**Background:** Iodine is essential for thyroid hormone synthesis, and requirements increase during pregnancy due to enhanced maternal hormone production, fetal transfer, and renal losses. Severe iodine deficiency clearly causes adverse outcomes including cretinism and growth retardation. However, the consequences of mild-to-moderate iodine deficiency (median UIC 50–99 µg/L and 20–49 µg/L, respectively) remain controversial, and the benefits of routine iodine supplementation in these settings are debated. This narrative review systematically evaluated evidence from meta-analyses published between 1969 and 2022 to clarify the relationship between iodine status and pregnancy/neonatal outcomes and the efficacy of supplementation trials.
**Methods:** A comprehensive search of Medline, Embase, and Cochrane databases was performed using terms for iodine, pregnancy, and meta-analysis. Publications from 1969 to 2022 were included. Only studies containing meta-analytic data were selected. Of nine initially identified meta-analyses, two were excluded (one lacked pregnancy-specific data; one addressed iodine-rich contrast media), leaving seven for final analysis. Four meta-analyses examined the relationship between iodine status and maternal/neonatal outcomes, and three evaluated intervention trials of iodine supplementation.
**Key Results — Observational Meta-Analyses:** (1) Nazeri et al. (2016): No correlation between maternal UIC and neonatal heel blood TSH, but cord blood TSH was significantly higher in iodine-deficient mothers (UIC <150 µg/L) vs. adequate mothers, suggesting cord blood TSH is a more sensitive marker. (2) Levie et al. (2019): A non-linear (U-shaped) association was found between maternal urinary iodine/creatinine ratio and offspring verbal IQ (assessed at median 1.5–8.6 years), with positive associations only when iodine was measured before 14 weeks gestation. No association was found with non-verbal IQ. (3) Nazeri et al. (2020): No significant association between maternal UIC and birth weight, length, or head circumference. (4) Wan et al.: In Chinese studies, excessive iodine (UIC ≥500 µg/L) was associated with higher rates of TgAb and TPOAb positivity and higher maternal TSH compared to UIC <500 µg/L.
**Key Results — Intervention Trial Meta-Analyses:** (1) Harding et al. (2017, Cochrane review, 11 trials, >2,700 women): Iodine supplementation reduced postpartum hyperthyroidism by 68% (low-quality evidence) but increased digestive intolerance 15-fold (single trial, very low-quality). No significant differences were found for maternal hypothyroidism, preterm birth, TPOAb elevation, perinatal mortality, low birthweight, or neonatal thyroid dysfunction. A non-significant 34% reduction in perinatal mortality was observed, driven by a single trial in a severely deficient area. (2) Dineva et al. (2 RCTs, 200–225 µg/day from first trimester): Supplemented women had lower TSH in second and third trimesters and lower FT4 in the third trimester. No effect was found on child cognitive, language, or motor Bayley scores at 1.5–2 years. (3) Nazeri et al. (5 RCTs): No differences in neonatal weight, length, head circumference, or cognitive/language/motor development in the first 2 years.
**Clinical Implications:** The review identifies a striking disconnect between observational data (suggesting a U-shaped relationship between iodine status and outcomes) and intervention trial data (showing no clear benefit of supplementation in mild-to-moderate deficiency). Key methodological issues include: lack of standardized iodine status definitions for pregnancy; high within-person UIC variability; pooling of studies across iodine-sufficient and deficient areas (dilution effect); late initiation of supplementation in trials (most starting after first trimester); short follow-up for neurodevelopmental outcomes; and the possibility that mild deficiency effects are too subtle for current tools. The authors note that the U-shaped association implies both low and high iodine may be harmful. Despite inconclusive meta-analytic evidence, current ATA guidelines recommend 150 µg/day iodine supplementation starting optimally 3 months before conception in regions with mild-to-moderate deficiency. The authors advocate for future high-quality RCTs with standardized iodine assessment, pre-conception supplementation initiation, long-term neurodevelopmental follow-up beyond age 2, and adjustment for confounders.