Study details

For the study, researchers screened 305 women, enrolling 75 nulliparous women —  women who had never given birth before — ages 18 to 50 who were seeking obstetric or gynecologic care between 2020 and 2021. Of the 75 women, 45 were pregnant and 61 completed the study.

Blood samples were collected from the women at enrollment and again postpartum — day 1 for pregnant women or 7 months for nonpregnant women — to measure epigenetic age using 11 molecular clocks.

According to the National Institute of Aging, epigenetics can mark accurate chronological time versus biological time.

"Our chronological age is based on our birthdate, but biological age means the true age that our cells, tissues, and organ systems appear to be, based on biochemistry," the institute said. A person's epigenome can be affected by their environment and experiences, according to the institute, "similar to how rings on the inside of a tree can tell us the tree's age and mark where it had encountered damage or stress."

The researchers found that, compared to nonpregnant women, pregnant women showed significant acceleration in biological aging across six of the 11 epigenetic clocks used.

Specifically, the researchers found that additional epigenetic age acceleration per 200 days among pregnant women ranged from 1.58 years to as much as 5.28 years. Each additional year of first trimester aging as measured by one of the epigenetic clocks, called GrimAge2, increased a person's odds of pregnancy complications by 36%.

Discussion

U.S. maternal mortality rates are notably higher than other high-income countries, which have been exacerbated by a significant increase in pregnancies in women over the age of 40. One study found there has been a 194% increase in the rate of babies born to older women in the United States since 1989.

However, while older age is an established risk factor for pregnancy complications, this new study suggests that chronological age alone isn't necessarily a reliable predictor of potential adverse outcomes.

"Ideally, translating this to clinical practice would mean that if you knew someone had accelerated epigenetic age early in pregnancy, you could initiate lifestyle interventions earlier, before they potentially go on to develop complications," she added.

In an accompanying editorial, Zev Williams and Yousin Suh, both from the department of obstetrics and gynecology at Columbia University, said the finding of an association between elevated GrimAge2-measured aging in early pregnancy and subsequent complications is "promising."

"GrimAge2, a second-generation epigenetic clock incorporating DNA methylation surrogates for plasma proteins, chronologic age, and smoking history, predicts mortality and morbidity risks in nonpregnant populations," they wrote. "Its early elevation in pregnancy suggests a potential future in which a simple first-trimester blood test might identify women at higher risk for complications, enabling timely interventions — from low-dose aspirin to nutritional counseling to enhanced surveillance."

Cynthia Chen-Joea, a family medicine physician who was not involved in the study, said the results of the study suggest what women's medicine could be in the future rather than what it currently is.

"The big take-away of this study is the fact that there are so many modifiable risk factors that we maybe have not focused on as much in maternal care," she said, adding that the study "is actually revolutionary and suggests how we're going to be providing maternal care in the future, by focusing on the individual person and the molecular levels of their risk factors."