Folic acid prevents functional and structural heart defects induced by prenatal ethanol exposure

Abstract

Increased regurgitant blood flow has been linked to endocardial cushion defects and resultant congenital heart diseases (CHDs). Prenatal alcohol exposure (PAE) has been shown to alter early blood flow resulting in abnormal endocardial cushions and CHDs. Compounds, including folic acid (FA), mitigate PAE effects and prevent CHDs, but few studies have assessed their effects on blood flow. We modeled binge drinking in quail embryos at gastrulation. Embryos were exposed to ethanol alone, FA (3.2 μg/egg) alone, and the two simultaneously. We quantified in cardiac looping stages (equivalent to 4 weeks of human gestation) regurgitant blood flow with Doppler optical coherence tomography (OCT) and endocardial cushion volumes using OCT imaging. Incidences of abnormal body curvature and heart rates were also measured. Embryos exposed to ethanol showed significantly increased regurgitant blood flow compared to controls, while embryos given FA with ethanol had significantly reduced regurgitant blood flow but did not return to control levels. Ethanol exposure led to significantly smaller, abnormal endocardial cushions and the addition of FA improved their size, but they remained smaller than controls. Abnormal body curvatures after PAE were reduced in incidence but not fully prevented by FA. FA supplementation partially alleviated PAE induced abnormal cardiovascular function and morphology. Normal blood flow and endocardial cushions are both required to produce a healthy four-chambered heart. These findings support that FA supplementation should begin early in pregnancy to prevent heart as well as neural tube defects. Investigations into the efficacy of combinations of compounds to prevent PAE-induced defects is warranted.

Dietary Intake Patterns and Lifestyle Behaviors of Pregnant Women Living in a Manitoba First Nations Community: Implications for Fetal Alcohol Spectrum Disorder

“…Although the compounding effects of EtOH and macro- and micro-nutrient deficiencies on the embryogenic and fetal development have not been elucidated, studies indicate that EtOH-induced insults are aggravated by poor nutrient intake and nutrient status [ 22 ]. A number of experimental reports link poor intake of nutrients with PAE to microcephaly, intrauterine growth retardation (IUGR), abnormalities in cardiogenesis, and severe valve malfunctions [ 22 , 46 ]. In light of this information, the findings of low folate, DHA, and iron intake in the risk group raise special concerns.…”

Epidemiological profile of paediatric outpatients followed in a tertiary paediatric cardiology centre in Brazil

“…alcohol and air pollutants), maternal diseases, and genetic disorders are related to CHD [5][6][7][8][9][10]. Some authors have proposed the use of folates, even in association with inositol, to prevent CHD due to the possible epigenetic effect acting on Wnt signalling and, therefore, on cell differentiation of the embryo [11,12].…”