maternal-Fetal Medicine Consult Series #58: Use of antenatal corticosteroids for individuals at risk for late preterm delivery

“…Ongoing studies in this population are needed. 30 Until that time, for patients with late preterm twins at risk of preterm delivery, shared decision-making is suggested regarding corticosteroid administration for the improvement of fetal lung maturity.…”