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Grand Rounds

NSAIDs During Early Pregnancy: Is There an Association with Premature Birth?

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BACKGROUND AND PURPOSE:

  • Quantin et al. (BJOG, 2021) assessed the risk of preterm birth associated with early NSAID exposure in pregnancy

METHODS:

  • Retrospective cohort study (2012 to 2014)
    • National population-database: French National Health Insurance Database
    • Hospital discharge data and health claims data
  • Participants
    • Women 15 to 45 years of age
    • Singleton pregnancies with a live birth
    • Exclusion: Anti-inflammatory agents prescribed >22 weeks
  • Exposures
    • NSAID dispensations <22 weeks’
  • Study design
    • The association between exposure and risk of preterm birth was evaluated
    • Adjustment was performed for socio-demographic variables, maternal comorbidities, prescription drugs, and pregnancy complications
  • Primary outcome
    • Prematurity (birth before 37 weeks’)

RESULTS:

  • 1,598,330 singleton pregnancies
  • Early exposure to NSAIDs was associated with a significantly increased risk of preterm birth
    • Extreme prematurity (22 to 27 weeks)
      •  aOR 1.76 (95% CI, 1.54 to 2.00)
    • Moderate prematurity (28 to 31 weeks)
      • aOR 1.28 (95% CI, 1.17 to 1.40)
    • Late prematurity (32 to 36 weeks)
      • aOR 1.08 (95% CI, 1.05 to 1.11)
  • Use of Indomethacin was associated with an increased risk of premature birth
    • Overall prematurity
      • aOR 1.92 (95% CI, 1.37 to 2.70)
    • Extreme prematurity
      • aOR 9.33 (95% CI, 3.75 to 23.22)
  • With removal of preeclampsia and placental abruption from the dataset, NSAIDs were still associated with prematurity
    • aOR 1.08 (1.06-1.11)

CONCLUSION:

  • The use of NSAIDs in the first half of pregnancy was associated with an increased risk of prematurity regardless of the severity
    • The association differed among NSAIDs
  • A limitation of the study includes unmeasured confounders, including indication for the use of NSAIDs
  • The authors conclude

This study suggests that there is an urgent need for complementary investigations since prematurity is a frequent event, with high rates of mortality and morbidity at the lowest gestational ages

These results should not be overestimated, because of the risk of unjustified maternal anxiety and discontinuation of useful treatments, but neither should they be underestimated

Learn More – Primary Sources:

Early exposure of pregnant women to non‐steroidal anti‐inflammatory drugs delivered outside hospitals and preterm birth risk: nationwide cohort study

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Related ObG Topics:

NSAIDs in Pregnancy: Is There an Association with Miscarriage?
Are NSAIDs Associated with Persistent Postpartum Hypertension in Women with Preeclampsia?
Does NSAID Use Impact Risk for Ovarian Cancer?

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