Maternal intake of folate and folic acid during pregnancy and pubertal timing in girls and boys: A population-based cohort study

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  • Anne Gaml-Sørensen
  • Nis Brix
  • Lea Lykke Harrits Lunddorf
  • Andreas Ernst
  • Birgit Bjerre Høyer
  • Olsen, Sjurdur F.
  • Charlotta Granström
  • Gunnar Toft
  • Tine Brink Henriksen
  • Cecilia Høst Ramlau-Hansen
Folate is essential for normal foetal development as it plays an important role for gene expression during different periods of foetal development. Thus, prenatal exposure to folate may have a programming effect on pubertal timing.

To study the association between maternal intake of folate during pregnancy and pubertal timing in girls and boys.

We studied 6585 girls and 6326 boys from a Danish population-based Puberty Cohort, 2000–2021. Information on maternal intake of folate from diet and folic acid from supplements was obtained from a food-frequency questionnaire in mid-pregnancy, and total folate was calculated as dietary folate equivalents. Information on age at menarche in girls, age at first ejaculation and voice break in boys, and Tanner stages, acne and axillary hair in both girls and boys was obtained every 6 months throughout puberty. We estimated mean monthly differences according to exposure groups for each pubertal milestone in addition to a combined estimate for the average age at attaining all pubertal milestones using multivariable interval-censored regression models. Total folate was analysed in quintiles, continuous and as restricted cubic splines.

Maternal intake of total folate in mid-pregnancy was not associated with pubertal timing in girls (combined estimate for overall pubertal timing per standard deviation (SD 325 μg/day) decrease in maternal intake of total folate: −0.14 months (95% confidence interval [CI] −0.51, 0.22)). Boys had slightly later overall pubertal timing per standard deviation (SD 325 μg/day) decrease in maternal intake of total folate (combined estimate: 0.40 months, 95% CI 0.01, 0.72). Spline plots supported these findings.

Prenatal exposure to low maternal intake of total folate in mid-pregnancy was not associated with pubertal timing in girls but associated with slightly later pubertal timing in boys. This minor delay is likely not of clinical importance.
TidsskriftPaediatric and Perinatal Epidemiology
Udgave nummer7
Sider (fra-til)618-629
Antal sider12
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
The study was funded by the Danish Council for Independent Research (DFF 4183–00152 to CHR‐H), the Independent Research Fund Denmark (FSS 0602‐02738B to CHR‐H), and the Faculty of Health at Aarhus University (AU R9‐A959‐13‐S804 to CHR‐H). In addition, this study was supported by Aarhus University and Independent Research Fund Denmark (9039‐00128B to CHR‐H). March of Dimes Birth Defects Foundation (6‐FY‐96‐0240, 6‐FY97‐0553, 6‐FY97‐0521, 6‐FY00‐407) and Innovation Fund Denmark (grant no 09–067124, Centre for Fetal Programming) supported collection and processing of the dietary data. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.

Funding Information:
The Danish National Birth Cohort was established with a significant grant from the Danish National Research Foundation. Additional support was obtained from the Danish Regional Committees, the Pharmacy Foundation, the Egmont Foundation, the March of Dimes Birth Defects Foundation, the Health Foundation, and other minor grants. The DNBC Biobank has been supported by the Novo Nordisk Foundation and the Lundbeck Foundation. Follow‐up of mothers and children have been supported by the Danish Medical Research Council (SSVF 0646, 271‐08‐0839/06‐066023, O602‐01042B, 0602‐02738B), the Lundbeck Foundation (195/04, R100‐A9193), The Innovation Fund Denmark 0603‐00294B (09‐067124), the Nordea Foundation (02‐2013‐2014), Aarhus Ideas (AU R9‐A959‐13‐S804), the University of Copenhagen Strategic Grant (IFSV 2012) and the Danish Council for Independent Research (DFF – 4183‐00594 and DFF – 4183‐00152).

Publisher Copyright:
© 2023 The Authors. Paediatric and Perinatal Epidemiology published by John Wiley & Sons Ltd.

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