New Research is Changing How We Understand Preterm Birth

Preterm birth remains one of the biggest challenges in obstetrics—but new research is starting to change that picture. Kristin Gerson, MD, PhD, of Penn Medicine’s Department of Maternal Fetal Medicine, explains how her groundbreaking research may be able to improve outcomes.

What are some of the biggest misconceptions about preterm birth?
Dr. Kristin Gerson: One of the biggest misconceptions surrounding preterm birth is that the patient did something to cause it. We know patients can optimize health coming into pregnancy, have routine prenatal care, adhere to medical advice—do all the “right things”—and still have this undesired outcome. This sad reality is rooted in our limited understanding of the diverse molecular causes of preterm birth and stresses the critical need for more mechanistic research in this space.

How do the vaginal and cervical microbiomes affect preterm birth risk?
KG: The cervix is key to keeping a fetus inside the uterus during pregnancy. During the birth process, the cervix softens, shortens and opens to allow passage of the fetus through the birth canal. My research aims to understand biologic mechanisms of spontaneous preterm birth with a specific focus on premature cervical remodeling, or early softening and shortening of the cervix. Certain vaginal bacteria and bacterial communities have been associated with increased risk of preterm birth. Our lab studies how these vaginal bacteria interact with the host immune system to drive premature cervical remodeling on the pathway to preterm birth. As part of this work, we study the vaginal metabolome, which is the collection of small biochemicals called metabolites produced by metabolism of both cervical cells and vaginal bacteria. We have identified certain vaginal metabolites that protect against cervical remodeling in the presence of high-risk bacteria. Our findings raise the possibility that vaginal metabolite supplementation, similar to probiotics used to support gut health, may be a promising therapeutic for preterm birth prevention in the future.

How does lipid nanotechnology play a role in preterm birth prevention?
KG: Lipid nanotechnology is a powerful and evolving medical platform that has been used historically in vaccine development, cancer treatment and gene therapy. Our research team is investigating how lipid nanoparticles, essentially small fat droplets that encapsulate different types of therapeutic molecules, can be administered vaginally to disrupt premature cervical softening and shortening. We believe this tool carries enormous translational potential to advance the field and shape preterm birth prevention strategies.

Preterm birth rates vary greatly by race and geography. What does your research tell us about that?
KG: From a biologic perspective, a high-risk vaginal microbiome confers increased risk of preterm birth and is more common in BIPOC populations. This higher prevalence is likely determined by the environment and not biologic differences. Still, not all individuals with this microbiome-related risk have preterm birth, suggesting other factors are at play. To reduce rates, we need a more granular understanding of the molecular mechanisms that link known risk factors to preterm birth so that we develop better diagnostic tools and effective targeted therapies.