Association between maternal thyroid function and adverse outcomes of pregnant women and offspring: evidence from an umbrella review

OBJECTIVE: To synthesize current evidence on the associations between maternal thyroid dysfunction and adverse outcomes in pregnant women and their offspring. METHODS: A systematic search of PubMed, Embase, Web of Science, and the Cochrane Database was conducted through September 2024. Systematic reviews and meta-analyses examining maternal thyroid function (i.e., subclinical/overt hypo- and hyperthyroidism, thyroid autoimmunity) and outcomes were included. The methodological quality and certainty of evidence were assessed using A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2) and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: A total of 25 meta-analyses covering 58 maternal and 90 offspring outcomes were included. Maternal thyroid dysfunction was significantly associated with increased risks of gestational diabetes, pre-eclampsia, miscarriage, preterm rupture of membranes, postpartum hemorrhage, and anemia. Thyroid autoimmunity was linked to reduced embryo implantation and live birth rates following assist reproduction technology. Offspring exposed to maternal thyroid dysfunction showed higher risks of preterm birth, low Apgar scores, intrauterine growth retardation (IUGR), macrosomia, autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), epilepsy, intellectual disability, and altered birth weight. Among included meta-analyses, 8.1% exhibited high heterogeneity, while 36.3% did not report heterogeneity statistics. No significant publication bias was detected. AMSTAR 2 assessments indicated moderate to high methodological quality, whereas GRADE ratings revealed low or very low certainty for most outcomes. CONCLUSION: This umbrella review indicates that maternal thyroid dysfunction is associated with a broad range of adverse maternal and offspring outcomes. However, the overall certainty of evidence remains low. High-quality prospective studies with standardized assessments are needed to confirm these associations and inform clinical practice.