Maternal thyroid disorders and risk of fetal CHD: a systematic review and meta-analysis

AIM: To evaluate whether thyroid disorders during pregnancy correlate with the risk of CHD. METHODS: Literature search was conducted across multiple databases, including PubMed/MedLine, Scopus, Cochrane Library, and grey literature repositories. Meta-analysis using a random-effect model was conducted. Newcastle-Ottawa Scale was used to determine the quality of studies. Grading of Recommendations, Assessment, Development, and Evaluations was used to evaluate the confidence in cumulative evidence. The study protocol was registered with the International Prospective Register of Systematic Reviews (CRD42024545867). RESULTS: A total of eight studies were included in the analysis. Maternal thyroid disorders were associated with the risk of CHDs (odd ratio 1.30, 95% confidence interval 1.07 to 1.57, P = 0.008). When categorised to specific subtypes, pooled studies reporting maternal hypothyroidism showed higher risk of developing CHD, even though it did not reach statistical significance (odds ratio 3.02, 95% confidence interval 0.57 to 16.05, P = 0.20). Exposure to maternal use of anti-thyroid drugs (odds ratio 4.44, 95% confidence interval 2.25 to 8.77, P < 0.0001) and levothyroxine (odds ratio 1.22, 95% confidence interval 1.08 to 1.37, P = 0.001) appeared to significantly increase the risk of CHD. All studies were judged to have good quality. The evidence generated from this study ranges from very low-to-low. CONCLUSION: Maternal thyroid disorders and exposure to thyroid-related medications appear to be associated with an elevated risk of CHD in fetuses.