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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