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Two models of vulnerability to socioenvironmental risk were examined in 337 African American children (= 7.8 years) recruited to overrepresent prenatal alcohol or cocaine exposure: The cumulative risk model predicted synergistic effects from exposure to multiple risk factors, and the fetal patterning of disease model predicted that prenatal insult will increase vulnerability to environmental risk. Four or more risks emerged as a threshold for poorer cognitive and behavioral outcome among the non-substance-exposed children, whereas substance-exposed children showed greater vulnerability to lower levels of environmental risk. Cumulative risk was associated with increased delinquent and internalizing behaviors only for the substance-exposed group. Results support the cumulative risk model for non-substance-exposed children and increased vulnerability to environmental risk among the substance-exposed group.