Maternal Morbidity and Mortality: Are We Getting to the "Heart" of the Matter?

Abstract

Cardiovascular disease (CVD), including hypertensive disorders of pregnancy (HDP) and peripartum cardiomyopathy, is a leading cause of pregnancy-related death in the United States. Women who are African American or American Indian/Alaskan Native, have HDP, are medically underserved, are older, or are obese have a major risk for the onset and/or progression of CVD during and after pregnancy. Paradoxically, women with no preexisting chronic conditions or risk factors also experience significant pregnancy-related cardiovascular (CV) complications. The question remains whether substantial physiologic stress on the CV system during pregnancy reflected in hemodynamic, hematological, and metabolic changes uncovers subclinical prepregnancy CVD in these otherwise healthy women. Equally important and similarly understudied is the concept that women's long-term CV health could be detrimentally affected by adverse pregnancy outcomes, such as preeclampsia, gestational hypertension, and diabetes, and preterm birth. Thus, a critical life span perspective in the assessment of women's CV risk factors is needed to help women and health care providers recognize and appreciate not only optimal CV health but also risk factors present before, during, and after pregnancy. In this review article, we highlight new advancements in understanding adverse, pregnancy-related CV conditions and will discuss promising strategies or interventions for their prevention, diagnosis, and treatment.

Keywords: adverse pregnancy outcomes; hypertensive disorders of pregnancy; long-term pregnancy-related cardiovascular disease; maternal mortality and morbidity; peripartum cardiomyopathy.

FIG. 1.

Signaling pathways, potential biomarkers, and therapeutic targets in PE. Placental ischemia-derived imbalance in proangiogenic (VEGF and PlGF) and antiangiogenic (sFlt-1 and sEng) factors, oxidative stress, and inflammation led to systemic vascular dysfunction reflected in hypertension and proteinuria in PE. Potential targeted interventions include blockade, removal, or competitive binding of sFlt-1 or supplementation of recombinant isoforms of proangiogenic factors. AT1-AA, AT1 receptor autoantibodies; PE, preeclampsia; PlGF, placental growth factor; sEng, soluble endoglin; sFlt-1, soluble fms-like tyrosine kinase-1; VEGF, vascular endothelial growth factor.

FIG. 2.

Pathophysiology of peripartum cardiomyopathy. In pathogenesis of peripartum cardiomyopathy, the role of cathepsin D-cleaved 16-kDa prolactin fragment, microRNA146a, and decreased VEGF signaling has been suggested. Suppression of prolactin production by bromocriptine had positive therapeutic effects in some preclinical and clinical studies. STAT3, signal transducer and activator of transcription 3.

FIG. 3.

Accumulation of cardiovascular risk factors from preconception through pregnancy and postpartum periods. Demographic, clinical, behavioral, social, and environmental risk factors for cardiovascular disease may contribute to adverse pregnancy outcomes. These may persist throughout pregnancy and postpartum periods. Additional cardiovascular risk may be acquired or uncovered during pregnancy, including maternal conditions (hypertensive disorders of pregnancy and gestational diabetes) and fetal conditions (small for gestational age). Preconception and pregnancy risks may persist during the postpartum period and/or emergence of additional cardiovascular risk factors may occur, including maternal conditions (hypertension, diabetes, and dyslipidemia).