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Journal of Pregnancy
Volume 2013, Article ID 320413, 11 pages
Review Article

The Heart-Placenta Axis in the First Month of Pregnancy: Induction and Prevention of Cardiovascular Birth Defects

USF Children’s Research Institute, CRI #2007, Department of Pediatrics, 140-7th Avenue South, St. Petersburg, FL 33701, USA

Received 8 November 2012; Revised 4 March 2013; Accepted 13 March 2013

Academic Editor: Riitta Luoto

Copyright © 2013 Kersti K. Linask. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Extrapolating from animal studies to human pregnancy, our studies showed that folate (FA) deficiency as well as one-time exposure to environmental factors in the first two to three weeks of human gestation can result in severe congenital heart defects (CHDs). Considering that approximately 49% of pregnancies are unplanned, this period of pregnancy can be considered high-risk for cardiac, as well as for neural, birth defects, as the woman usually is not aware of her pregnancy and may not yet be taking precautionary actions to protect the developing embryo. Using avian and mouse vertebrate models, we demonstrated that FA supplementation prevents CHD induced by alcohol, lithium, or elevation of the metabolite homocysteine, a marker for FA deficiency. All three factors affected the important Wnt signaling pathway by suppressing Wnt-mediated gene expression in the heart fields, resulting in a delay of cardiomyocyte migration, cardiomyogenesis, and CHD. Optimal protection of cardiogenesis was observed to occur with FA supplementation provided upon morning after conception and at higher doses than the presently available in prenatal vitamin supplementation. Our studies demonstrate pathways and cell processes that are involved with protection of one-carbon metabolism during heart development.