autism (autistic spectrum disorder, ASD)

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Introduction

Communication disorder of childhood, distinct from schizophrenia (DSM-IV) characterized by morbidly self-centered, wishful thinking.

Etiology

* children with autism their younger siblings are undervaccinated compared with unaffected children[78]

Epidemiology

  • prevalence of 0.05-1%[10]; 1.1% of children[20]
    • 2.1% in Utah (highest); 0.48% in Alabama (lowest)
    • prevalence higher in boys (1.85%) than in girls (0.4%)
    • variation might be attributable to diagnostic practices, underrecognition of ASD symptoms in some racial/ethnic groups, socioeconomic disparities in access to services, & regional differences in clinical or school-based reporting practices[41][47]
    • prevalence similar in white & black children[90]
    • 1 in 40-60 children with autism[84]; 1 in 54 by age 8[90]
  • associated with advanced paternal age[3]
  • 4 times as common in boys than girls
  • median age at diagnosis is 52 months[79]; 33 months[90]
  • mean annual precipitation positively correlates with autism prevalence[6] (California, Oregon, Washington)
  • 85% of children with autism have developmental concerns documented in the medical record by age 36 months, but only 42% receive a full evaluation[79]

Pathology

Genetics

Physical examination

  • because patients with autism have difficulty with physical contact, physical examination should be limited to essential maneuvers, performed slowly, & explained in detail before proceeding[11]

Clinical manifestations

  • onset prior to age 3
  • see diagnostic criteria
  • unaffected siblings may show some autistic features[13]
  • attention-deficit/hyperactivity disorder symptoms may mask underlying autism in young children[55]
  • manifestations somewhat at odds with diagnostic criteria[11]
    • persistent deficits in communication & social interaction associated with impaired function
      • inability to read body language
    • repetitive, inflexible non-functional behaviors

Diagnostic criteria

  • qualitative impairment in reciprocal social interaction:
    • marked lack of awareness of the existence of feelings of others
      • treats a person as if he or she was a piece of furniture
      • does not notice another person's distress
      • apparently has no concept of the need of others for privacy
    • failure or abnormality in seeking comfort at times of distress
      • does not come for comfort even when ill, hurt or tired
      • seeks comfort in stereotyped way (e.g. may repeat some irrelevant word when hurt)
    • failure of, impaired or otherwise abnormal imitation
      • does not wave goodbye
      • does not copy mother's domestic activities
      • mechanically imitates others' actions out of context
    • absence of or abnormal social play
      • does not actively participate in simple games
      • prefers solitary play activities
      • involves other children in play only as mechanical aids
    • gross impairment in ability to make peer friendships
      • no interest in making peer friendships
      • lack of understanding of essential principals of social interactions
  • qualitative impairment in verbal & non-verbal communication & in imaginative activity
    • no mode of communication
    • markedly abnormal nonverbal communication
    • absence of imaginative activity
      • no playacting
      • lack of interest in imaginary events
    • marked abnormalities in the form or content of speech - volume, pitch, stress, rate, rhythm, intonation
    • marked abnormalities in the form or content of speech -
    • marked impairment in the ability to initiate or sustain a conversation
  • restricted repertoire of activities & interests
    • stereotyped body movements
    • persistent preoccupation with parts of objects
    • marked distress over changes in trivial aspects of the environment
    • unreasonable insistence on following routine in precise detail
    • markedly restricted range of interests & a preoccupation with one narrow interest
  • onset during infancy or childhood

* At least 8 of 16 criteria, including:

  • 2 from qualitative impairment in reciprocal social interaction
  • 1 from impairment in communication
  • 1 from restricted repertoire of activities

Laboratory

* also see ARUP consult[89]

Radiology

Complications

Differential diagnosis

Management

Comparative biology

Notes

  • lifetime cost of supporting a child with autism is $1.4-$2.4 million[45]
    • most of the costs in childhood are related to special education
    • most of the costs in adulthood, they are due to residential accommodation, medical care, & loss of productivity[45]

More general terms

More specific terms

Additional terms

References

  1. ↑ DSM-IIIR
  2. ↑ Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision, DSM-IV-TR, American Psychiatric Association, Washington DC, 2000
  3. ↑ 3.0 3.1 Reichenberg A et al, Advancing paternal age and autism. Arch Gen Psychiatry 2006, 63:1026 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16953005
  4. ↑ 4.0 4.1 4.2 Prescriber's Letter 13(12): 2006 Drug treatment for behavioral symptoms associated with autism Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=221205&pb=PRL (subscription needed) http://www.prescribersletter.com
  5. ↑ 5.0 5.1 5.2 Marshall CR et alm Structural variation of chromosomes in autism spectrum disorder. Am J Hum Genet 2008, 82:477 PMID: https://www.ncbi.nlm.nih.gov/pubmed/18252227
    Weiss LA et al, Association between microdeletion and microduplication at chromosone 16p11.2 and autism. N Engl J Med 2008, 14:358 PMID: https://www.ncbi.nlm.nih.gov/pubmed/18184952
  6. ↑ 6.0 6.1 Waldman M et al. Autism prevalence and precipitation rates in California, Oregon, and Washington counties. Arch Pediatr Adolesc Med 2008 Nov; 162:1026. PMID: https://www.ncbi.nlm.nih.gov/pubmed/18981350
    Weiss NS. Precipitation and autism: Do these results warrant publication? Arch Pediatr Adolesc Med 2008 Nov; 162:1095. PMID: https://www.ncbi.nlm.nih.gov/pubmed/18981361
  7. ↑ Johnson CP et al. Identification and evaluation of children with autism spectrum disorders. Pediatrics 2007 Nov; 120:1183. PMID: https://www.ncbi.nlm.nih.gov/pubmed/17967920
  8. ↑ Myers SM et al. Management of children with autism spectrum disorders. Pediatrics 2007 Nov; 120:1162. PMID: https://www.ncbi.nlm.nih.gov/pubmed/17967921
  9. ↑ 9.0 9.1 King BH et al Lack of Efficacy of Citalopram in Children With Autism Spectrum Disorders and High Levels of Repetitive Behavior Arch Gen Psychiatry. 2009;66(6):583-590. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19487623
  10. ↑ 10.0 10.1 Rice C for the Centers for Disease Control (CDC) Prevalence of Autism Spectrum Disorders --- Autism and Developmental Disabilities Monitoring Network, United States, 2006 MMWR December 18, 2009 / 58(SS10);1-20 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/20023608 <Internet> http://www.cdc.gov/mmwr/preview/mmwrhtml/ss5810a1.htm
  11. ↑ 11.0 11.1 11.2 Medical Knowledge Self Assessment Program (MKSAP) 15, 16, 17 American College of Physicians, Philadelphia 2009, 2012, 2015
    Rao S, Salmon G. Autism spectrum disorders. Autism spectrum disorders. Br J Hosp Med (Lond). 2010 Dec;71(12):699-703. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21135768
  12. ↑ 12.0 12.1 Price CS et al. Prenatal and infant exposure to thimerosal from vaccines and immunoglobulins and risk of autism. Pediatrics 2010 Oct; 126:656. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20837594
  13. ↑ 13.0 13.1 Physician's First Watch, Nov 2, 2010 Massachessetts Medical Society http://www.jwatch.org Constantino JN et al Sibling recurrence and the genetic epidemiology of autism. Am J Psychiatry 2010 Oct 1 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/20889652 <Internet> http://dx.doi.org/10.1176/appi.ajp.2010.09101470
  14. ↑ 14.0 14.1 Miller JS et al. The Each Child Study: Systematic screening for autism spectrum disorders in a pediatric setting. Pediatrics 2011 May; 127:866 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21482605
  15. ↑ 15.0 15.1 Ozonoff s et al Recurrence Risk for Autism Spectrum Disorders: A Baby Siblings Research Consortium Study Pediatrics August 15, 2011 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/21844053 <Internet> http://pediatrics.aappublications.org/content/early/2011/08/11/peds.2010-2825.abstract
  16. ↑ Courchesne E et al. Neuron number and size in prefrontal cortex of children with autism. JAMA 2011 Nov 9; 306:2001. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22068992
    Lainhart JE and Lange N. Increased neuron number and head size in autism. JAMA 2011 Nov 9; 306:2031. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22068999
  17. ↑ 17.0 17.1 17.2 17.3 17.4 Geriatric Review Syllabus, 7th edition Parada JT et al (eds) American Geriatrics Society, 2010
    Geriatric Review Syllabus, 11th edition (GRS11) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2022
  18. ↑ 18.0 18.1 Wolff JJ et al. Differences in white matter fiber tract development present from 6 to 24 months in infants with autism. Am J Psychiatry 2012 Feb 17 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22362397 <Internet> http://psychiatryonline.org/article.aspx?articleid=668180&journalid=13
  19. ↑ 19.0 19.1 Krakowiak P et al Maternal Metabolic Conditions and Risk for Autism and Other Neurodevelopmental Disorders Pediatrics April 9, 2012 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22492772 <Internet> http://pediatrics.aappublications.org/content/early/2012/04/04/peds.2011-2583.abstract
  20. ↑ 20.0 20.1 Centers for Disease Control and Prevention Prevalence of Autism Spectrum Disorders - Autism and Developmental Disabilities Monitoring Network, 14 Sites, United States, 2008 MMWR March 30, 2012 / 61(SS03);1-19 http://www.cdc.gov/mmwr/preview/mmwrhtml/ss6103a1.htm
  21. ↑ Sanders SJ et al. De novo mutations revealed by whole-exome sequencing are strongly associated with autism. Nature 2012 Apr 4; <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22495306 <Internet> http://www.nature.com/nature/journal/vaop/ncurrent/full/nature10945.html
    O'Roak BJ et al. Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations. Nature 2012 Apr 4 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22495309 <Internet> http://www.nature.com/nature/journal/vaop/ncurrent/full/nature10989.html
    Neale BM et al. Patterns and rates of exonic de novo mutations in autism spectrum disorders. Nature 2012 Apr 4 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22495311 <Internet> http://www.nature.com/nature/journal/vaop/ncurrent/full/nature11011.html
  22. ↑ Prescriber's Letter 19(5): 2012 Management of Autism-Related Symptoms GUIDELINES: Therapies for Children With Autism Spectrum Disorders (2011) Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=280529&pb=PRL (subscription needed) http://www.prescribersletter.com
  23. ↑ Physician's First Watch, Aug 27 2012 Massachusetts Medical Society http://www.jwatch.org
    Kong A et al Rate of de novo mutations and the importance of father's age to disease risk Nature 488, 471-475 (23 August 2012) <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22914163 <Internet> http://www.nature.com/nature/journal/v488/n7412/full/nature11396.html
    Kondrashov A Genetics: The rate of human mutation Nature 488, 467-468 (23 August 2012) <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22914161 <Internet> http://www.nature.com/nature/journal/v488/n7412/full/488467a.html
  24. ↑ 24.0 24.1 Atladottir HO et al Autism After Infection, Febrile Episodes, and Antibiotic Use During Pregnancy: An Exploratory Study Pediatrics. Nov 12, 2012 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23147969 <Internet> http://pediatrics.aappublications.org/content/early/2012/11/06/peds.2012-1107.abstract
  25. ↑ 25.0 25.1 Fein D et al Optimal outcome in individuals with a history of autism. Journal of Child Psychology and Psychiatry. 54(2):195-205, 2013 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23320807 <Internet> http://onlinelibrary.wiley.com/doi/10.1111/jcpp.12037/full
  26. ↑ 26.0 26.1 Suren P et al Association Between Maternal Use of Folic Acid Supplements and Risk of Autism Spectrum Disorders in Children JAMA. 2013;309(6):570-577. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23403681 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=1570279
    Berry RJ et al Periconceptional Folic Acid and Risk of Autism Spectrum Disorders. JAMA. 2013;309(6):611-613 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23403688 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=1570262
  27. ↑ 27.0 27.1 Cross-Disorder Group of the Psychiatric Genomics Consortium Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet, Early Online Publication, 28 February 2013 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23453885 <Internet> http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)62129-1/abstract
  28. ↑ 28.0 28.1 28.2 Physician's First Watch for March 21, 2013 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org
    Blumberg SJ et al Changes in Prevalence of Parent-reported Autism Spectrum Disorder in School-aged U.S. children: 2007 to 20011-2012. National Health Statistics Reports. No 65, March 20, 2013 http://www.cdc.gov/nchs/data/nhsr/nhsr065.pdf
    Roberts AL et al Association of Maternal Exposure to Childhood Abuse With Elevated Risk for Autism in Offspring. JAMA Psychiatry. 2013;():1-8. March 20, 2013 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23553149 <Internet> http://archpsyc.jamanetwork.com/article.aspx?articleid=1666655
    Frans EM et al Autism Risk Across Generation. A Population-Based Study of Advancing Grandpaternal and Paternal Age. JAMA Psychiatry. 2013;():1-6. March 20, 2013 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23553111 <Internet> http://archpsyc.jamanetwork.com/article.aspx?articleid=1666654
  29. ↑ 29.0 29.1 Rai D et al Parental depression, maternal antidepressant use during pregnancy, and risk of autism spectrum disorders: population based case-control study BMJ 2013;346:f2059 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23604083 <Internet> http://www.bmj.com/content/346/bmj.f2059
  30. ↑ 30.0 30.1 Christensen J et al Prenatal Valproate Exposure and Risk of Autism Spectrum Disorders and Childhood Autism. JAMA. 2013;309(16):1696-1703 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23613074 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=1681408
    Meador KJ and Loring DW Risks of In Utero Exposure to Valproate. JAMA. 2013;309(16):1730-1731 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23613078 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=1681385
  31. ↑ 31.0 31.1 Roberts AL et al Perinatal Air Pollutant Exposures and Autism Spectrum Disorder in the Children of Nurses' Health Study II Participants. Environmental Health Perspectives. June 18, 2012 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23816781 <Internet> http://ehp.niehs.nih.gov/wp-content/uploads/121/6/ehp.1206187.pdf
  32. ↑ 32.0 32.1 Feinberg E et al. Improving maternal mental health after a child's diagnosis of autism spectrum disorder: Results from a randomized clinical trial. JAMA Pediatr 2013 Nov 11 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24217336 <Internet> http://archpedi.jamanetwork.com/article.aspx?articleid=1766504
  33. ↑ Brugha TS, McManus S, Bankart J et al Epidemiology of autism spectrum disorders in adults in the community in England. Arch Gen Psychiatry. 2011 May;68(5):459-65 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21536975
  34. ↑ 34.0 34.1 Hviid A et al. Use of selective serotonin reuptake inhibitors during pregnancy and risk of autism. N Engl J Med 2013 Dec 19; 369:2406 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24350950 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1301449
  35. ↑ Maenner MJ et al Potential Impact of DSM-5 Criteria on Autism Spectrum Disorder Prevalence Estimates. JAMA Psychiatry. Published online January 22, 2014 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24452504 <Internet> http://archpsyc.jamanetwork.com/article.aspx?articleid=1814891
  36. ↑ 36.0 36.1 36.2 Hsiao EY et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell 2013 Dec 19; 155:1451 PMID: https://www.ncbi.nlm.nih.gov/pubmed/24315484
  37. ↑ 37.0 37.1 37.2 Altieri L et al Urinary p-cresol is elevated in small children with severe autism spectrum disorder Biomarkers. May 2011, Vol. 16, No. 3 , Pages 252-260 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/21329489 <Internet> http://informahealthcare.com/doi/abs/10.3109/1354750X.2010.548010
  38. ↑ 38.0 38.1 Journal Watch Massachusetts Medical Society http://www.jwatch.org
    Tyzio R et al. Oxytocin-mediated GABA inhibition during delivery attenuates autism pathogenesis in rodent offspring. Science 2014 Feb 7; 343:675 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24503856 <Internet> http://www.sciencemag.org/content/343/6171/620
  39. ↑ 39.0 39.1 39.2 Geller B Journal Watch. March 26, 20144 Massachusetts Medical Society http://www.jwatch.org
    Stoner R et al. Patches of disorganization in the neocortex of children with autism. N Engl J Med 2014 Mar 27; 370:1209 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24670167 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1307491
  40. ↑ 40.0 40.1 Sparks BF et al. Brain structural abnormalities in young children with autism spectrum disorder. Neurology 2002 Jul 23; 59:184-92. PMID: https://www.ncbi.nlm.nih.gov/pubmed/12136055
    Aylward EH et al. Effects of age on brain volume and head circumference in autism. Neurology 2002 Jul 23; 59:175-83. PMID: https://www.ncbi.nlm.nih.gov/pubmed/12136053
    Mink JW and McKinstry RC. Volumetric MRI in autism: Can high-tech craniometry provide neurobiological insights? Neurology 2002 Jul 23; 59:158-9 PMID: https://www.ncbi.nlm.nih.gov/pubmed/12136049
  41. ↑ 41.0 41.1 Baio J for the Centers for Disease Control and Prevention Prevalence of Autism Spectrum Disorder Among Children Aged 8 Years - Developmental Disabilities Monitoring Network, 11 Sites, United States, 2010. MMWR March 28, 2014 / 63(SS02);1-21 http://www.cdc.gov/mmwr/preview/mmwrhtml/ss6302a1.htm
  42. ↑ 42.0 42.1 Suren P, Gunnes N, Roth C et al Parental Obesity and Risk of Autism Spectrum Disorder Pediatrics. April 7, 2014 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24709932 <Internet> http://pediatrics.aappublications.org/content/early/2014/04/02/peds.2013-3664.full.pdf+html
  43. ↑ 43.0 43.1 American College of Obsetricians and Gynecologists Labor Induction or Augmentation and Autism Committe Opinion. Number 597, May 2014 http://www.acog.org/Resources_And_Publications/Committee_Opinions/Committee_on_Obstetric_Practice/Labor_Induction_or_Augmentation_and_Autism
  44. ↑ 44.0 44.1 Sandin S et al The Familial Risk of Autism. JAMA. 2014;311(17):1770-1777 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24794370 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=1866100
    Schendel DE et al The Genetic and Environmental Contributions to Autism. Looking Beyond Twins. JAMA. 2014;311(17):1738-1739 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24794365 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=1866074
  45. ↑ 45.0 45.1 45.2 Buescher AV et al Costs of Autism Spectrum Disorders in the United Kingdom and the United States. JAMA Pediatr. June 09, 2014 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24911948 <Internet> http://archpedi.jamanetwork.com/article.aspx?articleid=1879723
    Shattuck PT and Roux AM Autism. Moving Toward an Innovation and Investment Mindset. JAMA Pediatr. June 09, 2014 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24911611 <Internet> http://archpedi.jamanetwork.com/article.aspx?articleid=1879720
  46. ↑ 46.0 46.1 Shelton JF et al Neurodevelopmental Disorders and Prenatal Residential Proximity to Agricultural Pesticides: The CHARGE Study. Environmental Health Perspectives. June 23, 2014 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24954055 <Internet> http://ehp.niehs.nih.gov/wp-content/uploads/advpub/2014/6/ehp.1307044.pdf
  47. ↑ 47.0 47.1 Hansen SN et al Explaining the Increase in the Prevalence of Autism Spectrum DisordersThe Proportion Attributable to Changes in Reporting Practices. JAMA Pediatr. Published online November 03, 2014 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25365033 <Internet> http://archpedi.jamanetwork.com/article.aspx?articleid=1919642
  48. ↑ 48.0 48.1 48.2 Geller H Can a Phytochemical Derived from Broccoli-Sprout Extract Alter Autistic Behavior? NEJM Journal Watch. Nov 4, 2014 Massachusetts Medical Society (subscription needed) http://www.jwatch.org
    Singh K et al. Sulforaphane treatment of autism spectrum disorder (ASD). Proc Natl Acad Sci U S A 2014 Oct 28; 111:15550 PMID: https://www.ncbi.nlm.nih.gov/pubmed/25313065
  49. ↑ 49.0 49.1 Young K. Sadough S, Sofair A Child with Autism Sees Improvement After Vitamin D Supplementation Physician's First Watch, Dec 15, 2014 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org
    Jia F, Wang B, Shan L et al Core Symptoms of Autism Improved After Vitamin D Supplementation. Pediatrics. Dec 15, 2014 PMID: https://www.ncbi.nlm.nih.gov/pubmed/25511123
  50. ↑ 50.0 50.1 Penagarikano O et al. Exogenous and evoked oxytocin restores social behavior in the Cntnap2 mouse model of autism. Sci Transl Med 2015 Jan 21; 7:271ra8. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25609168 <Internet> http://stm.sciencemag.org/content/7/271/271ra8
  51. ↑ 51.0 51.1 51.2 Xiang AH, Wang X, Martinez MP et al Association of Maternal Diabetes With Autism in Offspring. JAMA. 2015;313(14):1425-1434 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25871668 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=2247143
  52. ↑ 52.0 52.1 Jain A, MarshallJ, Buikema A et al Autism Occurrence by MMR Vaccine Status Among US Children With Older Siblings With and Without Autism. JAMA. 2015;313(15):1534-1540 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25898051 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=2275444
    King BH Promising Forecast for Autism Spectrum Disorders. JAMA. 2015;313(15):1518-1519 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25898047 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=2275426
  53. ↑ 53.0 53.1 Curran EA et al Association Between Obstetric Mode of Delivery and Autism Spectrum Disorder. A Population-Based Sibling Design Study. JAMA Psychiatry. Published online June 24, 2015 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26107922 <Internet> http://archpsyc.jamanetwork.com/article.aspx?articleid=2323630
  54. ↑ 54.0 54.1 USPSTF. Draft Recommendation Statement Autism Spectrum Disorder in Young Children: Screening http://www.uspreventiveservicestaskforce.org/Page/Document/draft-recommendation-statement15/autism-spectrum-disorder-in-young-children-screening
  55. ↑ 55.0 55.1 Miodovnik A et al Timing of the Diagnosis of Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder. Pediatrics peds.2015-1502; September 14, 2015 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26371198 <Internet> http://pediatrics.aappublications.org/content/early/2015/09/08/peds.2015-1502
  56. ↑ 56.0 56.1 Krol KM et al. Genetic variation in CD38 and breastfeeding experience interact to impact infants' attention to social eye cues. Proc Natl Acad Sci U S A 2015 Sep 29; 112:E5434 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26371313 <Internet> http://www.pnas.org/content/112/39/E5434?ijkey=d8ac2cb6121ef027533d2e4c602d00c60c994c34&keytype2=tf_ipsecsha
  57. ↑ 57.0 57.1 Yatawara CJ et al. The effect of oxytocin nasal spray on social interaction deficits observed in young children with autism: A randomized clinical crossover trial. Mol Psych 2015 Oct 27 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26503762 <Internet> http://www.nature.com/mp/journal/vaop/ncurrent/full/mp2015162a.html
  58. ↑ 58.0 58.1 Guastella AJ et al. The effects of a course of intranasal oxytocin on social behaviors in youth diagnosed with autism spectrum disorders: A randomized controlled trial. J Child Psychol Psychiatry 2015 Apr;56(4):444-52; ePub 2014 Aug 2 PMID: https://www.ncbi.nlm.nih.gov/pubmed/25087908
  59. ↑ 59.0 59.1 Boukhris T et al Antidepressant Use During Pregnancy and the Risk of Autism Spectrum Disorder in Children. JAMA Pediatr. Published online December 14, 2015 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26660917 <Internet> http://archpedi.jamanetwork.com/article.aspx?articleid=2476187
    King BH Assessing Risk of Autism Spectrum Disorder in Children After Antidepressant Use During Pregnancy. JAMA Pediatr. Published online December 14, 2015 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26660503 <Internet> http://archpedi.jamanetwork.com/article.aspx?articleid=2476185
  60. ↑ 60.0 60.1 Orciari Herman A, Fairchild DG, Di Francesco L Exposure to Certain Asthma Drugs in Utero Tied to Small Increase in Autism Risk. Physician's First Watch, Jan 6, 2016 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org Pediatrics article.
    Gidaya NB, Lee BK, Burstyn I et al In utero Exposure to beta-2-Adrenergic Receptor Agonist Drugs and Risk for Autism Spectrum Disorders. Pediatrics. February 2016, VOLUME 137 / ISSUE 2 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26738885 <Internet> http://pediatrics.aappublications.org/content/137/2/1.11
  61. ↑ 61.0 61.1 Siu AL, and the US Preventive Services Task Force (USPSTF) Screening for Autism Spectrum Disorder in Young Children. US Preventive Services Task Force Recommendation Statement. JAMA. 2016;315(7):691-696. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26881372 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=2491642
    Silverstein M, Radesky J Embrace the Complexity. The US Preventive Services Task Force Recommendation on Screening for Autism Spectrum Disorder. JAMA. 2016;315(7):661-662 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26881368 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=2491622
  62. ↑ 62.0 62.1 Carbone PS, Norlin C, Young PC et al. Improving early identification and ongoing care of children with autism spectrum disorder. Pediatrics 2016 Jun; 137:e20151850 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/2724484 <Internet> http://pediatrics.aappublications.org/content/early/2016/05/02/peds.2015-1850
  63. ↑ 63.0 63.1 63.2 63.3 Raghavan R, Fallin MD, Wang X Maternal plasma folate, vitamin B12 levels and multivitamin supplementation during pregnancy and risk of Autism Spectrum Disorder in the Boston Birth Cohort. FASEB Journal. April 2016, vol. 30 no. 1 Supplement 151.6 Not indexed in PubMed http://www.fasebj.org/content/30/1_Supplement/151.6.short?related-urls=yes&legid=fasebj;30/1_Supplement/151.6
  64. ↑ Lai MC, Lombardo MV, Baron-Cohen S. Autism. Lancet. 2014 Mar 8;383(9920):896-910. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/24074734
  65. ↑ 65.0 65.1 Wu YW, Kuzniewicz MW, Croen L et al. Risk of autism associated with hyperbilirubinemia and phototherapy. Pediatrics 2016 Sep 26; <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27669736 <Internet> http://pediatrics.aappublications.org/content/138/4/e20161813
  66. ↑ 66.0 66.1 Pickles A, Le Couteur A, Leadbitter K et al Parent-mediated social communication therapy for young children with autism (PACT): long-term follow-up of a randomised controlled trial. Lancet. Oct 26, 2016 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27793431 Free Article <Internet> http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)31229-6/fulltext
    Sigafoos J, Waddington H. 6 year follow-up supports early autism intervention. Lancet. Oct 26, 2016 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27793429 Free Article <Internet> http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)31656-7/abstract
  67. ↑ 67.0 67.1 Zerbo O, Qian Y, Yoshida C et al Association Between Influenza Infection and Vaccination During Pregnancy and Risk of Autism Spectrum Disorder. JAMA Pediatr. Published online November 28, 2016 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27893896 <Internet> http://jamanetwork.com/journals/jamapediatrics/fullarticle/2587559
  68. ↑ 68.0 68.1 Mahic M et al. Maternal immunoreactivity to herpes simplex virus 2 and risk of autism spectrum disorder in male offspring. MSphere 2017 Feb 22; 2:e00016. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28251181 Free PMC Article <Internet> http://msphere.asm.org/content/2/1/e00016-17
  69. ↑ 69.0 69.1 69.2 Mezzacappa A, Lasica PA, Gianfagna F et al Risk for Autism Spectrum Disorders According to Period of Prenatal Antidepressant ExposureA Systematic Review and Meta-analysis. JAMA Pediatr. Published online April 17, 2017. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28418571 <Internet> http://jamanetwork.com/journals/jamapediatrics/article-abstract/2616362
    Sujan AC, Rickert ME, Oberg AS et al Associations of Maternal Antidepressant Use During the First Trimester of Pregnancy With Preterm Birth, Small for Gestational Age, Autism Spectrum Disorder, and Attention-Deficit/Hyperactivity Disorder in Offspring. JAMA. 2017 Apr 18;317(15):1553-1562. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28418479 <Internet> http://jamanetwork.com/journals/jama/article-abstract/2618619
    Brown HK, Ray JG, Wilton AS, Lunsky Y, Gomes T, Vigod SN. Association Between Serotonergic Antidepressant Use During Pregnancy and Autism Spectrum Disorder in Children. JAMA. 2017 Apr 18;317(15):1544-1552. PMID: https://www.ncbi.nlm.nih.gov/pubmed/28418480
    Oberlander TF, Zwaigenbaum L. Disentangling Maternal Depression and Antidepressant Use During Pregnancy as Risks for Autism in Children. JAMA. 2017 Apr 18;317(15):1533-1534. No abstract available. PMID: https://www.ncbi.nlm.nih.gov/pubmed/28418464
  70. ↑ Agency for Healthcare Research and Quality (AHRQ) Medical Therapies for Children with Autism Spectrum Disorder --An Update. Research Review - Final - May 26, 2017 https://www.effectivehealthcare.ahrq.gov/index.cfm/search-for-guides-reviews-and-reports/
    Agency for Healthcare Research and Quality (AHRQ) Interventions Targeting Sensory Challenges in Children with Autism Spectrum Disorder - An Update. Research Review - Final - May 26, 2017 https://www.effectivehealthcare.ahrq.gov/index.cfm/search-for-guides-reviews-and-reports/
  71. ↑ 71.0 71.1 Hornig M, Bresnahan MA, Che X et al. Prenatal fever and autism risk. Mol Psychiatry 2017 Jun 13; PMID: https://www.ncbi.nlm.nih.gov/pubmed/28607458 https://www.nature.com/mp/journal/vaop/ncurrent/full/mp2017119a.html
  72. ↑ 72.0 72.1 Rai D, Lee BK, Dalman C, Newschaffer C, Lewis G, Magnusson C. Antidepressants during pregnancy and autism in offspring: population based cohort study BMJ 2017;358:j2811 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28724519 <Internet> http://www.bmj.com/content/358/bmj.j2811
  73. ↑ 73.0 73.1 73.2 Parker KJ, Oztan O, Libove RA et al. Intranasal oxytocin treatment for social deficits and biomarkers of response in children with autism. Proc Natl Acad Sci U S A 2017 Jul 25; 114:8119 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28696286 Free Article <Internet> http://www.pnas.org/content/114/30/8119
  74. ↑ 74.0 74.1 Bieleninik L, Geretsegger M, Mossler K et al Effects of Improvisational Music Therapy vs Enhanced Standard Care on Symptom Severity Among Children With Autism Spectrum Disorder: The TIME-A Randomized Clinical Trial. JAMA. 2017 Aug 8;318(6):525-535. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28787504 <Internet> http://jamanetwork.com/journals/jama/article-abstract/2647867
    Broder-Fingert S, Feinberg E, Silverstein M. Music Therapy for Children With Autism Spectrum Disorder. JAMA. 2017 Aug 8;318(6):523-524. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28787492 <Internet> http://jamanetwork.com/journals/jama/article-abstract/2647854
  75. ↑ 75.0 75.1 DeVilbiss EA, Magnusson C, Gardner RM et al Antenatal nutritional supplementation and autism spectrum disorders in the Stockholm youth cohort: population based cohort study. BMJ 2017;359:j4273 Free full text Free PMC Article http://www.bmj.com/content/359/bmj.j4273
  76. ↑ 76.0 76.1 Levine SZ, Kodesh A, Viktorin A et al Association of Maternal Use of Folic Acid and Multivitamin Supplements in the Periods Before and During Pregnancy With the Risk of Autism Spectrum Disorder in Offspring. JAMA Psychiatry. Published online January 3, 2018 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29299606 https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2667432
  77. ↑ 77.0 77.1 Rosman NP, Vassar R, Doros G et al Association of Prenatal Ultrasonography and Autism Spectrum Disorder. JAMA Pediatr. Published online Feb 12, 2018 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29435580 https://jamanetwork.com/journals/jamapediatrics/fullarticle/2672728
  78. ↑ 78.0 78.1 Zerbo O, Modaressi S, Goddard K et al. Vaccination patterns in children after autism spectrum disorder diagnosis and in their younger siblings. JAMA Pediatr 2018 Mar 26 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29582071 https://jamanetwork.com/journals/jamapediatrics/fullarticle/2676070
  79. ↑ 79.0 79.1 79.2 Baio J, Wiggins L, Christensen DL, et al. Prevalence of Autism Spectrum Disorder Among Children Aged 8 Years - Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2014. MMWR Surveillance Summaries. April 27, 2018;67(6):1-23. https://www.cdc.gov/mmwr/volumes/67/ss/ss6706a1.htm
  80. ↑ 80.0 80.1 Maher GM, O'Keeffe GW, Kearney PM et al Association of Hypertensive Disorders of Pregnancy With Risk of Neurodevelopmental Disorders in Offspring. A Systematic Review and Meta-analysis. JAMA Psychiatry. Published online June 6, 2018. PMID: https://www.ncbi.nlm.nih.gov/pubmed/29874359 https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2681643
  81. ↑ 81.0 81.1 81.2 Xu G, Snetselaar LG, Jing J et al Association of Food Allergy and Other Allergic Conditions With Autism Spectrum Disorder in Children. JAMA Network Open. 2018;1(2):e180279 Not indexed in PubMed https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2683952
    McDougle CJ Another Step Toward Defining an Immune-Mediated Subtype of Autism Spectrum Disorder. JAMA Network Open. 2018;1(2):e180280. Not indexed in PubMed https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2683949
  82. ↑ 82.0 82.1 82.2 82.3 82.4 Xiang AH, Wang X, Martinez MP et al Maternal Type 1 Diabetes and Risk of Autism in Offspring. JAMA. Published online June 23, 2018 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29936530 https://jamanetwork.com/journals/jama/fullarticle/2685775
  83. ↑ 83.0 83.1 Brooks M First Biomarker Evidence Autism Is Linked to DDT. Medscape - Aug 16, 2018. https://www.medscape.com/viewarticle/900776
    Brown AS, Cheslack-Postava K, Rantakokko P et al Association of Maternal Insecticide Levels With Autism in Offspring From a National Birth Cohort. Am J Psychiatry. Aug 16m 2018 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30111184 https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2018.17101129
    American Psychiatric Association. Aug 16, 2018 Study Links Mothers' Pesticide Levels with Autism in Children. https://www.psychiatry.org/newsroom/news-releases/study-links-mothers-pesticide-levels-with-autism-in-children
  84. ↑ 84.0 84.1 Kogan MD, Vladutiu CJ, Schieve LA et al. The prevalence of parent-reported autism spectrum disorder among US children. Pediatrics 2018 Dec; 142:e20174161. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/30478241 <Internet> http://pediatrics.aappublications.org/content/142/6/e20174161
  85. ↑ 85.0 85.1 Bai D, Yip BHK, Windham GC et al. Association of genetic and environmental factors with autism in a 5-country cohort. JAMA Psychiatry 2019 Jul 17; PMID: https://www.ncbi.nlm.nih.gov/pubmed/31314057 https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2737582
    Jutla A, Reed H, Veenstra-VanderWeele J. The architecture of autism spectrum disorder risk. What do we know and where do we go from here? JAMA Psychiatry 2019 Jul 17 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31314055 https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2737579
  86. ↑ 86.0 86.1 Sigmon ER, Kelleman M, Susi A et al Congenital Heart Disease and Autism: A Case-Control Study. Pediatrics. Oct. 2019 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31601611 https://pediatrics.aappublications.org/content/early/2019/10/08/peds.2018-4114
    Calderon J, Bellinger DC, Newburger JW. Autism and Congenital Heart Disease: Evidence and Unresolved Questions. Pediatrics. Oct. 2019 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31601612 https://pediatrics.aappublications.org/content/early/2019/10/08/peds.2019-2752
  87. ↑ 87.0 87.1 87.2 Hyman SL, Levy SE, Myers SM et al Executive Summary: Identification, Evaluation, and Management of Children With Autism Spectrum Disorder. Pediatrics. December 16, 2019, e20193448 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31843858 https://pediatrics.aappublications.org/content/early/2019/12/12/peds.2019-3448
    Hyman SL, Levy SE, Myers SM et al Identification, Evaluation, and Management of Children With Autism Spectrum Disorder. Pediatrics. 2019 Dec 16. pii: e20193447. PMID: https://www.ncbi.nlm.nih.gov/pubmed/31843864
  88. ↑ 88.0 88.1 88.2 Williams Buckley A, Hirtz D, Oskoui M, et al Practice guideline: Treatment for insomnia and disrupted sleep behavior in children and adolescents with autism spectrum disorder. Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. Feb. 12, 2012 PMID: https://www.ncbi.nlm.nih.gov/pubmed/32051244 https://n.neurology.org/content/early/2020/02/12/WNL.0000000000009033
  89. ↑ 89.0 89.1 ARUP Consult: Laboratory Testing for Developmental Delay, Intellectual Disability, and Autism Spectrum Disorder The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/developmental-delay-dd-or-intellectual-disability-id-testing
    ARUP Consult: Testing for Genetic Syndromes Related to Developmental Delay (DD), Intellectual Disability (ID), and Autism Spectrum Disorder (ASD). https://arupconsult.com/algorithm/developmental-delay-dd-testing-algorithm
    Autism and Intellectual Disability Comprehensive Panel https://arupconsult.com/ati/autism-and-intellectual-disability-comprehensive-panel
  90. ↑ 90.0 90.1 90.2 90.3 Shaw KA, Maenner MJ, Baio J, et al. Early Identification of Autism Spectrum Disorder Among Children Aged 4 Years - Early Autism and Developmental Disabilities Monitoring Network, Six Sites, United States, 2016. MMWR Surveill Summ 2020;69(No. SS-3):1-11 PMID: https://www.ncbi.nlm.nih.gov/pubmed/32214075 https://www.cdc.gov/mmwr/volumes/69/ss/ss6903a1.htm
    Maenner MJ, Shaw KA, Baio J, et al. Prevalence of Autism Spectrum Disorder Among Children Aged 8 Years - Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2016. MMWR Surveill Summ 2020;69(No. SS-4):1-12 PMID: https://www.ncbi.nlm.nih.gov/pubmed/32214087 https://www.cdc.gov/mmwr/volumes/69/ss/ss6904a1.htm
  91. ↑ 91.0 91.1 Qiu, C, MS1; Lin JC, Shi JM et al Association Between Epidural Analgesia During Labor and Risk of Autism Spectrum Disorders in Offspring. JAMA Pediatr. Published online October 12, 2020 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33044486 PMCID: PMC7551212 https://jamanetwork.com/journals/jamapediatrics/fullarticle/2771634
  92. ↑ 92.0 92.1 Gever J Preterm Birth, Autism Link Cemented. Big Swedish study documents "dose-response" relationship. MedPage Today August 11, 2021 https://www.medpagetoday.com/pediatrics/autism/93975
    Crump C, et al Preterm or early term birth and risk of autism. Pediatrics 2021 PMID: https://www.ncbi.nlm.nih.gov/pubmed/34380775
    McGowan EC, Sheinkopf SJ Autism and preterm birth: clarifying risk and exploring mechanisms. Pediatrics 2021 PMID: https://www.ncbi.nlm.nih.gov/pubmed/34380777
  93. ↑ 93.0 93.1 Whitehouse AJO, Varcin KJ, Pillar S et al Effect of Preemptive Intervention on Developmental Outcomes Among Infants Showing Early Signs of Autism. A Randomized Clinical Trial of Outcomes to Diagnosis. JAMA Pediatr. Published online September 20, 2021. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34542577 https://jamanetwork.com/journals/jamapediatrics/fullarticle/2784066
  94. ↑ Hirota T, King BH Autism Spectrum Disorder. A Review JAMA. 2023;329(2):157-168 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36625807 https://jamanetwork.com/journals/jama/fullarticle/2800182

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