Neonatal and Maternal Outcomes of Lower Versus Standard Doses of Antenatal Corticosteroids for Women at Risk of Preterm Delivery: A Systematic Review of Randomized Controlled Trials

OBJECTIVE: Our objective was to systematically review randomized and quasi-randomized trials on the neonatal and maternal effects of lower doses of antenatal corticosteroids (<24 mg of betamethasone or dexamethasone) compared with standard double doses of antenatal corticosteroids (24 mg of betamethasone or dexamethasone) administered to women at risk of preterm delivery. DATA SOURCES: Medline, Embase, CINAHL, Web of Science, Cochrane CENTRAL, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform, and the Australia New Zealand Clinical Trials Registry were searched from inception to December 8, 2019. STUDY SELECTION: A total of 2401 titles, abstracts, and protocols were independently screened by two reviewers, and subsequently 113 full-text articles were reviewed. DATA EXTRACTION: Our primary outcomes were perinatal death and severe respiratory distress syndrome. DATA SYNTHESIS: We identified one large in-progress trial comparing 11.4 mg versus 22.8 mg betamethasone and one published randomized controlled trial that compared a lower dose of dexamethasone (16 mg) to a standard dose of betamethasone (24 mg). The only relevant data from the published trial suggests minor changes in fetal heart rate variability between baseline and 24- to 48-hour follow-up between the two groups. Data for other outcomes had to be excluded due to the administration of weekly courses of antenatal corticosteroids. CONCLUSIONS: Randomized trial data comparing lower doses of antenatal corticosteroids to standard double doses are scarce. Given concerns regarding current antenatal corticosteroids dosing patterns, there is an urgent need for randomized controlled trials examining lower versus standard double doses of antenatal corticosteroids.