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Young pregnant women are also at an increased risk of mortality and severe illness due to coronavirus disease 2019: analysis of the Mexican National Surveillance Program

Published:December 17, 2020DOI:https://doi.org/10.1016/j.ajog.2020.12.1197

      Objective

      There is conflicting information regarding whether pregnant women are at increased risk of severe complications from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We sought to understand whether pregnant women are at increased risk of death or severe illness owing to coronavirus disease 2019 (COVID-19) compared with nonpregnant women and whether that risk varies by age.

      Study Design

      Data were extracted from the epidemiologic surveillance system of viral respiratory diseases of Mexico, which included 475 monitoring hospitals that are components of the Mexican Public Health Network, including the National Mexican Institute of Social Security, Institute of Security and Social Services for State Workers, Secretary of National Defense, Secretary of the Navy of the Mexican Republic, and the National Health Department. These monitoring hospitals were given the approval to perform reverse transcription polymerase chain reaction analysis for SARS-CoV-2 in Mexico and are, therefore, the reference centers for all patients with suspected COVID-19. We included 7028 pregnant and 255,721 nonpregnant women aged 15 to 45 years diagnosed as having COVID-19 between February 1, 2020, and October 27, 2020.

      Results

      We found that the risk of death and pneumonia increased with age for both pregnant and nonpregnant women (Figure, A and C). The adjusted case fatality rate for pregnant women was 1.3% overall but rose to 2.1% and 5.9% for those aged 35 to 39 years and 40 to 44 years, respectively. Pregnant women with COVID-19 consistently had a higher risk of death and pneumonia than nonpregnant women of similar age with COVID-19 (adjusted relative risk [RR] of death, 1.68; 95% confidence interval [CI], 1.36–2.08; adjusted RR of pneumonia, 1.97; 95% CI, 1.82–2.13) (Figure; Table). Although the risk was highest among older pregnant women, the highest RRs appeared among both younger and older pregnant women (Figure, B and D).
      Figure thumbnail gr1
      FigureRisk of death and pneumonia among pregnant and nonpregnant women
      A, Absolute risk of death and 95% confidence intervals by patient age, stratified by pregnant and nonpregnant women (nonlinear relationship between the risk of death and age modeled using restricted cubic splines). B, Relative risk of death of pregnant and nonpregnant women with COVID-19 by age categories. C, Absolute risk of pneumonia and 95% confidence intervals by patient age, stratified by pregnant and nonpregnant women (nonlinear relationship between the risk of death and age modeled using restricted cubic splines). D, Relative risk of pneumonia of pregnant and nonpregnant women with COVID-19 by age categories.
      COVID-19, coronavirus disease 2019.
      Martinez-Portilla. Young pregnant women are also at an increased risk of mortality and severe illness due to coronavirus disease 2019. Am J Obstet Gynecol 2021.
      TableRelative risk of death and pneumonia between pregnant and nonpregnant women with coronavirus disease 2019 (age, 15–44 years)
      Variables

      Death
      P value for interaction (maximum likelihood test comparing full and reduce models, 5 degrees of freedom) between pregnancy and age (5-year age bin categories) is equal to .46
      PregnancyNonpregnantRR (95% CI)P valueAdjusted RR (95% CI)
      Modified Poisson model adjusted for obesity, hypertension, diabetes, and smoking
      P value
      EventsTotalRisk per 100,000EventsTotalRisk per 100,000
      Overall93702813203221255,72112601.61 (1.28–2.02)<.0011.68 (1.36–2.08)<.001
      Age 15–<20 y24514445810,8445300.83 (0.20–3.38).790.83 (0.20–3.41).80
      Age 20–<25 y161505106012829,2574402.43 (1.45–4.08).00082.24 (1.29–3.90).004
      Age 25–<30 y18210286025549,5925101.67 (1.03–2.68).041.66 (1.02–2.71).04
      Age 30–<35 y231768130047453,3778901.47 (0.97–2.22).071.49 (0.97–2.27).07
      Age 35–<40 y20963208070952,24613601.53 (0.99–2.38).061.50 (0.95–2.36).08
      Age 40–<45 y142395860159760,40526402.22 (1.32–3.69).0022.30 (1.37–3.85).002
      Pneumonia
      P value for interaction (maximum likelihood test comparing full and reduce models, 5 degrees of freedom) between pregnancy and age (5-year age bin categories) is equal to .002.
      EventsTotalPercentageEventsTotalPercentageRR (95% CI)P valueAdjusted RR (95% CI)
      Modified Poisson model adjusted for obesity, hypertension, diabetes, and smoking
      P value
      Overall61170288.714,332255,7165.601.96 (1.81–2.12)<.0011.97 (1.82–2.13)<.001
      Age 15–<20 y324517.124968043.662.45 (1.72–3.48)<.00012.42 (1.70–3.46)<.0001
      Age 20–<25 y11015057.362718,7503.342.63 (2.17–3.19)<.00012.64 (2.18–3.21)<.0001
      Age 25–<30 y16921028.0150834,1624.412.07 (1.78–2.41)<.00012.08 (1.78–2.42)<.0001
      Age 30–<35 y16717689.5228537,4226.111.79 (1.54–2.08)<.00011.78 (1.54–2.07)<.0001
      Age 35–<40 y919639.5263637,1347.101.52 (1.25–1.85)<.00011.54 (1.26–1.88)<.0001
      Age 40–<45 y4223917.6427143,2529.872.03 (1.54–2.68)<.00012.07 (1.56–2.75)<.0001
      CI, confidence interval; RR, relative risk.
      Martinez-Portilla. Young pregnant women are also at an increased risk of mortality and severe illness due to coronavirus disease 2019. Am J Obstet Gynecol 2021.
      a Modified Poisson model adjusted for obesity, hypertension, diabetes, and smoking
      b P value for interaction (maximum likelihood test comparing full and reduce models, 5 degrees of freedom) between pregnancy and age (5-year age bin categories) is equal to .46
      c P value for interaction (maximum likelihood test comparing full and reduce models, 5 degrees of freedom) between pregnancy and age (5-year age bin categories) is equal to .002.

      Conclusion

      Earlier reports suggested that mortality may not be higher in pregnant women with COVID-19.
      • Zambrano L.D.
      • Ellington S.
      • Strid P.
      • et al.
      Update: characteristics of symptomatic women of reproductive age with laboratory-confirmed SARS-CoV-2 infection by pregnancy status—United States, January 22-October 3, 2020.
      However, a recent US study found a 1.7-fold increased risk of death in pregnant women (n=34) with COVID-19 compared with nonpregnant women (n=447).
      • Zambrano L.D.
      • Ellington S.
      • Strid P.
      • et al.
      Update: characteristics of symptomatic women of reproductive age with laboratory-confirmed SARS-CoV-2 infection by pregnancy status—United States, January 22-October 3, 2020.
      We confirm that pregnancy puts the women at increased risk of COVID-19–related death and pneumonia, as we have suggested in our previous article using a propensity score matching analysis.
      • Martinez-Portilla R.J.
      • Sotiriadis A.
      • Chatzakis C.
      • et al.
      Pregnant women with SARS-CoV-2 infection are at higher risk of death and severe pneumonia: propensity score-matched analysis of a nationwide prospective cohort study (COV19Mx).
      What was striking about our results was that although the risk was highest among older pregnant women, the RR was high among younger pregnant women aged between 20 and 30 years. This likely reflected both the excess risk conferred by pregnancy and the low baseline risk of death and severe disease among younger nonpregnant women. The finding was concerning. Younger populations have been reassured that they are at lower risk of experiencing COVID-19–related complications, and pregnant women may falsely believe that their young age protects them against severe diseases. Such inadequate health advice may render this vulnerable group to seek medical care too late, and care may not be prioritized appropriately if they are perceived to be at lower risk. Therefore, pregnancy puts the woman at an increased risk of COVID-19–related death and pneumonia. All pregnant women, irrespective of age, should be informed about the health risks associated with COVID-19 and should seek medical help at the earliest opportunity.

      References

        • Zambrano L.D.
        • Ellington S.
        • Strid P.
        • et al.
        Update: characteristics of symptomatic women of reproductive age with laboratory-confirmed SARS-CoV-2 infection by pregnancy status—United States, January 22-October 3, 2020.
        MMWR Morb Mortal Wkly Rep. 2020; 69: 1641-1647
        • Martinez-Portilla R.J.
        • Sotiriadis A.
        • Chatzakis C.
        • et al.
        Pregnant women with SARS-CoV-2 infection are at higher risk of death and severe pneumonia: propensity score-matched analysis of a nationwide prospective cohort study (COV19Mx).
        Ultrasound Obstet Gynecol. 2020; ([Epub ahead of print])