Antihistamines in Pregnancy

First developed in the 1930s, antihistamines are currently the most commonly used drugs for seasonal allergies. They have been used clinically in the general population and are available over-the counter or through prescription. In pregnancy, antihistamines are also sometimes used to treat nausea and vomiting of pregnancy. The prevalence of antihistamine use, anytime during pregnancy, ranges from 8 – 15%. First-generation antihistamines include clemastine fumarate, dimenhydrinate, diphenhydramine, doxylamine, hydroxyzine, meclizine, pheniramine, promethazine, and triprolidine. Whereas, second-generation anithistamines include cetirizine, fexofenadine, and loratadine. When used as suggested or prescribed, these medications can minimize symptoms of allergy by blocking the histamine reaction to allergens, thereby preventing other potential complications from untreated allergies. But how safe are antihistamines during pregnancy?

For the past 50 years, the data on the use of antihistamines during pregnancy has been limited. There are some studies suggesting an elevation of risk in the first trimester and there are others that do not. For example, one study found a possible association with loratadine and hypospadias. Subsequently, other studies found no association with loratadine and hypospadias. Overall, there has been no compelling evidence that antihistamines increase the risk for any adverse pregnancy outcomes. 

More recently, Gilboa et al, published Use of Antihistamine Medications during Early Pregnancy and Isolated Major Malformations, using data from the National Birth Defects Prevention Study (NBDPS) (Birth Defects Res A Clin Mol Teratol. 2009 Feb;85(2):137-50). NBDPS is an ongoing, multi-state, population based case-control study of environmental and genetic risk factors for major birth defects. In this study, they evaluated case and control mothers who delivered between 1997-2003. Cases were mothers of infants with isolated major birth defects and controls were mothers of infants with no major birth defect. Exposed cases and controls were women who recalled taking an antihistamine sometime between 1-month prior to pregnancy up the end of the 1st trimester. Study participants reported the use of 54 different antihistaminic agents. These agents were grouped into 14 analytical groups: one group included women who used any antihistamine and the other 13 groups were based on the similarity of formulations and mechanism of action of the antihistamine components. Gilboa et al. concluded that although some associations were suggested, overall there was a lack of evidence for an association of major birth defects with the use of antihistamines during early pregnancy. Their conclusions are consistent with the overall existing data on antihistamine use during early pregnancy.

Contrary to the finding of no increased risk for major birth defects when antihistamines are taken in early pregnancy, data was published years ago suggesting an association with increased of retrolental fibroplasia in premature infants when antihistamines are used during the last two weeks of pregnancy (Purohit DM et al, Pediatrics 1985 Sep;76(3):339-44). This is an eye condition in premature infants in which scarring and detachment of the retina may occur which, in turn, may lead to visual impairment. The incidence of retrolental fibroplasia in premature infants exposed to antihistamines during the last 2 weeks of gestation in this study was 22% as compared to only 11% of premature infants not exposed during this time. However, the authors could not determine if the association was due to the reasons that the mother was taking an antihistamine rather than medication itself. In summary, although no increased incidence of birth defects has been associated with antihistamine use in early pregnancy, women may wish to wean down and discontinue antihistamines during the third trimester due to the potential increased risk for retrolental fibroplasia if their delivery happens prematurely.