By Lorraine L. Janeczko
April 08, 2014
NEW YORK (Reuters Health) - Treating young infants and women who are pregnant or postpartum with macrolide antibiotics may be associated with infantile hypertrophic pyloric stenosis (IHPS), new research from Denmark suggests.
Macrolide use in young infants may be strongly associated with IHPS and should only be used if potential treatment benefits outweigh the risk, the authors advised in a paper online March 11 in BMJ.
"Our study was the first to report a significant association between maternal macrolide use after birth and IHPS," said lead author Dr. Marie Lund of the Statens Serum Institut in Copenhagen, Denmark, in an email to Reuters Health.
"Although the absolute risks for IHPS were smaller for maternal macrolides use when infants were less than two weeks old and when used in infants during days 14 through 120 after birth, the increased risks should still be considered when choosing treatment," she said.
"We also found a possible association with use during late pregnancy, but any real effect would be small in absolute terms," she said.
The data are from a nationwide register-based cohort in Denmark.
Dr. Lund and her colleagues reviewed data on 999,378 live-born singletons over about 15 years and linked individual information on macrolide prescriptions (use in infants, n=6,591; maternal use after birth, n=21,557; maternal use during pregnancy, n=30,091), and surgery for IHPS.
They looked at IHPS surgery according to three categories of macrolide use: in infants after birth, in mothers after birth, and in mothers during pregnancy.
Overall, 880 infants developed IHPS (0.9 cases per 1,000 births).
Compared with infants who did not receive macrolides, the adjusted rate ratio for IHPS in infants given macrolides during days 0 through 13 after birth was 29.8. For macrolide therapy during days 14 through 120, the adjusted rate ratio was 3.24. The corresponding absolute risk differences were 24.4 and 0.65 cases, respectively, per 1,000, infants exposed to macrolides.
The rate ratio for maternal macrolides use for days 0 through 13 after birth was 3.49, and for days 14 through 120, it was 0.70. The corresponding absolute risk differences were 2.15 and 0.11, respectively.
The rate ratios for maternal macrolides use during pregnancy were 1.02 for weeks 0 through 27, and 1.77 for weeks 28 through birth; and the corresponding absolute risk differences were 0.01 and 0.67.
The authors write, "Pertussis infection in infants is associated with serious complications and is potentially fatal if untreated. In infants younger than six weeks, the macrolides azithromycin and clarithromycin are the only treatment alternatives for pertussis according to recommendations from the UK Health Protection Agency and the US Centers for Disease Control and Prevention; no other agents are recommended for this age group."
"It seems probable that the absolute excess risk of IHPS, a condition treatable by a relatively uncomplicated surgical procedure, is outweighed by the risks of pertussis left untreated," they add.
"Conversely," they continue, "if effective and safe treatment alternatives exist (for example, for other infections) or if a clear and pertinent indication for treatment is missing, macrolides are best avoided in young infants."
"Most studies, including ours, implicate erythromycin; however, no study has been able to rule out associations with other macrolide agents with certainty. Therefore, a cautious prescription practice acknowledging the possibility of a class effect seems warranted pending additional data," they said.
Senior author Professor Mads Melbye, also of Statens Serum Institut and of Stanford University School of Medicine in Stanford, CA, said in an email, "This study is an incredibly good example of the uniqueness of the Danish registers."
"For obvious reasons, drug safety studies on pregnant women and infants are not possible. But the fact that the Danish registers are very detailed and include information on all citizens makes it possible for us to contribute new important knowledge to this field," Dr. Melbye said.
Reuters Health Information © 2014
Cite this article: Macrolide Antibiotics Associated With Infantile Hypertrophic Pyloric Stenosis. Medscape. Apr 07, 2014.