Pregnancy outcome after first-trimester exposure to fosfomycin for the treatment of urinary tract infection: an observational cohort study
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The primary aim of our study was to assess pregnancy outcome after first-trimester exposure to fosfomycin.
We performed an observational cohort study analysing prospectively ascertained pregnancies including 152 women exposed to fosfomycin in the first trimester of pregnancy in comparison with a randomly selected cohort comprising 456 pregnancies not exposed to fosfomycin. All pregnancies were identified through risk consultations using structured questionnaires between January 2000 and December 2016 by the German Embryotox pharmacovigilance institute in Berlin. Primary objectives were the risks of major birth defects and spontaneous abortion.
Only 1 out of 146 exposed infants was affected by a major birth defect (0.7%, 95% CI 0.04–4.33%) in comparison to 15/399 in the non-exposed cohort (3.8%, 95% CI 2.2–6.26%). Spontaneous abortions were observed in 5/152 cases in the fosfomycin cohort vs. 53/456 cases in the comparison cohort (cumulative incidence 6.2% vs. 23.1%; HR adjusted 0.35, 95% CI 0.14–0.90).
This is the first study specifically examining the teratogenic risk of fosfomycin. The study results do not indicate an increased risk of adverse pregnancy outcome after fosfomycin exposure during early pregnancy. However, larger studies are needed to confirm the safety of fosfomycin during the first trimester.
KeywordsFosfomycin Pregnancy Urinary tract infection Birth defects Spontaneous abortion
We would like to thank Regina Stegherr for her valuable statistical advice and support throughout the statistical analysis. We especially thank all patients and medical health care professionals for reporting pregnancies to our institute and our colleagues from the German Embryotox pharmacovigilance institute for diligent counseling and documenting cases.
The study was designed by WP (with contribution from SP, CS, AKF, TB and RM). KM acted as study assistant who was responsible for the observance of documentation standards. AKF, TB and RM analyzed the data. All the authors were involved in the interpretation of the data. WP drafted the article and all the authors participated in the revision and have approved the final version.
This work was partially funded by the Grants BE 4500/3-1, ME 910/2-1 and SCHA 1749/3-1 of the German Research Foundation (DFG) and the German Federal Institute for Drugs and Medical Devices (BfArM).
Compliance with ethical standards
The study was approved by the Ethics Committee of the Charité Universitätsmedizin Berlin (EA4/119/17) and registered at the German Clinical Trials Register (DRKS00013159).
Conflict of interest
The authors declare that they have no conflict of interest.
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