New Clues in Predicting Spontaneous Preterm Birth and Preeclampsia

A pregnant Caucasian woman is indoors in a doctor's office. Her female doctor is wearing medical clothing. The woman is holding her stomach which the doctor writes on a clipboard.Seven to eight percent of pregnancies end in spontaneous preterm birth. About five percent of pregnancies involve preeclampsia. The problem is, we do not do a good job predicting which women are at heightened risk for these issues.

“During early prenatal care, it’s almost as if we’re driving blind with respect to the risks of these conditions,” said Thomas F. McElrath, MD, PhD, associate obstetrician and gynecologist at the Brigham and Women’s Hospital Department of Obstetrics and Gynecology.

While obstetrics as a field has excelled in screening for relatively rare birth defects such as Down syndrome, it has lagged in screening for spontaneous preterm birth and preeclampsia—two issues that affect many more mothers and babies. “We’ve gotten used to tolerating these conditions that are such major sources of morbidity, but we haven’t focused on how to screen for them more effectively,” Dr. McElrath said.

Traditionally, screening for spontaneous preterm birth has been largely based on a women’s pregnancy history (which Dr. McElrath called “an imperfect method”) or on events that occur toward the end of a pregnancy (when a woman presents clinically). In his research, Dr. McElrath has instead concentrated on the 12-week mark of pregnancy.

In a 2016 study published in the American Journal of Obstetrics & Gynecology, Dr. McElrath and his co-authors analyzed plasma samples obtained as part of the prospectively collected LifeCodes birth cohort. Established by Dr. McElrath and David Cantonwine, PhD, also of the Department of Obstetrics and Gynecology, LifeCodes is an extensive biobank of samples, including blood, urine and placental samples, collected during almost 6,000 pregnancies. It is used to research biomarkers that may be associated with pregnancy complications as well as the effects of environmental exposures on pregnancy outcomes.

“Our study found that proteins that are being expressed within the maternal-fetal system at 10 to 12 weeks begin to predict the outcome later in pregnancy,” he said. “Long before it’s something that’s clinically recognizable as a potential risk, you’re already starting to see these early, subtle changes in women who go on to have spontaneous preterm birth versus those who don’t.”

The study authors noted that with further validation, “these changes…will allow the stratification of patients at risk of spontaneous preterm birth before clinical presentation.”

Dr. McElrath is the lead author of a paper currently under review that validates the findings of the 2016 study in a separate, multicenter population.

The possible therapeutic implications of these studies, explained Dr. McElrath, is that simply realizing a woman is at increased risk can have a positive impact. “If high-risk women receive increased attention—even just a nurse calling them every week, as was the case in one study—or have more frequent visits, they do better than women with the same risk background who receive standard care,” he said. “We don’t know exactly why, but just knowing something is going on and paying closer attention to the patient is effective in its own right.”

The next step, Dr. McElrath suggested, will be determining which of the known modalities—e.g. cerclage, cervical pessary, progesterone, aspirin—might be effective given the pattern of protein expression associated with each woman’s risk.

“Here’s the really intriguing part: Might there be therapy that can be tailored to a particular pattern?” Dr. McElrath asked. “Rather than treating all women at risk for preterm birth with the same therapy, which we do now, can we tailor each woman’s specific profile to a specific therapy?”

Over time, Dr. McElrath imagines creating a model similar to what is used in oncology today. That is, a patient diagnosed with cancer undergoes a battery of tests that characterize the cancer and ultimately inform the specific and individual type of chemotherapy recommended.

“I’d like to be able to test a pregnancy around 12 weeks and then apply the therapy that’s most appropriate based on the results of that test,” Dr. McElrath said. “The therapy may differ from individual to individual, but it will be based upon knowing the most effective therapy for that presentation.”

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