Fetal Growth and Schizophrenia: A Nested Case-Control and Case-Sibling Study

The association between low birth weight and schizophrenia has been suggested by many studies. Small for gestational age (SGA) is a measure used as a proxy for intrauterine growth restriction. We aim to examine if children who are born SGA are at increased risk of developing schizophrenia and whether an association may be explained by factors shared among siblings. We linked 3 population-based registers: the Danish National Medical Birth Register, the Danish Psychiatric Central Register, and the Danish Civil Registration register to identify all persons born between 1978 and 2000. A nested case-control study and a case-sibling study design were used. There were 4650 cases of schizophrenia. Incidence rate ratios (IRRs) were estimated using conditional logistic regression. SGA was defined as the lowest 10th birth weight percentile for a given sex and gestational age. SGA was associated with an IRR of 1.23 (95% CI: 1.11-1.37) for schizophrenia in the case-control study. An IRR of 1.28 (95% CI: 0.97-1.68) was found in the case-sibling study. There is a modest association between SGA and schizophrenia. Our results indicate that this association is due to an independent effect of factors associated with low birth weight for gestational age per se, rather than other factors shared by siblings.