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Unvaccinated pregnant people who get Covid-19 are at much higher risk for complications from the disease and death of their babies than their vaccinated counterparts, according to a new study from Scotland.

Authors of the population-level study, published Thursday in Nature Medicine, examined data from all pregnant people across Scotland between December 2020 and October 2021 that included information on Covid-19 vaccination status and infection. Almost all of the pregnant people who needed critical care for Covid-19 — 102 out of 104 overall — were unvaccinated. There were over 450 total fetal and newborn deaths that coincided with Covid-19 — all among unvaccinated mothers.

“Vaccination in pregnancy is the safest and most effective way for pregnant women to protect themselves and their babies,” said Sarah Stock, an author of the study who is an obstetrician and maternal and fetal medicine specialist at the University of Edinburgh. “This advice needs to go out to partners and parents and grandparents and friends.”

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The extended perinatal mortality rate — which measures the rate of babies who died from around 28 weeks of pregnancy until about one month after birth — was just over 22 deaths per 1,000 births for pregnant people diagnosed with Covid-19 within a month of giving birth. That’s much higher than Scotland’s background perinatal mortality rate during the pandemic of more than 5 deaths per 1,000 births.

Vaccination remains the key distinction. Once Covid-19 vaccines became available, 77% of infections among pregnant people were in those who were not vaccinated. Pregnant people who were vaccinated during their pregnancy had a substantially lower extended perinatal mortality rate, at slightly more than 4 deaths per 1,000 births.

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During the study period, which began just before vaccine distribution to the public, more than 130,000 people were pregnant in Scotland. By October 2021, only 32% of people who gave birth that month were vaccinated. Vaccine rates among pregnant people in the U.S. were similar at that time — 33% — though it’s risen to more than 41% in the new year, according to the Centers for Disease Control and Prevention. In both Scotland and the U.S., these rates are well behind the vaccination rate in the general population.

“The single best thing you can avoid, if you are pregnant, is getting infected with SARS-CoV-2,” the virus that causes Covid-19, said Kjersti Aagaard, a physician and researcher of obstetrics and gynecology at Baylor College of Medicine in Houston, Texas, who was not involved with the study. “The single best decision you can make, if you are pregnant, is to get fully vaccinated.”

While pregnancy puts Covid-19 patients at higher risk of complications, it doesn’t make a person more susceptible to catching the virus, according to the researchers. Infections among pregnant people in the study were evenly dispersed across trimesters, but the risk for complications increased with the duration of pregnancy. Hospital admissions among pregnant people rose from less than 7% of those with Covid-19 infections in the first trimester to more than 33% of those with infections in the third trimester. No pregnant people infected with SARS-CoV-2 in their first trimester were admitted for critical care associated because of Covid-19 complications, compared to over 4% of those in their third trimester.

Researchers can’t necessarily differentiate between hospitalizations due to Covid-19 versus those for other issues that happened to coincide with a Covid-19 infection. The study also doesn’t include any insight into how the Omicron variant may affect pregnancy. It’s part of the problem in researching Covid-19, experts said: By the time one insight is gained, the situation has already shifted.

“The plane is already flying and we’re trying to figure out how to rebuild it,” said Yalda Afshar, a maternal and fetal medicine researcher and physician at the University of California, Los Angeles, who was not involved with the study.

Smaller or less-representative studies have previously pointed to higher risks for pregnant people infected with SARS-CoV-2. But experts praised the research from Scotland for its longitudinal, population-level design. Such a study isn’t possible in the United States, Aagaard said, as there is no central electronic medical system from which to pull medical records. Even the CDC’s tracked data on Covid-19 and pregnancy comes from a network that state and local health departments must opt into for participation.

Data for the study was collected through the Covid-19 in Pregnancy in Scotland study, which continues to track everyone in the country who was or became pregnant after March 1, 2020. The researchers hope to continue analyzing the data, particularly confounding factors such as socioeconomic and demographic status.

For Aagaard, the study’s findings emphasize that pregnant people are a critical population when looking at Covid-19 and other diseases. She wonders how much more messaging around the importance of vaccines could have been done if the pregnant people had been included in clinical trials from the beginning.

“For the love of Pete, pregnant people need to be included in vaccine trials,” she said. “So we don’t have to guess at the best answer and then look back at one year of data to figure out if we did something wrong.”

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