BERKELEY, CA (UroToday Inc.) - Hypospadias affects approximately 7 in 1,000 male infants in the United States. A spectrum of clinical presentations exists. These range from mild distal forms (first-degree) to more severe forms such as scrotal and perineal hypospadias (second- and third-degree). In 2002, a study noted that male infants born to mothers who took loratadine while pregnant had an incidence of hypospadias twice that of the general population. The study, however, did not control for a number of potentially confounding variables such as family history or other maternal exposures. In addition, insufficient data was available to determine severity of the hypospadias.

To further examine this potential association, the Centers for Disease Control analyzed data from the National Birth Defects Prevention Study (NBDPS). The report was summarized and the data analyzed by M. Wener from Boston University's School of Public Health and C. McCloskey from the FDA and reported in the April 21, 2004 issue of JAMA.

The NBDPS is an ongoing, multistate, case-control study of environmental and genetic risk factors for major birth defects that can be used in response to public health concerns regarding rare drug exposures and birth defects. For this analysis, the case population was defined as male infants with second- or third degree hypospadias, as first-degree forms were noted to be much less completely ascertained by routine surveillance. Infants with known chromosomal abnormalities or syndromes were excluded. The study population consisted of 563 male infants with hypospadias and 1,444 male infant controls; all were born between 1997 and 2001.

Exposure was defined as any maternal use of loratadine from 1 month before pregnancy through the first trimester. Loratadine, or Claritin, available over the counter since November 2002, is an antihistamine commonly used to treat seasonal allergies and was estimated to be used by 3% of women of childbearing age in 1998.

Analysis of results showed that of 563 male infants with hypospadias, 517 (91.8%) had hypospadias associated with no other major birth defects. Among the 1,957 mothers in the case and control populations, 33 (1.7%) reported using loratadine during the exposure period. Univariate analysis showed no association between this use and the incidence of hypospadias. The results of this analysis might be useful for women and health-care providers in addressing concerns about loratadine use during pregnancy and the risk of hypospadias.

JAMA. 2004;291:181-2