Too much or too little folate during pregnancy may raise heart risk in offspring

In early to mid-pregnancy, low or excessively high maternal serum folate levels carry a heightened risk of congenital heart disease (CHD) in the offspring, as shown in a study.

Researchers recruited participants from one of China’s largest cardiac referral centres. The total study population comprised 129 CHD cases and 516 controls, matched according to maternal age (mean age at pregnancy 31.6 years).

Maternal serum levels of folate, vitamin B12, and homocysteine were measured around the gestational age of 16 weeks. The primary outcome of CHD was ascertained using echocardiography. Conditional logistic regression analyses were used to estimate the risk of CHD in offspring in relation to maternal folate levels. Interactions between folate, vitamin B12, and homocysteine, and CHD were assessed on a multiplicative scale.

Maternal serum folate levels at early to midpregnancy had a U-shaped association with CHD risk in the offspring. The odds of CHD were threefold higher among offspring in the lowest quartile of maternal folate (adjusted odds ratio [aOR], 3.09, 95 percent confidence interval [CI], 1.88–5.08) and 1.8-fold higher among those in the highest quartile (aOR, 1.81, 95 percent CI, 1.07–3.06) as compared with offspring in the second and third quartiles of maternal folate. When the World Health Organization criteria was applied to determine the normal range for serum folate levels, the ORs were higher.

Interaction analyses indicated that the CHD risk associated with low and high maternal folate might be further magnified by vitamin B12 deficiency or elevated homocysteine.

More research is needed to make causal inferences for the observed associations and elucidate the underlying mechanisms.