After Adverse Pregnancy Outcomes, Mortality Risk Lingers for Decades

Women who experienced major adverse pregnancy outcomes still had increased mortality risks decades later, a population-based cohort study of Swedish data found.

Adverse pregnancy outcomes independently associated with increased mortality across the entire follow-up of up to 46 years after delivery were preterm delivery, small for gestational age, preeclampsia, other hypertensive disorders, and gestational diabetes, with adjusted hazard ratios of 1.13-1.52.

All five associations remained significantly elevated even looking just at the period from 30-46 years after delivery, when women were typically in their 50s or 60s; and the risk was greater with multiple adverse pregnancy outcomes, Casey Crump, MD, PhD, of the University of Texas Health Science Center and McGovern Medical School in Houston, and colleagues reported in JAMA Internal Medicine.

Previously, Crump and team had studied how birth complications impact the long-term health of children and wanted to also look at the impacts on maternal health.

“We found that the higher mortality risks in women with adverse pregnancy outcomes were attributable to multiple different causes of death, including heart disease, diabetes, respiratory disorders, and cancer, suggesting that there are multiple different underlying pathways,” Crump told MedPage Today, adding that future research should look into those underlying mechanisms to inform potential interventions.

David Hackney, MD, a maternal-fetal medicine physician at Case Western Reserve University in Cleveland, who was not involved in the study, called the findings “somewhat anticipated, as we know broadly that several complications during pregnancy, particularly preeclampsia and gestational diabetes, are associated with health complications in later life, particularly cardiovascular disease and type 2 diabetes mellitus.”

However, Hackney said this study “highlights the clinical need to recognize adverse obstetric history as an overall signifier of medical risks.” Non-ob/gyn physicians do not always look back to obstetric records, he said, so they “may be unaware of risk factors for long-term morbidity and mortality.”

Researchers used the Swedish Medical Birth Register, which contains prenatal and birth data, to identify singleton pregnancies from 1973 to 2015. Deaths were identified using the Swedish Death Register, which includes causes of death. In total, nearly 2.2 million women with data on pregnancy duration and infant birth weight were included. Median age at birth was 27, and at the end of follow-up was 52.

In total, 4% of women died (median age 59), with 14% of the deaths attributed to cardiovascular disease, 49% to cancer, 4% to respiratory disorders, 1% to diabetes, and 32% to other causes.

Excess mortality was found with preterm delivery (aHR 1.41, 95% CI 1.37-1.44), small for gestational age (aHR 1.30, 95% CI 1.28-1.32), preeclampsia (aHR 1.13, 95% CI 1.10-1.16), other hypertensive disorders (aHR 1.27, 95% CI 1.19-1.37), and gestational diabetes (aHR 1.52, 95% CI 1.46-1.58).

Co-sibling analyses only partially attenuated the adjusted HRs for all-cause mortality across outcomes, which suggested the results “were only partially explained by genetic or environmental factors that may be shared determinants of adverse pregnancy outcomes and early mortality within families,” the authors wrote.

Crump noted that adverse pregnancy outcomes impact more than 40 million women worldwide and 1 million in the U.S. every year. In the cohort, 30% of women experienced one or more adverse pregnancy outcomes and 8% experienced two, although not necessarily in the same pregnancy. “The present findings may have even higher public health importance in U.S. racial and ethnic minority populations that have more restricted access to postpartum care and higher rates of adverse pregnancy outcomes and mortality,” Crump noted.

The authors concluded that “women with adverse pregnancy outcomes need early preventive actions and long-term follow-up for timely detection and treatment of chronic disorders associated with early mortality.”

Hackney cautioned about “intrinsic limitations to studies that reach back into the 1970s with regards to consistency of clinical diagnoses over such a long period of time.” For instance, diagnostic criteria and screening methodologies have changed for some conditions, like preeclampsia and gestational diabetes.

Crump and team noted several other limitations, including lack of information on behavioral factors, potential underdetection of gestational diabetes due to no national consensus on screening in Sweden, low racial diversity in the population studied, and potential for residual confounding in the co-sibling analysis despite controlling for several maternal and familial factors.

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