Folate Levels in Pregnancy and Congenital Heart Disease Risk

TOPLINE:

Maternal serum folate levels during early to midpregnancy show a U-shaped association with congenital heart disease (CHD) risk in offspring. Both low and high folate levels are linked to an increased risk, with vitamin B12 deficiency and elevated homocysteine levels further exacerbating this risk.

METHODOLOGY:

• Researchers conducted a case-control study with 129 participants with CHD and 516 matched control participants from Guangdong Provincial People’s Hospital in China between 2015 and 2018.
• Maternal serum levels of folate, vitamin B12, and homocysteine were measured at around 16 weeks of gestation using a chemiluminescence microparticle immunoassay.
• CHD was confirmed using echocardiography, and the participants were matched by maternal age at a ratio of 1:4.
• Covariates included periconceptional folic acid supplementation, maternal education, occupation, parity, abortion history, pregnancy complications, and genetic polymorphisms related to folate metabolism.
• Conditional logistic regression was used to assess the associations, with adjustments for various covariates and sensitivity analyses excluding participants with missing genetic data.

TAKEAWAY:

• A U-shaped association was found between maternal serum folate levels and CHD risk in offspring, with both low and high levels linked to increased risk (P
• Low maternal folate levels were associated with an adjusted odds ratio (aOR) of 3.09 (95% CI, 1.88-5.08) for CHD risk, whereas high levels had an aOR of 1.81 (95% CI, 1.07-3.06).
• Using World Health Organization criteria, folate deficiency ( 20 ng/mL) had an aOR of 5.71 (95% CI, 2.72-11.98) for CHD risk.
• Vitamin B12 deficiency and elevated homocysteine levels further increased the risk associated with both low and high maternal folate levels.

IN PRACTICE:

“Insufficient folate and vitamin B12 can lead to increased homocysteine levels, which is harmful to the cardiovascular system. Thus, homocysteine might act as a central mediator in the relationships between deficiencies in folate and vitamin B12 and the risk of CHD. Additionally, the role of folate extends beyond homocysteine mediation, contributing independently to placental implantation and vascular remodeling, irrespective of vitamin B12 and homocysteine levels,” the authors wrote.

SOURCE:

The study was led by Yanji Qu, PhD, and Jie Li, PhD, Global Health Research Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, China. It was published online on October 10 in JAMA Network Open.

LIMITATIONS:

The study’s limitations included the measurement of maternal serum folate levels at a single time point, which may not reflect preconception and early postconception periods. The study’s findings may not be generalizable to other populations as participants were recruited from a single cardiac referral center in Southern China. Additionally, the lack of dietary intake data limited the ability to account for related biases. The sample size, while relatively large for CHD research, may lack sufficient power for stratified analyses.

DISCLOSURES:

Michael S. Bloom, PhD, reported receiving personal fees from Guangdong Cardiovascular Institute outside the submitted work. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.