COVID-19 mRNA Vaccines During Pregnancy

Abstract

SARS-CoV-2 infection during pregnancy is associated with increased risk for maternal morbidity and adverse birth outcomes. 1,2 COVID-19 vaccines are effective for preventing severe disease, including in pregnant populations. 3 Although more than 100 countries recommend COVID-19 vaccination during pregnancy, 4 COVID-19 vaccination in pregnant people has lagged behind that for age-matched, nonpregnant adults. 5,6 As of February 2022, the US Vaccine Safety Datalink estimated that 68% of pregnant individuals have completed the primary COVID-19 vaccine series. 6 Persistent wide disparities in COVID-19 vaccination during pregnancy by race or ethnicity are likely to exacerbate longstanding disparities in maternal morbidity and mortality. 6 Vaccine hesitancy during pregnancy was understandable when COVID-19 vaccines were first authorized, 7 because pregnant people were excluded from the initial COVID-19 vaccine trials. Thus, initial data on pregnancy or birth outcomes after maternal COVID-19 vaccination were limited to inadvertent exposures among trial participants early in pregnancy. The mRNA vaccines were novel and their safety in pregnancy was presumed, but not yet proven. Over the past 14 months, a substantial body of evidence supporting the safety of the mRNA COVID-19 vaccines in pregnancy has accumulated. Observational studies from Norway, Israel, and the US have reported that the mRNA COVID-19 vaccines administered during pregnancy were not associated with increased risk for miscarriage, preterm birth, or other select obstetric and birth outcomes. [8][9][10][11] In this issue of JAMA, 2 population-based observational retrospective studies evaluating outcomes in more than 250 000 pregnancies from 3 countries together provide the strongest evidence to date regarding the safety of COVID-19 vaccines in pregnancy. 12,13 Fell and colleagues 12 used data from the Ontario birth registry, linked with the provincial immunization information system, to identify 97 590 pregnancies eligible for COVID-19 vaccination and with an expected delivery date or live birth from December 14, 2020, to September 30, 2021. Of these pregnant individuals, 23% were vaccinated during pregnancy; most were vaccinated in third trimester. Compared with those vaccinated after pregnancy and, in separate analyses, compared with those who were unvaccinated during pregnancy, COVID-19 vaccination during pregnancy was not associated with increased risks for postpartum hemorrhage, chorioamnionitis, cesarean delivery, neonatal care admission, or low Apgar score.

mRNA COVID‐19 vaccination early in pregnancy and the risk of spontaneous abortion in an international pregnancy registry

“…17 The lack of association between vaccination with mRNA vaccines and SAB adds to the accumulated evidence suggesting that the benefits of being immunized outweigh the risks. 18 This study was based on data collected from a general pregnancy cohort, unlike previous studies that focused on pregnant healthcare workers or other specific pregnancy populations. As such, findings from this study are more generalizable to a large pregnancy population.…”

“…The results of this study support current recommendations of vaccination for COVID‐19 during pregnancy for otherwise eligible individuals 17 . The lack of association between vaccination with mRNA vaccines and SAB adds to the accumulated evidence suggesting that the benefits of being immunized outweigh the risks 18 …”

SARS-CoV-2 Vaccine Booster Elicits Robust Prolonged Maternal Antibody Responses and Passive Transfer Via The Placenta And Breastmilk

“…The Centers of Disease Control and Prevention (CDC) now recommends vaccination against SARS-CoV-2 for persons who are pregnant or plan to become pregnant. 15 Despite mounting evidence that maternal vaccination is safe, decreases maternal and neonatal morbidity and mortality, and leads to passive newborn immunization via both placental transfer and breastfeeding, 16-20 there remains a high level of vaccine hesitancy, 21 resulting in only 71.5% of the pregnant population receiving a SARS-CoV-2 vaccination 22 and less than half receiving a booster dose. 23 Additionally, 46% of pregnant women recorded vaccine hesitancy 24 citing safety concerns 25 despite lack of significant adverse gestational outcomes, 26 a comparable antibody response in pregnant and nongravid females, 19 evidence of transplacental passive transfer of IgG antibodies, 16 and detectable antibody levels in breastmilk after the initial vaccination series.…”

Encourage women to receive COVID-19 vaccination before, during and after pregnancy

“…It is fully understood for vaccine hesitancy during pregnancy when COVID-19 vaccines were first authorized because pregnant people were excluded from the initial COVID-19 vaccine trials. 10 However, similar to the question as shown by McClymont conducting the study to clarify the association between COVID-19 and pregnancy outcome, 6 the audience may be interested in whether COVID-19 vaccination during pregnancy is associated with adverse peripartum or pregnancy outcomes or not? Although the question remains whether the evidence from the following two studies will convince those who remain unvaccinated to receive a COVID-19 vaccine during pregnancy, the strength of their results should be claimed, including the large and well-defined population-based cohorts, the availability of validated data on vaccine exposures and birth outcomes through regional and national registries, and the thoughtful approaches addressing the following common sources of bias in observational studies of maternal vaccination: healthy vaccinee bias and confounding by indication, immortal time bias, and cohort truncation.…”

“…Although the question remains whether the evidence from the following two studies will convince those who remain unvaccinated to receive a COVID-19 vaccine during pregnancy, the strength of their results should be claimed, including the large and well-defined population-based cohorts, the availability of validated data on vaccine exposures and birth outcomes through regional and national registries, and the thoughtful approaches addressing the following common sources of bias in observational studies of maternal vaccination: healthy vaccinee bias and confounding by indication, immortal time bias, and cohort truncation. 10–12…”