Hyperthermia as a possible teratogenic agent.

Hyperthermia has been shown to be a teratogenic agent in a number of animal species. We have attempted to determine if maternal hyperthermia during early gestation might also be responsible for problems in human development. Eight retrospectively ascertained cases, in which high fever had occurred at four to six weeks' gestation, revealed a similar clinical phenotype in the infants despite the fact that the maternal fever was caused by different infections. The most consistent manifestations were severe mental deficiency, seizures, hypotonia, microphthalmia, midface hypoplasia, and mild impairment of distal limb development. In five patients exposed to hyperthermia at seven to 16 weeks' gestation, predominant features were hypotonia, neurogenic arthrogryposis, and central nervous system dysgenesis. The cause of fever differed in each of these cases; in one, a patient with neurogenic arthrogryposis, the hyperthermia had been induced in a sauna bath. No apparent serious problem in morphogenesis was found following hyperthermia during the latter half of gestation. These findings are similar to those resulting from induced hyperthermia in animals. Further research on the effects of hyperthermia in the developing human being seems warranted.