Loratadine and hypospadias.(Drugs, Pregnancy, and Lactation)

Loratadine, available as Claritin since 1993 and now available in several generic and over-the-counter formulations, is a popular nonsedating antihistamine used by many women of child-bearing age.

For some time, we have been counseling women that the older, first-generation sedating antihistamines are safe to use during pregnancy, based on the large amount of data available on these drugs--mainly collected from their widespread use as a treatment for morning sickness. We still do not have enough data on loratadine and other newer antihistamines to reach the same conclusion with certainty, however, even though these agents are members of the same class and presumably work on the same histamine H1 receptors.

The uncertainty regarding the reproductive safety of loratadine was complicated by the publication of a retrospective analysis from Sweden in 2002 suggesting that the risk of hypospadias in babies exposed in utero to loratadine was twice that of the general population.

In March, the Centers for Disease Control and Prevention published a study of a U.S. population of male infants that refuted the Swedish

findings.

The study used data from the National Birth Defects Prevention Study and focused on male infants born between October 1997 and June 2001. A total of 517 male infants with second- and third-degree hypospadias but no other major birth defects were compared with more than 1,000 controls born during the same period. There was no association between loratadine use during the month before conception and the first trimester of pregnancy and an increased risk of hypospadias (MMWR 53[10]:219-21, 2004).

As the authors note, the study has some limitations and does not provide "definitive information on the overall safety of loratadine." But it is a prospective, more carefully designed study that addressed the degree of hypospadias. In the Swedish study, the severity of hypospadias could not be determined, and the researchers did not control for family history of hypospadias and other variables. Hypospadias is a difficult end point to measure because it is quite common, occurring in about 7 of 1,000 male infants born in the United States, so it is important to include an appropriate control group before linking it to drug exposure.