Observational Cohort Study of Pregnancy Outcome after First-Trimester Exposure to Fluoroquinolones

Abstract

bFluoroquinolones 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.

Use of antibiotics during pregnancy and risk of spontaneous abortion

“…These discrepancies may be explained by a lack of statistical power and a recall bias. [6][7][8] Metronidazole exposure was associated with a 70% increased risk of spontaneous abortion, which is consistent with a Medicaid cohort study that showed a 67% increased risk of spontaneous abortion. §Based on ICD-9 or ICD-10 codes or prescriptions filled for chronic diseases (depression, asthma, diabetes mellitus, chronic hypertension, thyroid disorder, epilepsy, and rheumatoid polyarthritis and systemic lupus erythematosus).…”

“…[1][2][3][4] In contrast, a Danish study based on data from a prescription database found an increased risk of spontaneous abortion associated with the use of clarithromycin. 5 Three studies using data from teratology information services failed to show a link between the use of quinolones and the risk of spontaneous abortion, [6][7][8] and an early Medicaid study showed an association with the use of metronidazole. 9 However, the studies were all limited by either small samples, or recall or indication bias.…”

“…9 However, the studies were all limited by either small samples, or recall or indication bias. [1][2][3][4][5][6][7][8][9] Studies of the risk of spontaneous abortion associated with tetracyclines and nitrofurantoin are lacking.…”

Reply to ‘Comment on “Use of antibiotics during pregnancy and the risk of major congenital malformations: a population based cohort study” by Muanda et al.’

“…Though, those previous studies, including published meta‐analyses, were limited by several methodological flaws (low power, recall and indication bias) as pointed out in our paper, their findings were overall similar to ours . Of the eight studies reported in our manuscript, only two studies were able to assess the risk of birth defect associated with the use of individual fluoroquinolone . The first study looked at the risk of major congenital malformations following in utero exposure to individual fluoroquinolone, and their findings were similar to ours as stated in our manuscript .…”

“…Of the eight studies reported in our manuscript, only two studies were able to assess the risk of birth defect associated with the use of individual fluoroquinolone . The first study looked at the risk of major congenital malformations following in utero exposure to individual fluoroquinolone, and their findings were similar to ours as stated in our manuscript . Unlike us, they could not examine the risk of organ specific malformations .…”