A Meta-Analysis of the Relationship Between Maternal Folic Acid Supplementation and the Risk of Congenital Heart Defects

Abstract

SummaryControversial opinions exist with respect to the relationship between maternal folic acid (FA) supplementation and birth prevalence of congenital heart defects (CHDs).Eligible articles were retrieved by searching databases, including PubMed, Cochrane library, EMBASE, CNKI, and WanFang up to September 2015. A meta-analysis was performed to evaluate the effects of FA on CHDs. Odds ratios (ORs) and 95% confidence interval (CIs) were merged using STATA 12.0. Meta-regression analysis was used to explore the possible sources of heterogeneity. Subgroup analysis according to the selected sources was also performed. Publication bias was assessed by Egger's test.Twenty studies were included in the meta-analysis. The overall analysis showed that FA supplementation was significantly associated with decreased risk of CHDs. The meta-regression analysis showed that geographical area could be an important source of heterogeneity. The subgroup analysis based on the geographical area revealed that FA supplementation during pregnancy was a protective factor against CHDs in Chinese and European patients, but not in American patients. Subgroup analysis according to literature quality also displayed positive associations between FA supplementation and the decreased risk of CHDs of China.FA supplementation during pregnancy significantly decreases the risk of CHDs in newborns in China and Europe. (Int Heart J 2016; 57: 725-728) Key words: Literature search, Meta-regression analysis, Geographical area, Pregnancy C ongenital heart defects (CHDs) are the most common structural abnormalities presenting at birth, and they are also one of the leading causes of perinatal and infant mortality.1) It is reported that the prevalence of CHDs accounts for 6% of all neonatal death factors, and also accounts for 46% of all congenital lethal factors.2-4) Recently, the survival of newborns with CHDs has increased due to massive breakthroughs in cardiovascular diagnostics and cardiothoracic surgery, 5,6) however, this trend consequently generates a completely novel and steady increasing population with grown-up congenital heart disease (GUCH). Patients with GUCH often need long-term expert medical care with high healthcare-related costs. 7) Moreover, recently, an increasing number of women have postponed conception to an older age, which consequently results in a higher birth prevalence of congenital defects. 8,9) These defects lead to great economic pressure and mental burdens on society and the families, therefore, searching for effective prevention measures for CHDs is of great practical significance.Folic acid (FA) is an essential nutrient and plays an important role in the development of the cardiovascular system.10-12) The association of FA or multivitamins containing FA supplementation during the critical periods of organ formation with the risk of the occurrence of CHDs has been recognized in past decades. [13][14][15] Several studies have reported that FA or multivitamins containing FA supplementation taken during pregnancy could signifi...

Exposure of the developing heart to diabetic environment and early cardiac assessment: A review

“…This metabolite is not only directly toxic against the dividing cells but also increases ROS level As a result, the developmental process of embryos can be disrupted secondary to intracellular FA shortage. Considering that, an association already exists between FA deficiency and an increased risk of congenital anomalies in the absence of DM . DM by itself may further worsen preexisting and therefore increases the rate of anomalies.…”

“…DM by itself may further worsen preexisting and therefore increases the rate of anomalies. Moreover, previous studies demonstrated that FA supplementation can decrease the incidence of diabetes‐induced congenital abnormalities . Understandably, FA deficiency is obviously not the only factor explaining the pathogenesis of diabetic embryopathy, but can take part in the pathogenesis.…”

“…Considering that, an association already exists between FA deficiency and an increased risk of congenital anomalies in the absence of DM. 27,28 DM by itself may further worsen preexisting and therefore increases the rate of anomalies. Moreover, previous studies demonstrated that FA supplementation can decrease the incidence of diabetes-induced congenital abnormalities.…”

Safety of folic acid

“…Furthermore, connecting folic acid to these outcomes lacks a strong biological and mechanistic premise. In some cases, folate intakes from all sources at or above the recommended dietary allowance and/or maintenance of adequate folate status have been shown to be protective for these and related outcomes …”

The pharmacokinetic advantage of 5-methyltetrahydrofolate for minimization of the risk for birth defects

“…If not complete by day 28, this results in neural tube defects (NTD) such as spina bifida, anencephaly, and encephalocele. Moreover, several studies suggest the risk for congenital anomalies of other structures requiring integration of migrating neural crest cells, such as the heart and the lip/palate, can also be decreased by maternal FA supplementation 1–5 . After about eight weeks cardiac outflow tracts and septation that depend on neural crest cells are complete.…”