Safety of SARS-CoV-2 vaccination during pregnancy- obstetric outcomes from a large cohort study

Abstract

Background COVID-19 during pregnancy is associated with adverse outcomes for mother and fetus. SARS-CoV-2 vaccination has significantly reduced the risk of symptomatic disease. Several small studies have reported the safety of SARS-CoV-2 vaccination during pregnancy, with no adverse effect on obstetric outcomes. Objective To examine the association between SARS-CoV-2 vaccination during pregnancy and maternal and neonatal outcomes in a large cohort study. Furthermore, to evaluate if timing of vaccination during pregnancy is related to adverse outcomes. Methods A retrospective cohort study of women who delivered between December 2020 and July 2021 at a large tertiary medical center. Excluded were women with multiple pregnancy, vaccination prior to pregnancy, COVID-19 infection during or before pregnancy, or unknown timing of vaccination. Primary outcomes were the incidence of preterm labor and of small for gestational age. Secondary outcomes were other maternal and neonatal complications. A secondary analysis investigating the association between time of vaccination and outcomes was also performed. Multivariable logistic regression models were used to adjust for potential confounders. Results There were 5618 women who met the inclusion criteria: 2,305 (41%) women were vaccinated and 3,313 (59%) were unvaccinated. There were no differences between vaccinated and non-vaccinated patients with respect to primary outcomes. The rate of preterm birth was 5.5% in the vaccinated group compared to 6.2% in the unvaccinated group (p = 0.31). Likewise, the rates of small for gestational age were comparable between the two groups (6.2% vs. 7.0% respectively, p = 0.2). In a secondary analysis focusing on time of vaccination and its relationship with outcomes, patients vaccinated in the second trimester (n = 964) and in the third trimester (n = 1329) were independently compared to their unvaccinated counterparts. Women who were vaccinated in the second trimester were more likely to have a preterm birth (8.1% vs. 6.2%, p < 0.001). This association persisted after adjusting for potential confounders (adjusted odds ratio 1.49, 95%CI 1.11, 2.01). Conclusions SARS-CoV-2 vaccine appears to be safe during pregnancy with no increase in incidence of preterm labor and small for gestational age compared to unvaccinated women. However, in women vaccinated during the second trimester there may be an increase in the rate of preterm birth.

COVID‐19 vaccine and pregnancy outcomes: A systematic review and meta‐analysis

“…These nine studies included 40 728 pregnant women, 21 297 (52.3%) of which received the COVID‐19 vaccine, while 19 431 (47.7%) pregnant women did not receive it. The majority of studies were performed in Israel 33–37 and the USA 38,39 ; one study was performed in Romania 40 and another in the UK 41 . Only two studies were prospective, 38,40 whereas the others were retrospective observational analyses.…”

“…This decision depends mainly on two reasons: first, there is heterogeneity among the included studies in what they reported, that is if the diabetes was gestational or pregestational, and in the way they reported, mainly in third trimester, so that it is difficult to prove that diabetes is a consequence of the vaccine, given that according to guidelines the diagnosis is made around 24–28 weeks at latest 46 . In detail, Dick et al, 34 Citu et al, 40 and Wainstock et al 37 describe only gestational diabetes mellitus but it is not specified whether it is diagnosed before or after the vaccine uptake; Beharier et al 33 and Rottenstreich et al 36 cumulate gestational and pregestational diabetes mellitus; Goldshtein et al, 35 Blakeway et al, 41 and Theiler et al 39 differentiate pregestational and gestational diabetes mellitus but the last is not mentioned in the subgroup analyses without COVID‐19‐affected pregnant women, so we took into consideration only the pregestational one.…”

“…Interestingly, it was also observed that the length of the time interval from vaccination to delivery influences the antibody titer in a directly proportional manner. 50,51 Likewise, an interesting objective for future research would be to clarify the impact of different vaccination timing on perinatal outcomes: Dick et al 34 showed an increased preterm birth rate and lower overall gestational age at delivery in women vaccinated during the second trimester compared with unvaccinated pregnant women. Goldshtein et al 35 observed no differences in the rate of preterm delivery, small-for-gestational-age neonate, and any congenital malformation between pregnant women vaccinated during the first trimester and unvaccinated pregnant women.…”

Prenatal maternal inactivated COVID-19 vaccination: the maternal and neonatal outcomes, a retrospective cohort study

“…They included a larger sample and explored the association between risk of preterm birth and vaccination in early, midterm and late pregnancy separately. They found a higher risk of preterm delivery in those who were vaccinated in the midterm of pregnancy (8.1% vs. 6.2%).We therefore hypothesized that unmeasured confounding factors associated with vaccination may have contributed to the results [19].…”

Individual‐level determinants of COVID‐19 vaccination in pregnant people in East Tennessee

“…As compared with individuals with uninfected pregnancies, infection with COVID‐19 during pregnancy increases the risk for preterm birth 2–4 and preterm birth via cesarean 3,5 ; premature rupture of membranes 5 ; lower neonatal Apgar score 5 ; venous thromboembolism 3 ; severe maternal morbidity 3 ; and maternal mortality 1,2 . Scientific evidence supporting the safety of the COVID‐19 vaccines during pregnancy continues to accumulate, with the evidence to date overwhelmingly suggesting the three COVID‐19 vaccines currently available in the United States are safe and effective during pregnancy, and that vaccination reduces the risk of adverse obstetric outcomes 6–21 . COVID‐19 vaccination during pregnancy, including the booster, also appears to provide passive protection and further protects the young infant 22–26 …”