Higher risk of offspring schizophrenia following antenatal maternal exposure to severe adverse life events.
BACKGROUND
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.


METHODS
Population-based study.


METHODS
Denmark.


METHODS
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.
Khashan
Ali S
AS
Centre for Women's Mental Health Research, University of Manchester, Manchester M13 9PL, England.
Abel
Kathryn M
KM
McNamee
Roseanne
R
Pedersen
Marianne G
MG
Webb
Roger T
RT
Baker
Philip N
PN
Kenny
Louise C
LC
Mortensen
Preben Bo
PB
D000328:Adult; D001601:Bereavement; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003718:Denmark; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008016:Life Change Events; D008297:Male; D008875:Middle Aged; D009035:Mothers / Q000523:psychology*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011297:Prenatal Exposure Delayed Effects; D012042:Registries; D012306:Risk; D012307:Risk Factors; D012559:Schizophrenia / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D012565:Schizophrenic Psychology