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Grand Rounds

Is Opioid Exposure During First Trimester Linked to Increased Risk of Congenital Malformations?

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BACKGROUND AND PURPOSE:

  • Some previous studies have suggested that there may be an increased risk of congenital malformations associated with prenatal exposure to opioid analgesics
  • Bowie et al. (Canadian Medical Association Journal, 2022) quantified the risk of anomalies after opioid analgesic exposure during the first trimester

METHODS:

  • Population-based cohort study
  • Population
    • Parent-infant pairs from singleton pregnancies without opioid use disorder
  • Exposure
    • Any opioid analgesic exposure in the first trimester
    • Specific opioid exposures
  • Study design
    • High-dimensional propensity scores (HDPS) used to ensure similarity of parent-infant pairs by exposure
    • Adjusted risk ratios (aRRs) were calculated between exposure and primary outcome
  • Primary outcome
    • Congenital anomalies diagnosed within first year of life
      • Any anomaly
      • Organ system anomalies
      • Major or minor anomalies
      • Specific anomalies

RESULTS:

  • 559,579 parent-infant pairs
    • Exposed to opioid analgesics: 2.0%
  • Prevalence of congenital anomalies
    • Exposed infants: 2.8%
    • Unexposed infants: 2.0%
  • After HDPS adjustment, opioid exposure was associated with a small, elevated risk of any congenital anomaly
    • aRR 1.14 (95% CI, 1.01 to 1.28)
    • Adjusted prevalence difference: 2.9 per 1000 infants
    • Increased risk with exposure to morphine (aRR 1.89; 95% CI, 1.28 to 2.79) and tramadol (aRR 1.79; 95% CI 1.23 to 2.60)
  • Compared to unexposed infants, those who were exposed to opioid analgesics had elevated risks for
    • Gastrointestinal anomalies
      • Any opioid analgesic: aRR 1.46 (95% CI, 1.15 to 1.85)
      • Codeine: aRR 1.53 (95% CI, 1.12 to 2.09)
      • Tramadol: aRR 2.69 (95% CI, 1.34 to 5.38)
    • Ankyloglossia
      • Any opioid analgesic: aRR 1.88 (95% CI, 1.30 to 2.72)
      • Codeine: aRR 2.14 (95% CI, 1.35 to 3.40)

CONCLUSION:

  • The absolute risk of congenital anomalies was low, but exposure to opioid analgesics in the first trimester was associated with increased risk for some congenital anomalies
  • Limitations of the study include
    • Diagnostic codes for billing were used for case identification, which may not be accurate
    • Minor anomalies with limited medical significance could result from exposure-dependent recording bias
  • The authors state

Although the absolute risk of anomalies was low, our study adds to those suggesting a small increased risk of congenital anomalies with exposure to opioid analgesics

Both the potential for harm or distress to the pregnant person as a consequence of forgoing treatment and the subsequent risk to the infant must be considered for effective treatment

Learn More – Primary Sources:

Prescribed opioid analgesics in early pregnancy and the risk of congenital anomalies: a population-based cohort study

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Does Analgesic Opioid Exposure During Pregnancy Increase the Risk of ADHD Diagnoses in Children?
Opioids in the First Trimester: Is There a Risk for Congenital Malformations?
The Opioid Crisis: Can Using A Decision Aid Decrease Opioid Prescribing Following Hysterectomy?

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