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Higher Risk of Offspring Schizophrenia Following Antenatal Maternal Exposure to Severe Adverse Life Events
Ali S. Khashan, MSc;
Kathryn M. Abel, MRCP, MRCPsych, PhD;
Roseanne McNamee, PhD;
Marianne G. Pedersen, MSc;
Roger T. Webb, PhD;
Philip N. Baker, DM, FRCOG;
Louise C. Kenny, PhD, MRCOG;
Preben Bo Mortensen, MD, DMSc
Arch Gen Psychiatry. 2008;65(2):146-152.
Context Most societies believe that a mother's psychological state can influence her unborn baby. Severe adverse life events during pregnancy have been consistently associated with an elevated risk of low birth weight and prematurity. Such events during the first trimester have also been associated with risk of congenital malformations.
Objective To assess the effect in offspring of antenatal maternal exposure to an objective measure of stress on risk of adverse neurodevelopment, specifically schizophrenia. We hypothesized that the strongest relationship would be to maternal exposures during the first trimester.
Design Population-based study.
Setting Denmark.
Participants In a cohort of 1.38 million Danish births from 1973 to 1995, mothers were considered exposed if 1 (or more) of their close relatives died or was diagnosed with cancer, acute myocardial infarction, or stroke syndrome up to 6 months before conception or during pregnancy. Offspring were followed up from their 10th birthday until their death, migration, onset of schizophrenia, or June 30, 2005; admissions were identified by linkage to the Central Psychiatric Register.
Main Outcome Measure Schizophrenia.
Results The risk of schizophrenia and related disorders was raised in offspring whose mothers were exposed to death of a relative during the first trimester (adjusted relative risk, 1.67 [95% confidence interval, 1.02-2.73]). Death of a relative during other trimesters or up to 6 months before pregnancy were not linked with a higher risk of schizophrenia.
Conclusions Our population-based study suggests that severe stress to a mother during the first trimester may alter the risk of schizophrenia in offspring. This finding is consistent with ecological evidence from whole populations exposed to severe stressors and suggests that environment may influence neurodevelopment at the feto-placental-maternal interface.
Author Affiliations: Centre for Women's Mental Health Research (Mr Khashan and Drs Abel and Webb), Biostatistics Group (Dr McNamee), and Maternal and Fetal Health Research Group (Mr Khashan, Prof Baker, and Dr Kenny), University of Manchester, Manchester, England; National Centre for Register-based Research, University of Aarhus, Aarhus, Denmark (Ms Pedersen and Prof Mortensen); and BUPA Ireland Research Center, Department of Obstetrics and Gynaecology, Cork University Maternity Hospital, Cork, Ireland (Dr Kenny).
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