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Grand Rounds

Do Common Antibiotics Increase Risk of Congenital Malformations?

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BACKGROUND AND PURPOSE:

  • Damkier et al. (AJOG, 2019) assessed the association between 10 antibiotics and congenital malformations

METHODS:

  • Cohort study (2000 to 2015)
    • Validated Danish health-care and civic registries
  • Participants
    • Singleton liveborn children in Denmark over a 15 year period
  • Data sets and analysis
    • Data collected from the first trimester included
      • Pregnancy information | Prescription drug purchases for the 10 most commonly prescribed antibiotics | Congenital malformations
    • Crude odds ratio (OR) were calculated and adjusted (aOR) using logistic regression models were applied to control for confounders
    • Covariates: Maternal age at delivery | Year of delivery | Parity | Pre-pregnancy BMI | Smoking | Educational status | Employment status | Personal income
  • 10 common antibiotics
    • Doxycycline | Amoxicillin | Pivmecillinam | Dicloxacillin | Sulfamethizole | Erythromycin | Roxithromycin | Azithromycin | Ciprofloxacin | Nitrofurantoin
  • Primary analysis
    • Exposed cohort vs exposure to penicillins considered safe in pregnancy: Ampicillin | Pivampicillin | Benzylpenicillin | Phenoxymethylpenicillin
  • Secondary analysis
    • Exposed cohort vs unexposed cohort (no antibiotics)

RESULTS:

  • No increased risk of congenital malformations found for any of the 10 antibiotics when compared to ‘safe’ penicillin exposure
  • Compared to no exposure, there was an increased risk of major malformations and cardiac malformations for the following
    • Pivmecillinam: Major OR 1.13 (95% CI, 1.06 to 1.19) | Cardiac OR 1.15 (95% CI, 1.04 to 1.28)
    • Sulfamethizole: Major OR 1.15 (95% CI, 1.07 to 1.24 | Cardiac OR 1.22 (95% CI, 1.07 to 1.39)
    • Azithromycin: Major OR 1.19 (95% CI, 1.03 to 1.38 | Cardiac OR 1.29 (95% CI, 0.99 to 1.67)

CONCLUSION:

  • No increased risk of congenital malformations was found for first trimester exposure to 10 common antibiotics vs 4 commonly prescribed ‘safe’ penicillins
  • Small increased risk found when compared to no antibiotic exposure (secondary outcome)

Learn More – Primary Sources:

In utero exposure to antibiotics and risk of congenital malformations: A population-based study

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Related ObG Topics:

ACOG Guidance on Use of Sulfonamides and Nitrofurantoin for UTIs in the First Trimester
Does Antibiotic Use Increase Risk of Spontaneous Abortion?
FDA Drug Safety Communication: Antiretroviral Dolutegravir in Pregnancy and Association with NTD in Offspring
Antiepileptic Drugs: What is the Impact on Risk for Birth Defects

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