Gestational Folate and Folic Acid Intake among Women in Canada at Higher Risk of Pre-Eclampsia

Abstract

Background: Periconceptional folic acid (FA) supplementation is recommended to prevent neural tube defects; however, the extent to which recommendations are met through dietary sources and supplements is not clear.

Objectives: Our objective was to evaluate the dietary and supplemental intakes of FA in a Canadian pregnancy cohort and to determine the proportions of pregnant women exceeding the Estimated Average Requirement (EAR) and Tolerable Upper Intake Level (UL).

Methods: FACT (the Folic Acid Clinical Trial) was an international multicenter, randomized, double-blinded, placebo-controlled, phase III trial investigating FA for the prevention of pre-eclampsia in high-risk pregnancies. Participants were enrolled from Canadian sites at 8-16 weeks of gestation. Dietary and supplemental FA intake data were collected through participant interviews and FFQs at the time of FACT enrollment. Categorical data were summarized as n (%) and continuous data as median (IQR).

Results: This study included 1198 participants. Participants consumed 485 μg dietary folate equivalents (DFE)/d (IQR: 370-630 μg DFE/d) from dietary sources of folate and FA. Through diet alone, 43.4% of participants consumed ≥520 μg DFE/d, the EAR for pregnant individuals. Of the 91.9% of participants who consumed daily FA supplements, 0.4% consumed <400 μg FA/d and 96.0% consumed ≥1000 μg/d, the UL for FA. Median (IQR) total folate intake was 2167 μg DFE/d (2032-2325 μg DFE/d); 95.3% of participants met or exceeded the EAR from all sources, but 1069 (89.2%) participants exceeded the UL.

Conclusions: The majority of participants in this Canadian pregnancy cohort did not consume the recommended amount of folate from dietary sources. However, most prenatal supplements contained 1000 μg FA, resulting in the majority of women exceeding the UL. With no additional benefit associated with FA intakes beyond the UL for most women, modification of prenatal supplement formulations may be warranted to ensure women meet but do not exceed recommended FA intakes.FACT was registered at clinicaltrials.gov as NCT01355159 and at isrctn.com as ISRCTN23781770.

Keywords: folate; folic acid; pregnancy; supplementation; vitamin B-9.

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

Figures

FIGURE 1

Derivation of the study cohort from FACT participants in Canada. This was a substudy of FACT. The analysis was limited to FACT participants in Canada who completed a dietary folate equivalent screener at 8–16 completed weeks of gestation. FACT, the Folic Acid Clinical Trial.

FIGURE 2

Folate (A) and FA (B) intake among Folic Acid Clinical Trial participants in Canada at 8–16 completed weeks of gestation (n = 1198). (A) DFE intake among study participants. Intake data are reported as folate intake from diet, FA intake from fortified foods, total folate and FA intake from diet, and total folate and FA intake from all food and supplement sources. The Estimated Average Requirement in pregnancy is indicated by a horizontal line (5). (B) FA intake among study participants. Data are presented as FA intake from fortified foods, FA intake from supplements, and total FA intake from foods and supplements. The Tolerable Upper Intake Level for FA intake is indicated by a horizontal line (5). Boxplots display the median values and IQRs. Whiskers demonstrate the highest and lowest values which are no more than 1.5 times the IQR away from the box. Points outside of the whiskers represent outliers. Supplemental Tables 1 and 2 provide corresponding tabular data, including stratification by Canadian province. DFE, dietary folate equivalents; FA, folic acid.