Perinatal and Neonatal Complications in Autism Etiology

  • Hannah GardenerEmail author
  • Kristen Lyall
Reference work entry


A vast and continually growing literature has examined peri- and neonatal factors in association with autism. Factors acting during this time period have particular relevance to autism due to potential influence on brain development. This chapter focuses on perinatal and neonatal complications, as well as maternal substance use, in association with autism. The perinatal complications with strongest evidence for an association with autism include general obstetric suboptimality, gestational diabetes, maternal medication use during pregnancy, bleeding during pregnancy, and multiple births. The neonatal complications with strongest evidence for an association with autism include, again, general occurrence of a range of complications, congenital malformations, low Apgar scores, and markers of hypoxia such as respiratory distress. The nature of associations with these complications has not been fully explained; while certain individual factors may increase risk of autism, associations may also be due to shared genetic risk or correlations between the factors. Future research studies are needed to clarify how these and other factors acting during the perinatal time period influence the development of autism.


Gestational Diabetes Cesarean Delivery Congenital Malformation Birth Order Broad Autism Phenotype 
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  1. Amaral DG, Schumann CM, Nordahl CW. Neuroanatomy of autism. Trends Neurosci. 2008;31(3):137–45.PubMedCrossRefGoogle Scholar
  2. Bilder D, Pinborough-Zimmerman J, Miller J, et al. Prenatal, perinatal, and neonatal factors associated with autism spectrum disorders. Pediatrics. 2009;123(5):1293–300.PubMedCrossRefGoogle Scholar
  3. Bolton PF, Murphy M, MacDonald H, Whitlock B, Pickles A, Rutter M. Obstetric complications in autism: consequences or causes of the condition? J Am Acad Child Adolesc Psychiatry. 1997;36(2):272–81.PubMedCrossRefGoogle Scholar
  4. Brimacombe M, Ming X, Lamendola M. Prenatal and birth complications in autism. Matern Child Health. 2007;J11(1):73–9.CrossRefGoogle Scholar
  5. Buchmayer S, Johansson S, Johansson A, et al. Can association between preterm birth and autism be explained by maternal or neonatal morbidity? Pediatrics. 2009;124(5):817–25.CrossRefGoogle Scholar
  6. Chess S. Autism in children with congenital rubella. J Autism Child Schizophr. 1971;1(1):33–47.PubMedCrossRefGoogle Scholar
  7. Chess S, Fernandez P, Korn S. Behavioral consequences of congenital rubella. J Pediatr. 1978;93(4):699–703.PubMedCrossRefGoogle Scholar
  8. Croen LA, Grether JK, Selvin S. Descriptive epidemiology of autism in a California population: who is at risk? J Autism Dev Disord. 2002;32(3):217–24.PubMedCrossRefGoogle Scholar
  9. Croen LA, Yoshida CK, Odouli R, et al. Neonatal hyperbilirubinemia and risk of autism spectrum disorders. Pediatrics. 2005;115(2):e135–8.PubMedCrossRefGoogle Scholar
  10. Croen LA, Grether JK, Yoshida CK, et al. Antidepressant use during pregnancy and childhood autism spectrum disorders. Arch Gen Psychiatry. 2011;68(11):1104–12.PubMedCrossRefGoogle Scholar
  11. Daniels JL, Forssen U, Hultman CM, et al. Parental psychiatric disorders associated with autism spectrum disorders in the offspring. Pediatrics. 2008;121(5):1357–62.CrossRefGoogle Scholar
  12. Dawson S, Glasson EJ, Dixon G, et al. Birth defects in children with autism spectrum disorders: a population-based, nested case–control study. Am J Epidemiol. 2009;169(11):1296–303.PubMedCrossRefGoogle Scholar
  13. Dodds L, Fell DB, Shea S, et al. The role of prenatal, obstetric and neonatal factors in the development of autism. J Autism Dev Disord. 2011;41(7):891–902.PubMedCrossRefGoogle Scholar
  14. Eidelman AI, Samueloff A. The pathophysiology of the fetus of the diabetic mother. Semin Perinatol. 2002;26(3):232–6.PubMedCrossRefGoogle Scholar
  15. Eliasen M, Tolstrup JS, Nybo Andersen AM, et al. Prenatal alcohol exposure and autistic spectrum disorders – a population-based prospective study of 80,552 children and their mothers. Int J Epidemiol. 2010;39(4):1074–81.PubMedCrossRefGoogle Scholar
  16. Finegan JA, Quarrington B. Pre-, peri-, and neonatal factors and infantile autism. J Child Psychol Psychiatry. 1979;20(2):119–28.PubMedCrossRefGoogle Scholar
  17. Fombonne E. Epidemiology of pervasive developmental disorders. Pediatr Res. 2009;65(6):591–8.PubMedCrossRefGoogle Scholar
  18. Gardener H, Spiegelman D, Buka SL. Prenatal risk factors for autism: comprehensive meta-analysis. Br J Psychiatry. 2009;195(1):7–14.PubMedCrossRefGoogle Scholar
  19. Gardener H, Spiegelman D, Buka SL. Perinatal and neonatal risk factors for autism: a comprehensive meta-analysis. Pediatrics. 2011;128(2):344–55.PubMedCrossRefGoogle Scholar
  20. Gillberg C, Gillberg IC. Infantile autism: a total population study of reduced optimality in the pre-, peri-, and neonatal period. J Autism Dev Disord. 1983;13(2):153–66.PubMedCrossRefGoogle Scholar
  21. Grether JK, Li SX, Yoshida CK, et al. Antenatal ultrasound and risk of autism spectrum disorders. J Autism Dev Disord. 2010;40(2):238–45.PubMedCrossRefGoogle Scholar
  22. Guinchat V, Thorsen P, Laurent C, et al. Pre-, peri- and neonatal risk factors for autism. Acta Obstet Gynecol Scand. 2012;91(3):287–300.PubMedCrossRefGoogle Scholar
  23. Harris SR, MacKay LL, Osborn JA. Autistic behaviors in offspring of mothers abusing alcohol and other drugs: a series of case reports. Alcohol Clin Exp Res. 1995;19(3):660–5.PubMedCrossRefGoogle Scholar
  24. Hultman CM, Sparen P, Cnattingius S. Perinatal risk factors for infantile autism. Epidemiology. 2002;13(4):417–23.PubMedCrossRefGoogle Scholar
  25. Jacobson JL, Jacobson SW. Effects of prenatal alcohol exposure on child development. Alcohol Res Health. 2002;26(4):282–6.PubMedGoogle Scholar
  26. Juul-Dam N, Townsend J, Courchesne E. Prenatal, perinatal, and neonatal factors in autism, pervasive developmental disorder-not otherwise specified, and the general population. Pediatrics. 2001;107(4):E63.PubMedCrossRefGoogle Scholar
  27. Kalkbrenner AE, Braun JM, Durkin MS, et al. Maternal smoking during pregnancy and the prevalence of autism spectrum disorders, using data from the autism and developmental disabilities monitoring network. Environ Health Perspect. 2012;120(7):1042–8.PubMedCrossRefGoogle Scholar
  28. Krakowiak P, Walker CK, Bremer AA, et al. Maternal metabolic conditions and risk for autism and other neurodevelopmental disorders. Pediatrics. 2012;129(5):1121–8.CrossRefGoogle Scholar
  29. Larsson HJ, Eaton WW, Madsen KM, Vestergaard M, Olesen AV, Agerbo E, et al. Risk factors for autism: perinatal factors, parental psychiatric history, and socioeconomic status. Am J Epidemiol. 2005;161(10):916–25; discussion 916–18.PubMedCrossRefGoogle Scholar
  30. Lee BK, Gardner RM, Dal H, et al. Brief report: maternal smoking during pregnancy and Autism Spectrum Disorders. J Autism Dev Disord. 2012;42(9):2000–5.PubMedCrossRefGoogle Scholar
  31. Lord C, Mulloy C, Wendelboe M, et al. Pre- and perinatal factors in high-functioning females and males with autism. J Autism Dev Disord. 1991;21(2):197–209.PubMedCrossRefGoogle Scholar
  32. Lotter V. Epidemiology of autistic conditions in young children: some characteristics of the parents and children. Soc Psychiatry. 1966;1:124–37.CrossRefGoogle Scholar
  33. Lyall K, Pauls DL, Santangelo SL, et al. Maternal early life factors associated with hormone levels and the risk of having a child with an autism spectrum disorder in the nurses’ health study II. J Autism Dev Disord. 2011;41(5):618–27.PubMedCrossRefGoogle Scholar
  34. Lyall K, Pauls DL, Spiegelman D, Ascherio A, Santangelo SL. Pregnancy complications and obstetric suboptimality in association with autism spectrum disorders in children of the Nurses’ Health Study II. Autism Res. 2012;5(1):21–30.PubMedCrossRefGoogle Scholar
  35. Maimburg RD, Vaeth M. Perinatal risk factors and infantile autism. Acta Psychiatr Scand. 2006;114(4):257–64.PubMedCrossRefGoogle Scholar
  36. Maimburg RD, Vaeth M, Schendel DE, et al. Neonatal jaundice: a risk factor for infantile autism? Paediatr Perinat Epidemiol. 2008;22(6):562–8.PubMedCrossRefGoogle Scholar
  37. Mann JR, McDermott S, Bao H, et al. Pre-eclampsia, birth weight, and autism spectrum disorders. J Autism Dev Disord. 2010;40(5):548–54.PubMedCrossRefGoogle Scholar
  38. Miles JH, Takahashi TN, Haber A, et al. Autism families with a high incidence of alcoholism. J Autism Dev Disord. 2003;33(4):403–15.PubMedCrossRefGoogle Scholar
  39. Moore SJ, Turnpenny P, Quinn A, et al. A clinical study of 57 children with fetal anticonvulsant syndromes. J Med Genet. 2000;37(7):489–97.PubMedCrossRefGoogle Scholar
  40. Piven J, Simon J, Chase GA, et al. The etiology of autism: pre-, peri- and neonatal factors. J Am Acad Child Adolesc Psychiatry. 1993;32(6):1256–63.PubMedCrossRefGoogle Scholar
  41. Previc FH. Prenatal influences on brain dopamine and their relevance to the rising incidence of autism. Med Hypotheses. 2007;68(1):46–60.PubMedCrossRefGoogle Scholar
  42. Qazi G. Obstetric and perinatal outcome of multiple pregnancy. J Coll Physicians Surg Pak. 2011;21(3):142–5.PubMedGoogle Scholar
  43. Rasalam AD, Hailey H, Williams JH, et al. Characteristics of fetal anticonvulsant syndrome associated autistic disorder. Dev Med Child Neurol. 2005;47(8):551–5.PubMedCrossRefGoogle Scholar
  44. Stromland K, Nordin V, Miller M, Akerstrom B, Gillberg C. Autism in thalidomide embryopathy: a population study. Dev Med Child Neurol. 1994;36:351–6.PubMedCrossRefGoogle Scholar
  45. Tsai LY, Stewart MA. Etiological implication of maternal age and birth order in infantile autism. J Autism Dev Disord. 1983;13(1):57–65.PubMedCrossRefGoogle Scholar
  46. Wallace A, Anderson G, Dubrow R. Obstetric and parental psychiatric variables as potential predictors of autism severity. J Autism Dev Disord. 2008;38(8):1542–54.PubMedCrossRefGoogle Scholar
  47. Wilkerson D, Volpe AG, Dean RS, Titus JB. Perinatal complications as predictors of infantile autism. Int J Neurosci. 2002;112(9):1085–98.PubMedCrossRefGoogle Scholar
  48. Williams GM, O’Callaghan M, Najman JM, et al. Maternal cigarette smoking and child psychiatric morbidity: a longitudinal study. Pediatr. 1998;102(1):e11.CrossRefGoogle Scholar
  49. Zhang X, Lv CC, Tian J, et al. Prenatal and perinatal risk factors for autism in China. J Autism Dev Disord. 2010;40(11):1311–21.PubMedCrossRefGoogle Scholar
  50. Zwaigenbaum L, Szatmari P, Jones MB, Bryson SE, MacLean JE, Mahoney WJ, et al. Pregnancy and birth complications in autism and liability to the broader autism phenotype. J Am Acad Child Adolesc Psychiatry. 2002;41(5):572–9.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Department of NeurologyUniversity of Miami Miller School of MedicineMiamiUSA
  2. 2.University of California DavisDavisUSA

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