Iodine, Selenium, and Vitamin D in Pregnancy: A Systematic Review of Their Integrated Effects on Thyroid and Glucose Metabolism, Maternal–Fetal Outcomes, and Risk-Tailored Supplementation Strategies

Pregnancy is characterized by profound endocrine adaptation, in which micronutrient availability plays a central but often compartmentalized role. Iodine, selenium, and Vitamin D are individually recognized as essential for thyroid function, glucose regulation, and immune balance; however, theirinterconnected actions within the maternal thyroid–glucose axis have not been systematically integrated. The objective of this study was to synthesize and critically appraise current evidence on how iodine, selenium, and Vitamin D – individually and in combination – influence maternal thyroid and glucose metabolism during pregnancy, maternal–fetal outcomes, and risk-informed supplementation strategies. This Preferred Reporting Items for Systematic Reviews and Meta-analyses 2020–guided systematic integrative review employed a comprehensive search of PubMed, Scopus, Embase, and Web of Science from inception to March 2025. Observational studies, randomized trials, systematic reviews, and mechanistic investigations examining at least one of the three micronutrients in relation to thyroid or glucose outcomes in pregnancy were eligible. Study quality was assessed using the Newcastle–Ottawa scale, A Measurement Tool to Assess Systematic Reviews 2, Risk of Bias in Systematic Reviews, and Animal Research: reporting of in vivo experiments guidelines. Given substantial heterogeneity in study designs and outcome measures, findings were synthesized using a structured narrative and mechanistic integration approach without quantitative meta-analysis. From 2432 records identified, 40 studies encompassing more than 25,000 pregnancies met the inclusion criteria. Across diverse settings, iodine imbalance – both deficiency and excess – was associated with altered thyroid hormone dynamics and gestational metabolic disturbance. Selenium adequacy supported deiodinase activity and antioxidant defense, consistently mitigating thyroid autoimmunity. Vitamin D status was repeatedly linked to insulin sensitivity and immunomodulatory pathways, partly through Vitamin D receptor-mediated signaling. Evidence converged on a pattern whereby concurrent adequacy across these micronutrients aligned with maternal euthyroidism, more stable glucose regulation, and favorable fetal metabolic trajectories. Risk-tailored, biomarker-guided supplementation emerged as a recurrent clinical theme. Rather than acting in isolation, iodine, selenium, and Vitamin D appear to function as an interdependent micronutrient network shaping endocrine–metabolic adaptation in pregnancy. This synthesis supports a shift toward integrated, precision-based micronutrient assessment to optimize maternal and fetal endocrine health.