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

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 1 492 709 singletons in Denmark born from 1978 to 2003. A total of 37 275 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. Pediatrics 2009; 123: 1102-1107