In utero exposure to caffeine causes delayed neural tube closure in rat embryos.

We have investigated the effect of caffeine on embryo growth and development. Caffeine (25 mg/kg) was administered on gestation day (g.d.) 8-9 and the embryos examined histologically 24 h after the final dose. The crown-rump length of caffeine treated embryos (1.92 +/- 0.08 mm) was significantly smaller (P < 0.001) than the controls (2.91 +/- 0.26 mm) as was the circumferential length (caffeine vs. controls, 3.79 +/- 0.16 mm vs. 6.03 +/- 0.61 mm; P < 0.001). Additional measures, such as development of the heart, eye, and limb buds, were also reduced in the caffeine treated embryos. The most striking difference between the control and caffeine treated embryos was the larger proportion of treated embryos with regions of open neural tube. This was most marked in the caudal region of the embryos where 91% of treated embryos had regions of open neural tube compared with 14% of controls. The amount of open neural tube in any individual caffeine treated embryo did not relate to the crown-rump or circumferential length of that embryo nor was the effect restricted to particular litters. These results indicate that caffeine had a significant effects on embryonic growth and development.