Alcohol teratogenicity in the human: a detailed assessment of specificity, critical period, and threshold.
Though the occurrence of alcohol-related birth defects is well documented in the human and in animal models, definition of specificity, critical period, and dose-response threshold with a precision adequate for clinical risk assessment and management has been lacking. Data from a cohort of 359 neonates, from a large prospective observational study in which chronic alcohol problems and maternal drinking were assessed during pregnancy and standardized neonatal examinations were blinded for prenatal information, were analyzed with the use of multivariate techniques, with uniform control for confounding by eight factors. Craniofacial abnormalities were found to be definitively related to prenatal alcohol exposure in a dose-response manner (p less than 0.001); a significant, but less striking, relationship was observed for other anomalies (p less than 0.01). The critical period for alcohol teratogenicity was confirmed to be around the time of conception. Risk for anatomic abnormalities in the offspring was clearly defined among the 5.6% of infants whose mothers drank more than three ounces of absolute alcohol, that is, more than six drinks, per day. Because of a trend toward an increase in craniofacial abnormalities with increasing embryonic alcohol exposure at lower levels, a clear threshold could not be defined. These are not experimental data and the results should not be overinterpreted. Nevertheless, pending further studies with larger samples, the findings suggest that to completely avoid alcohol-related anatomic abnormalities, advice to discontinue drinking or at least to reduce it to a minimal level before conception is clinically appropriate.