Severe acute respiratory syndrome coronavirus 2 and preterm birth, clinical implications-A register-based cohort study from Sweden.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy is associated with an increased risk of preterm birth (PTB). The aim of the study was to investigate the effect of timing of SARS-CoV-2 infection during pregnancy on PTB risk and whether the risk is related to the interval from infection onset. We also studied whether the association is driven primarily by spontaneous or iatrogenic PTB, as well as to what extent disease severity, viral variant, background characteristics, and vaccination status affect the risk for PTB. MATERIAL AND METHODS: This is a Swedish population-based register study including all singleton pregnancies registered in the Swedish Pregnancy Register with estimated date of birth between March 1, 2020 and May 31, 2022 (n = 233,335). Data on SARS-CoV-2 test positivity, vaccination status, and disease severity were retrieved from mandatory Swedish health registers. Cox regression analyses with time-varying covariates were performed to investigate the association of testing positive for SARS-CoV-2 during pregnancy and risk of PTB. RESULTS: There was a significant (p = 0.047) interaction between gestational age at the debut of SARS-CoV-2 infection and hazard ratio (HR) for PTB within 2 weeks. The adjusted HRs (aHRs and 95% confidence interval [CI]) for PTB within 2 weeks of a positive SARS-CoV-2 test were 6.0 (3.9-9.2), 6.1 (4.4-8.4), and 3.2 (2.7-3.7) for women with a positive test at 22-27, 28-31, or 32-36 gestational weeks, respectively. Two weeks or more after the start of a SARS-CoV-2 infection, only a slightly increased hazard for PTB could be observed (aHR, 1.2; 95% CI, 1.0-1.4, p = 0.016). Excluding women admitted for SARS-CoV-2 infection, the aHR for PTB within 2 weeks was aHR = 2.8 (95% CI, 2.4-3.3). The aHR for preterm birth among vaccinated infected women compared to non-infected was 1.6 (95% CI, 1.2-2.2). The corresponding aHR for women who had a SARS-CoV-2 infection without a previous vaccination was 3.2 (95% CI, 2.3-4.3). Thus, vaccinated infected women had a significantly lower risk for PTB than had women without vaccination before infection (p for homogeneity = 0.007). The viral variants Alpha and Delta were associated with a greater risk of PTB compared with Omicron, but the risk increase was found during the entire study period. CONCLUSIONS: Pregnant women are at particularly high risk of PTB within 14 days after a SARS-CoV-2 infection, and should be counselled on PTB symptoms to ensure that they seek medical care without delay. The increased PTB risk is partly mitigated by vaccination against SARS-CoV-2.