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The Outcomes of Pregnancy in Women Exposed to the New Macrolides in the First Trimester

A Prospective, Multicentre, Observational Study

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Abstract

Background: Macrolides are a group of commonly prescribed antibiotics. There is some doubt surrounding the use of the newer macrolides in pregnancy.

Objective: The present study aimed to compare outcomes of pregnancies exposed to the new macrolides clarithromycin, azithromycin and roxithromycin with non-teratogenic preparations.

Methods; In this prospective, multinational, multicentre, controlled, observational study, information was obtained either from pregnant women or their healthcare professionals who contacted their local teratogen information services in Italy, Israel, the Czech Republic, the Netherlands and Germany seeking information after exposure to macrolides. The comparison group included women or their healthcare professional who contacted these centreswithquestionsregardingknownnon-teratogenicpreparations. Information on obstetric and other background parameters was collected at enrollment; after delivery, subjects or their healthcare professionals were contacted to ascertain pregnancy outcome parameters and other exposures through the remainder of the pregnancy.

Results: A total of 608 women exposed to macrolides during pregnancy were enrolled; 511 of the exposures occurred during the first trimester. The comparison group comprised 773 women exposed to non-teratogenic preparations during the first trimester of pregnancy. No significant difference in the rate of major congenital malformations was found between the study group and the comparison group (3.4% vs 2.4%; p = 0.36; odds ratio (OR) 1.42; 95% CI 0.70, 2.88) or in the rate of cardiovascular malformations (1.6% vs 0.9%; p = 0.265; OR 1.91; 95% CI 0.63, 5.62).

No significant differences were found between subgroups of macrolides in the rates of major congenital malformations or cardiac malformations, although for azithromycin this was of borderline significance.

Conclusions: This study, in agreement with earlier smaller studies, suggests that the new macrolides do not pose a significantly increased risk of major congenital malformations or cardiac malformations.

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References

  1. Czeizel AE, Rockenbauer M, Sorensen HT, et al. Population-based case-control teratologic study of oral erythromycin treatment during pregnancy. Reprod Toxicol 1999; 13: 531–6

    Article  PubMed  CAS  Google Scholar 

  2. Källén BA, Otterblad Olausson P. Maternal drug use in early pregnancy and infant cardiovascular defect. Reprod Toxicol 2003; 17: 255–61

    Article  PubMed  Google Scholar 

  3. Källén BA, Otterblad Olausson P, et al. Is erythromycin therapy teratogenic in humans? Reprod Toxicol 2005; 20: 209–14

    Article  PubMed  Google Scholar 

  4. Erythromycin. In: Briggs GG, Freeman RK, Yaffe SJ, editors. Drugs in pregnancy and lactation. 8th ed. Philadelphia (PA): Lippincott Williams and Wilkins, 2008: 657-9

  5. Heikkinen T, Laine K, Neuvonen PJ, et al. The transplacental transfer of the macrolide antibiotics erythromycin, roxithromycin and azithromycin. Br J Obstet Gynaecol 2000; 107: 770–5

    Article  CAS  Google Scholar 

  6. Wilton LV, Pearce GL, Martin RM, et al. The outcomes of pregnancy in women exposed to newly marketed drugs in general practice in England. Br J Obstet Gynaecol 1998; 105: 882–9

    Article  PubMed  CAS  Google Scholar 

  7. Azithromycin. In: Briggs GG, Freeman RK, Yaffe SJ, editors. Drugs in pregnancy and lactation. 8th ed. Philadelphia (PA): Lippincott Williams and Wilkins, 2008: 158-60

  8. Clarithromycin. In: Briggs GG, Freeman RK, Yaffe SJ, editors. Drugs in pregnancy and lactation. 8th ed. Philadelphia (PA): Lippincott Williams and Wilkins, 2008: 379-80

  9. Sarkar M, Woodland C, Koren G, et al. Pregnancy outcome following gestational exposure to azithromycin. BMC Pregnancy Childbirth 2006; 6: 18

    Article  PubMed  Google Scholar 

  10. Drinkard CR, Shatin D, Clouse J. Postmarketing surveillance of medications and pregnancy outcomes: clarithromycin and birth malformations. Pharmacoepidemiol Drug Saf 2000; 9: 549–56

    Article  PubMed  CAS  Google Scholar 

  11. Einarson A, Phillips E, Mawji F, et al. A prospective controlled multicentre study of clarithromycin in pregnancy. Am JPerinatol 1998; 15: 523–5

    Article  CAS  Google Scholar 

  12. Bar-Oz B, Diav-Citrin O, Shechtman S, et al. Pregnancy outcome after gestational exposure to the new macrolides: a prospective multi-center observational study. Eur J Obstet Gynecol Reprod Biol 2008; 141: 31–4

    Article  PubMed  CAS  Google Scholar 

  13. Chun JY, Han JY, Ahn HK, et al. Fetal outcome following roxithromycin exposure in early pregnancy. J Matern Fetal Neonatal Med 2006; 19: 189–92

    Article  PubMed  CAS  Google Scholar 

  14. Czeizel AE, Rockenbauer M, Olsen J, et al. A case-control teratological study of spiramycin, roxithromycin, oleandomycin and josamycin. Acta Obstet Gynecol Scand 2000; 79: 234–7

    Article  PubMed  CAS  Google Scholar 

  15. Paulus W, Karl S, Frank S. Does roxithromycin affect embryo development?. Reprod Toxicol 2005; 20: 477

    Google Scholar 

  16. Finer LB, Henshaw SK. Disparities in rates of unintended pregnancy in the United States, 1994 and 2001. Perspect Sex Reprod Health 2006; 38: 90–6

    Article  PubMed  Google Scholar 

  17. Martin JA, Hamilton BE, Sutton PD, et al. Births: final data for 2004. Natl Vital Stat Rep 2006; 55: 1–101

    Google Scholar 

  18. Centers for Disease Control and Prevention. Metropolitan Atlanta Congenital Defects Program coding manual [online]. Available from URL: http://www.cdc.gov/ncbddd/bd/macdp.htm [Accessed 2012 May 10]

  19. Crider KS, Cleves MA, Reefhuis J, et al. Antibacterial medication use during pregnancy and risk of birth defects: National Birth Defects Prevention Study. Arch Pediatr Adolesc Med 2009; 163: 978–85

    Article  PubMed  Google Scholar 

  20. Koren G, Bologa M, Long D, et al. Perception of teratogenic risk by pregnant women exposed to drugs and chemicals during the first trimester. Am J Obstet Gynecol 1989; 160: 1190–4

    PubMed  CAS  Google Scholar 

  21. Schaefer C, Ornoy A, Clementi M, et al. Using observational cohort data for studying drug effects on pregnancy outcome: methodological considerations. Reprod Toxicol 2008; 26: 36–41

    Article  PubMed  CAS  Google Scholar 

  22. Rasmussen SA, Mulinare J, Khoury MJ, et al. Evaluation of birth defect histories obtained through maternal interviews. Am J Hum Genet 1990 Mar; 46(3): 478–85

    PubMed  CAS  Google Scholar 

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Acknowledgements

The first two authors have equally contributed to the manuscript. The authors state that no financial support or author involvement with organizations with financial interest in the subject matter exists, and that no actual or potential conflict of interest exists.

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Authors and Affiliations

  1. Department of Neonatology, Hadassah and Hebrew University Medical Center, Jerusalem, Israel

    Benjamin Bar-Oz

  2. Pharmakovigilanzzentrum Embryonaltoxikologie, BBGes/Charité Universitätsmedizin Berlin, Berlin, Germany

    Corinna Weber-Schoendorfer

  3. Clinical Pharmacology and Toxicology Unit, Teratogen Information Service, Assaf Harofeh Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, 70300, Israel

    Maya Berlin,  Ilan Youngster (MD) & Matitiahu Berkovitch

  4. Servizio Informazione Teratologica, Genetica, Clinica et Epidemiologica, University of Padova, Padova, Italy

    Maurizio Clementi & Elena Di Gianantonio

  5. Teratology Information Service, National Institute of Public Health and Environment, Bilthoven, the Netherlands

    Loes de Vries

  6. Department of Obstetrics & Gynecology, Catholic University of Sacred Heart, Rome, Italy

    Marco De Santis

  7. Beilinson Teratology Information Service, Rabin Medical Center, Sackler School of Medicine, Tel Aviv University, Beilinson Campus, Tel Aviv, Israel

    Paul Merlob & Bracha Stahl

  8. Department of Clinical Pharmacology, Centro antiveleni-Tossicologia clinica, Bergamo, Italy

    Giorgio Eleftheriou

  9. Division of Histology and Embryology, Center of Biomedical Sciences, Faculty of Medicine, Charles University, Prague, Czech Republic

    Eva Maňáková & Lucie Hubičková-Heringová

Authors
  1. Benjamin Bar-Oz
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  2. Corinna Weber-Schoendorfer
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  3. Maya Berlin
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  4. Maurizio Clementi
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  5. Elena Di Gianantonio
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  6. Loes de Vries
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  7. Marco De Santis
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  8. Paul Merlob
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  9. Bracha Stahl
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  10. Giorgio Eleftheriou
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  11. Eva Maňáková
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  12. Lucie Hubičková-Heringová
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  13. Ilan Youngster
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  14. Matitiahu Berkovitch
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Corresponding author

Correspondence to Ilan Youngster.

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Bar-Oz, B., Weber-Schoendorfer, C., Berlin, M. et al. The Outcomes of Pregnancy in Women Exposed to the New Macrolides in the First Trimester. Drug Saf 35, 589–598 (2012). https://doi.org/10.2165/11630920-000000000-00000

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  • DOI: https://doi.org/10.2165/11630920-000000000-00000

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