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Brief Report: Asperger’s Syndrome and Sibling Birth Order

Abstract

Prior investigations suggest that birth order position may be associated with the risk for developing a pervasive developmental disorder. This retrospective chart review examined the birth order status of 29 psychiatrically-referred patients with Asperger’s Syndrome (AS). Eighty-six percent of the subjects were first born. The finding was statistically significant when compared to an expected random distribution of AS subjects χ2 (1, N = 29) = 9.18, p < 0.01. The reasons for such an association are unclear though birth stoppage, obstetric complications, and immunological mechanisms may play a role.

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References

  1. American Psychiatric Association. (2000). Diagnostic and statistical manual for mental disorder, fourth edition, text revision. Washington, DC: American Psychiatric Association.

    Google Scholar 

  2. Atladóttir, H. O., Pedersen, M. G., Thorsen, P., Mortensen, P. B., Deleuran, B., Eaton, W. W., et al. (2009). Association of family history of autoimmune diseases and autism spectrum disorders. Pediatrics, 124, 687–694.

    PubMed  Article  Google Scholar 

  3. Bhatia, M. S., Nigam, V. R., Bohra, N., & Malik, S. C. (1991). Attention deficit disorder with hyperactivity among pediatric outpatients. Journal of Child Psychology and Psychiatry, 32(2), 297–306.

    PubMed  Article  Google Scholar 

  4. Bloemen, O. J. N., Deeley, Q., Sundram, F., Daly, E. M., Barker, G. J., Jones, D. K., et al. (2010). White matter integrity in Asperger syndrome: A preliminary diffusion tensor magnetic resonance imaging study in adults. Autism Research, 3, 203–213.

    PubMed  Article  Google Scholar 

  5. Bolton, P. F., Murphy, M., MacDonald, H., Whitlock, B., Pickles, A., & Rutter, M. (1997). Obstetric complications in autism: Consequences or causes of the condition. Journal of the American Academy of Child and Adolescent Psychiatry, 36(2), 272–281.

    PubMed  Article  Google Scholar 

  6. Braunschweig, D., Ashwood, P., Krakowiak, P., Hertz-Picciotto, I., Hansen, R., Croen, L. A., et al. (2008). Autism: Maternally derived antibodies specific for fetal brain proteins. NeuroToxicology, 29(2), 226–231.

    PubMed  Google Scholar 

  7. Braunschweig, D., Duncanson, P., Boyce, R., Hansen, R., Ashwood, P., Pessah, I. N., et al. (2011). Behavioral correlates of maternal antibody status among children with autism. Journal of Autism and Developmental Disorders,. doi:10.1007/s10803-011-1378-7.

    Google Scholar 

  8. Cederlund, M., & Gillberg, C. (2004). One hundred males with Asperger syndrome: A clinical study of background and associated factors. Developmental Medicine and Child Neurology, 46, 652–660.

    PubMed  Article  Google Scholar 

  9. Comi, A. M., Zimmerman, A. W., Frye, V. H., Law, P. A., & Peeden, J. N. (1999). Familial clustering of autoimmune disorders and evaluation of medical risk factors in autism. Journal of Child Neurology, 14(6), 388–394.

    PubMed  Article  Google Scholar 

  10. Croen, L. A., Braunschweig, D., Haapanen, L., Yoshida, C. K., Fireman, B., Grether, J. K., et al. (2008). Maternal mid-pregnancy autoantibodies to fetal brain protein: The early markers for autism study. Biological Psychiatry, 64, 583–588.

    PubMed  Article  Google Scholar 

  11. Croen, L. A., Grether, J. K., Yoshida, C. K., Odouli, R., & Van de Water, J. (2005). Maternal autoimmune diseases, asthma and allergies, and childhood autism spectrum disorders. Archives of Pediatrics and Adolescent Medicine, 159, 151–157.

    PubMed  Article  Google Scholar 

  12. Croen, L. A., Najjar, D. V., Fireman, B., & Grether, J. K. (2007). Maternal and paternal age and risk of autism spectrum disorders. Archives of Pediatric and Adolescent Medicine, 161, 334–340.

    Article  Google Scholar 

  13. Deykin, E. Y., & MacMahon, B. (1980). Pregnancy, delivery and neonatal complications among autistic children. Archives of Pediatrics and Adolescent Medicine, 134(9), 860–864.

    Article  Google Scholar 

  14. Durkin, M. S., Maenner, M. J., Newshaffer, C. J., Lee, L., Cunniff, C. M., Daniels, J. L., et al. (2008). Advanced parental age and the risk of autism spectrum disorder. American Journal of Epidemiology, 168(11), 1268–1276.

    PubMed  Article  Google Scholar 

  15. Eaton, W. W., Mortensen, P. B., Thomsen, P. H., & Frydenberg, M. (2001). Obstetric complications and risk for severe psychopathology in childhood. Journal of Autism and Developmental Disorders, 31(3), 279–285.

    PubMed  Article  Google Scholar 

  16. Eskenazi, B., Fenster, L., & Sidney, S. (1991). A multivariate analysis of risk factors for preeclampsia. Journal of the American Medical Association, 266(2), 237–241.

    PubMed  Article  Google Scholar 

  17. Gardener, H., Spiegelman, D., & Buka, S. L. (2009). Prenatal risk factors for autism: Comprehensive meta-analysis. The British Journal of Psychiatry, 195, 7–14.

    PubMed  Article  Google Scholar 

  18. Gaughran, F., Blizard, R., Mohan, R., Zammit, S., & Owen, M. (2007). Birth order and the severity of illness in schizophrenia. Psychiatry Research, 150, 205–210.

    PubMed  Article  Google Scholar 

  19. Ghaziuddin, M. (2010). Brief report: Should the DSM V drop Asperger syndrome. Journal of Autism and Developmental Disorders, 40, 1146–1148.

    PubMed  Article  Google Scholar 

  20. Gillberg, C. (1989). Asperger syndrome in 23 Swedish children. Developmental Medicine and Child Neurology, 31(4), 520–531.

    PubMed  Article  Google Scholar 

  21. Glasson, E. J., Bower, C., Petterson, B., de Klerk, N., Chaney, G., & Hallmayer, J. F. (2004). Perinatal factors and the development of autism: A population study. Archives of General Psychiatry, 61, 618–627.

    PubMed  Article  Google Scholar 

  22. Greenwood, M., & Yule, U. G. (1914). On the determination of size of family and of the distribution of characters in order of birth from samples taken through members of the sibships. Journal of the Royal Statistical Society, 77(2), 179–199.

    Article  Google Scholar 

  23. Happé, F. (2011). Criteria, categories, and continua: Autism and related disorders in DSM-5. Journal of the American Academy of Child and Adolescent Psychiatry, 50(6), 540–542.

    PubMed  Article  Google Scholar 

  24. Howlin, P., & Asgharian, A. (1999). The diagnosis of autism and Asperger syndrome: Findings from a survey of 770 families. Developmental Medicine and Child Neurology, 41, 834–839.

    PubMed  Article  Google Scholar 

  25. Johnson, W. G., Buyske, S., Mars, A. E., Sreenath, M., Stenroos, E. S., Williams, T. A., et al. (2009). HLA-DR4 as a risk allele for autism acting in mothers of probands possibly during pregnancy. Archives of Pediatricts and Adolescent Medicine, 163(6), 542–546.

    Article  Google Scholar 

  26. Jones, M. B., & Szatmari, P. (1988). Stoppage rules and genetic studies of autism. Journal of Autism and Developmental Disorders, 18(1), 31–40.

    PubMed  Article  Google Scholar 

  27. Karmaus, W., Arshad, H., & Mattes, J. (2001). Does the sibling effect have its origin in utero? Investigating birth order, cord blood immunoglobulin E concentration, and allergic sensitization at age 4 years. American Journal of Epidemiology, 154(10), 909–915.

    PubMed  Article  Google Scholar 

  28. Karmaus, W., Arshad, S. H., Sadeghnejad, A., & Twiselton, R. (2004). Does maternal immunoglobulin E decrease with increasing order of live offspring? Investigation into maternal immune tolerance. Clinical and Experimental Allergy, 34, 853–859.

    PubMed  Article  Google Scholar 

  29. Karmaus, W., & Botezan, C. (2002). Does a higher number of siblings protect against the development of allergy and asthma? A review. Journal of Epidemiology and Community Health, 56, 209–217.

    PubMed  Article  Google Scholar 

  30. Lee, A. C. C., Mullany, L. C., Tielsch, J. M., Katz, J., Khatry, S. K., LeClerq, S. C., et al. (2011). Incidence of and risk factors for neonatal respiratory depression and encephalopathy in rural Sarlahi. Nepal Pediatrics, 128(4), 915–924.

    Article  Google Scholar 

  31. Lee, L., Zachary, A. A., Leffell, M. S., Newschaffer, C. J., Matteson, K. J., Tyler, J. D., et al. (2006). HLA-DR4 in families with autism. Pediatric Neurology, 35(5), 303–307.

    PubMed  Article  Google Scholar 

  32. Lord, C., Mulloy, C., Wendelboe, M., & Schopler, E. (1991). Pre- and perinatal factors in high-functioning females and males with autism. Journal of Autism and Developmental Disorders, 21(2), 197–209.

    PubMed  Article  Google Scholar 

  33. Magalhães, E. S., Pinto-Mariz, F., Bastos-Pinto, S., Pontes, A. T., Prado, E. A., & deAzevedo, L. C. (2009). Immune allergic response in Asperger syndrome. Journal of Neuroimmunology, 216, 108–112.

    PubMed  Article  Google Scholar 

  34. Martin, L. A., Ashwood, P., Braunschweig, D., Cabanlit, M., Van de Water, J., & Amaral, D. G. (2008). Stereotypies and hyperactivity in rhesus monkeys exposed to IgG from mothers of children with autism. Brain, Behavior, and Immunity, 22, 806–816.

    PubMed  Article  Google Scholar 

  35. Mattila, M.-L., Hurtic, T., Haapsamo, H., Jussila, K., Kuusikko-Gauffin, S., Kielinen, M., et al. (2010). Comorbid psychiatric disorders associated with Asperger syndrome/high functioning autism: A community- and clinic-based study. Journal of Autism and Developmental Disorders, 40, 1080–1093.

    PubMed  Article  Google Scholar 

  36. O’Leary, C., de Klerk, N., Keogh, J., Pennell, C., de Groot, J., York, L., et al. (2007). Trends in mode of delivery during 1984–2003: Can they be explained by pregnancy and delivery complications. BJOG: An international Journal of Obstetrics and Gynaecology, 114(7), 855–864.

    Article  Google Scholar 

  37. Ogbuanu, I. U., Karmaus, W. J., Zhang, H., Sabo-Attwood, T., Ewart, S., Roberts, G., Arshad, S. H. (2010). Birth order modifies the effect of IL13 gene polymorphisms on serum IgE at age 10 and skin prick test at ages 4, 10 and 18: A prospective birth cohort study. Allergy, Asthma & Clinical Immunology, 6(6). doi:10.1186/1710-1492-6-6.

  38. Piven, J., Simon, J., Chase, G. A., & Wzorek, M. (1993). The etiology of autism: Pre-, peri- and neonatal factors. Journal of the American Academy of Child and Adolescent Psychiatry, 32(6), 1256–1263.

    PubMed  Article  Google Scholar 

  39. Rehnström, K., Ylisaukko-oja, T., Nieminen-von Wendt, T., Sarenius, S., Källman, T., Kempas, E., Wendt, L. von, Peltonen, L., & Järvelä, I. (2006). Independent replication and initial fine mapping of 3p21–24 in Asperger syndrome. Journal of Medical Genetics, 43(2), pp. 6. doi:10.1136/jmg.2005.033621.

  40. Reichenberg, A., Smith, C., Schmeidler, J., & Silverman, J. M. (2007). Birth order effects on autism symptom domains. Psychiatry Research, 150, 199–204.

    PubMed  Article  Google Scholar 

  41. Rosenberg, R. E., Kaufmann, W. E., Law, J. K., & Law, P. A. (2011). Parent Report of Community Psychiatric Comorbid Diagnoses in Autism Spectrum Disorders. Autism Research and Treatment, 2011, pp. 10. doi:10.1155/2011/405849.

    Google Scholar 

  42. Salyakina, D., Ma, D. Q., Jaworski, J. M., Konidari, I., Whitehead, P. L., Henson, R., et al. (2010). Variants in several genomic regions associated with Asperger disorder. Autism Research, 3(6), 303–310.

    PubMed  Article  Google Scholar 

  43. Singer, H. S., Morris, C. M., Gause, C. D., Gillin, P. K., Crawford, S., & Zimmerman, A. W. (2008). Antibodies against fetal brain in sera of mothers with autistic children. Journal of Neuroimmunology, 194, 165–172.

    PubMed  Article  Google Scholar 

  44. Singer, H. S., Morris, C., Gause, C., Pollard, M., Zimmerman, A. W., & Pletnikov, M. (2009). Prenatal exposure to antibodies from mothers of children with autism produces neurobehavioral alterations: A pregnant dam mouse model. Journal of Neuroimmunology, 211, 39–48.

    PubMed  Article  Google Scholar 

  45. Slager, S. L., Foroud, T., Haghighi, F., Spence, M. A., & Hodge, S. E. (2001). Stoppage: An issue for segregation analysis. Genetic Epidemiology, 20, 328–339.

    PubMed  Article  Google Scholar 

  46. Spiker, D., Lotspeich, L. J., Dimiceli, S., Szatmari, P., Myers, R. M., & Risch, N. (2001). Birth order effects on nonverbal IQ scores in autism multiplex families. Journal of Autism and Developmental Disorders, 31(5), 449–460.

    PubMed  Article  Google Scholar 

  47. Stanton-Chapman, T. L., Chapman, D. A., Bainbridge, N. L., & Scott, K. G. (2002). Identification of early risk factors for language impairment. Research in Developmental Disabilities, 23(6), 390–405.

    PubMed  Article  Google Scholar 

  48. Sunyer, J., Anto, J. M., Harris, J., Torrent, M., Vall, O., Cullinan, P., et al. (2001). Maternal atopy and parity. Clinical and Experimental Allergy, 31, 1352–1355.

    PubMed  Article  Google Scholar 

  49. Sweeten, T. L., Bowyer, S. L., Posey, D. J., Halberstadt, G. M., & McDougal, C. J. (2003). Increased prevalence of familial autoimmunity in probands wit pervasive developmental disorders. Pediatrics, 112(5), e420–e424. doi:10.1542/peds.112.5.e420.

    PubMed  Article  Google Scholar 

  50. Tsai, L. Y., & Stewart, M. A. (1983). Etiological implications of maternal age and birth order in infantile autism. Journal of Autism and Developmental Disorders, 133(1), 57–65.

    Article  Google Scholar 

  51. Via, E., Radua, J., Cardoner, N., Happé, F., & Mataix-Cols, D. (2011). Meta-analysis of gray matter abnormalities in autism spectrum disorder: Should Asperger disorder be subsumed under a broader umbrella of autistic spectrum disorder. Archives of General Psychiatry, 68(4), 409–418.

    PubMed  Article  Google Scholar 

  52. Wills, S., Cabanlit, M., Bennett, J., Ashwood, P., Amaral, D. G., & Van de Water, J. (2009). Detection of autoantibodies to neural cells of the cerebellum in the plasma of subjects with autism spectrum disorders. Brain, Behavior, and Immunity, 23(1), 64–74.

    PubMed  Article  Google Scholar 

  53. Zimmerman, A. W., Connors, S. L., Matteson, K. J., Lee, L., Singer, H. S., Castaneda, J. A., et al. (2007). Maternal antibrain antibodies in autism. Brain, Behavior, and Immunity, 21(3), 351–357.

    PubMed  Article  Google Scholar 

  54. Zimmerman, A. W., Jyonouchi, H., Comi, A. M., Connors, S. L., Milstien, S., Varsou, A., et al. (2005). Cerebrospinal fluid and serum markers of inflammation in autism. Pediatric Neurology, 33(3), 195–201.

    PubMed  Article  Google Scholar 

  55. Zwaigenbaum, L., Szatmari, P., Jones, M. B., Bryson, S. E., Maclean, J. E., Mahoney, W. J., et al. (2002). Pregnancy and birth complications in autism and liability to the broader autism phenotype. Journal of the American Academy of Child and Adolescent Psychiatry, 41(5), 572–579.

    PubMed  Article  Google Scholar 

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Conflict of interest

This project was funded under partial support from the Casa Colina Foundation.

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Correspondence to Charles Henry.

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Schmidt, K., Zimmerman, A., Bauman, M. et al. Brief Report: Asperger’s Syndrome and Sibling Birth Order. J Autism Dev Disord 43, 973–977 (2013). https://doi.org/10.1007/s10803-012-1620-y

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Keywords

  • Asperger’s syndrome
  • Pervasive developmental disorders
  • Birth order
  • Epidemiology