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Periconceptional maternal folate supplementation impacts a diverse range of congenital malformations

Pediatric Research volume 95, pages 880–882 (2024)Cite this article

It may be surprising to the readership that more infants per 100,000 newborns succumb to their congenital malformations than a comparable number of adults are lost to Alzheimer’s disease, stroke, diabetes, and influenza combined.1 It has been reported that there are 120,000 babies born each year in the United States present with some type of a congenital defect, and there are more than 8,000,000 newborns worldwide who are born with a variety of congenital abnormalities. These alarming numbers have remained steady and have only recently been reduced to some extent with the recognition that specific components from the diet impact normal embryogenesis, and that a nutritional imbalance could contribute to the prevalence of birth defects. Specifically, a maternal folate deficiency was known to be a risk factor for neural tube defects (NTDs) such as spina bifida, as far back as in the early 1950s, when an increase in the incidence of NTDs was demonstrated as a result of exposure to the folate antagonist aminopterin in animal models and in human fetuses.2,3 Several landmark clinical trials from 1960s to 1980s supported these findings.4 In 1991, the Medical Research Council Vitamin Study published the first large randomized trial showing a strong effect of folic acid (Vitamin B9) supplementation in preventing NTDs.5 The trial was launched in 1983 and ended in 1991 after conclusive results were achieved. Subsequently, several other large, randomized trials were conducted, including the US-China study,6 the Canadian study,7 and the Hungary trial,8 all supporting the conclusion that periconceptional folate supplementation could significantly decrease the prevalence of NTDs by 30–78%. One question that immediately came to mind is whether periconceptional folic acid supplementation had protective beneficial effects against other congenital malformations.3,9

There is no shortage of studies that have been published now over the last 20 + years addressing this very question. The most compelling data demonstrating a beneficial effect of periconceptional maternal folic acid consumption and a reduction in the prevalence of a significant birth defect can be found in numerous epidemiological studies demonstrating that maternal folic acid supplementation was associated with a decreased risk of congenital heart defects (CHDs) in offspring.10,11,12 Qu and co-workers reported that first-trimester folic acid supplementation, but not multivitamin use, reduced the risk of CHDs, especially the most severe CHDs, including single ventricle, anomalous pulmonary venous return, atrioventricular septal defect, coarctation of aorta, double-outlet right ventricle, hypoplastic left heart syndrome, hypoplastic right heart syndrome, interrupted aortic arch, left ventricular outflow tract obstruction, right ventricular outflow tract obstruction, d-transposition of the great arteries, tetralogy of Fallot, valvular aortic stenosis, and valvular pulmonary stenosis.13

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Authors and Affiliations

  1. Center for Precision Environmental Health, Departments of Molecular and Cellular Biology, Molecular and Human Genetics and Medicine, Baylor College of Medicine, Houston, TX, 77030, USA

    Richard H. Finnell

  2. To Cure A Rose Foundation, Austin, TX, 78701, USA

    Richard H. Finnell & Huiping Zhu

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Correspondence to Richard H. Finnell.

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Finnell, R.H., Zhu, H. Periconceptional maternal folate supplementation impacts a diverse range of congenital malformations. Pediatr Res 95, 880–882 (2024). https://doi.org/10.1038/s41390-023-02935-1

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