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Preterm birth and severe maternal morbidity associated with SARS-CoV-2 infection during the Omicron wave

      OBJECTIVE

      Data exploring adverse outcomes associated with SARS-CoV-2 infection in pregnancy during the Omicron wave are lacking. Therefore, we set out to evaluate the risk of preterm birth (PTB) and severe maternal morbidity (SMM) in pregnant patients with SARS-CoV-2 infection during the most recent wave of the COVID-19 pandemic.

      STUDY DESIGN

      This was a retrospective cohort study of all pregnant patients who underwent SARS-CoV-2 testing during their delivery hospitalization at 7 hospitals within a large health system in New York between December 1, 2021 and February 7, 2022. During the study period, the Omicron variant accounted for most of the new infections in New York,

      NYC health. COVID-19: data, new variants. Available at: https://www1.nyc.gov/site/doh/covid/covid-19-data-variants.page. Accessed January 30, 2022.

      and universal SARS-CoV-2 testing occurred for all patients admitted to labor and delivery. An institutional review board approval was obtained. The primary outcomes of PTB <37 weeks and SMM, derived from the Centers for Disease Control and Prevention list of 21 indicators,

      Centers for Disease Control and Prevention. Reproductive health, how does CDC identify severe maternal morbidity? Available at: https://www.cdc.gov/reproductivehealth/maternalinfanthealth/smm/severe-morbidity-ICD.htm. Accessed February 10, 2022.

      were compared between the following 2 groups: those who tested positive for SARS-CoV-2 infection during pregnancy via qualitative real-time polymerase chain reaction and those who tested negative. Two subgroup analyses comparing the rates of primary outcomes in vaccinated vs unvaccinated patients and in SARS-CoV-2 IgG antibody-positive (against the spike protein) vs antibody-negative patients among those who tested positive for SARS-CoV-2 infection were also performed. In those analyses, missing data regarding vaccination status (1.7%) were excluded, whereas missing data regarding antibody status (21.2%) were included as unknown. Backward selection with multivariable logistic regression was used to adjust for the following potential confounders in the primary analysis: maternal age, body mass index, race or ethnic group, parity, hypertensive disorders of pregnancy, multiple gestation, placenta previa or accreta, autoimmune disease or lupus, diabetes mellitus, sickle cell disease or bleeding disorder, previous cesarean delivery, and mode of delivery. Data were presented as adjusted odds ratios (aOR) with 95% confidence intervals (CI) and statistical significance set at P <.05.

      RESULTS

      Of the 4738 patients included, 631 (13.3%) tested positive for SARS-CoV-2 infection. Patients with the infection were more commonly younger, multiparous, and Hispanic or non-Hispanic Black; also, they used public insurance less commonly and reported English as their preferred language less often. The average body mass index and rates of hypertensive disorders of pregnancy, multiple gestations, and cesarean delivery were similar between the 2 groups. Patients with SARS-CoV-2 infection were at an increased risk of PTB than those without infection (10.8% vs 8.0%; aOR, 1.46; 95% CI, 1.08–1.97). The rate of SMM was similar between the groups (5.1% vs 4.1%; aOR, 1.15; 95% CI, 0.77–1.73) (Table 1). On subgroup analyses of patients in the SARS-CoV-2-positive group, the rates of PTB and SMM were similar between vaccinated and unvaccinated patients and SARS-CoV-2 IgG antibody-positive and -negative patients (Table 2). There was also no statistically significant difference in the rate of SMM between unvaccinated SARS-CoV-2-positive patients and unvaccinated SARS-CoV-2-negative patients (18/307 [5.9%] vs 70/1522 [4.6%]; P =.3).
      Table 1Preterm birth and severe maternal morbidity associated with SARS-CoV-2 infection
      Gulersen. Preterm birth and severe maternal morbidity associated with SARS-CoV-2 infection during the Omicron wave. Am J Obstet Gynecol MFM 2022.
      OutcomeSARS-CoV-2 PCR positive n = 631SARS-CoV-2 PCR negative n = 4107Unadjusted OR (95% CI)Adjusted OR (95% CI)
      Preterm birth <37 wk68 (10.8)329 (8.0)1.39 (1.05–1.83)1.46 (1.08–1.97)
      Model adjusted for maternal age (continuous), body mass index (categorical), race or ethnic group, hypertensive disorders of pregnancy, multiple gestation, placenta previa or accreta, autoimmune disease or lupus, diabetes mellitus, and mode of delivery
      Severe maternal morbidity32 (5.1)169 (4.1)1.24 (0.84–1.83)1.15 (0.77–1.73)
      Model adjusted for race or ethnic group, parity (categorical), hypertensive disorders of pregnancy, placenta previa or accreta, sickle cell disease or bleeding disorder, previous cesarean delivery, and mode of delivery.
      CI, confidence interval; OR, odds ratio; PCR, polymerase chain reaction.
      a Model adjusted for maternal age (continuous), body mass index (categorical), race or ethnic group, hypertensive disorders of pregnancy, multiple gestation, placenta previa or accreta, autoimmune disease or lupus, diabetes mellitus, and mode of delivery
      b Model adjusted for race or ethnic group, parity (categorical), hypertensive disorders of pregnancy, placenta previa or accreta, sickle cell disease or bleeding disorder, previous cesarean delivery, and mode of delivery.
      Table 2Preterm birth and severe maternal morbidity rates stratified by vaccination and SARS-CoV-2 immunoglobulin G antibody status in the SARS-CoV-2 polymerase chain reaction positive group
      Gulersen. Preterm birth and severe maternal morbidity associated with SARS-CoV-2 infection during the Omicron wave. Am J Obstet Gynecol MFM 2022.
      OutcomeSARS-CoV-2 PCR positive
      Vaccinated (n = 313)Unvaccinated (n = 307)P value
      Preterm birth <37 wks29 (9.3)34 (11.1).5
      Severe maternal morbidity13 (4.2)18 (5.9).3
      SARS-CoV-2 IgG positive (n = 405)SARS-CoV-2 IgG negative (n = 92)
      Preterm birth <37 wks41 (10.1)14 (15.2).2
      Severe maternal morbidity19 (4.7)4 (4.3).6
      Vaccination status and SARS-CoV-2 IgG antibody testing missing for 11 (1.7%) and 134 (21.2%) patients, respectively. Am J Obstet Gynecol MFM 2022.
      Ig, immunoglobulin; PCR, polymerase chain reaction.

      CONCLUSION

      During the Omicron wave, SARS-CoV-2 infection in pregnancy was associated with an increased risk of PTB than noninfected cases. Although this risk was not altered by vaccination or SARS-CoV-2 antibody status in our subgroup analyses, these findings should be interpreted with caution owing to our sample size and low prevalence of outcomes, which may have limited the power to detect significant differences between groups. Although the association between SARS-CoV-2 infection and PTB has been well-characterized during the early part of the COVID-19 pandemic,
      • Blitz MJ
      • Gerber RP
      • Gulersen M
      • et al.
      Preterm birth among women with and without severe acute respiratory syndrome coronavirus 2 infection.
      the risk of PTB was also increased during the most recent Omicron wave. These findings confirm that SARS-CoV-2 infection in pregnancy is a risk factor for PTB despite evidence suggesting less virulence with emerging variants and the available interventions aimed at reducing progression to severe disease.
      • Iuliano AD
      • Brunkard JM
      • Boehmer TK
      • et al.
      Trends in disease severity and health care utilization during the early omicron variant period compared with previous SARS-CoV-2 high transmission periods – United States, December 2020–January 2022.
      ,
      • Adhikari EH
      • MacDonald L
      • SoRelle JA
      • Morse J
      • Pruszynski J
      • Spong CY.
      COVID-19 cases and disease severity in pregnancy and neonatal positivity associated with delta (B.1.617.2) and omicron (B.1.1.529) variant predominance.
      Our results are in contrast to earlier reports suggesting an increased risk of SMM associated with SARS-CoV-2 infection.
      • Gulersen M
      • Rochelson B
      • Shan W
      • Wetcher CS
      • Nimaroff BMJ.
      Severe maternal morbidity in pregnant patients with severe acute respiratory syndrome coronavirus 2 infection.
      Whether these findings are owing to the reported less virulence of the Omicron variant or higher rates of passive and active immunity via increasing vaccination among pregnant patients or past exposure requires further study. Of note, our finding that patients with SARS-CoV-2 infection during the Omicron wave had public insurance less commonly is in contrast to previous reports evaluating outcomes in our patient population earlier in the COVID-19 pandemic.
      • Gulersen M
      • Rochelson B
      • Shan W
      • Wetcher CS
      • Nimaroff BMJ.
      Severe maternal morbidity in pregnant patients with severe acute respiratory syndrome coronavirus 2 infection.
      This may have been owing to differences in patient behaviors among those who were and were not previously exposed to infection or related to altered risk of reinfection during the 2 study periods. Future research exploring the sociodemographic differences associated with infection throughout the pandemic should be considered.

      References

      1. NYC health. COVID-19: data, new variants. Available at: https://www1.nyc.gov/site/doh/covid/covid-19-data-variants.page. Accessed January 30, 2022.

      2. Centers for Disease Control and Prevention. Reproductive health, how does CDC identify severe maternal morbidity? Available at: https://www.cdc.gov/reproductivehealth/maternalinfanthealth/smm/severe-morbidity-ICD.htm. Accessed February 10, 2022.

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        • et al.
        Preterm birth among women with and without severe acute respiratory syndrome coronavirus 2 infection.
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        • Iuliano AD
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        Severe maternal morbidity in pregnant patients with severe acute respiratory syndrome coronavirus 2 infection.
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