| Schizophrenia is a complexly determined disorder involving a substantial genetic component, as well as environmental factors. Among the environmental contributors, obstetric complications (OCs), especially maternal influenza and hypoxia-associated obstetric complications have been associated with increased incidence of psychotic outcome, as well as earlier age of symptom onset. Nevertheless, only one study has used serological confirmation of influenza and no study has used serological confirmation of fetal hypoxia to examine how these OCs operate within the neurodevelopmental course of schizophrenia.;This is the first study, using serological confirmation of influenza and fetal hypoxia, to examine whether exposure to these OCs confers increased incidence of risk for psychoses in offspring and whether the effects of these OCs are associated with an earlier age of first hospitalization and worsened premorbid cognitive performance. Participants were followed prospectively from gestation until age 7 (with cognitive assessments at 8 months, 4 years, and 7 years of age) and psychiatric morbidity was assessed by medical records review. Assays for erythropoietin (marker of fetal hypoxia) and IgC antibodies for influenza A and B were conducted from archived umbilical cord sera and maternal sera collected at birth.;Results indicated that fetal exposure to influenza B and exposure to fetal hypoxia was associated with subtle, but statistically detectable effects on early cognitive functioning, differentially in individuals who later developed psychotic disorders compared with controls. When controlling for multiple testing, decrements in performance at 8 months were significant, while analyses of the IQ and other measures at age 7 met the nominal, but not corrected threshold for significance. Restricting fetal hypoxia to severe cases led to significant effects on all of the aforementioned measures; however, the frequency of cases with severe hypoxia was small and therefore, results are tentative. Moreover, fetal exposure to influenza B, but not influenza A, led to worsened performance on WISC IQ scores at age 7 differentially among cases compared with controls and led to increased incidence of psychotic outcome. Overall, this pattern of results suggests that either a genetic or environmental factor associated with schizophrenia renders the fetal brain particularly vulnerable to the effects of OCs, a primary effect of which is to magnify the cognitive abnormalities appearing prior to the onset of psychotic symptoms. |
