a1 Norwegian Institute of Public Health, Bergen, Norway
a2 Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, Norway
a3 Locus of Registry-Based Epidemiology, Department of Public Health and Primary Health Care, University of Bergen, Norway
a4 Department of Pediatrics, Haukeland University Hospital, Bergen, Norway
a5 The Medical Birth Registry of Norway, Norwegian Institute of Public Health, Norway
a6 Division of Mental Health, Norwegian Institute of Public Health, Norway
a7 Institute of Psychiatry, University of Oslo, Norway
a8 Mailman School of Public Health and New York State Psychiatric Institute, Columbia University, New York, NY, USA
a9 Centre for Women's Mental Health, Community-Based Medicine, University of Manchester, UK
Background Accumulating evidence suggests that fetal growth restriction may increase risk of later schizophrenia but this issue has not been addressed directly in previous studies. We examined whether the degree of fetal growth restriction was linearly related to risk of schizophrenia, and also whether maternal pre-eclampsia, associated with both placental dysfunction and poor fetal growth, was related to risk of schizophrenia.
Method A population-based cohort of single live births in the Medical Birth Registry of Norway (MBRN) between 1967 and 1982 was followed to adulthood (n = 873 612). The outcome was schizophrenia (n=2207) registered in the National Insurance Scheme (NIS). The degree of growth restriction was assessed by computing sex-specific z scores (standard deviation units) of ‘birth weight for gestational age’ and ‘birth length for gestational age’. Analyses were adjusted for potential confounders. Maternal pre-eclampsia was recorded in the Medical Birth Registry by midwives or obstetricians using strictly defined criteria.
Results The odds ratio (OR) for schizophrenia increased linearly with decreasing birth weight for gestational age z scores (p value for trend = 0.005). Compared with the reference group (z scores 0.01–1.00), the adjusted OR [95% confidence interval (CI)] for the lowest z-score category (< − 3.00) was 2.0 (95% CI 1.2–3.5). A similar pattern was observed for birth length for gestational age z scores. Forty-nine individuals with schizophrenia were identified among 15 622 births with pre-eclampsia. The adjusted OR for schizophrenia following maternal pre-eclampsia was 1.3 (95% CI 1.0–1.8).
Conclusions Associations of schizophrenia risk with degree of fetal growth restriction and pre-eclampsia suggest future research into schizophrenia etiology focusing on mechanisms that influence fetal growth, including placental function.
(Received December 20 2011)
(Revised August 22 2012)
(Accepted October 23 2012)
(Online publication January 09 2013)
† These authors served as joint senior authors.