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A new study finds that COVID-19 is linked to a 60% to 97% increase in preterm birth.

Hannah Mckay/Reuters

Science’s COVID-19 reporting is supported by the Heising-Simons Foundation.

Since the start of the coronavirus pandemic, it has become increasingly clear that COVID-19 hits pregnant women harder than the general population. Now, one of the first large studies with a proper control group has firmed up earlier evidence for how the virus can alter the course of pregnancy and harm mothers and their newborns.

The study of more than 2100 pregnant women enrolled at hospitals in 18 countries found that, compared with uninfected pregnant women, those with COVID-19 are at higher risk for severe illness, death, pregnancy complications, and preterm birth. Those results underscore the importance of including pregnant women in priority groups for COVID-19 vaccines and limiting their exposure to ill people, says corresponding author Aris Papageorghiou, a fetal medicine specialist at the University of Oxford.

“This is a great study,” says physician, epidemiologist, and public health specialist Nathalie Auger of the University of Montreal Hospital Research Centre, who was not involved with the research. “They followed women through pregnancy, which is a really great design, and helped confirm the previous studies that are much easier to critique.”

Many studies have linked pregnancy to worse COVID-19 outcomes, but they have either included too few participants to draw firm conclusions, or have relied on health records that women agree to share after the fact. These registries tend to lack details such as when in pregnancy a woman got infected. They also attract sicker patients, which could make the effects of COVID-19 look worse than they actually are.

Such studies also often compare the outcomes for infected women with those for women who gave birth before the pandemic. This lack of a contemporary control group means researchers arent getting a realistic picture of the risks to uninfected women who gave birth after COVID-19 had upended global health care systems.

To avoid such biases, the new study enrolled women at any stage of pregnancy who received care at 43 medical centers, from Russia to India to Brazil, between March and October 2020. For each infected woman, the researchers immediately enrolled two pregnant women at the same hospital and same stage of pregnancy without a known infection. They then followed both groups of women—706 with a COVID-19 infection and 1424 without—through their babies deliveries and after discharge from the hospital.

Clear differences emerged between the two groups. Those with COVID-19 had a 76% greater chance of pregnancy-induced high blood pressure, known as preeclampsia or eclampsia. They were three times as likely to have a severe infection and five times as likely to be admitted to an intensive care unit, Papageorghious team reports today in JAMA Pediatrics. Eleven women with COVID-19 died, compared with just one woman in the uninfected group.

The study also linked COVID-19 to a 60% to 97% increased rate of preterm birth, and— in infected women with a fever and shortness of breath—to a fivefold increase in neonatal complications such as immature lungs, brain damage, and eye disorders. About 13% of babies tested positive for the virus, and cesarean delivery was linked to a higher risk of transmission. Breastfeeding didn’t appear to transmit the virus—a small bit of good news.

The risk estimates are roughly in line with what other studies have found, Papageorghiou says, including a recently published study that looked at health records for more than 400,000 U.S. pregnant women, nearly 6400 with COVID-19.

The new study helps makes the case for offering all pregnant women COVID-19 vaccines, Papageorghiou says. We believe pregnancy itself [puts women into] a sufficiently high-risk group,” he says. In the United States, the Centers for Disease Control and Prevention (CDC) includes pregnancy under high-risk medical conditions with priority for vaccines, but not all states have included pregnancy in priority groups. In the United Kingdom, pregnant women were only recently added to such groups.

Because the approved vaccines were not tested in pregnant women, some health authorities are hesitant to prioritize them for vaccination—despite reassurances from obstetrics experts that the shots appear safe in this group. Preliminary evidence published yesterday in The New England Journal of Medicine supports this view. Using data from a CDC reporting system, researchers found no obvious safety problems in more than 800 U.S. women who gave birth after receiving messenger RNA vaccines in December 2020, January, and February.

The higher rates of preterm birth found in the study are especially relevant in lower income countries, where health care systems are less able to care for premature infants, Papageorghiou adds. The challenge will be much more severe in those settings.”

With reporting by Meredith Wadman.

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