Increased Risk of Death Associated with Pregnancy Complications Persists up to 50 Years Later

Women who experience pregnancy complications could be at an increased risk of mortality for the next 5 decades, according to a new analysis.¹

Conducted by investigators at the Perelman School of Medicine at the University of Pennsylvania, results of the study provide an overview of total and cause-specific mortality associated with a bevy of pregnancy complications, including gestational diabetes,preeclampsia, induced labor, prelabor cesarean delivery, and more.¹

“We know that the context of childbirth has changed since the 1950s and ‘60s, but these findings demonstrate how crucial it is to people’s long-term health that we invest in preventive care and screenings for people with complicated pregnancies and deliveries, both then and today,” said lead investigator Stefanie Hinkle, PhD, an assistant professor of Epidemiology at Penn Medicine.²

Together with colleagues from Penn Medicine, Hinkle launched the current research endeavor citing a lack of diversity among former studies examining long-term mortality among women experiencing pregnancy complications. With funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, investigators designed the study as an analysis of data from the Collaborative Perinatal Project.

A 50-year prospective study, the Collaborative Perinatal Project included data from 48,197 pregnant participants with 58,760 pregnancies from 12 US sites between 1959-1966.³ Using linked data from the National Death Index and Social Security Death Master File, investigators planned to assess risk of all-cause and cause-specific mortality for preterm delivery, hypertensive disorders of pregnancy, gestational diabetes, and impaired glucose tolerance using Cox models adjusted for age, prepregnancy body mass index, smoking, race and ethnicity, previous pregnancies, marital status, income, education, previous medical conditions, site, and year.¹

After exclusion of those who died during the index pregnancy and those without vital status linkage, investigators identified a cohort of 46,551 individuals for inclusion in their final analyses. Of these, 45% were Black and 46% were White. The cohort had a median time between the index pregnancy and death/censoring was 52 (IQR, 45-54) years.¹

Initial analyses indicated 15% of patients had preterm delivery, 5% had hypertensive disorders of pregnancy, and 1% had gestational diabetes or impaired glucose tolerance. Investigators pointed out preterm delivery was more common among Black women (20%) than White women (10%).¹

When assessing risk of all-cause mortality, an increased risk was observed for women with preterm spontaneous labor (aHR, 1.07 [95% CI, 1.03–1.1]), premature rupture of membranes (aHR, 1.23 [1.05-1.44]), induced labor (aHR, 1.31 [1.03–1.66]), and prelabor cesarean delivery (aHR, 2.09 [1.75–2.48]) compared to their counterparts with full-term delivery. Compared to those who were normotensive, results suggested gestational hypertension (aHR, 1.09 [0.97-1.22]), preeclampsia or eclampsia (aHR, 1.14 [0.99-1.32]), and superimposed preeclampsia or eclampsia (aHR, 1.32 [1.20-1.46]). Additionally, compared with normoglycemic women, those with and gestational diabetes or impaired glucose tolerance were at an increased risk of all-cause mortality (aHR, 1.14 [1.00–1.30]).¹

Investigators highlighted analyses indicating the P values for effect modification between Black and White participants for preterm delivery,hypertensives disorders of pregnancy, and gestational diabetes or impaired glucose tolerance were 0.009, 0.05, and 0.92, respectively. Investigators also pointed out preterm induced labor was associated with greater mortality risk among Black women (aHR, 1.64 [1.10–2.46]) compared with White (aHR, 1.29 [0.97–1.73]) women, but preterm prelabor cesarean delivery was higher in White women (aHR, 2.34 [1.90–2.90]) compared with Black women (aHR, 1.40 [1.00–1.96]).¹

“Future work should seek to understand whether intervening earlier in the postpartum period among high risk patients prevents future disease incidence,” Hinkle added.² “Our group is also currently working to identify low-cost interventions to potentially prevent complicated pregnancies and deliveries.”

References

1. Hinkle SN, Schisterman EF, Liu D, et al. Pregnancy complications and long-term mortality in a diverse cohort. Circulation. March 2023. doi:10.1161/circulationaha.122.062177
2. Birth complications tied to death risk decades later. Birth Complications Tied to Death Risk Decades Later. https://www.pennmedicine.org/news/news-releases/2023/march/birth-complications-tied-to-death-risk-decades-later. Published March 14, 2023. Accessed March 15, 2023.
3. Klebanoff MA. The Collaborative Perinatal Project: A 50-year retrospective. Paediatric and Perinatal Epidemiology. 2009;23(1):2-8. doi:10.1111/j.1365-3016.2008.00984.x