The Methyl Donor Betaine Prevents Congenital Defects Induced by Prenatal Alcohol Exposure

Abstract

Over 500,000 women per year in the USA drink during pregnancy, and 1 in 5 of them binge drink. 20–50% of live‐born children with prenatal alcohol exposure (PAE) present with congenital heart defects including outflow and valvuloseptal anomalies that can be life‐threatening. We established a model of PAE (modeling a single binge drinking episode during the first trimester) in the avian embryo and used optical coherence tomography (OCT) imaging to assay early‐stage cardiac function/structure and late‐stage cardiac defects. We previously reported that at early stages, alcohol/ethanol‐exposed embryos had smaller cardiac cushions and increased retrograde flow. At late stages, they presented with gross morphological defects in the head and chest wall, and smaller or abnormal atrio‐ventricular (AV) valves, thinner interventricular septae (IVS), and smaller vessel diameters for the aortic trunk branches. In other models, the methyl donor betaine (found naturally in foods such as wheat bran, quinoa, beets and spinach) ameliorates neurobehavioral deficits associated with PAE but the effects on heart structure are unknown. In the current study using this model of PAE, betaine supplementation (23.5 ng per egg) led to a reduction in gross structural defects and certain types of cardiac defects such as ventricular septal defects and abnormal AV valvular morphology. Furthermore, great vessel diameters, IVS thicknesses and mural AV leaflet volumes were normalized while the septal AV leaflet volume was increased. In summary, betaine supplementation in our PAE model can improve survival rates and reduce gross morphological defects including cardiac defects, indicating its potential as a safe periconceptional supplement for prevention of alcohol‐induced congenital defects. Future studies will focus on whether DNA methylation levels in our PAE model are being altered by alcohol and subsequently normalized with betaine. Our findings could have significant implications for public health, especially for pregnant women who are not responsive to folic acid (already present in prenatal vitamins to prevent birth defects) and require an alternative.Support or Funding InformationResearch was supported by the National Institutes of Health (NIH) award numbers R01HL083048; R01HL126747; R21HL115373. Ganga Karunamuni was supported by14POST19960016 from the American Heart Association (AHA). The content is solely the responsibility of the authors and does not necessarily represent the views of the NIH or the AHA.