June 30, 2022 11:21 AM EDT

COVID-19 poses health risks during pregnancy for everyone involved. Pregnant people are at higher risk for severe disease, and the chances of negative outcomes for mother and baby—such as preeclampsia, preterm birth, and stillbirth—increase with infection. However, pregnant people were excluded from the original vaccine trials, so when the vaccines first became available, many soon-to-be-mothers were unsure about taking them.

Thousands of pregnant people have now been vaccinated in the U.S., and an abundance of data show that getting vaccinated during pregnancy is safe and protective for both mothers and babies, giving babies anti-SARS-CoV-2 antibodies and, according to a study published in June, a 69% lower chance of being hospitalized with the disease in their first 6 months of life.

Now, research published in the journal Nature Communications on June 28 shows that getting the COVID-19 vaccine during any of the three trimesters of pregnancy confers measurable benefits to the mother and child, and there may be ways to optimize protection based on when the shots are given.

Researchers from Massachusetts General Hospital and Brigham and Women’s Hospital analyzed the anti-SARS-CoV-2 antibodies of 158 women who were vaccinated during their pregnancies. Most received either Pfizer-BioNTech’s or Moderna’s vaccine, which both generated a superior immune response compared to Johnson & Johnson-Janssen’s shot. Those who were vaccinated with an mRNA vaccine during either the first or third trimesters had the strongest immune responses to vaccination. Antibody levels generated during second-trimester vaccination were somewhat weaker, which may be because pregnant people’s immune systems are more active during the first and third trimesters, and therefore may generate a greater response to the vaccine, says Dr. Andrea Edlow, a maternal fetal medicine specialist and physician scientist at Massachusetts General Hospital and Harvard Medical School, who co-authored the study.

The researchers also tested the levels of antibodies in women’s umbilical cords at birth, a measure that suggests how well mothers are able to transfer protection to their fetuses. They found that the transfer of antibodies from mother to baby was most efficient during the first and third trimesters, which suggests that babies whose mothers are vaccinated early in their pregnancies receive vaccine-derived COVID-19 antibodies right away. However, the absolute number of antibodies transferred was highest if the mother was vaccinated during the second or third trimester, which may mean that babies whose mothers were vaccinated later in pregnancy were offered more protection—likely because mothers’ COVID-19 immunity waned over time. Overall, this evidence points to the third trimester as the optimal time to get a COVID-19 booster, Edlow says. (The third trimester is also when the CDC recommends pregnant people get the Tdap vaccine for whooping cough in order to give babies the highest levels of protection after birth.)

Edlow says that while it’s important for unvaccinated women to get vaccinated as soon as possible, the study shows how to maximize the benefits for both mother and fetus. “If I were an unvaccinated pregnant person, I would definitely get vaccinated in the first trimester. But I would also probably use the opportunity then to be boosted in the third trimester,” says Edlow. (However, she emphasizes that during the pandemic, the priority is getting vaccinated as soon as possible, no matter what trimester you’re in.)

The study was kept small so that scientists could use in-depth methods to analyze the quality of the antibody production, but its size means that it can’t give a complete picture of how vaccines work in pregnant women, Edlow says. However, now that scientists have accumulated a wealth of data showing that vaccination is safe and effective in pregnant people, studies like this can help scientists fine-tune their understanding of how COVID-19 antibodies and immunity work during pregnancy. In the long term, this research may inform future recommendations for COVID-19 vaccination during pregnancy.

“We can say with confidence to pregnant individuals at this point, it’s safe to be vaccinated in pregnancy, it doesn’t cause an increased risk of miscarriage, it doesn’t cause birth defects,” says Edlow. “It does protect the mother against severe disease and death, and it does protect against pregnancy complications.”

The results of this study do not directly apply to pregnant people who are already fully vaccinated and boosted, as they were not included in the study. The CDC also does not currently recommend a second booster shot to most people who are pregnant, unless they are immunocompromised. But Edlow said that she suspects the guidance will change over time, as periodic boosting for COVID-19 is expected to become more routine.

Vaccination rates among pregnant people have increased over time since the shots first became available, as more data showing the benefits have been published. As the charts below show, the vaccine gap between pregnant and non-pregnant people has closed over the last year. However, women who are pregnant or trying to become pregnant are less likely to have received a booster shot than other women.

 

If they choose to get boosted during their pregnancy, says Edlow, these women might have an opportunity to further protect themselves and their babies during the first months of life. (More research is needed to know for sure; the study did not include people who had received booster shots.) The CDC recommends that pregnant people get a booster shot when they are eligible, and Edlow says that doing so after 20 weeks of pregnancy may maximize protection for the baby.

However, Edlow adds that mothers should also weigh their individual risk of severe illness when deciding whether to get a booster sooner—since a mother’s health is a top priority during pregnancy. “The important message for pregnant people is: by protecting yourself, you’re doing the best thing that you can do to protect your baby,” she says.

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