Acetazolamide: Maternal toxicity, pattern of malformations, and litter effect

Authors

  • Dr. Lewis B. Holmes,

    Corresponding author
    1. Embryology-Teratology Unit, Massachusetts General Hospital, Boston, Massachusetts 02114
    2. Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02114
    • Embryology-Teratology Unit, Massachusetts General Hospital, Boston, MA 02114
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  • Hiroaki Kawanishi,

    1. Embryology-Teratology Unit, Massachusetts General Hospital, Boston, Massachusetts 02114
    2. Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02114
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  • Alvaro Munoz

    1. Channing Laboratory, Brigham and Women's Hospital, Boston, Massachusetts 02114
    2. Department of Medicine, Harvard Medical School, Boston, Massachusetts 02114
    Current affiliation:
    1. Department of Epidemiology, the Johns Hopkins School of Hygiene and Public Health, Baltimore, MD 21205
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Abstract

Thirty litters of C57BL 6J mice were administered intraperitoneally one of four doses (0, 500, 750, and 1,000 mg/kg maternal weight) of acetazolamide on day 9 of gestation. The fetuses were removed on day 18 and fixed, stained, cleared, and examined for the pattern of malformations. The forelimb postaxial limb deficiency was the most common abnormality, but forelimb postaxial polydactyly and a postaxial deficiency in the hindlimb were also observed. Males were significantly more likely to be malformed than females at all doses, in contrast to the predominance of females observed in rat fetuses exposed to acetazolamide (Scott et al.: Teratology 6:239–240, '73). The occurrence of limb malformations did not correlate with maternal weight loss, the birth weight of the fetus, or the position of the fetus in the uterus. A “litter effect” was demonstrated in that there was a nonuniform distribution of litters with different proportions of malformed fetuses.

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