Fetal safety of erythromycin. An update of Swedish data

In previous studies from the Swedish Medical Birth Register, a possible association between erythromycin therapy and an increased risk for cardiovascular defects was found. Other studies using different methodology have not verified this observation. The finding resulted in a warning for the use of erythromycin in early pregnancy, followed by a marked decline in such use. The present study was conducted to follow up on the previous observations and to find methodological explanations for the variation in results in these different published studies. Data on Swedish women who gave birth during the period 1996-2011 were studied using the drug information in the Medical Birth Registry, obtained from midwife interviews conducted toward the end of the first trimester. Data on the presence of congenital malformations were ascertained from national health registers. Odds ratios were then determined using the Mantel-Haenszel methodology. A persistent association was seen between erythromycin use and the occurrence of cardiovascular defects, with a risk estimate of 1.70 (95 % confidence interval (CI): 1.26-2.39), of similar strength during the first and last 8 years of observation. We discussed the contradictory findings of the other published studies and pointed out possible methodological problems that may explain the absence of an effect in studies based on prescription registers. Our study verified an association between early pregnancy erythromycin use and infant cardiovascular defects; most defects were mild. The cause of this association is unclear.