The Role of Selenium During Pregnancy in Maternal and Neonatal Thyroid Function: A Systematic Review

Background: Selenium (Se) is a fundamental trace element integral to thyroid hormone metabolism, antioxidant defense, and immune regulation. Pregnancy places a profound physiological strain on the maternal thyroid axis, increasing hormone demands. While current guidelines advise against routine Se supplementation during pregnancy due to insufficient evidence, the specific impact of maternal Se status on maternal and neonatal thyroid outcomes remains poorly characterized. Objectives: This systematic review aims to synthesize existing evidence regarding the role of Se exposure and supplementation on maternal thyroid function during pregnancy and its subsequent effects on neonatal thyroid health. Methods: Original studies evaluating maternal Se status via supplementation or quantification in biological matrices, in relation to maternal or neonatal thyroid outcomes up to one month post-birth were eligible. Non-English and animal studies were excluded. PubMed, Embase, and Cochrane Library were searched through December 2025. Risk of bias was assessed using Cochrane RoB 2 and NIH/NHLBI tool. The certainty of evidence was evaluated using the GRADE approach. Results: From 2743 unique identified records, 33 studies (29 assessing maternal outcomes, seven assessing neonatal outcomes) were included, of which four were randomized controlled trials (RCTs). Regarding maternal thyroid autoimmunity, RCTs indicate an inverse effect of Se supplementation on antibody trajectories; all groups showed a natural pregnancy-related decline in TPOAb, with high-dose (200 µg/day) L-selenomethionine significantly attenuating the postpartum antibody rebound compared to placebo. Available RCTs did not demonstrate prevention of thyroid dysfunction during pregnancy, whereas some trials suggested reduced postpartum thyroid autoimmunity and thyroid disease, including reduced permanent hypothyroidism in one study. No consistent linear associations were found between maternal Se levels and TSH, FT4, or FT3. Evidence regarding thyroid structure and stress markers was inconsistent, though low Se status was associated with elevated thyroglobulin. Available evidence has not demonstrated a consistent association between maternal or umbilical cord Se levels and neonatal thyroid hormone output. Additionally, the analysis revealed that urinary Se is less suitable than circulating or tissue Se for assessing long-term systemic nutritional status, especially when evaluating associations with thyroid function during pregnancy. Methodological quality varied significantly; while full-text RCTs demonstrated high overall quality, the observational literature was consistently suboptimal, primarily due to a systematic failure to achieve adequate statistical adjustment for critical confounders like iodine. The certainty of evidence ranged from very low to moderate, universally downgraded for risk of bias. Conclusions: While currently available evidence does not support that Se supplementation alters gestational thyroid hormone levels or prevents antenatal thyroid dysfunction, indications for a possible protective effect against postpartum autoimmunity and thyroid disease are noted and further validation is required. Available evidence points against an association of maternal Se status and neonatal thyroid function. Future high-quality prospective studies adequately controlling for confounders, among which iodine status, are warranted.