Pregnancy Complications Impart Higher Death Risk for Decades

Women who experience adverse pregnancy outcomes (APOs) face an increased likelihood of death decades later, according to an observational study of more than 2 million Swedish women.

Investigators looked at several APO types—gestational diabetes, preterm delivery, small for gestational age, other hypertensive disorders, and preeclampsia—and several different causes of death.

“It was striking that all five adverse pregnancy outcomes were independently linked with increased mortality risks even more than 40 years after delivery,” lead investigator Casey Crump, MD, PhD (University of Texas Health Science Center, Houston), told TCTMD in an email. These increases, though not all statistically significant over the longest time frame, extended to the various causes of death as well, “suggesting that there are multiple different underlying pathways,” he said. “Additional research is needed to delineate the underlying mechanisms, which may reveal new targets for intervention.”

Natalie Bello, MD, MPH (Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA), commenting on the study for TCTMD, said its results are the most recent confirmation that complications during pregnancy can have long-lasting fallout for female patients and even their children. Yet, these risks continue to be underappreciated.

“Primary prevention guidelines for cardiovascular disease do consider adverse pregnancy outcomes as a risk enhancer,” knowledge that can inform decisions on preventive measures like whether to start statin therapy, Bello explained.

It’s important for patients, if they’re not asked directly, to “bring up their pregnancy history when they’re meeting with all of their care team to discuss their personal risk” so that other factors, such as blood pressure and cholesterol, can be tracked, she said. “Our care is very fragmented in this country—you see an OB who delivers your child and if you’re lucky that’s in an integrated healthcare system where [clinicians] can see that, but often we may not be going back to those records.”

Understandably, these conversations can get skipped over, because “primary care doctors are really busy,” Bello noted. “They’re doing depression screening and [addressing] domestic violence: all these things are on their plates.” Pregnancy, she added, can fit in with that routine as part of medical history taking.

Women who experience adverse pregnancy outcomes need close follow-up with their primary care physician, starting soon after delivery, for regular preventive care. Casey Crump

For their paper, published online recently in JAMA Internal Medicine, Crump and colleagues looked at data on 2,195,667 Swedish women who gave birth during the years 1973 to 2015. Thirty percent had at least one APO and 8% had at least two, though not necessarily in the same pregnancy. The most common of these outcomes were delivery of an infant small for gestational age and preterm delivery.

The women were followed to a median age of 52, with the dataset reaching a total of 56 million person-years of follow-up by the end of 2018. Four percent of the women died, and the median age at death was 59 years. The most common cause of death was cancer (49%), followed by “other” causes (32%), cardiovascular disease (14%), respiratory disorders (4%), and diabetes (1%).

Each of the five APOs considered in the study were linked to all-cause mortality risk.

All-Cause Mortality Risk by Adverse Pregnancy Outcome

Women with APOs continued to have elevated risk even 30 to 46 years after delivering their babies: the associations were statistically significant for preterm delivery (HR 1.35), small for gestational age (HR 1.23), and gestational diabetes (HR 1.38).

Regarding cause-specific mortality, the likelihood of CV death was higher with each of the APOs. For cancer and respiratory death, risks were significantly elevated with preterm delivery and small for gestational age. Diabetes-related deaths were increased with preterm delivery, preeclampsia, and gestational diabetes.

To bolster their findings, the researchers also did an analysis that compared the female study participants with their siblings, which offered a way to control for unmeasured genetic or environmental factors that could be shared determinants of pregnancy complications and premature death. While this somewhat attenuated the associations, the added risk with each of the APO types remained significant.

For Crump, pregnancy is a time of “opportunity to identify high-risk women and start interventions earlier in life, before other health problems develop.

“Women who experience adverse pregnancy outcomes,” he continued, “need close follow-up with their primary care physician, starting soon after delivery, for regular preventive care to help reduce these risks and protect their long-term health.”