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Maternal and pediatric nutrition

Folic acid supplementation and fecundability: a Danish prospective cohort study

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Abstract

Background/Objectives:

Periconceptional folic acid (FA) supplementation reduces the risk of neural tube defects and has been associated with ovulatory function. However, only two studies have associated supplementation with multivitamins (MVs) that contained FA with increased pregnancy rates. We aimed to examine the association between FA supplementation (obtained either through single FA tablets or through MVs) and fecundability.

Subjects/Methods:

A prospective cohort study of 3895 Danish women who were planning a pregnancy between 2007 and 2011. We estimated fecundability ratios (FRs) and 95% confidence intervals (CIs) in relation to FA supplementation (either through single FA tablets or MV) using a proportional probabilities regression model, with adjustment for potential socio-demographic, reproductive and lifestyle confounders. In stratified analyses, we also estimated FR with 95% CI in relation to FA supplementation for women with regular and irregular cycles, respectively, and for women with short (<27 days), medium (27–29 days) and long cycles (⩾30 days), respectively.

Results:

FA supplementation was associated with increased fecundability (FR=1.15, 95% CI=1.06–1.25), compared with non-use. The adjusted FRs for FA supplement use relative to non-use were 1.35 (95% CI=1.12–1.65) and 1.11 (95% CI=1.01–1.22) for women with irregular and regular cycles, respectively, and 1.36 (95% CI=0.95–1.95), 1.10 (95% CI=0.98–1.22) and 1.24 (95% CI=1.10–1.41) for women with short (<27 days), medium (27–29 days) and long cycles (⩾30 days), respectively.

Conclusions:

FA supplementation was associated with increased fecundability, and this association appeared to be stronger among women with irregular cycles and among women with either short or long cycle length.

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Acknowledgements

We are grateful to Tina Christensen for her support with data collection and media contacts. The study was supported by the US National Institute of Child Health and Human Development (R21-050264) and the Danish Medical Research Council (271-07-0338). The funding sources had no influence on the study or the manuscript.

This study was supported by the National Institute of Child Health and Human Development (R21-050264) and the Danish Medical Research Council (271-07-0338). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

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Authors and Affiliations

  1. Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark

    H T Cueto, A H Riis, K J Rothman, H T Sørensen & E M Mikkelsen

  2. Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA

    E E Hatch, L A Wise, K J Rothman & H T Sørensen

  3. Slone Epidemiology Center, Boston University, Boston, MA, USA

    L A Wise

  4. RTI International, Research Triangle Park, NC, USA

    K J Rothman

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  1. H T Cueto
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  2. A H Riis
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Correspondence to H T Cueto.

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Cueto, H., Riis, A., Hatch, E. et al. Folic acid supplementation and fecundability: a Danish prospective cohort study. Eur J Clin Nutr 70, 66–71 (2016). https://doi.org/10.1038/ejcn.2015.94

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