The relationship between COVID-19 vaccination status in pregnancy and birthweight

Abstract

Background: Despite findings that maternal COVID-19 infection in pregnancy is associated with low birthweight (weight of ≤2500 g), previous studies demonstrate no difference in low birthweight risk between COVID-19 vaccinated and unvaccinated pregnant persons. Few studies, however, have examined the association between unvaccinated, incomplete vaccination, and complete vaccination on low birthweight, and they have been limited by small sample sizes and lack of adjustment for covariates.

Objective: We sought to address key limitations of prior work and evaluate this association between unvaccinated, incomplete, and complete COVID-19 vaccination status in pregnancy and low birthweight. We predicted a protective association of vaccination on low birthweight that varies by number of doses received.

Study design: We performed a population-based retrospective study using the Vizient clinical database, which included data from 192 hospitals in the United States. Our sample included pregnant persons who delivered between January 2021 and April 2022 at hospitals that reported maternal vaccination data and birthweight at delivery. Pregnant persons were categorized into 3 groups as follows: unvaccinated; incompletely vaccinated (1 dose of Pfizer or Moderna); or completely vaccinated (1 dose of Johnson & Johnson or ≥2 doses of Moderna or Pfizer). Demographics and outcomes were analyzed using standard statistical tests. We performed multivariable logistic regression to account for potential confounders between vaccination status and low birthweight in the original cohort. Propensity score matching was used to reduce bias related to the likelihood of vaccination, and the multivariable logistic regression model was then applied to the propensity score-matched cohort. Stratification analysis was performed for gestational age and race and ethnicity.

Results: Of the 377,995 participants, 31,155 (8.2%) had low birthweight, and these participants were more likely to be unvaccinated than those without low birthweight (98.8% vs 98.5%, P<.001). Incompletely vaccinated pregnant persons were 13% less likely to have low birthweight neonates compared to unvaccinated persons (odds ratio, 0.87; 95% confidence interval, 0.73-1.04), and completely vaccinated persons were 21% less likely to have low birthweight neonates (odds ratio, 0.79; 95% confidence interval, 0.79-0.89). After controlling for maternal age, race or ethnicity, hypertension, pregestational diabetes, lupus, tobacco use, multifetal gestation, obesity, use of assisted reproductive technology, and maternal or neonatal COVID-19 infections in the original cohort, these associations remained significant for only complete vaccination (adjusted odds ratio, 0.80; 95% confidence interval, 0.70-0.91) and not incomplete vaccination (adjusted odds ratio, 0.87; 95% confidence interval, 0.71-1.04). In the propensity score-matched cohort, pregnant persons who were completely vaccinated against COVID-19 were 22% less likely to have low birthweight neonates compared to unvaccinated and incompletely vaccinated individuals (adjusted odds ratio, 0.78; 95% confidence interval, 0.76-0.79).

Conclusion: Pregnant persons who were completely vaccinated against COVID-19 were less likely to have low birthweight neonates compared to unvaccinated and incompletely vaccinated individuals. This novel association was observed among a large population after adjusting for confounders of low birthweight and factors influencing the likelihood of receiving the COVID-19 vaccine.

Keywords: COVID-19 infection; cesarean delivery; low birthweight; neonatal intensive care unit admission; prematurity; primary series; unvaccinated; vaccine hesitancy.

Figure 1

Consolidated Standards of Reporting Trials (CONSORT) diagram of how participants were selected

Figure 2

Directed Acyclic Graph (DAG) showing the association between exposure (COVID-19 vaccination), outcome (LBW), and confounding variables