Birth by Caesarean Section and the Risk of Adult Psychosis: A Population-Based Cohort Study.

Despite the biological plausibility of an association between obstetric mode of delivery and psychosis in later life, studies to date have been inconclusive. We assessed the association between mode of delivery and later onset of psychosis in the offspring. A population-based cohort including data from the Swedish National Registers was used. All singleton live births between 1982 and 1995 were identified (n= 1,345,210) and followed-up to diagnosis at age 16 or later. Mode of delivery was categorized as: unassisted vaginal delivery (VD), assisted VD, elective Caesarean section (CS) (before onset of labor), and emergency CS (after onset of labor). Outcomes included any psychosis; nonaffective psychoses (including schizophrenia only) and affective psychoses (including bipolar disorder only and depression with psychosis only). Cox regression analysis was used reporting partially and fully adjusted hazard ratios (HR) with 95% confidence intervals (CI). Sibling-matched Cox regression was performed to adjust for familial confounding factors. In the fully adjusted analyses, elective CS was significantly associated with any psychosis (HR 1.13, 95% CI 1.03, 1.24). Similar findings were found for nonaffective psychoses (HR 1.13, 95% CI 0.99, 1.29) and affective psychoses (HR 1.17, 95% CI 1.05, 1.31) (χ(2)for heterogeneityP= .69). In the sibling-matched Cox regression, this association disappeared (HR 1.03, 95% CI 0.78, 1.37). No association was found between assisted VD or emergency CS and psychosis. This study found that elective CS is associated with an increase in offspring psychosis. However, the association did not persist in the sibling-matched analysis, implying the association is likely due to familial confounding by unmeasured factors such as genetics or environment.

[1]  A. Macfarlane,et al.  Wide differences in mode of delivery within Europe: risk‐stratified analyses of aggregated routine data from the Euro‐Peristat study , 2016, BJOG : an international journal of obstetrics and gynaecology.

[2]  P. Kearney,et al.  Association Between Obstetric Mode of Delivery and Autism Spectrum Disorder: A Population-Based Sibling Design Study. , 2015, JAMA psychiatry.

[3]  E. Huerta-Ramos,et al.  Birth weight and obstetric complications determine age at onset in first episode of psychosis. , 2015, Journal of psychiatric research.

[4]  K. Maršál,et al.  Predicting the chance of vaginal delivery after one cesarean section: validation and elaboration of a published prediction model. , 2015, European journal of obstetrics, gynecology, and reproductive biology.

[5]  D. A. Lewis,et al.  Changes in the adolescent brain and the pathophysiology of psychotic disorders. , 2014, The lancet. Psychiatry.

[6]  M. Owen,et al.  Schizophrenia genetics: emerging themes for a complex disorder , 2014, Molecular Psychiatry.

[7]  R. Young,et al.  Subclinical psychotic experiences in healthy young adults: associations with stress and genetic predisposition. , 2014, Genetic testing and molecular biomarkers.

[8]  T. Dinan,et al.  Microbiota and neurodevelopmental windows: implications for brain disorders. , 2014, Trends in molecular medicine.

[9]  V. Lehti,et al.  Perinatal factors and the risk of bipolar disorder in Finland. , 2014, Journal of affective disorders.

[10]  E. Susser,et al.  Severe bereavement stress during the prenatal and childhood periods and risk of psychosis in later life: population based cohort study , 2014, BMJ : British Medical Journal.

[11]  J. Cryan,et al.  Microbial genes, brain & behaviour – epigenetic regulation of the gut–brain axis , 2014, Genes, brain, and behavior.

[12]  Katherine M Keyes,et al.  On sibling designs. , 2013, Epidemiology.

[13]  C. Cho,et al.  Cesarean section and development of the immune system in the offspring. , 2013, American journal of obstetrics and gynecology.

[14]  D. Mackay,et al.  Obstetric factors and different causes of special educational need: retrospective cohort study of 407 503 schoolchildren , 2013, BJOG : an international journal of obstetrics and gynaecology.

[15]  T. Dinan,et al.  Mind-altering Microorganisms: the Impact of the Gut Microbiota on Brain and Behaviour , 2022 .

[16]  Arvid Sjölander,et al.  Sibling comparison designs: bias from non-shared confounders and measurement error. , 2012, Epidemiology.

[17]  Karel G M Moons,et al.  Missing covariate data in clinical research: when and when not to use the missing-indicator method for analysis , 2012, Canadian Medical Association Journal.

[18]  Martin Grann,et al.  Perinatal risk factors in offenders with severe personality disorder: a population-based investigation. , 2012, Journal of personality disorders.

[19]  J. Os,et al.  An updated and conservative systematic review and meta-analysis of epidemiological evidence on psychotic experiences in children and adults: on the pathway from proneness to persistence to dimensional expression across mental disorders , 2012, Psychological Medicine.

[20]  Chiara Nosarti,et al.  Preterm birth and psychiatric disorders in young adult life. , 2012, Archives of general psychiatry.

[21]  N. Eisenberger,et al.  Social neuroscience and health: neurophysiological mechanisms linking social ties with physical health , 2012, Nature Neuroscience.

[22]  M. Cannon,et al.  Prevalence of psychotic symptoms in childhood and adolescence: a systematic review and meta-analysis of population-based studies , 2012, Psychological Medicine.

[23]  M. Landén,et al.  Validity of bipolar disorder hospital discharge diagnoses: file review and multiple register linkage in Sweden , 2011, Acta psychiatrica Scandinavica.

[24]  Peter B. Jones,et al.  Increased risk of schizophrenia from additive interaction between infant motor developmental delay and obstetric complications: evidence from a population-based longitudinal study. , 2011, The American journal of psychiatry.

[25]  Johannes Textor,et al.  DAGitty: a graphical tool for analyzing causal diagrams. , 2011, Epidemiology.

[26]  J. Ludvigsson,et al.  External review and validation of the Swedish national inpatient register , 2011, BMC public health.

[27]  Ezra Susser,et al.  Commentary : Advent of sibling designs , 2011 .

[28]  A. Ekbom The Swedish Multi-generation Register. , 2011, Methods in molecular biology.

[29]  J. Ludvigsson,et al.  The Swedish personal identity number: possibilities and pitfalls in healthcare and medical research , 2009, European Journal of Epidemiology.

[30]  T. Anderson Caesarean section for non-medical reasons at term. , 2006, The practising midwife.

[31]  J. Neilson,et al.  Caesarean section for non-medical reasons at term. , 2006, The Cochrane database of systematic reviews.

[32]  M. Vares,et al.  Evaluation of diagnostic procedures in Swedish patients with schizophrenia and related psychoses , 2005, Nordic journal of psychiatry.

[33]  O. Axelsson The Swedish Medical Birth Register , 2003, Acta obstetricia et gynecologica Scandinavica.

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

[35]  Tyrone D. Cannon,et al.  Obstetric risk factors for early-onset schizophrenia in a Finnish birth cohort. , 2000, The American journal of psychiatry.

[36]  D. Weinberger,et al.  Relationship of obstetric complications and differences in size of brain structures in monozygotic twin pairs discordant for schizophrenia. , 2000, The American journal of psychiatry.

[37]  P. Allebeck,et al.  Obstetric complications and the risk of schizophrenia: a longitudinal study of a national birth cohort. , 1999, Archives of general psychiatry.

[38]  R. Murray,et al.  Obstetric complications and age at onset in schizophrenia: an international collaborative meta-analysis of individual patient data. , 1997, The American journal of psychiatry.

[39]  Eric R. Ziegel,et al.  Survival analysis using the SAS system , 1995 .