Nutrients, Vol. 18, Pages 1474: Maternal Iodine Status During Pregnancy and Child Neurodevelopment: A Systematic Review and Dose–Response Meta-Analysis of Prospective Cohort Studies
Nutrients doi: 10.3390/nu18091474
Authors:
Qingshan Luo
Zhou Wang
Jie Jiang
Xianru Luo
Tingxuan Feng
Chao Wang
Shasha Ruan
Xiaoheng Li
Background: Iodine deficiency during pregnancy remains a leading cause of preventable neurodevelopmental impairment worldwide, yet quantitative characterization of the dose–response relationship between maternal iodine status and child neurodevelopment is lacking. Methods: A systematic search of PubMed, Embase, the Cochrane Library, and Web of Science was conducted for prospective cohort studies published up to February 2026 reporting associations between maternal iodine status and child neurodevelopmental outcomes across at least three exposure categories. All continuous effect estimates were converted to standardized mean differences (Hedges’ g) to permit pooling across heterogeneous assessment instruments, and meta-analyses were stratified by neurodevelopmental domain (cognitive, language, motor, behavior, academic). A two-stage dose–response meta-analysis was used to characterize non-linearity. Risk of bias was evaluated using the Newcastle–Ottawa Scale (NOS). Results: Ten prospective cohort publications corresponding to eight independent cohorts were included. After converting all continuous effect estimates to standardized mean differences (Hedges’ g) and consolidating the three overlapping MoBa publications into a single cohort, the pooled analysis revealed a significant negative association between suboptimal maternal iodine status and child neurodevelopmental performance (Hedges’ g = −0.13, 95% CI: −0.20 to −0.06, p < 0.001; I2 = 95.2%). Domain-stratified analysis identified cognitive outcomes as most consistently affected (g = −0.22, 95% CI: −0.30 to −0.14; I2 = 37.5%), followed by motor (g = −0.17; I2 = 0%) and language outcomes (g = −0.16; I2 = 92.5%), with between-domain heterogeneity explaining 38.6% of the total variance (p = 0.012). Binary outcome analysis confirmed increased odds of adverse neurodevelopmental outcomes (OR = 1.19, 95% CI: 1.03 to 1.39, p = 0.026). Subgroup analysis by iodine exposure indicator showed directionally consistent negative effects across dietary intake (g = −0.11), UIC (g = −0.11) and UI/Cr (g = −0.28), with no significant between-subgroup difference (p = 0.237). Exploratory dose–response modeling on the Hedges’ g scale suggested that neurodevelopmental performance in the fitted curves approached its maximum within a mid-range of dietary iodine intake (approximately 150–300 µg/d); however, the quadratic non-linearity terms did not reach statistical significance after cohort consolidation (p = 0.612 for dietary intake; p = 0.436 for UI/Cr), and these findings should therefore be interpreted as exploratory. Conclusions: Suboptimal maternal iodine status during pregnancy was associated with modest decrements in child neurodevelopmental performance, with exploratory dose–response analyses suggesting that the fitted curves approached their maximum within a mid-range of dietary iodine intake. Although statistical evidence for quadratic non-linearity was attenuated after consolidating overlapping cohorts, the directional pattern across indicators remained consistent with an inverted U-shaped relationship, supporting maintenance of adequate but not excessive iodine nutrition during pregnancy.
Background: Iodine deficiency during pregnancy remains a leading cause of preventable neurodevelopmental impairment worldwide, yet quantitative characterization of the dose–response relationship between maternal iodine status and child neurodevelopment is lacking. Methods: A systematic search of PubMed, Embase, the Cochrane Library, and Web of Science was conducted for prospective cohort studies published up to February 2026 reporting associations between maternal iodine status and child neurodevelopmental outcomes across at least three exposure categories. All continuous effect estimates were converted to standardized mean differences (Hedges’ g) to permit pooling across heterogeneous assessment instruments, and meta-analyses were stratified by neurodevelopmental domain (cognitive, language, motor, behavior, academic). A two-stage dose–response meta-analysis was used to characterize non-linearity. Risk of bias was evaluated using the Newcastle–Ottawa Scale (NOS). Results: Ten prospective cohort publications corresponding to eight independent cohorts were included. After converting all continuous effect estimates to standardized mean differences (Hedges’ g) and consolidating the three overlapping MoBa publications into a single cohort, the pooled analysis revealed a significant negative association between suboptimal maternal iodine status and child neurodevelopmental performance (Hedges’ g = −0.13, 95% CI: −0.20 to −0.06, p < 0.001; I2 = 95.2%). Domain-stratified analysis identified cognitive outcomes as most consistently affected (g = −0.22, 95% CI: −0.30 to −0.14; I2 = 37.5%), followed by motor (g = −0.17; I2 = 0%) and language outcomes (g = −0.16; I2 = 92.5%), with between-domain heterogeneity explaining 38.6% of the total variance (p = 0.012). Binary outcome analysis confirmed increased odds of adverse neurodevelopmental outcomes (OR = 1.19, 95% CI: 1.03 to 1.39, p = 0.026). Subgroup analysis by iodine exposure indicator showed directionally consistent negative effects across dietary intake (g = −0.11), UIC (g = −0.11) and UI/Cr (g = −0.28), with no significant between-subgroup difference (p = 0.237). Exploratory dose–response modeling on the Hedges’ g scale suggested that neurodevelopmental performance in the fitted curves approached its maximum within a mid-range of dietary iodine intake (approximately 150–300 µg/d); however, the quadratic non-linearity terms did not reach statistical significance after cohort consolidation (p = 0.612 for dietary intake; p = 0.436 for UI/Cr), and these findings should therefore be interpreted as exploratory. Conclusions: Suboptimal maternal iodine status during pregnancy was associated with modest decrements in child neurodevelopmental performance, with exploratory dose–response analyses suggesting that the fitted curves approached their maximum within a mid-range of dietary iodine intake. Although statistical evidence for quadratic non-linearity was attenuated after consolidating overlapping cohorts, the directional pattern across indicators remained consistent with an inverted U-shaped relationship, supporting maintenance of adequate but not excessive iodine nutrition during pregnancy. Read More