Prenatal folic acid supplementation linked to lower birth defect risk: China study

Periconception folic acid supplementation is a primary measure in preventing birth defects, particularly neural tube defects (NTDs). Early randomised controlled studies (RCTs) and cohort studies  have underscored the efficacy of this intervention but there remains a need for informed understanding of the benefits of folic acid supplementation in primary care.

Currently, there is a dearth of new prospective studies evaluating the benefits of folic acid supplements among women intending to conceive, posing a challenge to public health interventions. Subsequent observational and case-control studies have failed to consistently demonstrate a protective association with birth defects like NTDs, possibly due to factors such as bias, misclassification or recall bias.

Additionally, ethical considerations make conducting placebo-controlled randomised trials challenging, limiting the ability to conclusively establish the protective properties of folic acid supplementation in real-world maternal healthcare scenarios. Despite known confounding variables like maternal age, education, smoking, and alcohol consumption, the potential influence of paternal factors like smoking and alcohol intake cannot be overlooked.

Complimentary acid trip​

The National Free Preconception Health Examination Project (NFPHEP) launched by the Chinese government in 2010 offered a unique opportunity for investigation. Women planning pregnancy within six months are provided with a daily 0.4mg folic acid supplement free of charge. Under this nationwide initiative, the timing and duration of folic acid supplementation, alongside pregnancy outcomes, are meticulously monitored.

Using the project’s database — comprising data from 220 districts across 31 provinces and province-level municipalities — a recent population-based cohort study conducted in Mainland China revealed a significant association between periconception folic acid supplementation and a reduced risk of birth defects. Conducted between 2010 and 2012, the study included data from 567,547 married Chinese couples planning pregnancies within a six-month timeframe.

The couples received preconception education and advocacy on reproductive health, facilitated by local family planning service agencies or maternal and children’s care service centres. Couples with incomplete information regarding folic acid supplementation or pregnancy outcomes were excluded from the final analysis to ensure data integrity.

Women participating in the study (aged between 20 and 49) were provided with folic acid supplementation from three months before conception to three months after conception. The study collected a wealth of information, including details on folic acid supplementation, socio-demographic factors, clinical information, exposure to harmful substances and maternal adverse pregnancy history. Birth defects were self-reported at a follow-up conducted 42 days post-partum.

Data on defects​

Of the couples included in the final analysis, 74.7% of women had received folic acid supplementation. The study found a lower incidence of birth defects among women who had taken folic acid compared to those who had not (0.102% versus 0.116%). Multiple logistic regression analyses further confirmed a decreased risk of birth defects, particularly NTDs, among couples wherein the mothers had received folic acid supplementation.

Moreover, the timing of folic acid supplementation played a crucial role in mitigating birth defect risk. Women who commenced supplementation at least three months before conception exhibited significantly lower odds of birth defects compared to those who started supplementation later or did not take supplements at all. This effect was consistent across various types of birth defects, including congenital heart disease, limb anomalies, clefts, digestive tract anomalies, gastroschisis and NTDs.

However, the study acknowledged certain limitations, including the potential for recall bias regarding the dosage and duration of folic acid supplementation, as well as the reliance on self-reported birth defects. Still, despite these limitations, the study's robust methodology, including comprehensive data analysis and adjustment for confounding factors, strengthened the validity of its findings.

Prospective study perspectives​

The study underscores the importance of periconception folic acid supplementation as a primary prevention intervention for reducing the risk of not only with NTDs but also with other birth defects, like clefts, congenital heart diseases, limb anomalies and digestive tract anomalies (including gastroschisis).

As such, this prospective cohort study serves as an optimal platform for evaluating the protective association of periconception folic acid supplements, providing valuable insights for public health policymakers in formulating strategies aimed at improving birth outcomes and quality of life for offspring.

Furthermore, this research contributes to a growing body of evidence supporting the benefits of folic acid supplementation in reducing the risk of birth defects, aligning with previous RCTs and cohort studies. The high coverage of folic acid supplementation among women in the study suggests the feasibility and effectiveness of implementing such interventions as part of preconception care initiatives.

The study’s findings advocate for preconception care programmes to emphasise the early commencement of folic acid supplementation, potentially leading to improved maternal and child health outcomes.Top of FormBottom of Form Further research is therefore warranted to explore the long-term effects and optimal dosage regimens of folic acid supplementation in improving birth outcomes.

Source: BMC Pregnancy and Childbirth​

“​Preconception folic acid supplementation for the prevention of birth defects: a prospective, population-based cohort study in mainland China​”​

https://doi.org/10.1186/s12884-024-06283-8​

Authors: Qiongjie Zhou, et al​.