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Impact of the COVID-19 pandemic on the incidence of prematurity: critical role of gestational age and environment

Published:February 23, 2022DOI:https://doi.org/10.1016/j.ajog.2022.02.028

      Objective

      Data on the incidence of prematurity during the COVID-19 pandemic are contradictory, with some reports showing decreased preterm births and others showing no effect.
      • Harvey E.M.
      • McNeer E.
      • McDonald M.F.
      • et al.
      Association of preterm birth rate with COVID-19 statewide stay-at-home orders in Tennessee.
      ,
      • Handley S.C.
      • Mullin A.M.
      • Elovitz M.A.
      • et al.
      Changes in preterm birth phenotypes and stillbirth at 2 Philadelphia hospitals during the SARS-CoV-2 pandemic, March-June 2020.
      We propose that multiple biologic effects of SARS-CoV-2 infection and environmental changes during the pandemic exert competing effects on the preterm birth rate.
      SARS-CoV-2 infection may increase preterm births by increasing preeclampsia and medically indicated preterm births,
      • Conde-Agudelo A.
      • Romero R.
      SARS-CoV-2 infection during pregnancy and risk of preeclampsia: a systematic review and meta-analysis.
      but its effects on spontaneous preterm births are unknown. Infection is the most commonly identified etiologic contributor to spontaneous preterm births at <28 weeks’ gestation.
      • Goldenberg R.L.
      • Culhane J.F.
      • Iams J.D.
      • Romero R.
      Epidemiology and causes of preterm birth.
      Our preliminary data demonstrated that SARS-CoV-2 placental infection increases the expression of placenta-specific microRNA 519c, which protects against infection-induced preterm birth.
      • Tiozzo C.
      • Bustoros M.
      • Lin X.
      • et al.
      Placental extracellular vesicles-associated microRNA-519c mediates endotoxin adaptation in pregnancy.
      Furthermore, environmental effects of the COVID-19 pandemic (lockdowns, quarantine, decreased travel) may decrease pathogen exposures that can trigger infection-induced preterm birth.
      • Racicot K.
      • Mor G.
      Risks associated with viral infections during pregnancy.
      Therefore, the effects of the COVID-19 pandemic on the rates of prematurity likely reflect a balance between increased preeclampsia-induced preterm births and decreased infection-induced spontaneous preterm births.
      New York was the first epicenter of the COVID-19 pandemic in the United States. The prevalence of SARS-CoV-2 infection exploded in March 2020, with a surge in the urban center. Lockdowns were initiated in all jurisdictions by mid-March. We compared the incidence of extreme prematurity (with and without preeclampsia) in 2020 with that of 2019 in a large cross-sectional study of hospitals in the New York City area.

      Study Design

      Data were collected from urban medical centers (New York University Tisch Hospital, Lenox Hill Hospital, Montefiore Medical Center, Mount Sinai Hospital) and suburban medical centers (New York University Langone Hospital—Long Island, Long Island Jewish Medical Center, North Shore University Hospital, Westchester Medical Center, and Stony Brook University Hospital) in New York. Rates of prematurity with and without preeclampsia were compared using the inverted skew-corrected score test for binomial distributions and Poisson regression.

      Results

      Total deliveries decreased from 63,327 in 2019 to 62,020 in 2020, with a SARS-CoV-2 positivity rate of 30.1 per 1000 (Table 1). Extreme prematurity (<28 weeks’ gestation) decreased from 5.6 to 4.7 per 1000 deliveries in 2020 (P<.0001), but the rate of moderate prematurity (28–35 weeks’ gestation) did not change. Preeclampsia increased in 2020, from 123.9 to 179.9 per 1000 in mothers who delivered at <28 weeks’ gestation.
      Table 1Number and rates of preterm deliveries in 2019 and 2020
      Variables20192020Difference (95% CI)P value
      NRate/1000NRate/1000
      Deliveries63,32762,020−1307.0002
      Delivery <35 wk225535.6215334.7−0.9 (−1.9 to 0.1).08
      Delivery 28–35 wk190030.0186430.10.1 (−0.9 to 1.0).9
      Delivery <28 wk3555.62894.7−0.9 (−1.3 to −0.6)<.0001
       With preeclampsia44123.952179.956.0 (28.0–83.0)<.0008
      COVID-19 positive187030.15
      CI, confidence interval.
      Weinberger. Impact of the COVID-19 pandemic on the incidence of prematurity. Am J Obstet Gynecol 2022.
      At the suburban sites, overall prematurity dropped significantly (33.9 to 30.9/1000, P=.0001), primarily driven by decreased rates of extreme prematurity (3.5 to 2.5/1000, P<.0001). In contrast, at urban sites, total and extreme prematurity did not significantly decrease, and moderate prematurity increased (31.1 to 32.6/1000, P=.03). The rates of SARS-CoV-2 positivity were significantly higher in urban than in suburban sites (40.2 vs 18.4/1000, P<.0001) (Table 2).
      Table 2Number and rate of preterm deliveries at urban and suburban hospitals
      VariablesUrban
      20192020Difference (95% CI)P value
      NRate/1000NRate/1000
      Total deliveries35,46633,471
      Delivery <35 wk131137.0126937.90.9 (−0.5 to 2.4).2
      Delivery 28–35 wk110331.1109132.61.5 (0.2–2.8).03
      Delivery <28 wk2085.91785.3−0.5 (−1.1 to 0.0).06
       With preeclampsia21101.028157.356.3 (22.2–88.6).001
      COVID-19 positive134440.2
      Suburban
      Total deliveries27,86128,549
      Delivery <35 wk94433.988430.9−2.9 (−4.4 to −1.5).0001
      Delivery 28–35 wk84730.481228.4−2.0 (−3.4 to −0.6).06
      Delivery <28 wk973.5722.5−1.4 (−2.0 to −0.8)<.0001
       With preeclampsia23156.524216.259.8 (11.5–105.7).01163
      COVID-19 positive52618.4
      CI, confidence interval.
      Weinberger. Impact of the COVID-19 pandemic on the incidence of prematurity. Am J Obstet Gynecol 2022.

      Conclusion

      In 2020, the COVID-19 pandemic in New York was associated with an overall decreased rate of extreme preterm births (<28 weeks’ gestation) despite an increased rate of preeclampsia. This is consistent with the fact that extreme preterm births usually occur spontaneously secondary to infection. Decreased intrapartum infection was likely related to both the environmental effects of lockdowns and possible biologic effects of SARS-CoV-2 infection on the placenta. In contrast, the rates of moderate prematurity (>28 weeks’ gestation) did not decrease. This is most likely related to the relative impact of increased preeclampsia and other medical indications for preterm delivery. Conflicting results in earlier reports may be related to the diversity in the gestational ages and the contributing etiologic factors for preterm birth in the studied population.
      The effects of the pandemic in New York were different in urban and suburban populations. Total prematurity decreased at suburban sites, driven by significant decreases in extreme prematurity. In contrast, at urban sites, total and extreme prematurity remained unchanged, and moderate prematurity increased. It is possible that lockdowns were less effective in the urban locations, as demonstrated by the increased prevalence of COVID-19 infection. Our findings highlight the importance of providing socioeconomic data in reports on the population effects of the pandemic.

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