COVID-19 Infection Late in Pregnancy Linked to Sevenfold Risk for Preterm Birth

Will Pass

July 21, 2022

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Pregnant women who get infected with SARS-CoV-2 in their third trimester are almost three times as likely to have a preterm birth, while infection after 34 weeks' gestation raises this risk sevenfold, based on the largest matched population-based cohort study published to date.

These findings support previous studies, underscoring the need for pregnant women and their families to take preventive measures against infection, lead author Noga Fallach, MA, of the Kahn-Sagol-Maccabi Research and Innovation Center, Tel Aviv, and colleagues reported.

Past research has suggested that COVID-19 may cause low birth weights and preterm birth in pregnant women, but those studies didn't report outcomes for each trimester, the investigators wrote in PLoS ONE, noting that "timing of viral infection during fetal development may affect birth and other health outcomes."

To address this knowledge gap, the investigators looked back at data from 2,703 pregnant women in Israel who tested positive for SARS-CoV-2 from Feb. 21, 2020, to July 2, 2021. Pregnancy outcomes in these women were compared with outcomes in an equal number of uninfected pregnant women. Vaccination status was not reported.

Comparing the two groups showed that catching COVID-19 in the third trimester was linked with nearly triple the risk of preterm birth (odds ratio, 2.76; 95% confidence interval, 1.63-4.67), and more than quadruple the risk if COVID-19 symptoms were present (OR, 4.28; 95% CI, 1.94-9.41). Women who tested positive for SARS-CoV-2 after 34 weeks' gestation were seven times more likely than uninfected women to deliver early (OR, 7.10; 95% CI, 2.44-20.61).

Pregnant women who caught COVID-19 in the first two trimesters were not significantly more likely to have a preterm birth. Infection was not associated with abnormally low birth rates, or pregnancy loss, in any trimester.

Tal Patalon, MD, coauthor and head of the Kahn-Sagol-Maccabi Research and Innovation Center, focused on these more optimistic findings in an interview.

"The results are encouraging, and reassuring that COVID-19 infection during pregnancy is not associated with any type of pregnancy loss," Patalon said.

She also pointed out that the women in the study were infected with SARS-CoV-2 variants that are no longer common.

"It should be remembered that the research group tested the COVID-19 pre-Delta variants, and does not refer to the dominant variant today, which is Omicron," Patalon said.

Still, the investigators concluded that the "results underline the importance of preventive measures taken against SARS-CoV-2 infection among pregnant women and their families."

Sonja A. Rasmussen, MD, of the University of Florida, Gainesville, said that the issue with out-of-date variants in published research has been one of the "real challenges" in studying the ever-evolving COVID-19 pandemic; however, it's not a good enough reason to dismiss this study.

"I think at this point, we need to assume that it applies to Omicron too," Rasmussen said, noting that other respiratory viruses, like influenza, have also been shown to increase the risk of preterm birth when contracted in late pregnancy.

While the present findings highlight the risk of infection in the third trimester, Rasmussen advised women in all stages of pregnancy to protect themselves against COVID-19, based on the knowledge that illness in a mother can affect normal growth and development in a fetus, even if it doesn't lead to preterm birth.

"A mom getting sick during pregnancy is not good for the baby," Rasmussen said. "The baby's really dependent on the mom. So you want that baby to have good nutrition throughout the pregnancy. It's just as important earlier on as later. And you want that baby to get good oxygenation no matter what time [in the pregnancy]. I know that people want a little bit of a break [from preventive measures]. But I would emphasize that if you're pregnant, we do all sorts of things during pregnancy to make sure that our babies are safe and healthy, and I would continue that for the whole pregnancy."

Specifically, Rasmussen advised social distancing, use of an N95 mask, and vaccination. Getting vaccinated during pregnancy helps newborns fight off infection until 6 months of age, she added, when they become eligible for vaccination themselves. This added benefit was recently reported in a study published in the New England Journal of Medicine , for which Rasmussen cowrote an editorial .

"Vaccines have been approved for 6 months and older," Rasmussen said. "But what do you do in those first 6 months of life? That's a high-risk time for kids."

Despite these risks, convincing pregnant women to get vaccinated remains a key challenge for health care providers, according to Rasmussen, even with an abundance of safety data. "Early on [in the pandemic], we said we didn't know a lot about risks. We knew that other vaccines were safe during pregnancy, but we didn't have a lot of information about a COVID-19 vaccine. But now we have a lot of data on safety during pregnancy, and these vaccines appear to be completely safe, based on the information we have. There have been many, many pregnant women vaccinated in the United States and in other countries."

For reluctant expecting mothers, Rasmussen offered some words of advice: "I know that you worry about anything you do when you're pregnant. But this is something that you can do to help your baby — now, to make a preterm birth less likely, and later, after the baby is born.

"The most important thing is for the pregnant person to hear this [vaccine recommendation] from their doctor," she added. "If they're going to listen to anybody, they're going to listen to their physician. That's what the data have shown for a long time."

The investigators and Rasmussen disclosed no conflicts of interest.

This article originally appeared on, part of the Medscape Professional Network.


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