Maternal COVID-19 vaccination in early pregnancy is not associated with fetal abnormalities detectable on ultrasound, finds a study yesterday in JAMA Pediatrics.

The retrospective study, conducted by Northwestern University and Penn State College of Medicine researchers, used electronic medical records to identify any link between COVID-19 vaccination in early pregnancy and the risk of major fetal structural abnormalities on ultrasound.

Major structural fetal abnormalities were defined as those identifiable on ultrasound in the second semester (18 to 24 weeks' gestation) that may affect the newborn's life expectancy, health, or functioning. Examples included malformation of the heart or spine. Functional defects were excluded from the study because they can't be assessed using ultrasound, the researchers said.

"If the baby's heart isn't forming correctly, that could lead to the baby needing major cardiac surgery or long-term medication," senior author Emily Miller, MD, MPH, said in a Northwestern University news release.

"However, if the ultrasound identified extra fluid in the fetus' kidney, that might end up fixing itself down the road. We looked for those extremes and everything in between."

Similar findings among unvaccinated, vaccinated

A total of 3,156 pregnant women with vaccination records had a 19-week ultrasound from March through November 2021 at Northwestern Medicine Prentice Women's Hospital. Average patient age was 33.4 years, 83.1% had received at least one COVID-19 vaccine dose from 30 days before conception to 14 weeks' gestation, and 43.8% were unvaccinated as of 14 weeks.

Among the 534 unvaccinated patients, ultrasound showed a fetal abnormality in 5.1%, compared with 4.2% among the 2,622 who had received at least one vaccine dose.

After adjustment for age at delivery, the number of previous births, chronic high blood pressure, and first-semester hemoglobin A1c (a high level of which may indicate gestational diabetes), vaccination up to 14 weeks' gestation was not tied to congenital anomalies identified on ultrasound (adjusted odds ratio, 1.05).

For reference, about 3% to 5% of US babies are born with structural defects, which are linked with higher rates of infant illness and death and billions in healthcare costs, the researchers noted.

Data bridge gap in initial vaccine trials

"This is yet another important piece of data that helps bridge the chasm that was left when pregnant individuals were excluded from those initial vaccine trials," Miller said. She is chief of obstetrics at Northwestern Medicine and assistant professor of maternal fetal medicine at Northwestern's Feinberg School of Medicine. 

Miller added that the study used contemporary controls rather than historic data to build on findings from a US Centers for Disease Control and Prevention (CDC) study presented to the Advisory Committee on Immunization Practices in September 2021.

"I think the big strength of this study is that we compared against other women who were vaccinated, but at different point in their pregnancies," Miller said. "People who choose vaccination are often different from people who choose not to be vaccinated. Our study design helps account for some of those differences."

First author Rachel Ruderman, MD, MPH, who received a third dose of COVID-19 vaccine in her 12th week of pregnancy, said in the release that some patients say they doubt the data on vaccination during pregnancy and don't want to expose their baby to an unnecessary risk.

"Then I tell people, 'Actually, the data is really good,' and I feel like they're receptive," she said. "So, these findings will only add to that."