Congenital Heart Diseases and Neurodevelopmental Disorders

Central Illustration. In Utero Environmental Exposures, Fetal Programming, and Congenital Heart Disease–Associated Neurodevelopment Disorders The early interconnection between the placenta, heart, and brain may explain the common dysregulations observed in these 3 organs, simultaneously. Placental functions can be disrupted by in utero exposures, with consequences for fetal heart and brain defects and early and late clinical outcomes.7,13

Figure 1. Placental, Cardiac, and Cerebral Development During Pregnancy The 3 organs develop in parallel from endoderm, mesoderm, and ectoderm, respectively. Similar signaling pathways regulate vasculogenesis and angiogenesis. At week 13, blood begins to circulate in blood vessels, connecting the placenta and the fetus to ensure more efficient exchanges of nutrients, oxygen, and wastes with the maternal circulation.9,11,55 w = week.

Figure 2. Maternal-Fetal Exchanges Through the Placental Barrier The maternal blood supplies the placenta and fetal heart and brain with essential nutrients (N) and oxygen (O2) but can also carry toxins (T) to the fetus (red arrows). Wastes (W) are removed from the fetal blood (blue arrows). Hormones (H) are produced from essential nutrients in the placenta to support fetal development and the fetal brain.9

Figure 3. Mitochondrial ATP Production From Glucose and FA The mitochondria convert glucose and fatty acid (FA) (via β-oxidation) to ATP to provide energy for the placenta and developing fetal organs. CPTI/II = carnitine palmitotransferase I/II; MPC = mitochondrial pyruvate carrier.45,48