Potential reversibility of skeletal effects in rats exposed in utero to caffeine

Groups of Osborne-Mendel rats, killed at three time intervals following mating, were studied to determine whether prenatal skeletal ossification delays observed following low-level caffeine administration represent transient or persistent ossification problems. Group A litters were killed on gestation day 20; group B neonates were killed on post-natal day 0; and group C pups were killed on post-natal day 6. Within each group, dose levels of 0, 0.018, 0.036 or 0.07% caffeine in distilled water were available ad lib. to groups of 30-60 dams from gestation day 0 to day 20. Average daily caffeine consumption was 24.7-29.0 mg/kg body weight for the 0.018% group, 42.7-48.8 mg/kg body weight for the 0.036% group and 70.6-75.1 mg/kg body weight for the 0.07% group. In group A litters, the mean number of viable foetuses was significantly less in the mid-dose and high-dose animals than in the controls. In the same group, the average number of foetuses per litter with at least one sternebral ossification delay was increased significantly in all treated groups and the average number of foetuses per litter with at least two sternebral variations was significantly increased in the mid- and high-dose groups. The percentages of litters containing foetuses with at least two and at least three sternebral variations and the average number of foetuses per litter with at least three sternebral variations were significantly increased only in the high-dose group. Foetuses from the mid- and high-dose groups also had significant increases in certain skeletal defects, namely missing centra and reduced ossification of the dorsal arch. Foetuses from the high-dose group also had significant increases in bipartite supraoccipital, and reduced ossification of the hyoid, metacarpals and metatarsals. In group B, day 0 neonates from all treated groups showed a significantly increased incidence of delayed sternebral ossification (average number of foetuses per litter with one or more missing, incomplete or bipartite sternebrae). The percentages of litters containing neonates with delayed sternebral ossification were also increased significantly in all treated groups. Neonates from the 0.07% level in group B also exhibited a significant increase in the incidence of supernumerary rib bud, and in reduced ossification of the metacarpals, metatarsals and calcaneus bones. Significant increases were also seen, in group B, in the low- and mid-dose animals, respectively, in supernumery rib bud and in reduced ossification of the metatarsals.(ABSTRACT TRUNCATED AT 400 WORDS)