A study of the potential teratogenic effect of large doses of promethazine used for a suicide attempt by 32 pregnant women.

In Hungary, promethazine, a phenothiazine antihistamine, is the second most frequently used drug during pregnancy. The purpose of this study was to examine the effects of very large doses of promethazine that were used for a suicide attempt during pregnancy on embryo-fetal development. Self-poisoned pregnant women were identified from patients of the Department of Toxicology Internal Medicine, Korányi Hospital, Budapest, who were admitted from the three million people of Budapest and surrounding region. The rate of congenital abnormalities, intrauterine development (based on pregnancy age at delivery and birth weight), and cognitive-behavioral status of exposed children born to mothers who attempted suicide with promethazine alone or in combination with other drugs during pregnancy was compared with their sib controls. In all, 89 of the 1044 women with self-poisoning during pregnancy between 1960 and 1993 used promethazine for a suicide attempt. Of these 89 women, 32 delivered newborn babies. The dose of promethazine taken by these women for self-poisoning ranged between 125 mg and 1750 mg (mean of 544 mg, i.e., 21.8 tablets). Of the 32 promethazine-exposed children, nine (28.1 %) were affected with congenital abnormalities. However, of 11 pregnant women who attempted suicide with promethazine between the 3rd and 12th postconceptional week, that is, the critical period for production of most major congenital abnormalities, only three were affected with defects, and the critical periods for producing these defects did not overlap with the time of the suicide attempt during pregnancy. Of 34 unexposed sibs, five (14.7%) had congenital abnormalities; the difference in the total rate of congenital abnormalities between the exposed children and their sib controls was not significant. There also was no difference in pregnancy age-specific birth weight between exposed children and their sibs. Mean intelligence quotient was not reduced, and the incidence of behavioral deviation was not increased in the exposed children. The findings of this study did not indicate teratogenic or fetotoxic (including neurotoxic) effects of large doses of promethazine in children born to mothers who self-poisoned during pregnancy, although the total rate of congenital abnormalities was very high. Our experience shows the feasibility and benefits of using the self-poisoning model in estimating human teratogenic/fetotoxic risks of exposure to drugs.