On the nature and mechanisms of obstetric influences in schizophrenia: a review and synthesis of epidemiologic studies

Obstetric complications are robust correlates of schizophrenia, but it remains controversial whether more than one neurally-disruptive mechanism is involved and whether such influences covary with, depend on, or are independent of the disorder's genetic basis. Labor and delivery complications (LDCs), particularly perinatal hypoxia, are the most consistently-replicated obstetric correlates of schizophrenia and appear as risk factors in a larger proportion of cases than pregnancy complications (including viral exposure) and signs of fetal maldevelopment. However, the vast majority of individuals exposed to such LDCs, even in the extreme, do not develop schizophrenia, indicating that they are unlikely to cause the disorder on their own. In addition, unaffected siblings and offspring of schizophrenics are no more likely to have a history of LDCs than are unaffected individuals from the general population, indicating that such factors are not likely to be caused by genetic predisposition to the disorder. Findings from prospective studies of high-risk samples and representative birth cohorts are consistent in showing that the association of LDCs with schizophrenia (and with severity of its neuropathological features) is greater among those with an elevated genetic risk, suggesting that predisposing genes for schizophrenia may confer a heightened susceptibility of the fetal brain to the neurotoxic consequences of oxygen deprivation (and, possibly, other obstetric mechanisms). These findings encourage the search for candidate genes that mediate the brain's vulnerability to hypoxic-ischemic neuronal injury and suggest the use of preventive obstetric practices in high-risk pregnancies.