The risk of congenital heart defects associated with corticosteroids use during the first trimester of pregnancy: a systematic review and meta-analysis

Background Prior studies have suggested that maternal corticosteroids exposure during the first trimester may be associated with an increased risk of congenital heart defects (CHDs) in offspring. However, the findings are discrepant. Moreover, a complete overview of the existing data in the literature is lacking. Our objective was to identify whether such an association exists. Methods and results Relevant studies were identified via searching PubMed, Web of Science, Embase, Chinese databases, and the Cochrane Library databases (search date July 15, 2021) and through checking the reference lists of retrieved articles. The overall pooled risk estimate was calculated using random-effect models. We used the GRADE approach to assess the overall strength of the evidence and the Newcastle-Ottawa Scale to assess study quality. Subgroup analyses were performed to evaluate the association within studies or samples with different characteristics. Sensitivity analyses were performed to assess the robustness of the results. Nine studies involving 1,901,599 participants were included in the final analysis. All studies were evaluated as high quality. In the meta-analysis, no statistically significant association was found between maternal corticosteroids exposure during the first trimester and increased risk of CHDs in offspring (OR = 1.06, 95% CI: 1.00-1.13, P = 0.06, low certainty of evidence). Additionally, we also did not find significant differences in subgroup analyses of corticosteroids exposure patterns, including oral corticosteroids exposure (OR = 1.23, 95% CI: 1.00-1.52), ointment corticosteroids exposure (OR = 1.03, 95% CI: 0.90-1.19), inhalation corticosteroids exposure (OR = 1.06, 95% CI: 0.96-1.17), topical corticosteroids or systemic corticosteroids exposure (OR = 0.95, 95% CI: 0.79-1.15), and nasal corticosteroids exposure (OR = 1.12, 95% CI: 0.80-1.57). Conclusions Our study does not find an association between maternal corticosteroids exposure during the first trimester and offspring CHDs. However, the existing evidence is of low quality; thus, long-term prospective cohort studies are warranted to verify the safety of corticosteroids in this population, with adequate adjustments for confounding variables.

Automated summary

This study did not find an association between maternal corticosteroids exposure during the first trimester and offspring congenital heart defects. However, the existing evidence is of low quality, and further research is needed to confirm these findings.