Gestational vitamin D concentration and child cognitive development: A longitudinal cohort study in the ECHO Program

Melissa M Melough; Monica McGrath; Meredith Palmore; Brent R Collett; Jean M Kerver; Christine W Hockett; Rebecca J Schmidt; Rachel S Kelly; Kristen Lyall; Qi Zhao; Alison E Hipwell; Susan A Korrick; Diane Gilbert-Diamond; Scott T Weiss; Su H Chu; Hooman Mirzakhani; Jennifer M Porter; Sheela Sathyanarayana; for the ECHO Cohort Consortium

doi:10.1016/j.ajcnut.2025.06.017

Gestational vitamin D concentration and child cognitive development: A longitudinal cohort study in the ECHO Program

Am J Clin Nutr. 2025 Jun 23:S0002-9165(25)00339-9. doi: 10.1016/j.ajcnut.2025.06.017. Online ahead of print.

Authors

Melissa M Melough¹, Monica McGrath², Meredith Palmore², Brent R Collett³, Jean M Kerver⁴, Christine W Hockett⁵, Rebecca J Schmidt⁶, Rachel S Kelly⁷, Kristen Lyall⁸, Qi Zhao⁹, Alison E Hipwell¹⁰, Susan A Korrick¹¹, Diane Gilbert-Diamond¹², Scott T Weiss⁷, Su H Chu⁷, Hooman Mirzakhani⁷, Jennifer M Porter¹³, Sheela Sathyanarayana¹⁴; for the ECHO Cohort Consortium

Affiliations

¹ Department of Health Behavior and Nutrition Sciences, University of Delaware, Newark, DE. Electronic address: melough@udel.edu.
² Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
³ Center for Child Health, Behavior and Development, Seattle Children's Research Institute, Seattle, WA.
⁴ Department of Epidemiology and Biostatistics, College of Human Medicine, Michigan State University, East Lansing, MI.
⁵ Department of Pediatrics, University of South Dakota School of Medicine, Sioux Falls, SD; Avera Research Institute, Sioux Falls, SD.
⁶ Department of Public Health Sciences, School of Medicine, University of California at Davis, Davis, CA.
⁷ Channing Division of Network Medicine, Department of Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, MA.
⁸ AJ Drexel Autism Institute, Drexel University, Philadelphia, PA.
⁹ Department of Preventive Medicine, College of Medicine, University of Tennessee Health Science Center, Memphis, TN.
¹⁰ Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA.
¹¹ Channing Division of Network Medicine, Department of Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, MA; Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA.
¹² Departments of Epidemiology, Medicine and Pediatrics, Geisel School of Medicine at Dartmouth, Hanover, NH.
¹³ Department of Pediatrics, Norton Children's and University of Louisville School of Medicine, Louisville, KY.
¹⁴ Center for Child Health, Behavior and Development, Seattle Children's Research Institute, Seattle, WA; Departments of Pediatrics, Epidemiology, and Environmental and Occupational Health Sciences, University of Washington, Seattle, WA.

PMID: 40562362
DOI: 10.1016/j.ajcnut.2025.06.017

Abstract

Background: Low vitamin D levels are common - especially among those with darker pigmented skin - and are frequently observed during pregnancy. Given its important role in brain development, inadequate gestational vitamin D may impair child cognitive development.

Objective: We aimed to evaluate associations of gestational vitamin D concentrations with childhood cognitive scores, explore whether this relationship differs by self-reported race, and examine sensitive exposure windows within pregnancy.

Methods: This prospective cohort study included 912 mother-child dyads (37.3% Black, 52.3% White) from the Environmental influences on Child Health Outcomes program. 25-hydroxyvitamin D [25(OH)D] concentrations were measured in prenatal or cord blood collected between 4-42 weeks gestation (median: 23). Children's cognition was assessed at ages 7-12 years using the NIH Toolbox Cognition Battery. Relationships of 25(OH)D and cognitive scores were examined using mixed effects linear models adjusted for confounders. Potential sensitive periods were explored by estimating population 25(OH)D patterns across gestation for varying levels of the cognitive outcomes.

Results: Mean gestational 25(OH)D was 23.8 ng/mL (SD: 10.0). Each 10 ng/mL increase was associated with greater overall (β = 1.11, 95% CI: 0.08, 2.14) and fluid cognition scores (1.21 (0.07, 2.34)), but not crystallized cognition. Although these associations were not significantly modified by self-reported race, associations appeared stronger in children of Black mothers (2.99 (0.82, 5.16)) than non-Black mothers (0.43 (-0.93, 1.78)) for fluid cognition. Early pregnancy may be a critical exposure period, evidenced by the greatest divergence in the pattern of 25(OH)D during this period between the mothers of children in the 90^th versus 10^th percentiles of cognitive outcomes.

Conclusions: Gestational 25(OH)D concentrations were positively associated with cognitive scores, especially in children of Black mothers. Given higher deficiency risk among Black women, vitamin D repletion prior to or in early pregnancy may be an important strategy for reducing racial disparities in child neurodevelopment.

Keywords: childhood cognitive development; fluid cognition; prenatal nutrition; racial health disparities; vitamin D.