Retrolental fibroplasia

Antihistamines comprise a large, fairly diverse group of compounds that are so prevalent that many women are probably exposed to these drugs at some point during pregnancy.

In general, first-generation antihistamines are usually safe during pregnancy when used occasionally, but should not be used for frequent, chronic allergy symptoms. There is little human pregnancy information on second-generation antihistamines.

During the first trimester, it is best to avoid antihistamines. But if an antihistamine is indicated, the best option is the oral first-generation drug chlorpheniramine, which is marketed over the counter under several names, including Chlor-Trimeton. If an injectable antihistamine is indicated, diphenhydramine (Benadryl)would be the first choice.

Most published data on antihistamine use during pregnancy concern these two drugs and indicate that they are relatively safe when used occasionally. There have been no signals or clusters of birth defects found in multiple studies of these agents.

The three second-generation antihistamines--cetirizine (Zyrtec), loratadine (Claritin), and fexofenadine (Allegra)--have not been shown to be teratogenic in animals. Nevertheless, they should be avoided if possible during the first trimester because of the sparse amount of data in humans on use of these drugs during pregnancy These data include a 1997 study of pregnant women that found no significant difference in the rates of major or minor malformations, gestational age at delivery, birth weight, or neonatal distress among 39 women who took cetirizine (most included first-trimester use), 81 women who took hydroxyzine (Vistaril or Atarax), and 110 controls who did not take either agent.

In a 1998 study of 18 women who took loratadine during the first trimester, 16 had normal infants with no major malformations; the other two had elective abortions. But this study is small and did not look for minor malformations. Loratadine is considered by many authors to be an acceptable alternative to a first-generation antihista mine, except during the first trimester.

To date, there have been no reports of human pregnancies exposed to Allegra, but problems with implantation have been reported in rats administered three times the human dose.

Neonatal withdrawal symptoms have been reported rarely in conjunction with commonly used antihistamines when used continuously during pregnancy, with the most cases reported for diphenhydramine. A woman who took 150 mg a day of diphenhydramine throughout pregnancy gave birth to a baby who developed withdrawal symptoms on the fifth day of life. Hydroxyzine has also been reported to cause withdrawal symptoms in newborns.

Diphenhydramine also has dose-related oxytocic properties and, if administered intravenously during labor, can stimulate the uterus.

A drug interaction between diphenhydramine (50 mg) and the sleeping medication temazepam (Restoril 30mg) may have led to the stillbirth of a term fetus. The mechanism of the interaction is unknown, but a high fetal death rate was confirmed in one animal study when the two drugs were combined.

A significantly increased risk of retrolental fibroplasia in premature babies whose mothers had taken a first-generation antihistamine during the last 2 weeks of gestation was also found in a 1986 multicenter study of premature newborns. This defect has not been re ported in full-term babies exposed to antihistamines in utero.

All antihistamines are excreted in breast milk, but there is little information on these drugs during lactation, particularly for second-generation agents.

Irritability and drowsiness in nursing infants are potential complications, and lactating mothers taking antihistamines should watch their infants for these ad verse effects. In one case with clemastine (Tavist), the infant also had neck stiffness and high-pitched crying.

In a study of loratadine, the drug and its metabolites were detected in the milk of six women who took four times the recommended dose. The author estimated that the infants received about 0.5% of their mother's total dose and concluded that there appeared to be little risk to the exposed infants. This was a one-time dose, and again, the message of this study is that occasion al use of these drugs during lactation does not seem to present a major risk, if any, but may cause problems when taken routinely.

GERALD G. BRIGGS is clinical pharmacist, Women's Hospital, Long Beach Memorial Medical Center; clinical professor of pharmacy, University of California, San Francisco.

COPYRIGHT 2001 International Medical News Group
COPYRIGHT 2001 Gale Group