Not getting a COVID-19 vaccine could lead to preterm birth in pregnant women, new study shows
COVID-19 infection can lead to preterm birth, a study published last week in the journal Proceedings of the National Academy of Sciences shows, but getting vaccinated protects against it.
Researchers found a serious adverse effect on preterm birth from COVID infection during pregnancy, a risk that had plummeted to zero by fall 2022, following widespread COVID vaccination among pregnant women.
Doctors at local hospital systems have noticed similar trends and mirrored results among pregnant patients in Allegheny County, Pennsylvania.
“We had pregnant patients who would come in very ill,” said Dr. Michael Aziz, a maternal fetal medicine specialist at Allegheny Health Network, which he said pushed to vaccinate the pregnant population early on.
“We saw more pregnant patients getting vaccinated … and then a reduction in emergency room visits, ICU visits and a reduction in preterm births and stillbirths,” he said.
Physicians still encourage those who can to get updated shots of the COVID vaccine, citing years of evidence that it reduces severe disease and the likelihood of hospitalization.
“All evidence indicates that the vaccine is very safe and effective,” said Jenna Nobles, a demographer and professor of sociology at University of Wisconsin-Madison and study coauthor. “In addition, it shows that avoiding the vaccine is what is potentially harmful for the pregnancy. This is an important piece of information for patients to have.”
When COVID vaccines from biotech companies Moderna and Pfizer-BioNTech first launched in December 2020, little was known about how the shots might affect pregnant people. As scientists conducted more studies, evidence mounted that the shots were safe and effective for that group, which could get vaccinated in spring 2021.
A 2022 review article published in Nature Communications examined 23 studies that represented more than 100,000 vaccinated pregnant people. The study found no increased risk of adverse effects from vaccination, as well as a 15% reduction in the risk of stillbirth for those who received the vaccine.
“Pregnancy is an immune-suppressed state,” said Dr. Aziz, also an Allegheny County Medical Society board member.
The fetus is seen as a foreign object, and the body suppresses the immune system to avoid rejecting it. This becomes harder for the immune system to do when a person is sick. “The body’s natural mechanism during illness is to deliver,” said Dr. Aziz.
That some illnesses are linked to preterm birth during pregnancy is not new: Influenza has been linked to preterm birth as well.
Preterm birth, which is defined as birth before 37 weeks gestation, is one main marker for infant health and is associated with chronic health conditions later in life, such as asthma, hearing problems and heart issues.
For the new study, researchers from the University of Wisconsin-Madison and Stanford University used population data and hospital birth information from California to understand the impact of COVID-19 infection on birth outcomes. They also tracked vaccination rates by ZIP code to see whether immunity from the COVID vaccine played a role in how the preterm birth rate changed.
The study looked at restricted-access birth rate data from California hospitals, which was representative of 40 million people and specified birthing location, patient residence, infection at time of delivery and sibling identification. Most California hospitals were testing for COVID infection upon admission, giving researchers insight into how many pregnant people had a COVID infection when checking in to deliver their baby.
Knowing where pregnant patients lived allowed researchers to cross-reference this data with ZIP code information about vaccination rates. Ms. Nobles said that while individual-level vaccination data would have been difficult to access, the ZIP code method allowed them to look at the likelihood of a mother being vaccinated in a certain area.
“The probability that a mom drawn from (a ZIP code with a high vaccination rate) is vaccinated is very high,” she said. “It’s as close as you can get.”
Their results showed that the risk of preterm birth from COVID infection was initially similar among places that would become high- and low-vaccination ZIP codes, as vaccines were not available in July 2020, when data first became available. By May of 2021, in the high vaccination group the risk drops to nearly zero excess risk, yet risk remains large through 2021 in the low vaccination group.
“They demonstrated that, as people became more vaccinated against COVID-19, preterm birth rate went down,” said Dr. Aziz. “I think we can say that COVID-19 infection during pregnancy causes preterm delivery.”
The word “cause” is a sticky one in the science world — a common adage is “correlation does not equal causation.” In this case, however, Ms. Nobles and Dr. Aziz think the evidence approaches the strength to support causation.
“Any alternate explanation for these patterns would have to match … the timing of the change and effects,” said Ms. Nobles, referencing the change observed by spring of 2021.
The researchers discussed the possibility that those in highly vaccinated areas maintained stronger public health hygiene habits such as masking, handwashing and social distancing. If that were the contributor, explained Ms. Nobles, the preterm birth risk pre-vaccination would have varied between these groups, and it was largely the same.
Another factor strengthening the power of the results was that Ms. Nobles and coauthor Florencia Torche, of Stanford, implemented a kind of control group, in which they identified the pre-pandemic siblings of the babies born during the pandemic to the same families, and further analyzed preterm birth risk without COVID as a factor.
At Allegheny Health Network, Dr. Aziz found that pregnant patients were likely to get more sick from COVID-19 than people their same age and the same health problems.
While UPMC Magee Women’s Hospital president Dr. Richard Beigi didn’t think the study provided direct evidence to point to causation, he does concur with the importance of vaccination in this population and said the results were “encouraging in regard to additional benefits of vaccination in pregnancy.”
Dr. Beigi, a professor at Pitt School of Medicine specializing in studying respiratory infections in pregnant women, also noted similar trends at the hospital, specifically those that shifted as different variants, like the Delta variant, came on the scene.
“As the vaccine started rolling out and as the Delta wave subsided, we did seem to see less severe disease at Magee,” he said. “There’s a lot of benefit to pregnant women taking immunization.”
With the study conducted on California residents, he noted that vaccination rates in California are generally higher than in other areas, but that based on prior evidence of respiratory illness in pregnant women and vaccines, he had “no reason to believe” the same effect wouldn’t be seen in other regions of the U.S.
Dr. Aziz thought that because “California is quite heterogeneous,” the results would be generalizable.
So what’s next? Ms. Nobles noted that, due to a combination of widespread vaccination and immunity from exposure to coronavirus, preterm birth risk remains low, but that still could change. Vaccination rates have plateaued, as there has been less interest in getting updated shots. Doctors have since shifted to promoting the idea of annual COVID vaccinations — just like flu — to keep up with an ever-changing virus.
“As the virus continues to evolve, it’s likely that the low level of boosting will become an issue,” she said. “We just don’t know how long we’ll be able to ride out the early wave of vaccinations.”
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