The impact of COVID-19 vaccination and boosters on maternal SARS-CoV-2 infections and birth outcomes

During the coronavirus disease 2019 (COVID-19) pandemic, pregnancy was recognized to be a high-risk condition for adverse outcomes following infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

However, since vaccine trials did not include pregnant women, there was considerable hesitancy to accept COVID-19 vaccination in this subgroup. A new paper in The Lancet Digital Health reports on the observed effects of vaccination against COVID-19, including boosters, on maternal and fetal outcomes during pregnancy.

Introduction

Following COVID-19 vaccination, the antibodies elicited in the mother’s body are transferred to the fetus via the umbilical circulation. The highest antibody levels in the blood of both mother and child were measured following a third booster dose with a nucleic acid vaccine, given during the third trimester, according to earlier research.

Babies born to vaccinated mothers were also less likely to be hospitalized for reasons linked to COVID-19 during the first six months of infancy, and more so if the mother was also boosted. Other outcomes, such as preterm birth, low birth weight, and stillbirth, as well as overall hospitalization rates during neonatal life, have not been compared between vaccinated and unvaccinated people.

The authors carried out a retrospective study on almost 100,000 mothers who delivered their babies at a single hospital chain, covering seven American states in the west of the country. All had singleton pregnancies, and none had documented COVID-19 before they conceived.

The study period was extended from January 26, 2021, to October 26, 2022.

What did the study show?

Of the total number, the vaccination cohort included approximately 36,000 mothers who had received at least two doses of a nucleic acid vaccine, either the Pfizer/BioNTech or Moderna vaccine. About 56,000 people were unvaccinated.

Approximately 11,000 of these had received three or more doses, including one or more booster doses, while 13,000 had completed the primary course but were not boosted.

The researchers also created two matched cohorts for vaccinated vs. unvaccinated people and vaccinated unboosted vs. boosted people, including ~17,000 unvaccinated, and 4,400 vaccinated unboosted people, respectively. This was to reduce the effects of confounding factors on the final outcomes.

The analysis showed that those who were vaccinated were more likely to have their babies later in the course of the pandemic. This group had a higher mean age, were heavier, lived in less vulnerable households, and were covered by commercial insurance, compared to unvaccinated people.

People who took one or more booster doses following the primary vaccination course had a longer lag time after the second dose of vaccine, had earlier conception dates, and were more likely to be on commercial insurance. They were older and lived in lower-risk households than vaccinated, unboosted people.  

Vaccinated people were more often Asian or non-Hispanic, were less likely to smoke, drink, or abuse drugs, have chronic diabetes, hypertension, and had fewer children.

Compared to unboosted mothers, those who received a booster dose were likely to be non-smokers, less likely to use drugs or alcohol, and have a lower body mass index. Vaccinated people in general had a higher socioeconomic status than the unvaccinated, had no history of preterm birth, and lived in better housing.

The risk of COVID-19 complicating pregnancy was 4% and 5.3% among mothers who had been vaccinated vs unvaccinated. When compared with matched vaccinated but unboosted mothers, whose risk was 5.6%, it was only 3.2%      among those who had received booster doses as well.

Most COVID-19 cases occurred among unvaccinated mothers, especially during the pre-Omicron period. Once Omicron became dominant, vaccinated mothers were at greater risk for COVID-19, with boosted people having the highest incidence compared to unboosted vaccinated mothers.

Overall, the risk of COVID-19 in pregnancy was 25% lower among vaccinated mothers than the unvaccinated matched. Booster shots reduced the risk by 40% compared to the vaccinated unboosted matched cohort.

Maternal outcomes did not show any significant differences with vaccination or boosting when the analysis was limited to the Omicron-dominant era, though three maternal deaths were reported, all during or just before the Delta wave.  COVID-19 severity, hospitalization, and the need for supplemental oxygen and vasopressors were comparable between cohorts use rates.

Vaccination was associated with a lower risk of preterm birth, stillbirth, and very low birth weight (VLBW) babies, though the differences in percentage points were small. The risk of stillbirth was halved, and that of preterm births reduced by one-eighth in the vaccinated cohort. The risk of VLBW dropped by a third, and the low birth weight risk was also lower.

When the boosted group was compared to the vaccinated-only group, the stillbirth rate was 40% lower, but preterm and VLBW rates showed no significant change.  This is the first study to report this result.

What are the implications?

The results of this study appear to support the protective effect of COVID-19 vaccination in reducing the incidence of several adverse outcomes, both maternal and fetal, associated with COVID-19 in pregnancy. There was a slight improvement in preterm birth risk in vaccinated boosted women.

“These protective effects might be explained in part by healthy vaccinee bias, in which people who are in better health conditions are more likely to adhere to vaccination recommendations,” the researchers state.

Even as they recommend further studies on the benefits of providing additional vaccine doses during pregnancy, the authors conclude, “Pregnant people should be high priority for vaccination and stay up to date with their COVID-19 vaccination schedule.”