Protein analysis of amniotic fluid reveals clues about preterm birth

Identifying protein biomarkers predicts success for cervical stitching

Doctors treating pregnant women with threatened preterm birth sometimes sew the cervix closed, a procedure known as cerclage. Despite this traditional intervention, many women still lose the pregnancy. While the causes of preterm labor are not well understood, researchers at the University of Maryland School of Medicine and Yale University report that they can now predict who will benefit from cerclage by rapidly identifying the presence of several distinct proteins in amniotic fluid. Study results will be published in the March 1 issue of the American Journal of Obstetrics and Gynecology.

“We looked at a group of women with pregnancies between 18 to 22 weeks. These women had a condition called incompetent cervix, where their cervix dilates in the absence of labor,” says Carl P. Weiner, M.D., professor of obstetrics, gynecology and reproductive sciences at the University of Maryland School of Medicine.

The researchers tested the amniotic fluid for four distinct proteins they previously had linked to inflammation, a known cause of preterm labor. “Women with these four protein biomarkers went on to deliver early even though their cervix was sewn shut. And, for the first time, our research identified another protein biomarker in the amniotic fluid, this one linked to decidual hemorrhage or bleeding into the lining of the uterus,” explains Dr. Weiner who is a maternal/fetal medicine specialist at the Center for Advanced Fetal Care at the University of Maryland Medical Center. “Women with the biomarker for decidual hemorrhage also went on to deliver early, despite efforts to stop preterm labor.”

Researchers believe these protein biomarkers will not only allow doctors to predict whose preterm labor can be stopped, but that the identification of these proteins opens a window of understanding into the causes of preterm labor. With that knowledge, they hope to develop more effective treatments for preterm birth.

Dr. Weiner says, “Right now, drug therapies, compared to placebo, can at best delay delivery by 48 to 72 hours. And, as we’ve shown, cerclage, or sewing the cervix closed, won’t help women with the biomarkers for either inflammation or decidual hemorrhage. This research takes us a giant step forward into mapping out the mechanisms of preterm birth and perhaps finding new ways to attack the problem.”

Dr. Weiner notes that for the women whose amniotic fluid did not contain the protein biomarkers, cerclage helped them carry their pregnancies further to term or near term. However, about 50 percent of them still went on to deliver prematurely. “This shows that there are other causes, besides inflammation and decidual hemorrhage, that lead to preterm birth, suggesting additional biomarkers will be found,” explains Dr. Weiner.

Because preterm birth may result from a range of problems, researchers suspect that successful treatment will require combination therapy. “There probably isn’t a single, magic bullet that will prevent preterm birth. We need to expand our horizons. Right now, it appears a combination of treatments will prove the key to success,” says Dr. Weiner.

Another important component of this protein analysis is that it can be performed quickly. Recent laboratory advances will allow doctors to get test results in about one hour. Dr. Weiner and his colleagues worked with proteomic chip technology from Ciphergen Inc. to develop this new method of protein analysis called MR scoring.

In the United States, about 11 percent of women deliver preterm, and about three percent deliver before 32 weeks, resulting in high infant mortality rates. Normal gestation for pregnancy is about 40 weeks.

Dr. Weiner’s co-investigators for the study were Keun-Young Lee, M.D., Department of Obstetrics and Gynecology, Kangnam Sacred Heart Hospital, Hallym University, Seoul, Korea; Catalin S. Buhimschi, M.D., and Irina A. Buhimschi, M.D., Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University, New Haven, CT; and Rob Christner, Ph.D., Ciphergen Biosystems, Fremont, CA.