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.

[1]  P. Patterson,et al.  Placental regulation of maternal‐fetal interactions and brain development , 2012, Developmental neurobiology.

[2]  N. Hussain.  Epigenetic influences that modulate infant growth, development, and disease. , 2012, Antioxidants & redox signaling.

[3]  J. Suvisaari,et al.  An association between high birth weight and schizophrenia in a Finnish schizophrenia family study sample , 2011, Psychiatry Research.

[4]  O. Mors,et al.  The Danish Psychiatric Central Research Register , 2011, Scandinavian journal of public health.

[5]  C. Pedersen,et al.  The Danish Civil Registration System , 2011, Scandinavian journal of public health.

[6]  Peter B. Jones,et al.  Deviant intrauterine growth and risk of schizophrenia: A 34-year follow-up of the Northern Finland 1966 Birth Cohort , 2010, Schizophrenia Research.

[7]  S. Ozanne,et al.  Early life nutrition and metabolic programming , 2010, Annals of the New York Academy of Sciences.

[8]  Ezra Susser,et al.  Invited commentary: The use of sibship studies to detect familial confounding. , 2010, American journal of epidemiology.

[9]  P. Mortensen,et al.  Autoimmune diseases, bipolar disorder, and non-affective psychosis. , 2010, Bipolar disorders.

[10]  E. Susser,et al.  Birth weight, schizophrenia, and adult mental disorder: is risk confined to the smallest babies? , 2010, Archives of general psychiatry.

[11]  J. McGrath,et al.  NEONATAL VITAMIN D STATUS AND RISK OF SCHIZOPHRENIA: A POPULATION-BASED CASE-CONTROL STUDY , 2010, Schizophrenia Research.

[12]  Jill M. Goldstein,et al.  Early Life Programming and Neurodevelopmental Disorders , 2010, Biological Psychiatry.

[13]  P. Mortensen,et al.  The impact of maternal celiac disease on birthweight and preterm birth: a Danish population-based cohort study. , 2010, Human reproduction.

[14]  R. Horgan,et al.  Risk factors for small for gestational age infants. , 2009, Best practice & research. Clinical obstetrics & gynaecology.

[15]  J. Dodd,et al.  The prevention and treatment of intrauterine growth restriction. , 2009, Best practice & research. Clinical obstetrics & gynaecology.

[16]  Wolff Schlotz,et al.  Fetal origins of mental health: Evidence and mechanisms , 2009, Brain, Behavior, and Immunity.

[17]  P. Mortensen,et al.  Psychiatric family history and schizophrenia risk in Denmark: which mental disorders are relevant? , 2009, Psychological Medicine.

[18]  W. Honer,et al.  Predictors of starting to smoke cigarettes in patients with first episode psychosis , 2009, Schizophrenia Research.

[19]  P. Mortensen,et al.  Obstetric conditions and risk of first admission with schizophrenia: A Danish national register based study , 2007, Schizophrenia Research.

[20]  J. Olsen,et al.  Assessing fetal growth impairments based on family data as a tool for identifying high-risk babies. An example with neonatal mortality , 2007, BMC pregnancy and childbirth.

[21]  K. Haram,et al.  [Foetal growth retardation]. , 2007, Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke.

[22]  R. Ness,et al.  Association of periconceptional multivitamin use and risk of preterm or small-for-gestational-age births. , 2007, American journal of epidemiology.

[23]  T. Powell,et al.  Role of the placenta in fetal programming: underlying mechanisms and potential interventional approaches. , 2007, Clinical science.

[24]  R. Kemperman,et al.  Folate and long-chain polyunsaturated fatty acids in psychiatric disease. , 2006, The Journal of nutritional biochemistry.

[25]  P. Mortensen,et al.  The Danish Civil Registration System. A cohort of eight million persons. , 2006, Danish medical bulletin.

[26]  F. Rasmussen,et al.  The association of fetal and childhood growth with risk of schizophrenia. Cohort study of 720,000 Swedish men and women , 2005, Schizophrenia Research.

[27]  E. Bramon,et al.  Obstetric complications in patients with schizophrenia and their unaffected siblings , 2005, European Psychiatry.

[28]  P. Mortensen,et al.  Sibship characteristics during upbringing and schizophrenia risk. , 2004, American journal of epidemiology.

[29]  J. Os,et al.  Association between short birth intervals and schizophrenia in the offspring , 2004, Schizophrenia Research.

[30]  Michael K Parides,et al.  Separation of individual‐level and cluster‐level covariate effects in regression analysis of correlated data , 2003, Statistics in medicine.

[31]  Peter B. Jones,et al.  Obstetric complications and schizophrenia: historical and meta-analytic review. , 2002, The American journal of psychiatry.

[32]  Gary King,et al.  Estimating risk and rate levels, ratios and differences in case‐control studies , 2002, Statistics in medicine.

[33]  P. Mortensen,et al.  Family history, place and season of birth as risk factors for schizophrenia in Denmark: A replication and reanalysis , 2001, British Journal of Psychiatry.

[34]  R. Murray,et al.  Intra-uterine physical growth in schizophrenia: evidence confirming excess of premature birth , 2000, Psychological Medicine.

[35]  P. Mortensen,et al.  Preterm birth and intra-uterine growth retardation among children of women with schizophrenia , 1999, British Journal of Psychiatry.

[36]  R. Murray,et al.  Prenatal and perinatal risk factors for schizophrenia, affective psychosis, and reactive psychosis of early onset: case-control study. , 1999, BMJ.

[37]  J. Olsen,et al.  The Danish Medical Birth Registry. , 1998, Danish medical bulletin.

[38]  D. Klein,et al.  Birth Weight and Length in Schizophrenics Personality Disorders and Their Siblings , 1971, British Journal of Psychiatry.

[39]  G. Albee,et al.  Comparative Birth Weights of Schizophrenics and Their Siblings , 1966 .

[40]  J. Neu.  Prevention and Schizophrenia—The Role of Dietary Factors , 2011 .

[41]  J. Eriksson,et al.  Association of schizophrenia with low maternal body mass index, small size at birth, and thinness during childhood. , 2001, Archives of general psychiatry.

[42]  B. Diamond,et al.  Autoimmune diseases , 2000, Bone Marrow Transplantation.

[43]  D. Barker.  Fetal origins of cardiovascular disease. , 1999, Annals of medicine.