SARS-CoV-2 infection during pregnancy and preterm birth in Massachusetts from March 2020 through March 2021

Background: SARS-CoV-2 infection during pregnancy has been linked to preterm birth, but this association is not well understood.

Objectives: To examine the association between SARS-CoV-2 infection and spontaneous and provider-initiated preterm birth (PTB), and how timing of infection, and race/ethnicity as a marker of structural inequality, may modify this association.

Methods: We conducted a retrospective cohort study among pregnant people who delivered singleton, liveborn infants (22-44 weeks gestation) from 1 March 2020 to 31 March 2021 (n = 68,288). We used Cox proportional hazards models to compare the hazard of PTB between pregnant people with and without laboratory-confirmed SARS-CoV-2 infection during pregnancy. We evaluated this association according to the trimester of infection, timing from infection to birth, and timing of PTB. We also examined the joint associations of SARS-CoV-2 infection and race/ethnicity with PTB using the relative excess risk due to interaction (RERI).

Results: Positive SARS-CoV-2 tests were identified for 2195 pregnant people (3.2%). The prevalence of PTB was 7.2% (3.8% spontaneous, 3.6% provider-initiated). SARS-CoV-2 infection during pregnancy was associated with an increased risk of PTB overall (adjusted hazard ratio [HR] 1.53, 95% confidence interval [CI] 1.34, 1.74), and provider-initiated PTB (HR 1.79, 95% CI 1.50, 2.12) but not spontaneous PTB (HR 1.09, 95% CI 0.89, 1.36). Second trimester infections were associated with an increased risk of provider-initiated PTB, and third trimester infections were associated with an increased risk of both PTB subtypes. A joint inverse association between White non-Hispanic race/ethnicity and SARS-CoV-2 infection and spontaneous PTB (HR 0.56, 95% CI 0.34, 0.94; RERI -0.6, 95% CI -1.0, -0.2) was also observed.

Conclusions: SARS-CoV-2 infections were primarily associated with an increased risk for provider-initiated PTB in this study. These findings highlight the importance of promoting infection-prevention strategies among pregnant people.