Fetal and maternal hemodynamics in pregnancy: new insights in the cardiovascular adaptation to uncomplicated pregnancy, twin-to-twin transfusion syndrome and congenital diaphragmatic hernia

The fetal and the maternal cardiovascular compartment undergo dramatic functional changes during pregnancy. In this thesis we examined the heart of fetuses with twin-to-twin transfusion syndrome (TTTS) and congenital diaphragmatic hernia (CDH) using two new ultrasound parameters of ventricular function : the myocardial performance index and speckle tracking derived myocardial strain. Fetal cardiac function was grossly abnormal in recipient fetus of TTTS, yet normalized within 6 weeks after therapy. Ultrasound based cardiac function assessment could not predict short term fetal survival after therapy, nor could it predict eventual further progression to full-blown TTTS in a pre-disease stage. Fetuses with CDH on the other hand, have normal myocardial function, yet smaller left ventricles leading to decreased left ventricular output. We showed that the lower output leads to decreased cerebral perfusion, yet without apparent impact on brain and cranial growth. On the maternal side, plasma volume strongly increases in pregnancy, in parallel with an increase in insulin-like-growth factor(IGF) II which is secreted at the level of the placenta. Experimental administration of IGF-II by continuous infusion leads to increases in plasma volume whereas decreasing IGF-II by reduction of the feto-placental mass leads to decreased plasma volumes. In contrast to IGF-II, the highly vasoactive peptide apelin decreases near term due to a faster elimination as a consequence of an increase in placental angiotensin-converting-enzyme 2. Our experiments with IGF-II and apelin substantiate an important role for the feto-placental unit in regulating maternal plasma volume expansion and (auto)regulating uterine perfusion and fetal growth.