Spina Bifida Phenotypes and Sex‐Specific Prevalence Among Offspring of Folic Acid Users
Authors: Berry Robert John , Patimeteeporn Calvin , Moore Cynthia 
Published: November 2023

Background

Periconceptional consumption of folic acid can reduce a woman's risk of having a neural tube defect (NTD)‐affected pregnancy, particularly in high‐prevalence areas such as northern China; however, information about the effect of folic acid on sex‐specific or phenotype‐specific spina bifida prevalence is lacking.

Methods

We used data from the China‐U.S. NTD Prevention Project during which women were asked to take a daily pill containing 400 μg of folic acid without other vitamins to reduce their risk of having an NTD‐affected pregnancy. We used data from birth defect surveillance and births from 1993 through 1996 from a high‐prevalence region located in five counties in northern China to evaluate these effects. We also examined the distribution of spina bifida phenotypes‐‐categorizing lesions in the cervicothoracic region as high lesions and those in the lumbosacral region as low lesions.

Results

Among 21,536 women who took folic acid at any time before and during early pregnancy and 56,541 women who did not take folic acid, we identified 18 and 115 women, respectively, with spina bifida‐affected pregnancies of ≥ 20 weeks’ gestation. Among the women who did and did not take any folic acid, the prevalences of spina bifida were 8.4 per 10,000 pregnancies and 20.3 per 10,000, respectively (risk reduction ~59%). Among women who did and did not take any folic acid as part of the prevention project, the spina bifida prevalences among female offspring were 8.8 and 24.2 per 10,000 pregnancies, respectively (risk reduction ~64%), and the prevalences among male offspring were 8.0 and 17.0 per 10,000, respectively (risk reduction ~53%). Among women who did and did not take any folic acid, the prevalences of high spina bifida lesions among offspring were 3.3 and 11.0 per 10,000 pregnancies, respectively (risk reduction ~70%), and prevalences of low spina bifida lesions among offspring were 4.6 and 8.5 per 10,000 pregnancies, respectively (risk reduction ~45%). This difference was statistically significant at p<0.01 and among women with female offspring, the risk reduction was even greater for high lesions vs. low lesions.

Discussion and Conclusions

These findings suggest that the folic acid effect on neural tube closure is not limited to any one spina bifida phenotype; however, it appears that the effect may differ by level of lesion and offspring sex. Among women who consumed 400 μg of folic acid daily, compared with those with male offspring those with female offspring experienced a greater reduction in risk of spina bifida this reduction in risk among female offspring was greater for high lesions than for low lesions. The findings are also consistent with observations in seven Canadian provinces where the proportion of cervicothoracic lesions decreased in all regions after fortification. Examination of these variations in folic acid effects may be helpful in identifying factors important in the pathogenesis of spina bifida and other neural tube defects.

Support or Funding Information

CDC internal funding only