Observational cohort study of pregnancy outcome after first-trimester exposure to fluoroquinolones.
Fluoroquinolones are avoided during pregnancy due to developmental toxicity in animals. The aim of this study was to assess the fetal risk after intrauterine fluoroquinolone exposure. We performed an observational study of a prospectively ascertained cohort of pregnant women exposed to a fluoroquinolone during the first trimester. Pregnancy outcomes were compared to those of a cohort exposed to neither fluoroquinolones nor teratogenic or fetotoxic drugs. The outcomes evaluated were major birth defects (structural abnormalities of medical, surgical, or cosmetic relevance), spontaneous abortion, and elective termination of pregnancy. Pregnancy outcomes of 949 women with fluoroquinolone treatment were compared with those of 3,796 nonexposed controls. Neither the rate of major birth defects (2.4%; adjusted odds ratio [OR(adj)], 0.91; 95% confidence interval [CI], 0.6 to 1.5) nor the risk of spontaneous abortion (adjusted hazard ratio [HR(adj)], 1.01; 95% CI, 0.8 to 1.3) was increased. However, there was a nonsignificant increase in major birth defects after exposure to moxifloxacin (6/93, 6.5%; crude odds ratio [OR(crude)], 2.40; 95% CI, 0.8 to 5.6). Neither a critical exposure time window within the first trimester nor a specific pattern of birth defects was demonstrated for any of the fluoroquinolones. The rate of electively terminated pregnancies was increased among the fluoroquinolone-exposed women (HR(adj), 1.32; 95% CI, 1.03 to 1.7). The gestational ages at delivery and birth weights did not differ between groups. Our study did not detect an increased risk of spontaneous abortion or major birth defects. These reassuring findings support the recommendation to allow fluoroquinolone use in early pregnancy in selected cases. After the use of moxifloxacin, a detailed fetal ultrasound examination should be considered.
Pharmakovigilanz- und Beratungszentrum für Embryonaltoxikologie (Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy), Charité Universitätsmedizin Berlin, Berlin, Germany stephanie.padberg@charite.de.
Stephanie
S
Padberg
Pharmakovigilanz- und Beratungszentrum für Embryonaltoxikologie (Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy), Charité Universitätsmedizin Berlin, Berlin, Germany.
Evelin
E
Wacker
Department of Mathematics, Beuth Hochschule für Technik Berlin (University of Applied Sciences), Berlin, Germany.
Reinhard
R
Meister
Pharmakovigilanz- und Beratungszentrum für Embryonaltoxikologie (Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy), Charité Universitätsmedizin Berlin, Berlin, Germany.
Mary
M
Panse
Pharmakovigilanz- und Beratungszentrum für Embryonaltoxikologie (Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy), Charité Universitätsmedizin Berlin, Berlin, Germany.
Corinna
C
Weber-Schoendorfer
Pharmakovigilanz- und Beratungszentrum für Embryonaltoxikologie (Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy), Charité Universitätsmedizin Berlin, Berlin, Germany.
Marc
M
Oppermann
Pharmakovigilanz- und Beratungszentrum für Embryonaltoxikologie (Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy), Charité Universitätsmedizin Berlin, Berlin, Germany.
Christof
C
Schaefer
D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000029:Abortion, Legal / Q000706:statistics & numerical data; D000022:Abortion, Spontaneous / Q000503:physiopathology; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D001724:Birth Weight; D016022:Case-Control Studies; D005260:Female; D024841:Fluoroquinolones / Q000008:administration & dosage* / Q000009:adverse effects; D005865:Gestational Age; D006801:Humans; D000077266:Moxifloxacin; D016017:Odds Ratio; D011247:Pregnancy; D011256:Pregnancy Outcome; D011261:Pregnancy Trimester, First / Q000187:drug effects*; D047928:Premature Birth / Q000503:physiopathology; D011446:Prospective Studies
D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D000077266:Moxifloxacin