Stanford researchers share new findings on preeclampsia pathogenesis, the effects of wildfires on preterm birth and hypertensive disorders at SMFM23

Ob/Gyn faculty, staff, and trainees
Photo by Anna Girsen

Earlier this month, the Society of Maternal-Fetal Medicine held its annual pregnancy meeting in the city of fog, San Francisco. Just north of Stanford, the conference drew thousands of researchers, clinicians, and trainees to engage with cutting-edge science in maternal-fetal medicine and network with leaders and innovators in the field. Stanford Medicine’s Obstetrics and Gynecology department had amazing representation with two oral presentations and 15 poster presentations from work led by our investigators under the Dunlevie Maternal-Fetal Medicine Center for Discovery, Innovation and Clinical Impact.

Turning a Corner on Preeclampsia

Postdoctoral researcher Yanming Wu, MD, PhD, shared preeclampsia research from Virginia D. Winn’s, MD, PhD, lab to a packed floor on the first day of the convening. Preeclampsia is a well-known but not well understood pregnancy-specific condition that occurs in 5-7% of pregnancies. In our modern day, this complication is the leading cause of maternal and neonatal mortality and morbidities. Using a novel in vitro endothelial cell model, Wu and researchers worked to advance the mechanistic study of maternal endothelial dysfunction in the development of preeclampsia — what this comes down to is determining if factors in preeclamptic sera impact endothelial cell function.

Preeclampsia remains a difficult condition to trace pathogenetically and to treat because it affects multiple systems of the body. Endothelial cell dysfunction is the leading theory as it connects many of symptoms presented by preeclampsia, which include hypertension, pulmonary edema, proteinuria, seizures, and liver dysfunction. A unique cell type, endothelial cells, form the inner lining of blood vessels and come in direct contact with blood circulating in the body — in fact, the endothelial cell model Wu and the team were working with was invented by cardiologists Joseph Wu, MD, PhD, and Nazish Sayed, MD, PhD. The ability to use this replenishable, genetically manipulable maternal cell model is a huge breakthrough because the access to endothelial cells previously relied on biopsies or difficult isolation processes from blood samples with limited growth potential. (Majority of primary endothelial cell models are of fetal origin.)

Working with three patient-derived cell lines, the research team was able to confirm that the preeclamptic sera significantly impacted endothelial cell functions because the cells imitated the mechanisms of endothelial dysfunction, with the preeclamptic sera affecting the endothelial cell’s vasodilation (measured through nitric oxide release), migrations, and tube formation. Notably, this was not a result of reduced cell viability — that is the cells were not functioning at a lower rate because they were dying due to the exposure to preeclamptic sera versus the control treatments.

One interesting but unproven observation was that the postpartum sera had a compensating effect in regard to tube formation and cell migration, which could hint at restorative factors that come after giving birth. While an interesting outcome, the team hopes to hone in more on pathogenesis on a genetic level. “What’s next is that we would like to look further into how gene expression profiles would be impacted by exposure to patients’ sera and use gene editing techniques to explore the genotype-phenotype effect in the development of preeclampsia,” Wu said.

Clearing the Smoke on Wildfires and Pregnancy

Maternal-fetal medicine fellow Anne Waldrop, MD, discussed new findings about the harms of exposure to wildfire smoke to an attentive and eager audience on the Saturday of the conference. Over the last decade, California has been ravaged by devastating wildfires, almost to the point that it is becoming a seasonal element for the west coast. Many will remember photos from September 2020 of San Francisco and the surrounding Bay Area tinged with a deep orange smog.

Smoke carries particulates (think pollutants like carbon monoxide) that not only enter the airway and obstruct lung function, but because some of the particulates are so small (30 times smaller than the human hair), these particles and droplets can also enter the bloodstream. While it is known that smoke’s particulate matter can affect human health, the impacts on pregnancy have not been observed and recorded in a way that can lead to clear recommendations and assessment of risks for pregnant patients.

Studies have shown that exposure in the first trimester can lead to hypertensive disorders and preeclampsia as well DNA damage and inflammation. One study by Heft-Neal, et al. found that one day of exposure to any wildfire smoke during pregnancy was associated with an 0.49 % increase in risk of preterm birth, anything earlier than 37 weeks gestation. Waldrop and the research team worked to add this current knowledge about the effects of particulate matter on pregnancy by focusing in on its connection to hypertensive disorders.

Using state birth certificate data from 2007-2012 (the most recent and available dataset) in combination with smoke plume records, the team was able to extract level of smoke intensity down to the zip code for each day. The study included over 2.5 million pregnant individuals, with 86% of which were exposed to at least one day of wildfire smoke. On average, pregnant individual experienced exposure to wildfire smoke for 7.5 days.

Waldrop and the research team found that exposure at any level of intensity was associated with preterm birth confirming prior findings and added that exposure at any gestational age increases risk with each passing day. What is new is that the team’s analysis pointed to a connection between wildfire smoke intensity with spontaneous preterm birth but not medically indicated preterm birth nor with hypertensive pregnancy disorders.

Most likely a lot of these [people] didn’t recognize the days that they were being exposed.

What’s worrisome is no counties in California are in the clear when it comes to exposure and the number of wildfires is on the rise throughout the western part of the United States. “Not all smoke exposures are these dramatic smog- and smoke-filled days.” Waldrop told NBC News. “Most likely a lot of these [people] didn’t recognize the days that they were being exposed.”