Perfect timing

The key to pregnancy clockwork

Illustration by Greg Clarke

Pregnancy usually lasts nine months, but until recently it’s been a mystery why. Now researchers have discovered that meticulously timed changes in pregnant women’s immune responses are an important key to keeping their babies from arriving too early. The findings, which were published Sept. 1 in Science Immunology , reveal that there is an immune clock of pregnancy and suggest it may help doctors predict preterm birth.

Immune changes are a normal part of pregnancy, designed to protect a woman’s body from rejecting her fetus, but previous data suggest that related inflammation could trigger early labor. A group of researchers at the March of Dimes Prematurity Research Center at Stanford wanted to examine the characteristics of the changes, in terms of both timing and immune properties, that are present as women progress through pregnancy.

Almost 10 percent of babies born in the United States are born too soon. They face a range of risks that include respiratory problems, eye disease, deafness, brain injury and death.

“It’s really exciting that an immunological clock of pregnancy exists,” says 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.”

For the study, researchers used mass cytometry, a technique developed at Stanford, to simultaneously measure as many as 50 properties of each immune cell in the blood samples from 18 pregnant women who had full-term babies. The samples were taken at various times for each woman — once during each trimester of pregnancy and once six weeks after their babies were born.

The data were then analyzed using an advanced statistical modeling technique, which was introduced with this study, to detail immune system changes throughout pregnancy.

“This algorithm is telling us how specific immune cell types are experiencing pregnancy,” says the study’s senior author, Brice Gaudilliere, MD, PhD, assistant professor of anesthesiology, perioperative and pain medicine.

“The immune system does not act in isolation, and we’re now very interested in profiling its interplay with other aspects of mothers’ biology, such as their genetics, metabolism and the body’s microbial communities to come up with a holistic biological clock of pregnancy,” Aghaeepour adds.

The next step, the scientists say, is to conduct similar research using blood samples from women who deliver their babies early, to see whether their immune functions were different. “We’re especially interested in understanding more precisely what is happening very early and very late in pregnancy,” says Gaudilliere. “Ultimately, we want to be able to ask, ‘Does your immune clock of pregnancy run too slow or too fast?’”

The hope is to identify which immune properties are present in women who go on to deliver early and to design a blood test to detect them.

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Erin Digitale

Erin Digitale is the pediatrics senior science writer in the Office of Communications. Email her at

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