Increased risk of schizophrenia from additive interaction between infant motor developmental delay and obstetric complications: evidence from a population-based longitudinal study.

OBJECTIVE: Obstetric complications and developmental delay are well-established risk factors for schizophrenia. The authors investigated whether these risk factors interact in an additive manner to further increase risk for schizophrenia. METHOD: The study population encompassed all individuals born in Helsinki between 1962 and 1969 who had developmental records archived in the Helsinki City Archives. Through linkage between the Finnish Population Register, the Finnish Hospital Discharge Register, and the Child Health Archives, child health cards were traced for 189 individuals who had received a diagnosis of schizophrenia and 189 healthy comparison subjects, individually matched to case subjects on gender and year of birth. Child health cards from the Child Health Archives contain detailed prospective developmental data from birth as well as an indicator of fetal distress, as measured by the Apgar score. Detailed developmental data from the first year of life were extracted. RESULTS: Delayed attainment of milestones in infancy significantly increased the risk of later development of schizophrenia in a dose-response manner. There was no significant main effect of obstetric complications on risk for schizophrenia and no significant association between obstetric complications and subsequent developmental delay. However, the additive effect of obstetric complications and delayed attainment of developmental milestones significantly increased the risk of schizophrenia beyond that associated with each factor independently (odds ratio=4.6, 95% confidence interval=1.3-17.2). CONCLUSIONS: These data provide evidence that underlying neurodevelopmental vulnerability, as indexed by delayed attainment of milestones, combined with obstetric adversity significantly increases the risk of schizophrenia in adulthood.