Autism and Probable Prerequisites: Severe and Scheduled Prenatal Stresses at Spotlight

  • Seyyed Mohammad MOUSAVI Cellular and Molecular Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran Genetic and Identification Lab, Legal Medicine Center, Isfahan, Iran
  • Elahe KAMALI Division of Genetics, Dept. of Biology, Faculty of Sciences, University of Isfahan, Isfahan, Iran
  • Fatemeh FATAHI Cellular and Molecular Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran
  • Hadi BABAIE Dept. of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran Genetic and Identification Lab, Legal Medicine Center, Rasht, Iran
  • Mansoor SALEHI Dept. of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran Medical Genetics Center of Genome, Genome Building, Isfahan, Iran
Keywords: Autism, Prenatal stress, Epigenetic


AbstractBackground: Due to the importance of prenatal maternal stress as environmental factor on autism, the influence of prenatal maternal psychological agitations was assessed in relation with the risk of autism.Methods: In this case-control study, some mothers of autistic children in Isfahan, central Iran, in 2014, were retrospectively compared with control mothers in terms of quantity, quality, andschedule of exposure to 45 stressful events in a 15-month period. In addition, dividing the stressors into two groups of genome-dependent/independent events, their prevalence was separately scrutinized and compared among patient and control families.Results: Although the child’s risk of autism increases significantly with the increase of maternal stress during months 4-7 of pregnancy, the increased stress during months 2-3 of pregnancy can lead to a significant increase in the severity of autism affliction as well as a slight but significant increase in the possibility of LFA in afflicted children (P<0.05). The overall prevalence of genome-dependent stressful events among two patient and control groups was significantly higher than that of genome-independent events (P=0.000), but genome-dependent events led to more stress inpatient families.Conclusion: Although the present study consistent with recent findings in the fields of epigenetics and gene-environment interactions can confirm the role of severe and scheduled prenatal stresses in causing autism, it does not deny the necessity of a perspective and wider study in Isfahan and Iran.  


Landa RJ (2008). Diagnosis of autism spectrum disorders in the first 3 years of life. Nat Clin Pract Neurol, 4:138-147.

Ritvo ER, Freeman BJ, Mason-Brothers A, Mo A, Ritvo AM (1985). Concordance for the syndrome of autism in 40 pairs of afflicted twins. Am J Psychiatry, 142:74-7.

Freitag CM (2007). The genetics of autistic disorders and its clinical relevance: a review of the literature. Mol Psychiatry, 2(1):2-22.

Maestrini E, Paul A, Monaco AP, Bailey A (2000). Identifying autism susceptibility genes. Neuron, 28:19-24.

Yang MS, Gill M (2007). A review of gene linkage, association and expression studies in autism and an assessment of convergent evidence. Int J Dev Neurosci, 25:69-85.

Hallmayer J, Cleveland S, Torres A et al (2011). Genetic heritability and shared environmental factors among twin pairs with autism. Arch Gen Psychiatry, 68:1095-1102.

Ward AJ (1990). A comparison and analysis of the presence of family problems during pregnancy of mothers of “autistic” children and mothers of normal children. Child Psychiatry Hum Dev, 20:279-288.

Beversdorf DQ, Manning SE, Hillier A et al (2005). Timing of prenatal stressors and autism. J Autism Dev Disord, 35:471-478.

Kinney DK, Miller AM, Crowley DJ et al (2008). Autism prevalence following prenatal exposure to hurricanes and tropical storms in Louisiana. J Autism Dev Disord, 38:481-488.

Ronald A, Pennell CE, Whitehouse AJ (2011). Prenatal maternal stress associated with ADHD and autistic traits in early childhood. Front Psychol, 1:223.

Li J, Vestergaard M, Obel C et al (2009). A nationwide study on the risk of autism after prenatal stress exposure to maternal bereavement. Pediatrics, 123:1102-1107.

Rai D, Golding J, Magnusson C et al (2012). Prenatal and early life exposure to stressful life events and risk of autism spectrum disorders: population-based studies in Sweden and England. PLoS One, 7:e38893.

Malek A, Dadashzadeh H, Pourafkari N, Safaeian A (2008). Ranking of Stressful Life Events in General Population of Tabriz, Iran. Research Journal of Biological Sciences,993-998.

Holmes TH, Rahe RH (1967). The social readjustment rating scale. J Psychosom Res, 11:213-218.

Casey RL, Masuda M, Holmes TH (1967). Quantitative study of recall of life events. J Psychosom Res, 11:239-247.

Rice F, Harold G, Boivin J et al (2010). The links between prenatal stress and offspring development and psychopathology: disentangling environmental and inherited influences. Psychol Med, 40:335-345.

Khashan AS, Wicks S, Dalman C et al (2012). Prenatal stress and risk of asthma hospitalization in the offspring: a Swedish population-based study. Psychosom Med, 74:635-641.

Li J, Vestergaard M, Obel C et al (2012). Antenatal maternal bereavement and childhood cancer in the offspring: a population-based cohort study in 6 million children. Br J Cancer, 107:544-548.

Stroud LR, Papandonatos GD, Shenassa E et al (2014). Prenatal glucocorticoids and maternal smoking during pregnancy independently program adult nicotine dependence in daughters: a 40-year prospective study. Biol Psychiatry, 75:47-55.

Holloway T, Moreno JL, Umali A et al (2013). Prenatal stress induces schizophrenia-like alterations of serotonin 2A and metabotropic glutamate 2 receptors in the adult offspring: role of maternal immune system. J Neurosci, 33:1088-1098.

Li J, Vestergaard M, Obel C et al (2008). Prenatal stress and epilepsy in later life: a nationwide follow-up study in Denmark. Epilepsy Res, 81:52-57.

Markham JA, Koenig JI (2011). Prenatal stress: role in psychotic and depressive diseases. Psychopharmacology (Berl), 214:89-106.

Wainstock T, Lerner-Geva L, Glasser S et al (2013). Prenatal stress and risk of spontaneous abortion. Psychosom Med, 75:228-235.

Lemaire V, Koehl M, Le Moal M, Abrous DN (2000). Prenatal stress produces learning deficits associated with an inhibition of neurogenesis in the hippocampus. Proc Natl Acad Sci U S A, 97:11032-11037.

Huang, L. T. (2011). The link between perinatal glucocorticoids exposure and psychiatric disorders. Pediatr Res, 69(5), 19R-25R.

Wadhwa PD, Sandman CA, Porto M et al (1993). The association between prenatal stress and infant birth weight and gestational age at birth: a prospective investigation. Am J Obstet Gynecol, 169:858-865.

Entringer S, Epel ES, Kumsta R et al (2011). Stress exposure in intrauterine life is associated with shorter telomere length in young adulthood. Proc Natl Acad Sci U S A, 108:E513-E518.

Charil A, Laplante DP, Vaillancourt C, King S (2010). Prenatal stress and brain development. Brain Res Rev, 65:56-79.

Buss C, Davis EP, Muftuler LT et al (2010). High pregnancy anxiety during mid-gestation is associated with decreased gray matter density in 6–9-year-old children. Psychoneuroendocrinology, 35:141-153.

Uno H, Eisele S, Sakai A et al (1994). Neurotoxicity of glucocorticoids in the primate brain. Horm Behav, 28:336-348.

Mairesse J, Lesage J, Breton C et al (2007). Maternal stress alters endocrine function of the feto-placental unit in rats. Am J Physiol Endocrinol Metab, 292:E1526-E1533.

Sandman CA, Glynn L, Schetter CD et al (2006). Elevated maternal cortisol early in pregnancy predicts third trimester levels of placental corticotropin releasing hormone (CRH): priming the placental clock. peptides, 27:1457-1463.

Grossniklaus U, Kelly WG, Ferguson-Smith AC, Pembrey M, Lindquist S (2013) Transgenerational epigenetic inheritance: how important is it? Nature Rev Genet, 14: 228-235.

Crews D, Gillette R, Scarpino SV et al (2012). Epigenetic transgenerational inheritance of altered stress responses. Proc Natl Acad Sci, 109: 9143-9148.

Daxinger L, Whitelaw E (2010). Transgenerational epigenetic inheritance: more questions than answers. Genome Res, 20: 1623-1628.

Daxinger L, Whitelaw E (2012). Understanding transgenerational epigenetic inheritance via the gametes in mammals. Nature Rev Genet, 13:153-162.

Youngson NA, Whitelaw E (2008). Transgenerational epigenetic effects. Annu Rev Genomics Hum Genet, 9:233-257.

How to Cite
MOUSAVI SM, KAMALI E, FATAHI F, BABAIE H, SALEHI M. Autism and Probable Prerequisites: Severe and Scheduled Prenatal Stresses at Spotlight. IJPH. 47(9):1387-95.
Original Article(s)