Understanding what occurs in the cervicovaginal space during pregnancy shows promise as a way to identify and offer therapeutic treatments to those most likely to have spontaneous preterm birth, according to this year’s presenter of the March of Dimes Annual Lecture.
Michal A. Elovitz, MD, director of the Prematurity Prevention Program, director of the Maternal and Child Health Research Program, and associate professor of obstetrics and gynecology at the University of Pennsylvania, presented “Emerging Concepts in the Pathogenesis of Preterm Birth” on Saturday afternoon, showing how specific molecular and microbial profiles can identify those at high risk for preterm birth and, if the future research matches the early positive results, lead to therapies to prevent preterm births.
Dr. Elovitz said that the accepted paradigm about how preterm birth happens has been that bacteria starts in the vagina, reaches the placenta through the uterus and begins an inflammatory response that leads to uterine contractility, and then cervical remodeling resulting in preterm birth. But several clinical trials targeting that paradigm failed to prevent preterm births.
So her research program decided to re-think preterm birth. The researchers looked at other biological systems that might have relevance to the cervix, vagina, and uterus. That led to a focus on the epithelial mucosal barriers in the CV space.
Very little was known about how the CV microbiome affected pregnancy, so Dr. Elovitz reached out to experts working in mucosal immunology and gut microbiology to begin understanding how the epithelial and mucosal barriers in the cervicovaginal space might play a role in preterm birth.
Those conversations and subsequent work led to a new hypothesis brought forward by Dr. Elovitz and her colleagues. This hypothesis says that the instigators of preterm birth are the biological and cellular events that take place in the CV space which lead to premature cervical remodeling, then uterine contractility and preterm birth.
One study showed that women who eventually had preterm births had different CV microbial communities than women who had term births eight to 12 weeks before the onset of any clinical symptoms relating to preterm birth, Dr. Elovitz said.
Suggesting that the CV space is active metabolically during pregnancy and that differences in the activity might play a role in preterm birth, in a separate nested-case control study, Dr. Elovitz explored the metabolome in CV fluid that was collected between 20-24 weeks and again between 24-28 weeks. Of the 313 biochemicals identified in the fluid, 82 were different in the fluid taken at the first collection in women who went on to have preterm births and 48 were different at the second collection period when compared to those who had term births.
Another study, Dr. Elovitz said, found that distinct microRNA profiles of the cervix were found in women who later had preterm births.
“This profile can be assessed non-invasively during pregnancy. It can also be used to determine how the cervix prematurely remodels into target novel therapeutics,” she said.
A test similar to a Pap smear allows for collection of cervical epithelial cells. This “RNA Pap” offers a valid, non-invasive method to assess the cervix at the molecular level during pregnancy, Dr. Elovitz said.
These are all early results, but the investigations continue, she said. Researchers now want to use these data to find feasible, biologically relevant mediators that can be targeted with therapeutics to reduce the rate of preterm birth.
“We are at a fork in the road,” she said. “Biomedical research, with the microbiome and mucosal immunology, is taking a whole new avenue, and we need to take advantage of it. And there is amazing work that can be done in just the next couple of years that can change how we think about preterm birth and hopefully change how we actually prevent this adverse outcome.”