First trimester pregnancy exposure to fosfomycin and risk of major congenital anomaly: a comparative study in the EFEMERIS database

Infection. 2023 Feb;51(1):137-146. doi: 10.1007/s15010-022-01861-4. Epub 2022 Jun 11.

Abstract

Purpose: Fosfomycin trometamol has been recommended as first-line bactericidal antibiotic for urinary tract infections in pregnant women since 2015 in France. However, studies assessing fosfomycin safety in pregnancy are sparse. This study aimed to assess the risk of major Congenital Anomaly (CA) after fosfomycin exposure during the first trimester of pregnancy.

Methods: We performed a comparative study in EFEMERIS, the French database including expecting mothers covered by the French Health Insurance System of Haute-Garonne from July 1st, 2004 to December 31th, 2018. EFEMERIS contains prescribed and dispensed reimbursed medications during pregnancy and pregnancy outcomes. Logistic regressions have been conducted to compare three groups: (1) pregnancies exposed at least once to fosfomycin; (2) pregnancies exposed at least once to nitrofurantoin; and (3) pregnancies exposed neither to fosfomycin nor to nitrofurantoin, another antibiotic prescribed for urinary infections, before and during pregnancy.

Results: A total of 2724 (2.0%) pregnant women received at least one fosfomycin prescription during the first trimester, 650 (0.5%) received nitrofurantoin during the first trimester, and 133,502 (97.5%) pregnant women were not exposed to fosfomycin nor to nitrofurantoin. First trimester pregnancy exposure to fosfomycin was not associated with an increased risk of major CA, compared to first trimester exposure to nitrofurantoin (2.0% versus 2.5%; ORa = 0.80 [0.44-1.47]), or to pregnancies unexposed to fosfomycin and nitrofurantoin (2.0% versus 2.1%; ORa = 0.97 [0.73-1.30]).

Conclusion: This is the first large comparative study assessing fosfomycin safety in pregnancy. It does not exhibit an increased risk of major CA after fosfomycin exposure during the first trimester of pregnancy.

Keywords: EFEMERIS database; Fosfomycin; Major congenital anomaly; Pharmacoepidemiology; Pregnancy; Urinary tract infection.

MeSH terms

  • Anti-Bacterial Agents / adverse effects
  • Female
  • Fosfomycin* / adverse effects
  • Humans
  • Nitrofurantoin / adverse effects
  • Pregnancy
  • Pregnancy Outcome
  • Pregnancy Trimester, First
  • Urinary Tract Infections* / drug therapy
  • Urinary Tract Infections* / epidemiology

Substances

  • Fosfomycin
  • Nitrofurantoin
  • Anti-Bacterial Agents