Maternal intake of folate during pregnancy and risk of cerebral palsy in the MOBAND-CP cohort

Jonathan Groot, Tanja G Petersen, Pål Suren, Anne Lise Brantsæter, Peter Uldall, Torben Martinussen, Charlotta Granström, Sjurdur F Olsen, Allen J Wilcox, Katrine Strandberg-Larsen

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Abstract

BACKGROUND: Folate prevents neural tube defects and may play a role in some neurodevelopmental disorders.

OBJECTIVE(S): To investigate whether higher intakes of periconceptional or midpregnancy folate as recommended were associated with a reduced risk of offspring cerebral palsy (CP).

METHODS: We included participants from the Nordic collaboration cohort consisting of mother-child dyads in the Danish National Birth Cohort and the Norwegian Mother, Father and Child Cohort Study (MOBAND-CP). A total of 190 989 live-born children surviving the first year of life were included. Missing covariate data were multiply imputed. Our exposures were defined as any or no folic acid supplementation in gestational weeks (GWs) -4 to 8 (periconceptional), GWs 9 to 12, and -4 to 12, and supplemental, dietary, and total folate during midpregnancy (GWs 22 to 25). CP overall and the unilateral and bilateral spastic subtypes, as well as CP with low or moderate/high gross motor function impairment were our outcomes of interest.

RESULTS: Periconceptional folic acid supplementation was not associated with CP (adjusted odds ratio (aOR) 1.02; 95% confidence intervals (CI) 0.82, 1.28). However, supplementation in GWs 9 to 12 was associated with a reduced risk of CP (aOR 0.74; 0.57, 0.96), and inverse associations were indicated for both the unilateral (aOR 0.68; 0.46, 1.02) and bilateral (aOR 0.70; 0.49, 1.02) spastic subtypes, although not statistically significant. Supplemental or dietary folate in midpregnancy alone were not associated with CP. Strong inverse associations were observed with low gross motor function impairment (aOR 0.49; 0.29, 0.83), while for unilateral CP the aOR was 0.63 (0.34, 1.22) for intakes of ≥ 500 compared to ≤ 199 dietary folate equivalents/day during midpregnancy.

CONCLUSIONS: Our findings suggested that folate intakes in GWs 9 to 12 and midpregnancy were associated with a lower risk of CP, while no association was observed for periconceptional supplementation.

Original languageEnglish
Article numbernqab351
JournalThe American Journal of Clinical Nutrition
Volume115
Issue number2
Pages (from-to)397–406
Number of pages8
ISSN0002-9165
DOIs
Publication statusPublished - 2022

Bibliographical note

© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.

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