One of the most important concepts in pediatric pharmacology is that exposure to drugs or chemicals may have latent, unforeseen effects on the child later in life. Some of the most dramatic occurrences, other than teratogenesis, are those in which hormonal exposure during the fetal or newborn period alters adult sexual development. However, none of these episodes is more impressive and ominous than that reported by Herbst et al.1 Herbst, an obstetrician at the Massachusetts General Hospital, was intrigued by the presentation of seven patients with adenocarcinoma of the vagina, an extremely rare tumor not previously seen at the hospital. The patients ranged in age from 14 to 22 years and sought medical advice because of vaginal bleeding. Several had benign adenosis, suggesting that the malignant change seen in all was based on a fundamental alteration in the biology of the vaginal epithelium. Six of the patients were treated with radical surgery, and one was treated with wide, local excision. One of the patients died after surgery.

In what could serve as a model of a scientifically conducted, epidemiologic study, each of the seven patients, plus an additional patient from another hospital, was matched with four controls born in the same hospital within four days. Thus, the "control" group was chosen in a manner to eliminate many biases of artificially contrived control populations. A wide variety of possible influences in both mothers and offspring were considered, e.g., maternal age, smoking habits, exposure to X-rays, breast-feeding, birth weight, age at menarche, medications during pregnancy, and so forth.

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