The association of fetal and childhood growth with risk of schizophrenia. Cohort study of 720,000 Swedish men and women.

Previous investigations of the association of schizophrenia with patterns of pre- and post-natal growth have been based on small numbers of cases or have not taken account of the effects of prematurity on birthweight. We investigated the association of fetal growth with schizophrenia in a large cohort of Swedish males and females. We linked data from the Swedish Medical Birth Register (1973-1980), Inpatient and Discharge Register (1988-2002), Military Service Conscription Register (1990-1997), and the Population and Housing Censuses (1970 and 1990). Altogether 719,476 males and females were followed up from the age of 16 for a mean of 9.9 years. There were 736 incident cases of schizophrenia. Even in models that did not control for gestational age there was little evidence of an association between birthweight and schizophrenia (hazard ratio per kg increase in birthweight: 0.90 (95% CI 0.78 to 1.03); the hazard ratio in babies weighing <2.5 kg compared to 3.5-4.0 kg was 1.29 (95% CI 0.85 to 1.96). There was an inverse association of birth length with schizophrenia across the range of birth lengths. Short babies were at an increased risk (hazard ratio per 10 cm increase in birth length: 0.53, 95% CI 0.31 to 0.89 (fully adjusted model)). All associations were little changed when analyses were restricted to term (>36 week gestation) babies. In males, low body mass index and short height at age 18 were associated with increased risk. There is some evidence that patterns of risk in relation to fetal growth differ depending on post-natal growth patterns: the increased risk associated with low body mass index was restricted to long babies who became light adults. The exposures underlying these associations and the biological mechanisms mediating them require clarification.