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In a prospective cohort study of 50,282 gravidas and their offspring, over-all rates of congenital malformations were similar in 1,309 children of women exposed to phenothiazine drugs during the first four lunar months of pregnancy and in 48,973 children of women who were not exposed. There was a suspicion of association between phenothiazine exposure and cardiovascular malformations. In a cohort reduced to 41,337 mother-child pairs for technical reasons, perinatal mortality rates and mean birth weight were similar according to phenothiazine exposure or nonexposure, as were intelligence quotient scores measured at four years of age in 28,358 of the children. Control of potential confounding factors with a variety of multivariate techniques did not materially alter the findings.

The results of two studies, one in Finland and one in the U.S.A., raise the possibility that fetal damage previously attributed to phenytoin and other anticonvulsant drugs, principally phenobarbitone, may be due to epilepsy itself. In the U.S.A., drug-exposure information was collected before delivery in a cohort of 50 282 mother/child pairs. The total malformation rate in 305 children born to epileptic mothers was 10.5%, as against 6.4% in the remainder (p less than 0.01); corresponding rates for major malformations were 6.6% and 2.7%. When the fathers had epilepsy, the malformation-rates in their children were intermediate. The rates did not vary significantly according to maternal anticonvulsants therapy. Mental and motor scores as 8 months of age, and intelligence quotient scores at 4 years were lower in children of epileptic mothers, but not in children of epileptic fathers. The scores showed only random variation according to maternal anticonvulsant therapy. In Finland, 2784 children with craniofacial anomalies were compared with an equal number of normal children; 8 and 2 mothers, respectively, received anticonvulsants, while pregnant, for epilepsy. In that study, the separate effects of the disease and its treatmet could not be evaluated. Both studies did not find evidence of fetal damage when phenobarbitone was taken for indications other than epilepsy.

In a prospective cohort study of 20, 282 gravidas and their offspring, congenital malformation rates were similar in the children of over 1,000 women exposed and those not exposed to two components of Bendectin (doxylamine succinate and dicyclomine hydrochloride) during the first four lunar months of pregnancy. In a cohort reduced to 41,337 mother-child pairs for technical reasons, mean birth weight and perinatal mortality rates were similar according to exposure or nonexposure to either drug, as were intelligence quotient scores measured at four years of age in 28,358 of the children. Control of potential confounding factors with a variety of multivariate techniques did not materially alter these findings.

In a follow-up study of 50,282 pregnancies (lasting at least five lunar months) and the offspring, malformations identified before the first birthday, or at death before the fourth birthday, were identified in 3248 children (6.5 per cent). A total of 1870 children exposed in utero to meprobamate or chlordiazepoxide were compared with 48,412 children who were not. No significant differences were found either overall or in specific outcomes; rates were also similar when exposures occurred during the first trimester or at other times during pregnancy. Deaths (stillbirth to the fourth birthday) occurred in 2227 children (4.4 per cent), and there was no evidence that antenatal exposure to either drug increased the death rate. Finally, as judged by mental and motor scores at the age of eight months, and intelligence quotient scores at four years, there was no evidence that the drugs cause brain damage.

Medication is one important aspect of health care delivery. The sources of information used to select appropriate medication include drug advertisements which appear in professional journals. There is a need to monitor the quality of these advertisements. The study reported in this paper includes a longitudinal (1961 to 1977) and cross-societal (Britain, United States and Australia) content analysis of drug advertisements. Such a comparison contributes to the debate concerning the type of regulation likely to be effective for this form of advertising.