Placental Metabolism Is Linked to Prenatal Vitamin Supplement Use in the First Month of Pregnancy in the MARBLES Cohort

Mariana Parenti; Rebecca J Schmidt; Daniel J Tancredi; Meghan Miller; Irva Hertz-Picciotto; Cheryl K Walker; Carolyn M Slupsky

doi:10.1016/j.tjnut.2025.05.016

Placental Metabolism Is Linked to Prenatal Vitamin Supplement Use in the First Month of Pregnancy in the MARBLES Cohort

J Nutr. 2025 Jul;155(7):2185-2194. doi: 10.1016/j.tjnut.2025.05.016. Epub 2025 May 23.

Authors

Mariana Parenti¹, Rebecca J Schmidt², Daniel J Tancredi³, Meghan Miller⁴, Irva Hertz-Picciotto², Cheryl K Walker⁵, Carolyn M Slupsky⁶

Affiliations

¹ Department of Nutrition, University of California, Davis, CA, United States.
² Department of Public Health Sciences, University of California, Davis, CA, United States; MIND Institute, University of California, Davis, CA, United States.
³ Department of Pediatrics, School of Medicine, University of California, Davis, CA, United States.
⁴ MIND Institute, University of California, Davis, CA, United States; Department of Psychiatry & Behavioral Sciences, School of Medicine, University of California, Davis, CA, United States.
⁵ MIND Institute, University of California, Davis, CA, United States; Department of Obstetrics & Gynecology, School of Medicine, University of California, Davis, CA, United States.
⁶ Department of Nutrition, University of California, Davis, CA, United States; Department of Food Science and Technology, University of California, Davis, CA, United States. Electronic address: cslupsky@ucdavis.edu.

PMID: 40414302
DOI: 10.1016/j.tjnut.2025.05.016

Abstract

Background: The first month of pregnancy is a key time in early developmental programming. Prenatal vitamin/mineral supplement use during the first month of pregnancy (PNVmo1) was associated with reduced risk of autism spectrum disorder (ASD) in the Markers of Autism Risk in Babies, Learning Early Signs (MARBLES) cohort.

Objectives: We aimed to evaluate the associations between PNVmo1, the placental and umbilical cord serum metabolomes, and the child's later neurodevelopmental outcome in the MARBLES pregnancy cohort.

Methods: Placental (n = 78) and umbilical cord serum (n = 132) metabolomes were investigated using ¹H nuclear magnetic resonance spectroscopy. PNVmo1 was determined by self-report. At 36 mo of age, child neurodevelopmental outcomes were classified by MARBLES clinicians into 3 groups: typically developing (TD), ASD, or nontypically developing (Non-TD) but not ASD, which was dominated by developmental delays and/or elevated autism symptoms but not meeting ASD criteria.

Results: After adjustment for covariates, permutational multivariate analysis of variance revealed that PNVmo1 was significantly (P < 0.05) associated with the placental and umbilical cord serum metabolomes. In the placenta, higher concentrations of amino acids were observed in the PNVmo1 group (false discovery rate <0.1). After adjustment for PNVmo1 and other covariates, permutational multivariate analysis of variance revealed a significant association (P < 0.05) between the placental metabolome and Non-TD outcome status. No associations were observed in the analyses of umbilical cord serum metabolism or with ASD outcome. We tested for but did not find evidence that the placental metabolome explained the relationship between PNVmo1 and Non-TD outcome in an exploratory mediation analysis.

Conclusions: These findings suggest that the placental metabolome could be sensitive to nutrient supplementation during the earliest stages of pregnancy.

Keywords: metabolomics; neurodevelopment; placenta; prenatal supplementation; umbilical cord serum.

MeSH terms

Adult
Autism Spectrum Disorder* / prevention & control
Child, Preschool
Cohort Studies
Dietary Supplements*
Female
Fetal Blood / chemistry
Fetal Blood / metabolism
Humans
Infant
Male
Metabolome
Placenta* / metabolism
Pregnancy
Vitamins* / administration & dosage

Substances

Vitamins