In animal studies, fetal loss, decreased fetal weight and size, and major skeletal defects have been reported when dosages of more than 80 mg/kg of caffeine were used. Human epidemiologic studies that examine the relationship between caffeine use and congenital abnormalities are not conclusive; however, there is some evidence to suggest a caffeine effect upon fetal growth patterns. Because caffeine drinking is so often associated with the use of other drugs such as tobacco, it is difficult to ascertain which drug has the effect on growth, or if it is a combined effect from both drugs. A tripling of the half-life of caffeine in the last two trimesters of pregnancy resulting in much higher caffeine blood levels for both mother and fetus, combined with the neonate's inability to metabolize caffeine, could account for the indications of neonatal caffeine withdrawal observed in the first week after birth.