Perinatal outcomes following periconceptual steroid exposure: a population-wide cohort study.

ImportanceGlucocorticoid steroids are increasingly prescribed during the periconceptual period with the hypothesis that they reduce intrauterine inflammation and improve pregnancy rates. There is no robust evidence to support this practice, and the potential harm has not been well characterised. ObjectiveTo examine the risk of adverse perinatal outcomes associated with non-medically indicated glucocorticoid steroid use during the periconceptual period. DesignPopulation-wide linked retrospective cohort study. SettingVictoria, Australia. ParticipantsAfter excluding women with medical indications for steroid use (autoimmune disease, chronic asthma and previous organ transplant), our total cohort included 805,353 births between 2009 and 2021. ExposurePrescriptions of glucocorticoid steroids dispensed during the periconceptual period (12 weeks prior to conception - end of first trimester). Main Outcome(s) and Measure(s)Four primary outcomes were examined - spontaneous preterm birth before 37 completed weeks gestation, small for gestational age (<10th birthweight centile), major congenital abnormality and perinatal mortality. A doubly robust inverse probability weighted regression adjustment model was used to estimate the association between glucocorticoid steroid exposure and outcomes and presented as adjusted relative risks (aRR) with corresponding 95% confidence intervals (95% CI). ResultsThere were 12,301 (1.5%) pregnancies exposed to glucocorticoid steroids during the periconceptual period and 793,052 unexposed. Among the steroid-exposed cohort, major congenital abnormalities occurred in 4.5% of pregnancies, compared with 3.5% among those unexposed to steroids. This resulted in a 23% increased risk of major congenital abnormality (aRR 1.23, 95%CI 1.13-1.34). There were no significant associations between steroid exposure and spontaneous preterm birth (2.4 vs 2.5%; aRR 1.05, 95%CI 0.93-1.19), small for gestational age neonates (9.4 vs 9.3%; aRR 1.02, 95%CI 0.97-1.07) or perinatal mortality (0.5 vs 0.7%; aRR 1.05, 95%CI 0.87-1.26). Conclusions and RelevanceIn our cohort, periconceptual steroid exposure was associated with an increased risk of major congenital abnormality. In the absence of clear clinical indications, avoiding the prescription of periconceptual steroids is critically important. KEY POINTSO_ST_ABSQuestionC_ST_ABSWhat are the risks of adverse perinatal outcomes among patients prescribed glucocorticoid steroids during the periconceptual period? FindingsPericonceptual steroid use is associated with an increased risk of major congenital abnormality. MeaningIn the absence of an indication, periconceptual steroid use does not have clear evidence of benefit, there is now also evidence of significant harm and this practice should not be recommended.