Forty weeks. That’s the magic number nature says it takes a woman to make a new, fully-developed life. It’s how long it takes, starting from a woman’s last menstrual period, for sperm to fertilize an egg, an embryo to form, body parts to take shape, organs to grow, and a future little one to be equipped with all the systems necessary to heartily take on the world outside its mother’s womb. But according to the Centers for Disease Control and Prevention (CDC), about one in ten pregnant women every year in the United States go into labor well before the proverbial clock strikes 40.
Labor that occurs on its own before week 37 and results in a birth is labeled as “spontaneous preterm birth,” and that tag is associated with a host of potential complications resulting from incomplete fetal development. Spontaneous preterm birth is also the number one cause of neonatal death around the world. Perhaps the scariest fact of all is that even in 2020, doctors admit they’re not entirely sure why some babies come early. But new research from experts at Penn’s Perelman School of Medicine is adding key data that may steer future investigations toward the elusive answer.
“We do not understand the precise mechanisms by which women go into labor at full-term any more than we understand why some women go spontaneously into labor weeks, if not months, prior to the expected delivery date,” said Michal Elovitz, MD, a professor of Obstetrics and Gynecology and the director of the Maternal and Child Health Research Center at Penn Medicine. “It does not help that, in general, there has been significantly less funding for research in women’s health, but important clues are keying us into health during reproductive age and pregnancy and helping us bolster our understanding.”
Likely, Elovitz said, there’s a myriad of factors that contribute to a woman’s risk of spontaneous preterm birth. Many of the risk factors have been known for years, Elovitz said. For example, the CDC reports that the risk of preterm birth increases in women who are black, teenagers, those carrying more than one baby, and those who’ve previously had a preterm birth. Additionally, women who use tobacco or cocaine are also among those with higher risks.
But, as any middle school science teacher will tell you, correlation is not causation: an association between one thing and another does not mean that thing one necessarily causes thing two. The plus side: by exploring known associations and looking for others, experts at Penn Medicine are focused on finding the actual mechanisms at play so that targeted approaches can be used to help more women bring their babies to a full term. Specifically, the outside world may be a key driver of the internal health of an expectant mother.
Last year, Elovitz and her colleagues looked at 2000 women and found strong associations between bacteria (microbiota) in the vaginal space and risk for preterm birth. Non-optimal microbiota was associated with about a 2.5 fold increase in spontaneous birth among all women. In other body systems, such as the gut, manipulating bacteria is a way for clinicians to positively influence a patient’s health.
“That study promoted many more questions,” Elovitz said. “‘What contributes to a non-optimal microbiota?’ ‘Are there other external factors and or environmental determinants that shape the vaginal microbiota and or the risk of preterm birth?’”
Just this month, Penn experts in maternal-fetal medicine, including Elovitz, traveled to Dallas to present new findings that begin to answer some questions about environmental determinants at the Society of Maternal-Fetal Medicine (SMFM) Annual Pregnancy Meeting. Previously, scientists were unable to definitively say whether air pollution has ties to spontaneous preterm birth. But research led by Elovitz and Heather Burris, MD, MPH, an assistant professor of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania and an attending physician at Children’s Hospital of Philadelphia found that pregnant women who lived in areas with high levels of air pollution were more likely to face spontaneous preterm birth. This association held true even when controlling for factors like race. The study earned Burris a research award at the meeting.
The type of air pollution Burris assessed, Particulate Matter 2.5, is a class of pollutants 2.5 micrometers and smaller. (That’s .0025 millimeters.) It’s so fine that when inhaled, it can break through many barriers in the body and circulate in the blood. Luckily, and thanks to environmental regulations, levels of Particulate Matter 2.5 in the United States have declined over the past few years.
“It’s certainly naïve to think that most pregnant women have the luxury of staying inside their homes on high-pollution days or choosing to live in areas with little pollution,” Burris said. “Our research would suggest that it’s ideal to stay inside on days when high-pollution levels are forecasted, but it’s mostly incumbent on government officials to keep monitoring air pollution and working to continue the trend of decreasing levels of these microscopic pollutants within the United States.”
Burris and Elovitz have also found that air pollution is associated with an unfavorable vaginal microbiota suggesting a relationship between environmental and biological risk factors that may further increase the risk of preterm birth.
Besides physical factors, social factors may also play a role in preterm birth. Additional research, presented in Dallas, from Kristin Gerson, MD, PhD, a fellow in Maternal-Fetal Medicine, and Elovitz, found that among women who had non-optimal vaginal microbiota, those who reported feeling high levels of stress during pregnancy were more likely to go experience preterm birth than those who reported lower levels of stress.
“The efforts of our prematurity research center at Penn over the past few years have yielded exciting results and suggest that risks for preterm birth may compound,” said Samuel Parry, MD, interim chair of Obstetrics and Gynecology. “Along with the research presented at the SMFM meeting, my colleagues and I are earnestly looking at placental metabolism and abnormal cervical remodeling, and we believe those are areas that might hold key answers, too.”
For now, the best advice for expectant moms is to keep appointments with their physicians, see a maternal-fetal medicine expert if there are specific concerns, and use general best-practices to take care of their health, said Joseph Teel, MD, an obstetric provider and vice chair for Clinical Operations in the Department of Family Medicine and Community Health.
“I tell my patients to focus on the things we know are good for fetal development and their own health,” Teel said. “Regular checkups, prenatal vitamins, healthy food, proper sleep, and vaccinations all can directly impact the health of your baby. And, it’s easier said than done, but try to avoid things or environments you find stressful.”
It’s also important for patients and their physicians to communicate about odds of a healthy pregnancy when patients plan to have a child, Teel said. “Because we know associations tied to unfavorable outcomes, there are many measures we can use to help counsel hopeful parents so that, at the very least, they have a good sense of risks before they decide to have a baby.”
With funding support from the National Institutes of Health and the March of Dimes, Elovitz and her colleagues have made critical discoveries over the past five years. In the years to come, Elovitz says ongoing research that focuses on the cervix, immunology, microbiology, and compounding risks could fill in the blanks and provide answers that the medical community — and mothers — have been hoping for. As scientists continue searching for those answers, Penn Medicine plans to stay at the forefront.
“We’re confident that the discoveries we’ve made on preterm birth will lead to new opportunities for treatments and more healthy moms and babies,” Elovitz said. “Until then, we’ll be hard at work.”