title: Fetal safety of macrolides.
abstract: Macrolide antibiotics are largely used in pregnancy for different bacterial infections. Their fetal safety has been studied by several groups, yielding opposing results. In particular, there have been studies claiming an association between macrolides and cardiovascular malformations. Exposure in early infancy has been associated with pyloric stenosis and intussusception. This has led to an avoidance in prescribing macrolides to pregnant women in several Scandinavian countries. The Objectives of the present study was to investigate the fetal safety of this class of drug by linking a large administrative database of drug dispensing and pregnancy outcome in Southern Israel. A computerized database of medications dispensed from 1999 to 2009 to all women registered in the Clalit health maintenance organization in southern Israel was linked with two computerized databases containing maternal and infant hospitalization records. Also, medical pregnancy termination data were analyzed. The following confounders were controlled for: maternal age, ethnicity, maternal pregestational diabetes, parity, and the year the mother gave birth or went through medical pregnancy termination. First- and third-trimester exposures to macrolide antibiotics as a group and to individual drugs were analyzed. During the study period there were 105,492 pregnancies among Clalit women that met the inclusion criteria. Of these, 104,380 ended in live births or dead fetuses and 1,112 in abortion due to medical reasons. In the first trimester of pregnancy, 1,033 women were exposed to macrolides. There was no association between macrolides and either major malformations [odds ratio (OR), 1.08; 95% confidence interval (CI), 0.84 to 1.38)] or specific malformations, after accounting for maternal age, parity, ethnicity, prepregnancy diabetes, and year of exposure. During the third trimester of pregnancy, 959 women were exposed to macrolides. There was no association between such exposure and perinatal mortality, low birth weight, low Apgar score, or preterm delivery. Similarly, no associations were demonstrated with pyloric stenosis or intussusception. Use of macrolides in the first trimester of pregnancy is not associated with an increased risk of major malformations. Exposure in the third trimester is not likely to increase neonatal risks for pyloric stenosis or intussusception in a clinically meaningful manner.
authors: Department of Public Health, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors: Anat
authors: A
authors: Bahat Dinur
authors: Gideon
authors: G
authors: Koren
authors: Ilan
authors: I
authors: Matok
authors: Arnon
authors: A
authors: Wiznitzer
authors: Elia
authors: E
authors: Uziel
authors: Rafael
authors: R
authors: Gorodischer
authors: Amalia
authors: A
authors: Levy
mesh_terms: D000014:Abnormalities, Drug-Induced; D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000009:adverse effects; D001424:Bacterial Infections / Q000188:drug therapy; D018376:Cardiovascular Abnormalities / Q000139:chemically induced*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007443:Intussusception / Q000139:chemically induced*; D007557:Israel; D018942:Macrolides / Q000009:adverse effects* / Q000627:therapeutic use; D008875:Middle Aged; D054238:Perinatal Mortality; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy; D011256:Pregnancy Outcome; D011261:Pregnancy Trimester, First; D011707:Pyloric Stenosis / Q000139:chemically induced*; D012042:Registries / Q000706:statistics & numerical data; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D018942:Macrolides
references: Curr Pharm Des. 2004;10(25):3045-53
references: 15544496
references: Drug Saf. 2012 Jul 1;35(7):589-98
references: 22702640
references: J Matern Fetal Neonatal Med. 2006 Mar;19(3):189-92
references: 16690513
references: Birth Defects Res A Clin Mol Teratol. 2003 Mar;67(3):193-201
references: 12797461
references: BMC Pregnancy Childbirth. 2006 May 30;6:18
references: 16734900
references: J Matern Fetal Med. 1999 Jan-Feb;8(1):12-6
references: 10052839
references: Obstet Gynecol. 1994 Jul;84(1):61-3
references: 8008325
references: Arch Pediatr Adolesc Med. 2002 Jul;156(7):647-50
references: 12090829
references: Am J Perinatol. 1998;15(9):523-5
references: 9890248
references: Br J Clin Pharmacol. 2012 Dec;74(6):1053-62
references: 22463376
references: BJOG. 2000 Jun;107(6):770-5
references: 10847234
references: Infect Dis Obstet Gynecol. 1996;4(6):333-7
references: 18476121
references: J Antimicrob Chemother. 2009 Sep;64(3):642-8
references: 19549670
references: N Engl J Med. 2009 Jun 11;360(24):2528-35
references: 19516033
references: Obstet Gynecol. 1998 Feb;91(2):165-8
references: 9469269
references: J Clin Pharmacol. 2012 Jan;52(1):78-83
references: 21343345
references: Drug Saf. 2002;25(13):929-42
references: 12381214
references: Birth Defects Res A Clin Mol Teratol. 2003 Sep;67(9):617-24
references: 14703783
references: Eur J Obstet Gynecol Reprod Biol. 2008 Nov;141(1):31-4
references: 18760873
references: N Engl J Med. 1998 Apr 16;338(16):1128-37
references: 9545362
references: Pharmacoepidemiol Drug Saf. 2000 Dec;9(7):549-56
references: 11338912
references: Am J Obstet Gynecol. 2003 Mar;188(3):714-8
references: 12634646
references: Reprod Toxicol. 2003 May-Jun;17(3):255-61
references: 12759093