Abstract
High doses of caffeine (C) have been reported to be teratogenic in animals and persistent behavioral effects have been seen in the offspring of rodents fed C during pregnancy. We have characterized methylxanthine exposure and effects on fertility and fetal growth resulting from continuous prenatal infusion of C at doses comparable to human dietary intake in the rabbit. The rabbit was chosen for its similarities to the human in metabolism of C. 26 rabbits were administered C during gestation at rates of 0, 10 or 20 mg/kg/day via an implanted infusion pump. Does were sacrificed at 10, 20 or 29 days, and amniotic fluid, fetal CSF, plasma and gastric fluid were collected. Fluids were analyzed for C and its major metabolite paraxanthine (P), and fertility and fetal growth were assessed. P and C were homogeneously distributed in fetal fluids. Mean amniotic fluid to maternal plasma concentration ratios were 0.4 and 0.6 for P and C, respectively, increasing to 0.7 and 0.9 by the end of gestation. Methylxanthine exposure did not affect pregnancy rate, litter size or fetal weight. Length, brain weight and liver weight at 29 days were not significantly different (p>0.1). We have demonstrated that prenatal administration of C to rabbits results in significant fetal exposure to both C and P. This exposure at clinically relevant levels did not lead to structural teratology or adversely affect fertility or fetal growth. The potential for long-term alterations in behavior (behavioral teratology), however, remains to be defined by studies now in progress.
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Mercik, S., Dorrbecker, B., Kramer, P. et al. EFFECT OF CAFFEINE EXPOSURE ON FETAL GROWTH IN THE RABBIT. Pediatr Res 18 (Suppl 4), 156 (1984). https://doi.org/10.1203/00006450-198404001-00377
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DOI: https://doi.org/10.1203/00006450-198404001-00377