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.

Summary and Conclusion: Framing a New Research Agenda on Maternal Morbidities and Mortality in the United States

“…Third, we need to get a lot better at tertiary prevention—preventing the serious and long-term sequelae of pregnancy complications. Silva et al 15 call attention to the “effects of maternal dysglycemia on mothers later in life and the transgenerational cycle of metabolic disease risk rooted in maternal dysglycemia.” Similarly, Varagic et al 14 observe that women's long-term cardiovascular health could be linked to adverse pregnancy outcomes. They review several large cohort studies and meta-analyses that found pregnancy complications—such as preeclampsia and other hypertensive disorders of pregnancy, gestational diabetes, preterm birth, pregnancy loss, and small for gestational age—to be associated with long-term risk for cardiovascular diseases in women.…”

“…Despite significant progress in the past decades, several articles in this volume continue to find critical knowledge gaps in our understanding of the causes and prevention of a whole range of pregnancy complications, including hypertensive disorders of pregnancy, 14 peripartum cardiomyopathy, 14 gestational diabetes, 15 infectious diseases ranging from influenza to intra-amniotic infections, 16 and perinatal depression. 17 Reducing and ultimately eradicating maternal mortality will require us to get a lot better at preventing pregnancy complications.…”

“…We also need more research on effective early interventions, including increased drug safety testing in pregnancy and lactation, as well as development of novel therapeutics targeting specific pathogenic mechanisms of pregnancy complications, such as sepsis or peripartum cardiomyopathy, before they spiral out of control. 14 , 16 Dagher et al 17 discuss the problems of underdiagnosis and undertreatment of perinatal depression and the need to expand available treatment options ranging from interpersonal psychotherapy, cognitive behavioral therapy, and pharmacologic interventions to complementary and integrative health approaches—these may include folate supplementation, yoga, acupuncture, and mindfulness, although the evidence for their full efficacy and safety remains limited. Thomas et al 21 also call for more research to better address pain during and after pregnancy.…”

“…They review several large cohort studies and meta-analyses that found pregnancy complications—such as preeclampsia and other hypertensive disorders of pregnancy, gestational diabetes, preterm birth, pregnancy loss, and small for gestational age—to be associated with long-term risk for cardiovascular diseases in women. 14 In light of the growing body of evidence supporting both pregnancy as a window to a woman's future health outlooks and intergenerational transmission of health risks to the offspring, an urgent need exists to identify effective interventions for tertiary prevention of the long term and perhaps intergenerational sequelae of pregnancy complications.…”

“…Prevention requires better elucidation of predisease pathways leading up to the complications, as well as identification of effective interventions preconceptionally and in early pregnancy. As Varagic et al 14 point out, ''there is growing recognition that the occurrence of pregnancy complications reliably identifies women with underlying, often unrecognized [cardiovascular] risk factors who may benefit from screening and preventive actions, such as preconception counseling to address risk and prepregnancy control of blood pressure, blood glucose, lipids, and weight.'' A number of established (e.g., high sensitivity C-reactive protein, triglycerides, lipids, glucose) and novel cardiovascular risk biomarkers (e.g., soluble fms-like tyrosine kinase 1, placental growth factor, vascular endothelial growth factor, endoglin) have been found to be altered in early pregnancy in women who later develop preeclampsia or peripartum cardiomyopathy, yet their utility in the primary prevention of cardiovascular complications in pregnancy remains to be shown.…”