BACKGROUND AND PURPOSE:

• There is conflicting evidence whether opioid exposure may cause congenital malformations
• Bateman et al. (BMJ, 2021) evaluated the risk for major congenital malformations with first trimester exposure to prescription opioids

METHODS:

• Population based cohort study
• Data sources
  • Publicly insured database (2000 to 2014)
  • Commercially insured database (2003 to 2015)
• Participants
  • Pregnant women and their infants
• Exposure
  • Prescription opioids
  • 2 or more dispensations during the first trimester
• Study design
  • Propensity score stratification was used to adjust for potential confounders and/or proxies for confounders
  • Estimates from each database were combined using meta-analysis
• Primary outcomes
  • Major malformations overall
  • Cardiac malformations overall | VSD | ASD | Patent foramen ovale
  • NTD, clubfoot, and oral cleft

RESULTS:

• 1,602,580 publicly insured women | 1,177,676 commercially insured women
  • Publicly insured women (Medicaid): 4.4%
  • Commercially insured (MarketScan) women: 1.1%
• Absolute risk of malformations overall
  • Publicly insured cohort
    • Exposed: 41.0 per 1000 pregnancies (95% CI, 39.5 to 42.5)
    • Unexposed: 32.0 per 1000 pregnancies (95% CI, 31.7 to 32.3)
  • Commercially insured cohort
    • Exposed: 42.6 per 1000 pregnancies (95% CI, 39.0 to 46.1)
    • Unexposed: 37.3 per 1000 pregnancies (95% CI, 37.0 to 37.7)
• Relative risk (RR) estimates were higher for all outcomes with exposure, but shifted toward the null after adjustment
  • Malformations overall: RR 1.06 (95% CI, 1.02 to 1.10)
  • Cardiovascular malformations: RR 1.09 (95% CI, 1.00 to 1.18)
  • Ventricular septal defect: RR 1.07 (95% CI, 0.95 to 1.21)
  • Atrial septal defect/patent foramen ovale: RR 1.04 (95% CI,  0.88 to 1.24)
  • Neural tube defect: RR 0.82 (95% CI, 0.53 to 1.27)
  • Clubfoot: RR 1.06 (95% CI, 0.88 to 1.28)
• There was a higher risk of cleft palate: RR 1.62 (95% CI, 1.23 to 2.14)

CONCLUSION:

• Prescription opioid use in the first trimester of pregnancy is generally not associated with major congenital malformations
  • However, there may be a small increased risk of cleft palate
• Limitations include observational study design that carries a risk for risidual confounding
• The authors conclude

The results inform the selection of analgesic drugs for women who are pregnant and women of reproductive age who might inadvertently become pregnant 

Learn More – Primary Sources:

Association of first trimester prescription opioid use with congenital malformations in the offspring: population based cohort study

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