Periconceptional folic acid supplementation and sex difference in prevention of neural tube defects and their subtypes in China: results from a large prospective cohort study.

Jufen Liu,Rongwei Ye,Jianmeng Liu,Zhiwen Li,Aiguo Ren

doi:10.1186/s12937-018-0421-3

Jufen Liu, Rongwei Ye + Show 3 more

Open Access

https://doi.org/10.1186/s12937-018-0421-3

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Abstract

BackgroundFolic acid (FA) supplementation is known to prevent neural tube defects (NTDs). We examined whether this preventive effect differs by the sex of the infant.MethodsData were gathered from a large population-based cohort study in China that evaluated the effects of FA supplementation on NTDs. All births at 20 complete gestational weeks, including live births, stillbirths, and pregnancy terminations, and all NTDs, regardless of gestational age, were recorded. In a northern China province, a total of 30,801 singleton live births to women whose use of FA supplements during the first trimester was known at the time were included in the study. The birth prevalence of NTDs was classified by sex, subtype, and maternal FA supplementation. Male to female rate ratios [RR] and their 95% confidence intervals [CI] were calculated.ResultsA total of 106 NTDs cases were recorded. The overall prevalence of NTDs was 2.5‰ among males and 4.4‰ among females; NTDs were less prevalent among males than among females (RR, 0.58; 95% CI, 0.54–0.63). There was a higher prevalence of anencephaly (RR, 0.34; 95% CI, 0.27–0.43) and spina bifida (RR, 0.73; 95% CI, 0.63–0.84) among females. However, FA supplementation led to significantly greater decreases in the rates of anencephaly (4.8‰) and total NTDs (7.6‰) in females than in males (1.6‰ and 2.8‰, respectively).ConclusionsFA supplementation successfully reduces the prevalence of NTDs in both male and female infants, although we found a significantly greater decrease in anencephaly and total NTDs in females than in males. How the protective effects of FA supplementation affect the sexes differently needs to be studied further.

Highlights

Many congenital malformations and birth defects, such as defects of the sex organs, urinary tract defects, gastrointestinal tract defects, are sex specific [1,2,3]
Periconceptional Folic acid (FA) use reduces Neural tube defects (NTD) risk, but whether the effect differs by infant sex is unknown
In a study that compared the effectiveness of periconceptional vitamin supplementation for the prevention of NTDs recurrence in England and Ireland, beneficial effects were apparent in both countries, and all but one recurrence occurred in male fetuses [8]

Summary

Introduction

Many congenital malformations and birth defects, such as defects of the sex organs, urinary tract defects, gastrointestinal tract defects, are sex specific [1,2,3]. A subsequent population study revealed that females tend to have craniorachischisis, spina bifida involving the upper spine, anencephaly, and encephalocoeles more often than males, while males more often have spina bifida affecting the lower spine [9] These findings support the supposition that the less commonly affected sex may be less responsive to environmental therapy, the different rates of NTDs according to sex are difficult to explain because neural tubes close before sex differentiation occurs [8]. The pattern of variation between the sexes seems to suggest that there are two causes of anencephaly; 1) an environmental cause that predominantly affects female embryos, or 2) an environmental or genetic cause that seems to affect the sexes in roughly equal numbers [6] This difference could be due to other reasons including sex differences in genetic risk, epigenetic factors, timing of neural tube formation, fetal loss rates, and susceptibility to environmental influences [11, 12]. We examined whether this preventive effect differs by the sex of the infant

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