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Stanford scientists find the immune clock of pregnancy to help understand preterm birth

Much of human development happens on a flexible timeline. One kid might lose her first tooth at age five; another at age six. Both are normal.

Pregnancy is different: It's nine months, and being born just a few weeks early can mean real problems for the baby. But until now, the body's timekeeping mechanism during pregnancy has been a mystery.

Today, in a paper published online in Science Immunology, a Stanford team reveals that the immune system is intimately involved in the timing of pregnancy. A pregnant woman's immune function changes in a precisely-timed way throughout the course of her pregnancy, the researchers found. The new study examined what happens to the immune system in women who deliver their babies near the due date, and provides an important foundation for future work to understand preterm birth, our press release explains:

'It's really exciting that an immunological clock of pregnancy exists,' said the study's lead author, Nima Aghaeepour, PhD, instructor in anesthesiology, perioperative and pain medicine. 'Now that we have a reference for normal development of the immune system throughout pregnancy, we can use that as a baseline for future studies to understand when someone's immune system is not adapting to pregnancy the way we would expect.'

To conduct the study, the researchers collected blood samples from 18 pregnant women who had full-term pregnancies. The blood was analyzed with time of flight mass cytometry, a technique that allows extremely detailed characterization of which immune cells are present and how they respond to a variety of stimuli, such as compounds that simulate different types of infections. The scientists then used an advanced statistical modeling technique to figure out how a panoply of immune changes during pregnancy are timed. They validated the resulting model using blood samples from an additional 10 pregnant women who were not part of the first phase of the research.

When I talked with Agheepour about the new findings, I asked if he thought the immune system was actually driving the timing of pregnancy, or if it was something else. "In biology it's rarely black and white," he told me. "I think the immune system drives part of the outcome, and the immune system is affected by pregnancy as well. I'm sure it goes both ways."

The research team, which also includes senior study author Brice Gaudilliere, MD, PhD, has several ideas for what they'd like to study next to understand the immune clock better. One important project will be to compare blood samples from women who deliver their babies too early to those with full-term pregnancies, with the hope of learning how to predict and prevent dangerously early births. Again, from our press release:

'We're especially interested in understanding more precisely what is happening very early and very late in pregnancy,' Gaudilliere said. 'We'd like to see if there is really a switch we can catch, a sweet spot where deviation from the norm would be maximal with pathology.'

Notably, a separate team of Stanford researchers is studying how different types of vaginal bacteria influence preterm birth risk. Over the next few years, it'll be quite interesting to see how these metabolomic and immunologic strands of research come together to increase our understanding of premature birth.

Previously: Stanford researchers refine bacterial signature associated with premature birth, Stanford/VA study finds link between PTSD and premature birth and Scientists create a placenta-on-a-chip to safely study process and pitfalls of pregnancy
Photo by GirlInLimbo

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