Effects of antenatal corticosteroid therapy in animal models of fetal growth restriction: a systematic review and meta-analysis

Abstract

Background: Antenatal corticosteroids (CCS) reduce the risks of neonatal morbidity and mortality following spontaneous preterm birth. It is however debated whether effects of antenatal CCS hold for pregnancies complicated by fetal growth restriction (FGR) at risk for preterm birth. This study aimed to summarize effects of antenatal CCS in animal models of FGR by performing a systematic review and meta-analysis. Methods: The protocol for this systematic review was registered prospectively at PROSPERO (CRD42022318861). A systematic search was performed in PubMed and Embase from inception to April 5th 2023. Animal studies reporting on effects of antenatal CCS compared to placebo or non-treatment in FGR and appropriately grown offspring were included. Primary outcomes were fetal or neonatal mortality, organ developmental parameters (i.e. cardiac, brain, lung), glucose metabolism and fetal weight. Meta-analysis was performed using a random effects model. The quality of the included studies was assessed with the SYRCLE’s risk of bias tool. Results: The literature search yielded 10,386 unique hits. Eight studies were included in the systematic review. In terms of therapeutic effects, lung development and surfactant production were significantly accelerated by antenatal CCS in both FGR and non-FGR. Regarding drug safety, effects of antenatal CCS on fetal weight and brain development were similar for FGR and appropriately grown offspring except for one marker (4-hydroxynonenal) of brain injury, which was more pronounced in FGR offspring. Risk of bias appeared to be unclear for most studies across all domains. Conclusion: This systematic review illustrates that therapeutic and side effects of antenatal CCS are mainly similar in animal models of FGR as in non-FGR. These findings could therefore support the current recommendation of international guidelines to administer CCS to patients diagnosed with FGR at risk for preterm birth.