Cardiovascular Management in Pregnancy

2066 Cardiovascular diseases (CVDs) constitute a particular challenge during pregnancy because physiological changes and fetal demands create an additional burden and fetal safety concerns limit treatment options. Other articles of this series review the physiological changes during pregnancy, the management of cardiovascular conditions most likely to endanger maternal and fetal health, and their long-term consequences for the cardiovascular health of the mother. This article focuses on their consequences in offspring. Developmental programming resulting from in utero or early postnatal exposure to specific risk factors is increasingly recognized to determine CVD in later life. Clinically manifest cardiovascular conditions during pregnancy such as preeclampsia/eclampsia and gestational hypertension may not only affect maternal health and pregnancy outcome but also reduce fetal growth, which is associated with increased adult CVD. Furthermore, extensive evidence indicates that maternal cardiovascular risk factors (hypercholesterolemia, smoking, obesity, and diabetes mellitus) program endothelial dysfunction, insulin resistance (IR), hypertension, atherosclerosis, and type 2 diabetes mellitus in offspring. The mechanisms of developmental programming remain largely unknown, but specific factors affecting in utero programming have been identified and experimental models established in which causal relationships, mechanisms, and protective effects of maternal treatment can be explored. These findings suggest that interventions targeting in utero programming may reduce the susceptibility to CVD in offspring, a high priority given the increasing prevalence of obese and dysmetabolic mothers and the concomitant increase in lifestyle risk in children. However, neither the cardiovascular consequences of many maternal risk factors nor the efficacy of maternal prevention and treatment is sufficiently supported by prospective double-blind studies. The present review provides a critical evaluation of the associations between maternal cardiovascular conditions during pregnancy and offspring CVD, the role of low birth weight, and the evidence for developmental programming of CVD by other maternal cardiovascular risk factors. It then proposes an integrated view of in utero programming of CVD and its mechanisms based on emerging consensus and highlights priorities for future clinical and basic research. Finally, it discusses the promises and caveats of targeting developmental programming, that is, treating mothers to reduce CVD in offspring. Cardiovascular Conditions of Particular Clinical Importance During Pregnancy Congenital Heart Disease and Maternal Cardiomyopathy Maternal congenital heart disease requires particular attention during pregnancy and often leads to premature birth. The same is true for gestational cardiomyopathy, a rare condition with an enigmatic pathogenesis. As expected for any condition with a polygenic mode of inheritance, maternal congenital heart disease is associated with a high offspring recurrence risk, which varies depending on the type of cardiac defect. However, family history contributes only a small percentage to the overall prevalence of congenital heart disease and a strong case can be made for an involvement of nongenetic factors. Establishing whether in utero programming by maternal cardiac disease contributes to the cardiac condition in offspring or their CVD risk in general is further complicated by confounding effects of maternal treatment, premature birth, and related neonatal care, in particular treatment with oxygen. In fact, in experimental animals without predisposing genetic defects, a combination of systemic maternal inflammation and neonatal hyperoxia was sufficient to alter cardiac structure and function and ultimately led to cardiac failure. The most prominent argument for an involvement of fetal programming is that maternal heart conditions often impair fetal growth (see The Role of Altered Fetal Growth). Although to date there is little hard evidence that maternal heart conditions contribute to offspring CVD by developmental programming, epidemiology clearly indicates that cardiac pathologies in offspring may be programmed by maternal dysmetabolic conditions. For example, maternal diabetes mellitus is associated with fetal ventricular hypertrophy and less frequently with congenital heart disease. Maternal obesity during early pregnancy is also linked to congenital heart defects, possibly as a result of increased inflammation. Finally, both maternal diabetes mellitus and obesity are associated with complete atrioventricular canal defects.