Pregnancy Outcomes Following Exposure to Quinolone Antibiotics – a Systematic-Review and Meta-Analysis
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Quinolones, and the fluoroquinolones subgroup, are a class of antibiotics commonly used for the treatment of a wide variety of infections. However, their safety profile in pregnant women is controversial. The association between fluoroquinolones and arthropathy was primarily described in immature animals, and only rarely in humans, yet it has led to the restricted use of quinolones during pregnancy. We aimed to assess their safety during pregnancy.
A systematic review and meta-analysis assessing the safety of quinolone exposure during any time of pregnancy, and during first trimester alone, was performed. The systematic review was performed using MEDLINE and EMBASE, and followed the PRISMA guidelines. Pooled effect sizes with corresponding 95% confidence intervals (CI) were calculated using random effects models, comparing fetal outcomes of quinolone exposed and non-exposed pregnancies. Only cohort and case control studies were included in the meta-analysis.
Twelve studies met the inclusion criteria. Exposure to quinolones during first trimester was not associated with an increased risk for birth defects (pooled odds ratio (OR) = 0.89, 95% CI 0.72–1.09, I2 = 0%), stillbirth (OR = 1.32, 95% CI 0.33–5.34, I2 = 16%), preterm birth (OR = 1.10, 95% CI 0.83–1.48, I2 = 41%) and low birth weight (OR = 1.29, 95% CI 0.54–3.12, I2 = 67%).
The use of quinolones during the first-trimester of pregnancy was not associated with an increased risk of birth defects, stillbirths, preterm births or low birth weight.
Key Wordsbirth defects congenital abnormalities congenital malformations fluoroquinolones pregnancy outcomes pregnancy
- 1.Phillips I, King A, Shannon K. The Quinolones. The Quinolones, Elsevier; 2000. Available from: http://www.sciencedirect.com/science/article/pii/B9780120595174500040. cited 2016 Feb 19.
- 9.Kaguelidou F, Turner MA, Choonara I, Jacqz-Aigrain E. Ciprofloxacin Use in Neonates. Pediatr Infect Dis J. 2011;30:e29–37. Available from: http://content.wkhealth.com/linkback/openurl?sid=WKPTLP:landingpage&an=00006454-201102000-00032. cited 2018 Jan 10.
- 10.Research C for DE and. Bioterrorism and Drug Preparedness - CIPRO (Ciprofloxacin) Use by Pregnant and Lactating Women. Center for Drug Evaluation and Research; Available from: https://www.fda.gov/drugs/emergencypreparedness/bioterrorismanddrugpreparedness/ucm130712.htm. cited 2017 Jul 19.
- 12.Loebstein R, Addis A, Ho E, Andreou R, Sage S, Donnenfeld AE, et al. Pregnancy Outcome Following Gestational Exposure to Fluoroquinolones: a Multicenter Prospective Controlled Study. 1998;42:1336–9.Google Scholar
- 14.Oral Health Care During Pregnancy Expert Workgroup. Oral Health Care During Pregnancy: A national consensus statement.Washington, DC: National Maternal and Child Oral Health Resource Center. 2012.Google Scholar
- 17.Research C for DE and. Drug Safety and Availability - FDA Drug Safety Communication: FDA updates warnings for oral and injectable fluoroquinolone antibiotics due to disabling side effects. Center for Drug Evaluation and Research; Available from: https://www.fda.gov/Drugs/DrugSafety/ucm511530.htm. cited 2018 Jan 26.
- 19.Moniz MH, Gavin LE, Dalton VK. Performance measures for contraceptive care. Obstet Gynecol. 2017;130:1. Available from: http://insights.ovid.com/crossref?an=00006250-900000000-98278 Google Scholar
- 20.Moher D, Liberati A, Tetzlaff J, Altman DG, Altman D, Antes G, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097. https://doi.org/10.1371/journal.pmed.1000097
- 21.Wells GA, Shea B, O’Connell D, et al. The Newcastle-Ottawa scale (NOS) for assessing the quality of nonrandomized studies in meta-analyses. Ottawa Hosp Res Inst. http://www.ohri.ca/programs/clinical_epidemiology/nosgen.pdf. cited 2017 Mar 10.
- 25.Matok I, Koren G, Gorodischer R, Levy A. Exposure to Quinolones during Pregnancy: Lack of Association with an Increased Risk for Birth Defects and Other Adverse Pregnancy Outcomes. Pharmacoepidemiol Drug Saf. 2010;19:S245. Available from: https://insights.ovid.com/pharmacoepidemiology-drug-safety/pads/2010/08/001/578-exposure-quinolones-during-pregnancy-lack/578/01445491. cited 2017 Jul 19.
- 26.Watanabe O, Nakajima K, Ishii M, Yakuwa N, Murashima A. Pregnancy outcome after first trimester exposure to quinolones. Birth Defects Res Part A - Clin Mol Teratol. 2013;97(5):367. Available from: http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=emed15&AN=71430619 Google Scholar
- 28.Wogelius P, Nørgaard M, Gislum M, Pedersen L, Schønheyder HC, Toft H. Further analysis of the risk of adverse birth outcome after maternal use of fluoroquinolones. 2005;26:323–326.Google Scholar
- 30.Cooper WO, Hernandez-diaz S, Arbogast PG, Dudley JA, Dyer SM, Gideon PS, et al. Antibiotics potentially used in response to bioterrorism and the risk of major congenital malformations. Paediatr Perinat Epidemiol. 2008;23(1):18–28.Google Scholar
- 31.Berkovitch M, Pastuszak A, Gazarian M, Lewis M. Koren G. Safety of the new quinolones in pregnancy. 1994;84:535. Available from: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=cin20&AN=107299379 Google Scholar
- 32.Muanda FT, Sheehy O, Bérard A. Use of antibiotics during pregnancy and risk of spontaneous abortion. Can Med Assoc J. 2017;189:E625–33. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28461374. cited 2017 Jul 19.
- 39.Ozyuncu O, Nemutlu E, Katlan D, Kir S, Beksac MS. International journal of antimicrobial agents maternal and fetal blood levels of moxifloxacin, levofloxacin, cefepime and cefoperazone. Int J Antimicrob Agents Elsevier BV 2010;36:175–178. Available from: https:doi.org/ https://doi.org/10.1016/j.ijantimicag.2010.03.011
- 40.Giamarellou[RM1] H, Kolokmhas E. Pharmacokinetics of three newer quinolones in pregnant and lactating women. Am J Med. 1989;87:49–51.Google Scholar
- 43.Yefet E, Salim R, Chazan B, Akel H, Romano S, Nachum Z. The Safety of Quinolones in Pregnancy. Obstet Gynecol Surv. 2014;69:681–94. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25409160. cited 2017 Jul 19.
- 44.Mazor-Dray E, Levy A, Schlaeffer F, Sheiner E. Maternal urinary tract infection: is it independently associated with adverse pregnancy outcome? J Matern Neonatal Med. Taylor & Francis; 2009;22:124–8. Available from: http://www.tandfonline.com, doi: https://doi.org/10.1080/14767050802488246. cited 2017 Nov 30.