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Evaluation of the Effects of Prenatally Administered Caffeine on Skeletal Development and Postnatal Function in Rats

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Specific aims: (1) to evaluate skeletal development in rats exposed to caffeine prenatally, and (2) to evaluate physiological and behavioral function in rats exposed to caffeine prenatally. The study was designed to assess abnormal skeletal development and postnatal function in rats prenatally exposed to intravenous (IV) caffeine. Twelve pregnant CD rats/dose group were given one IV injection of 0, 75, or 150 mg/kg caffeine on gestation day 11. Dams were weighed on gestation days 0, 11, and 20. On postnatal day (PND 1), pups were examined for morphological defects and the litters were randomly culled to 8 pups (4 + or - 1 of each sex). Pups were weighed during development and the following functional evaluations were conducted: gait analysis and landing foot spread on PND 20 and 24; swimming behavior on PND 24; activity on PND 12, 16, 20, 30, 60, and 90; and blood pressure measurements at PND 90, 120, and 240. Rats were sacrificed at 25, 90, 120, or 240 days of age and the skeletons were examined for defects. At birth, 15% of the pups in the 150 mg/kg group had tail defects and when examined at later ages, 50% of the rats in this group showed defects in the lumbar and caudal regions.

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