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

ArticleinPEDIATRICS 123(4):1102-7 · May 2009with42 Reads
Impact Factor: 5.47 · DOI: 10.1542/peds.2008-1734 · Source: PubMed
Abstract

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. 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. 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). 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.

    • "Subsequent research has shown evidence of elevated ASD risk in Louisiana parishes following prenatal exposure to tropical storms during this same gestational period (Kinney, Miller, Crowley, Huang, & Gerber, 2008 ). One study of the Danish national registry failed to find an association between maternal bereavement and autism (Li et al., 2009 ). However, an association was present when maternal psychiatric conditions were included in the analysis. "
    [Show abstract] [Hide abstract] ABSTRACT: Stress exposure during gestation is implicated in several neuropsychiatric conditions, including autism spectrum disorder (ASD). Previous research showed that prenatal stress increases risk for ASD with peak exposure during the end of the second and the beginning of the third trimester. However, exposures to prenatal stress do not always result in ASD, suggesting that other factors may interact with environmental stressors to increase ASD risk. The present study examined a maternal genetic variation in the promoter region of the serotonin transporter gene (5-HTTLPR) affecting stress tolerance and its interaction with the effect of environmental stressors on risk for ASD. Two independent cohorts of mothers of ASD children recruited by the University of Missouri and Queen's University were surveyed regarding the prenatal environment and genotyping on 5-HTTLPR was performed to explore this relationship. In both samples, mothers of children with ASD carrying the stress susceptible short allele variant of 5-HTTLPR experienced a greater number of stressors and greater stress severity when compared to mothers carrying the long allele variant. The temporal peak of stressors during gestation in these mothers was consistent with previous findings. Additionally, increased exposure to prenatal stress was not reported in the pregnancies of typically developing siblings from the same mothers, regardless of maternal genotype, suggesting against the possibility that the short allele might increase the recall of stress during pregnancy. The present study provides further evidence of a specific maternal polymorphism that may affect the risk for ASD with exposure to prenatal stress. Autism Res 2016. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
    Full-text · Article · Apr 2016 · Autism Research
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    • "The importance of timing of the stressor in pregnancy on various areas of infant and child development has been previously demonstrated (Davis & Sandman, 2010; DiPietro et al., 2006). Other PNMS research studying psychosocial stressors, or even independent stressors (such as the death of a relative; Li et al., 2015) which may have been preceded by a long period of chronic stress, are unable to test hypotheses about timing in gestation with as much precision as studies of a sudden-onset natural disaster. Natural disaster research shows that various domains of development are affected by PNMS when it occurs at different times during gestation. "
    [Show abstract] [Hide abstract] ABSTRACT: The current study examined the effects of a natural disaster (a sudden onset flood) as a stressor in pregnancy on infant fine and gross motor development at 2, 6, and 16 months of age. Whether the timing of the stressor in pregnancy or sex of the infant moderated the impact of the prenatal maternal stress on motor development was also explored. Mothers' objective experiences of the flood, emotional reactions and distress, and their cognitive appraisal of the event were assessed retrospectively. Infants' fine and gross motor skills were assessed with the Ages and Stages Questionnaire, and results showed age-related changes in the effects of prenatal maternal stress on these domains. At 2 months, higher levels of prenatal maternal stress was positively related to infant motor development, yet at 6 and 16 months of age there was a negative association, particularly if flood exposure occurred later in pregnancy and if mothers had negative cognitive appraisals of the event. Results also showed differential effects of the maternal stress responses to the floods on infants' fine and gross motor development at each age and that infant sex did not buffer these effects. © 2016 Wiley Periodicals, Inc. Dev Psychobiol 9999: 1-20, 2016.
    No preview · Article · Mar 2016 · Developmental Psychobiology
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    • "Studies have also shown a reduction in cognitive performance associated with prenatal stress (Laplante et al. 2008; Barker et al. 2011). Some research (Beversdorf et al. 2005; Kinney et al. 2008b; Class et al. 2013), although not all (Li et al. 2009), has found an association between prenatal stress and increased risk of autism or autistic spectrum disorder. Two studies have found an increased risk of schizophrenia in adults born to mothers who experienced stress during pregnancy (van Os and Selten 1998; Khashan et al. 2008). "
    [Show abstract] [Hide abstract] ABSTRACT: Many prospective studies have shown that if a mother is depressed, anxious or stressed while pregnant, this increases the risk for her child having a wide range of adverse outcomes including emotional problems, symptoms of attention deficit hyperactivity disorder (ADHD) or impaired cognitive development. Although genetics and postnatal care clearly affect these outcomes, evidence for a prenatal causal component also is substantial. Prenatal anxiety/depression may contribute 10–15 % of the attributable load for emotional/behavioural outcomes. The mechanisms underlying these changes are just starting to be explored. One possible mediating factor is increased exposure of the fetus to cortisol, as has been shown in animal studies. However, the human hypothalamic–pituitary–adrenal (HPA) axis which makes cortisol functions differently in human pregnancy from in most animals. The maternal HPA axis becomes gradually less responsive to stress as pregnancy progresses. And there is only a weak, if any, association between a mother’s prenatal mood and her cortisol level, especially later in pregnancy. Cytokines are alternative possible mediators. An additional explanation is that stress or anxiety causes increased transfer of maternal cortisol across the placenta to the fetus. The placenta plays a crucial role in moderating fetal exposure to maternal factors and presumably in preparing the fetus for the environment in which it is going to find itself. There is some evidence in both rat models and in humans that prenatal stress can reduce placental 11β-HSD2, the enzyme which metabolises cortisol to inactive cortisone. The level of cortisol in the amniotic fluid, surrounding the baby in the womb, has been shown to be inversely correlated with infant cognitive development. However, several other biological systems are likely to be involved. Serotonin is another possible mediator of prenatal stress induced programming effects on offspring neurocognitive and behavioural development. The role of epigenetic changes in mediating alterations in offspring outcome following prenatal stress is likely to be important and starting to be explored.
    Full-text · Article · Jan 2015 · Advances in neurobiology
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