Maternal periconceptional folic acid supplements use and fetus risk for limb defects

Abstract

Background Associations between the periconceptional folic acid only (FAO) or multiple micronutrients containing folic acid (MMFA) supplementation and risk for limb defects are inconsistent. Objective To explore the association between periconceptional folic acid supplements use and risk for limb defects, including clubfoot, polydactyly, syndactyly, and limb deficiencies. Methods Data were derived from a cohort based on a pregnancy registry in a district of Beijing, China, from 2013 to 2018. Information on maternal periconceptional FAO and MMFA supplementation was collected via face‐to‐face interviews at first trimester. Pregnancy outcomes including limb defects were ascertained in livebirths, stillbirths, and elective pregnancy terminations and were recorded into the system. Propensity score methods were used to adjust for potential confounders. Results A total of 63 969 women with a singleton delivery were included. The overall prevalence of limb defects was 47.5 per 10 000 (n = 63 969) singleton deliveries. Decreased prevalence of limb defects was found among FAO/MMFA users compared with women who did not take supplements (nonusers) (46.1 vs. 61.9 per 10 000 births, adjusted risk ratio [RR] 0.80, 95% confidence interval [CI] 0.56, 1.12). Compared with nonusers (n = 6462, 10.2%), women who took either FAO (n = 26 567, 42.0%) or MMFA (n = 30 259, 47.8%) had a lower risk for total clubfoot (RR 0.40, 95% CI 0.20, 0.84), and for isolated clubfoot (RR 0.41, 95% CI 0.17, 0.97). For other limb defects except clubfoot, FAO supplementation did not appear to be associated with reduced risk, while MMFA supplementation group had 30%‐50% reduced risks for other limb defects. A lower risk for limb defects or isolated limb defects was found with MMFA supplementation when FAO supplementation was used as a control. Conclusions Maternal periconceptional supplements with either FAO or MMFA had inverse association with clubfoot in offspring, and MMFA was associated with lower risk for isolated limb defects compared with FAO.

Periconceptional Folic Acid Only Versus Multiple Micronutrients Containing Folic Acid and Association with Gestational Diabetes Mellitus — Beijing Municipality, China, 2017–2021

“…This suggests that GDM prevalence in Beijing is relatively high and continues to increase. Furthermore, only 3.2% of participants did not take FA periconceptionally, and more women opted for MMFA than FAO, which aligns with another survey conducted in Beijing ( 6 ). These findings underline the importance of exploring the effects of FAO/MMFA supplementation on GDM.…”

“…First, a dose-response relationship may exist between FA and GDM. The main brand of MMFA contains twice the amount of FA (0.8 mg/tablet) as a simple FA tablet (0.4 mg/tablet) ( 6 ). Excessive FA can lead to increased circulating unmetabolized folate, which in turn elevates homocysteine levels.…”

The relationship between maternal periconceptional micronutrient supplementation and non‐syndromic cleft lip/palate in offspring

“…The general characteristics of the participants were similar to those in our previous study (Zhang et al, 2021) (see Appendix S3). The prevalence of non‐syndromic cleft lip/palate in this study was 17.98 per 10,000 singleton births and did not change over time.…”

“…Studies have evaluated the preventive effects of the Populational Folic Acid Supplementation to Prevent Neural Tube Defects program on NTDs (Jin et al, 2020), congenital heart defects (Mao et al, 2017), and limb defects (Zhang et al, 2021) in Beijing. However, the impact of the program on the prevalence of cleft lip/palate has not yet been assessed.…”

Initiation and duration of folic acid supplementation in preventing congenital malformations

“…FA supplementation is a routine measure for the prevention of malformations in women of childbearing age in China [ 46 , 47 ]. In contrast, the potential harms of FA are of high concern [ 3 ].…”