Published online March 30, 2009
PEDIATRICS Vol. 123 No. 4 April 2009, pp. 1102-1107 (doi:10.1542/peds.2008-1734)

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ARTICLE

A Nationwide Study on the Risk of Autism After Prenatal Stress Exposure to Maternal Bereavement

Jiong Li, MD, PhD^a, Mogens Vestergaard, MD, PhD^b, Carsten Obel, MD, PhD^b, Jakob Christensen, MD, PhD^c, Dorthe Hansen Precht, MD, PhD^d, Michael Lu, MD^e and Jørn Olsen, MD, PhD^a,f

^a Department of Epidemiology, Danish Epidemiology Science Centre
^b Department of General Practice, Institute of Public Health, University of Aarhus, Aarhus, Denmark
^c Department of Neurology, Aarhus University Hospital, Aarhus, Denmark
^d Department of Pediatrics, Holbaek University Hospital, Region Zealand, Denmark
^e Departments of Obstetrics and Gynecology and Community Health Sciences, Schools of Medicine and Public Health
^f Department of Epidemiology, School of Public Health, University of California, Los Angeles, California

OBJECTIVE. Prenatal stress has been linked to several adverse neurobehavioral outcomes, which may share a common pathophysiology with autism. We aimed to examine whether prenatal stress exposure after maternal bereavement is associated with an increased risk of autism later in life.

METHODS. We conducted a nationwide population-based cohort study of all 1492709 singletons in Denmark born from 1978 to 2003. A total of 37275 children were born to women who lost a close relative during pregnancy or up to 1 year before pregnancy. These children were included in the exposed group, and the remaining children were in the unexposed group. All children were followed up from birth until their death, migration, onset of autism, or the end of 2006. Information on autism was obtained from the Danish Psychiatric Central Register. We used Cox regression models to estimate hazard ratios in the exposed group compared with those in the unexposed group.

RESULTS. Maternal bereavement during the prenatal period was not associated with an increased risk of autism in the offspring. The hazard ratios did not differ by the nature of the exposure (maternal relationship to the deceased or cause of death). The hazard ratios were comparable between the 5 prenatal exposure periods under study (7–12 months before pregnancy, 0–6 months before pregnancy, first trimester, second trimester, and third trimester).

CONSLUSIONS. This is the first population-based cohort study to examine the effect of prenatal stress on autism in childhood. Our data do not support any strong association between prenatal stress after maternal bereavement and the risk of autism.

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Key Words: bereavement • prenatal • stress • autism • glucocorticoids • fetal programming

Abbreviations: CPR—civil personal registration • HR—hazard ratio • ICD—International Classification of Diseases • CI—confidence interval

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Accepted Aug 6, 2008.

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