When reviewing poor maternal health outcomes in the U.S., it is clear we cannot keep doing the same thing and expect to make pregnancy safe and healthy for all. A new approach is needed that harnesses the power of molecular advances to bring precision medicine to pregnancy health. Preeclampsia, one of the most dangerous complications in pregnancy, is a disorder of high blood pressure that has eluded the ability to effectively predict who will develop the condition.
Preeclampsia has been documented as far back as the Greeks and Hippocrates in 400 BC, who described it to be associated with headaches, drowsiness, and convulsions during pregnancy.
The word “eclampsia,” Greek for lightning, alludes to the suddenness with which a pregnant woman could start having seizures seemingly without warning during pregnancy or labor.
Our understanding of the disease has made modest progress as time has passed. By the early 19th century, leading researchers in obstetrics started to recognize additional indicators associated with the condition, including tissue swelling and protein in the urine. The early 20th century established the recognition of high blood pressure as a marker with the advent of the blood pressure cuff. These hallmark symptoms are all now classified as diagnostic attributes for what we label as preeclampsia.
Impacting 1 in 12 pregnancies, preeclampsia can have a profound impact on the health of families. Preeclampsia poses a serious risk to pregnancy that can lead to seizure, stroke, organ failure in the mother, and even maternal death. Survivors also face a fourfold increased risk of heart failure and a twofold increased risk of coronary heart disease, stroke, and death because of cardiovascular disease across their lifetime. Often striking without warning, the disease is also a leading cause of poor fetal growth, preterm birth, and can result in prolonged NICU and hospital stays.
Improved outcomes in medical fields like oncology and cardiology have not translated to pregnancy care. While our understanding of the signs and symptoms of preeclampsia has improved since the time of the Greeks, we still don’t know the “why” behind what’s driving the risk of preeclampsia. The prenatal care model—designed nearly 100 years ago to deal with preeclampsia—has largely remained unchanged.
What has hindered progress? Research on preeclampsia has been stifled on several fronts. For starters, preeclampsia appears to be a uniquely human disease. We cannot design research using animal models because this is a disease we don’t share with other species. Additionally, only in the past three decades has there been a concerted effort to include women in clinical research, let alone pregnant women.
For those of us who have been in the practice of obstetrics for years, we’ve recognized that preeclampsia may be more of a syndrome than a single disease. Several biologic paths ultimately lead to similar signs and symptoms. When trying to find a single therapy for a condition with multiple underlying causes, a one-size-fits-all approach is unlikely to work.
Since the 1920s, obstetricians have diagnosed preeclampsia based on the symptoms exhibited by patients during the second and third trimester—not based on the underlying causes or biological drivers. But we are on the precipice of a paradigm shift from reactive to proactive care based on a new biological discovery of preeclampsia.
Recent research published in Nature Communications, in which we were both investigators, uncovered unique molecular signatures clearly distinguishing severe and mild forms of the condition. The study also validated the first simple blood test to predict preterm preeclampsia, months before a patient has symptoms, in pregnant women without pre-existing high-risk medical conditions.
Molecular signatures prevalent in preterm preeclampsia cases are placental-driven vs. those for preeclampsia at term, which are more immune-driven. These advancements in understanding the biology of pregnancy health are reminiscent of breast cancer in the 1990s as the discovery of molecular subtyping of tumors created the opportunity for proactive, personalized, and preventive care.
Current guidelines from the U.S. Preventive Services Task Force and the American College of Obstetrics and Gynecology rely on generalized risk factors like pregnancy history, race, socioeconomic status, body mass index, and medical history that are not adequately addressing the underlying biologic pathways leading to preeclampsia. For the first time, understanding the associated molecular signatures helps physicians identify and potentially address the root causes of the condition.
With better prediction tools that are grounded in the underlying biology of the disease, pregnant patients and care teams can intervene on preeclampsia months before symptoms and more confidently implement an evidence-based preventive care plan to improve the chance for a full-term pregnancy and healthy delivery. This breakthrough also opens the door to discovering targeted therapeutics, uncovering new uses for existing pharmacologics for different molecular subtypes of preeclampsia, and improved clinical trial recruitment based on the patients’ underlying biology.
We’re extremely enthusiastic about these molecular discoveries and how a biology-first approach to preeclampsia can finally contribute to reducing complications rather than simply managing symptoms. By being able to predict the risk of complications like preeclampsia, we can begin to usher in a new standard of care that is proactive and preventive.
Thomas McElrath and Kara Rood are maternal-fetal medicine physicians.
