The etiology of neurodevelopmental disorders (NDs), such as dyslexia, language and speech disorder, attention deficit hyperactivity disorder, autism, mental retardation, cerebral palsy, and epilepsy, is largely unexplained. Since NDs are generally more prevalent in boys than girls, the current proposal seeks to identify causative agents for this sex difference. Two recent theories, which have received widespread attention, propose that this male vulnerability is due to events antecedent to the time of labor and delivery. One theory proposes maternal immune attack of the fetus; the other, emphasizes intrauterine endocrinological imbalance. The current proposal suggests that these two model are complementary rather than contradictory and that some combination of these gestational factors is most predictive of ND in the child. Prior studies collected data on only one or two relevant variables in a small or narrowly defined sample. No comprehensive large-scale study has been undertaken in which data from ND and non-ND children are compared. However, the National Collaborative Perinatal Project (NCPP) collected medical data during approximately 50,000 pregnancies and followed the children's cognitive and physical development until age eight. Many of the gestational and perinatal variables relevant to the two alternative theories were recorded. The purpose of this proposal is to use this extensive data set to test eight specific hypotheses relevant to these two theories. Then, by using structural equation modeling, the extent to which these two theories are competing versus complementary will be determined.
