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Stanford researchers are getting closer to understanding prematurity predictors

The nerve-wracking thing about being pregnant is that growing a baby is a black-box endeavor. Yes, you can read online about what piece of fruit your fetus resembles each week, and there are thrilling opportunities to see your little one's wiggles during prenatal ultrasounds. But there's also a lot of looking at your expanding midsection and saying "What is going on in there?"

And lurking behind that, the thornier question, "How will I know if something goes wrong?"

These questions don't just trouble expectant mothers; they are at the heart of a huge research effort to figure out what happens in pregnancies where the baby is born dangerously early. Premature birth, the most common form of "something going wrong" during pregnancy, affects nearly half a million U.S. families each year and recently surpassed infectious disease as the top killer of children under age 5 around the world.

As I report in my latest feature story for Stanford Medicine magazine, doctors would love to be able to predict and prevent preterm births. Right now, they mostly can't.

"At present, we usually identify women who are likely to deliver early by their medical history, unfortunately," said high-risk obstetrician Jane Chueh, MD, when I interviewed her for the story. "Someone with a previous preterm birth has the biggest risk; other than that, there's nothing special, no screening tool."

But researchers at the March of Dimes Prematurity Research Center at Stanford University, and at four other similar centers across the country, are changing that. As I reported on their broad and varied discoveries, I was particularly struck by Stanford-driven advances in our understanding of the connection between inflammation and preterm birth. The story explains:

Inflammation is the immune system’s and body’s way of getting rid of potentially harmful material. It’s also associated with obesity, stress, infections and diabetes — a litany of prematurity risk factors.

[Martin Angst, MD,] and his collaborators published a study comparing immune cells from the blood of mothers who had preterm deliveries against similar cells from mothers who had full-term pregnancies. The researchers used a relatively new technique, called cytometry by time-of-flight mass spectrometry, to test the inflammatory response of specific immune cell subsets. The technique lets scientists take a simultaneous look at all immune cell subsets represented in blood. They wanted to see if, under lab conditions, immune cells taken from women who had had a preterm birth were more sensitive to an inflammation trigger.

Indeed, immune cells called monocytes from women who had given birth prematurely responded differently when the researchers induced inflammation in the lab. In particular, certain components of the toll-like receptor 4 pathway, which acts like the stone that starts the avalanche of the inflammatory response, were more readily activated in these mothers’ monocytes.

“There is a change in the immune disposition of these people and we can see it,” [prematurity research center principal investigator David Stevenson, MD,] says. A future in which at-risk women receive targeted immunotherapy to block the pathways involved in preterm birth now seems possible, he adds.

Weaving together all the threads of new evidence into a complete picture of how preterm birth happens will be a complicated endeavor, but these discoveries are a great sign for the future of expectant mothers and their babies.

Previously: Precision health: a special report from Stanford Medicine magazineStanford microbiome research offers clues to the mystery of preterm birth, Counseling parents of the earliest-born preemies: A mom and two physicians talk about the challenges and Stanford/VA study finds link between PTSD and premature birth
Photo by Greyerbaby

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