Gestation complications make babies biologically younger, study finds

A study co-authored by a Keck School of Medicine professor found an extremely rare aging pattern in which newborns with certain gestation complications could be born biologically younger than their peers.

Preeclampsia, a serious blood pressure condition that develops during pregnancy, and gestational diabetes were significantly associated with decelerated gestational aging in newborns in comparison to infants unexposed to these pregnancy implications. The national multisite cohort study that resulted in these findings was conducted under the National Institute of Health’s Environmental Influences on Child Health Outcomes program and was published in JAMA Network Open in February.

This decelerated aging pattern is almost unprecedented in epigenetics — the study of how chemical modifications to genomes might influence gene expression or the magnitude of gene expression.

“In aging research, if your epigenetic ‘clock’ shows an older age than your chronological age — due to exposures to various stressors — that’s viewed as bad, as putting people at increased risks for illness,” said corresponding author Carrie Breton, a professor of population and public health sciences at Keck. “So, I [thought] we might see the same thing in the womb, but we didn’t. We saw the opposite effect.”

Researchers compiled data from 1,801 infants born between 1998 and 2008 to mothers diagnosed with preeclampsia, gestational diabetes or gestational hypertension — three of the most common pregnancy complications.

The team collected blood biospecimens from participants at birth, then measured the DNA methylation, a heritable epigenetic mark, from those samples to determine their epigenetic ages. The research team then compared these ages to those of infants who were unexposed to such complications, as well as the participants’ chronological age at birth, measured in pregnancy weeks.

Researchers found that babies who were exposed to preeclampsia or gestational diabetes during pregnancy showed decelerated gestational age in comparison to those who were unexposed to these two complications. 

Exposure to gestational hypertension did not produce a measurable impact on the epigenetic age of infants.

Because the study was a collaborative effort among almost 70 cohorts across the country, Breton and her team endeavored to balance the needs of every cohort and accordingly integrate data about participants’ epigenetic ages in different ways.

“We actually tried to take a very flexible approach because many cohorts had measured their epigenetic marks differently,” Breton said. “We used and harmonized data across all of the platforms to be as inclusive as possible.”

Even though the consortium-type study was a massive assemblage of experts in epigenetics, which proved a challenge for Breton’s team to coordinate, Breton eventually embraced and enjoyed the  collaboration.

“Corralling the troops, keeping things going, trying to balance everyone’s needs and get the science done, and publishing it in a semi-timely fashion is the challenge,” Breton said. “What was neat and different about this was meeting more people from across the country who have similar research interests, learning more about their own cohorts and pulling it all together.”

The rare aging pattern observed in the study has raised intriguing questions for experts in the field. 

“It’s a really exciting study, and I think one of the next steps that they can explore is linking decelerated epigenetic aging to other child health outcomes, so we can continue to validate the neurodevelopmental effects,” said Max Aung, an assistant professor in the division of environmental health at Keck.

Given the advantage of epigenetic age data collected many years ago, Breton said, her team has planned to continue their research with the same cohort of children and investigate if these epigenetic changes detected at birth could be linked to health implications later in childhood.

“One of the things that we are pretty poised for within ECHO would be to start to look at what health outcomes [decelerated epigenetic age] might be associated with,” Breton said. “One of the things that ECHO’s very interested in is understanding the potential effects on obesity risk and on respiratory health.”

Subsequent research could help doctors and researchers use that knowledge to develop targeted interventions that might mitigate those epigenetic quirks.

“It could be something that serves as a biomarker, and maybe there’s a way to use it to screen for children who might be at higher risk for something,” Breton said.