Can Awareness of Medical Pathophysiology in Autism Lead to Primary Care Autism Prevention Strategies?

Authors

  • Elizabeth Mumper, MD, FAAP

Keywords:

primary care, autism, prevention strategies

Abstract

Emerging research suggests that the timing of environmental factors in the presence of genetic predispositions has influenced the increase in autism spectrum disorders over the past several decades. A review of the medical literature suggests that autism may be impacted by environmental toxicants, breastfeeding duration, gut flora composition, nutritional status, acetaminophen use, vaccine practices and use of antibiotics and/or frequency of infections.  The author reports her retrospective clinical research in a general pediatric practice (Advocates for Children), which shows a modest trend toward lower prevalence of autism than her previous pediatric practice or recent CDC data.  Out of 294 general pediatrics patients followed since 2005 there were zero new cases of autism (p value 0.014).  Given the prevalence of autism for that cohort of 1 in 50 children in the United States, it is important to consider implementing strategies in primary care practice that could potentially modify environmental factors or affect the timing of environmental triggers contributing to autism.  

[N A J Med Sci. 2013;6(3):134-144.   DOI:  10.7156/najms.2013.0603134]


References

Blumberg SJ, Bramlett MD, Kogan MD, Schieve LA, Jones JR, Lu MC. Changes in prevalence of parent-reported autism spectrum disorder in school-aged children: 2007 to 2011-12. In: reports Nhs, ed. Vol 65. Hyattsville, MD: National Center for Health Statistics; 2013.

Rice C. Prevalence of Autism Spectrum Disorders - Autism and Developmental Disabilities Monitoring Network, United States, 2006. In: Disabilities NCoBDaD, ed. Vol 58. Atlanta: Centers for Disease Control; 2009:1-20.

Blaxill MF. What's going on? The question of time trends in autism. Public Health Rep. 2004;119(6):536-551.

Blaxill MF, Baskin DS, Spitzer WO. Commentary: Blaxill, Baskin, and Spitzer on Croen et al. (2002), the changing prevalence of autism in California. J Autism Dev Disord. 2003;33(2):223-226. [discussion 227-229]

Hertz-Picciotto I, Delwiche L. The rise in autism and the role of age at diagnosis. Epidemiology. 2009;20(1):84-90.

Byrd RS, Sage AC, Keyzer J, MIND researchers. Report to the Legistlature on the Principal Findings from the Epidemiology of Autism in California: A Comprehensive Pilot Study. In: Institute M, ed. Sacramento: Davis UC; 2002.

Windham GC, Zhang L, Gunier R, Croen LA, Grether JK. Autism spectrum disorders in relation to distribution of hazardous air pollutants in the san francisco bay area. Environ Health Perspect. 2006;114(9):1438-1444.

Becerra TA, Wilhelm M, Olsen J, Cockburn M, Ritz B. Ambient air pollution and autism in Los Angeles county, California. Environ Health Perspect. 2013;121(3):380-386.

Volk HE, Hertz-Picciotto I, Delwiche L, Lurmann F, McConnell R. Residential proximity to freeways and autism in the CHARGE study. Environ Health Perspect. 2011;119(6):873-877.

Palmer RF, Blanchard S, Stein Z, Mandell D, Miller C. Environmental mercury release, special education rates, and autism disorder: an ecological study of Texas. Health Place. 2006;12(2):203-209.

Volk HE, Lurmann F, Penfold B, Hertz-Picciotto I, McConnell R. Traffic-related air pollution, particulate matter, and autism. JAMA Psychiatry. 2013;70(1):71-77.

Shelton JF, Hertz-Picciotto I, Pessah IN. Tipping the balance of autism risk: potential mechanisms linking pesticides and autism. Environ Health Perspect. 2012;120(7):944-951.

Davis MK. Breastfeeding and chronic disease in childhood and adolescence. Pediatr Clin North Am. 2001;48(1):125-141.

Henriksson C, Bostrom AM, Wiklund IE. What effect does breastfeeding have on coeliac disease? A systematic review update. Evid Based Med. 2013;18(3):98-103.

Ivarsson A, Hernell O, Stenlund H, Persson LA. Breast-feeding protects against celiac disease. Am J Clin Nutr. 2002;75(5):914-921.

Chen A, Rogan WJ. Breastfeeding and the risk of postneonatal death in the United States. Pediatrics. 2004;113(5):e435-439.

Newburg DS, Walker WA. Protection of the neonate by the innate immune system of developing gut and of human milk. Pediatr Res. 2007;61(1):2-8.

Grummer-Strawn LM, Mei Z. Does breastfeeding protect against pediatric overweight? Analysis of longitudinal data from the Centers for Disease Control and Prevention Pediatric Nutrition Surveillance System. Pediatrics. 2004;113(2):e81-e86.

Bachrach VR, Schwarz E, Bachrach LR. Breastfeeding and the risk of hospitalization for respiratory disease in infancy: a meta-analysis. Arch Pediatr Adolesc Med. 2003;157(3):237-243.

Schultz ST, Klonoff-Cohen HS, Wingard DL, et al. Breastfeeding, infant formula supplementation, and Autistic Disorder: the results of a parent survey. Int Breastfeed J. 2006;1:16.

Al-Farsi YM, Al-Sharbati MM, Waly MI, et al. Effect of suboptimal breast-feeding on occurrence of autism: a case-control study. Nutrition. 2012;28(7-8):e27-e32.

Dee DL, Li R, Lee LC, Grummer-Strawn LM. Associations between breastfeeding practices and young children's language and motor skill development. Pediatrics. 2007;119(Suppl 1):S92-S98.

Walker SJ, Fortunato J, Gonzalez LG, Krigsman A. Identification of unique gene expression profile in children with regressive autism spectrum disorder (ASD) and ileocolitis. PLoS One. 2013;8(3):e58058.

Round JL, Mazmanian SK. The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol. 2009;9(5):313-323.

Saavedra JM. Use of probiotics in pediatrics: rationale, mechanisms of action, and practical aspects. Nutr Clin Pract. 2007;22(3):351-365.

Turnbaugh PJ, Ridaura VK, Faith JJ, Rey FE, Knight R, Gordon JI. The effect of diet on the human gut microbiome: a metagenomic analysis in humanized gnotobiotic mice. Sci Transl Med. 2009;1(6):6ra14.

Wu F, Dassopoulos T, Cope L, et al. Genome-wide gene expression differences in Crohn's disease and ulcerative colitis from endoscopic pinch biopsies: insights into distinctive pathogenesis. Inflamm Bowel Dis. 2007;13(7):807-821.

Finegold SM, Molitoris D, Song Y, et al. Gastrointestinal microflora studies in late-onset autism. Clin Infect Dis. 2002;35(Suppl 1):S6-S16.

Molloy CA, Morrow AL, Meinzen-Derr J, et al. Elevated cytokine levels in children with autism spectrum disorder. J Neuroimmunol. 2006;172(1-2):198-205.

Vojdani A, Mumper E, Granpeesheh D, et al. Low natural killer cell cytotoxic activity in autism: the role of glutathione, IL-2 and IL-15. J Neuroimmunol. 2008;205(1-2):148-154.

Balfour Sartor R. Bacteria in Crohn's disease: mechanisms of inflammation and therapeutic implications. J Clin Gastroenterol. 2007;41(Suppl 1):S37-S43.

Kalliomaki M, Salminen S, Arvilommi H, Kero P, Koskinen P, Isolauri E. Probiotics in primary prevention of atopic disease: a randomised placebo-controlled trial. Lancet. 2001;357(9262):1076-1079.

Brandtzaeg PE. Current understanding of gastrointestinal immunoregulation and its relation to food allergy. Ann N Y Acad Sci. 2002;964:13-45.

Moayyedi P, Ford AC, Talley NJ, et al. The efficacy of probiotics in the treatment of irritable bowel syndrome: a systematic review. Gut. 2010;59(3):325-332.

Borody TJ, Khoruts A. Fecal microbiota transplantation and emerging applications. Nat Rev Gastroenterol Hepatol. 2012;9(2):88-96.

Duplessis CA, You D, Johnson M, Speziale A. Efficacious outcome employing fecal bacteriotherapy in severe Crohn's colitis complicated by refractory Clostridium difficile infection. Infection. 2012;40(4):469-472.

Grehan MJ, Borody TJ, Leis SM, Campbell J, Mitchell H, Wettstein A. Durable alteration of the colonic microbiota by the administration of donor fecal flora. J Clin Gastroenterol. 2010;44(8):551-561.

Schmidt RJ, Tancredi DJ, Ozonoff S, et al. Maternal periconceptional folic acid intake and risk of autism spectrum disorders and developmental delay in the CHARGE (CHildhood Autism Risks from Genetics and Environment) case-control study. Am J Clin Nutr. 96(1):80-89.

Schmidt RJ, Hansen RL, Hartiala J, et al. Prenatal vitamins, one-carbon metabolism gene variants, and risk for autism. Epidemiology. 2011;22(4):476-485.

Krakowiak P, Walker CK, Bremer AA, et al. Maternal metabolic conditions and risk for autism and other neurodevelopmental disorders. Pediatrics. 2012;129(5):e1121-1128.

Nyquist AC, Gonzales R, Steiner JF, Sande MA. Antibiotic prescribing for children with colds, upper respiratory tract infections, and bronchitis. JAMA. 1998;279(11):875-877.

Watson RL, Dowell SF, Jayaraman M, Keyserling H, Kolczak M, Schwartz B. Antimicrobial use for pediatric upper respiratory infections: reported practice, actual practice, and parent beliefs. Pediatrics. 1999;104(6):1251-1257.

NIEHUS R, LORD C. Early Medical History of Children with Autism Spectrum Disorders. J Dev Behav Pediatr. 2006;27(2):S120-S127.

Damoiseaux RA, van Balen FA, Hoes AW, Verheij TJ, de Melker RA. Primary care based randomised, double blind trial of amoxicillin versus placebo for acute otitis media in children aged under 2 years. BMJ. 5 2000;320(7231):350-354.

Herbert MR. Contributions of the environment and environmentally vulnerable physiology to autism spectrum disorders. Curr Opin Neurol. 2010;23(2):103-110.

Waring RH. Sulphation and Autism: What are the links? Autism File; 2012.

Alberti A, Pirrone P, Elia M, Waring RH, Romano C. Sulphation deficit in "low-functioning" autistic children: a pilot study. Biol Psychiatry. 1999;46(3):420-424.

Horvath K, Waring RH, Rabsztyn A, Blagg S, CampbeIl Z, Klovrza LV. P0788Abnormal sulfate metabolism in autism. J Pediatr Gastroenterol Nutr. 2004;39(Suppl 1):S356.

James SJ, Cutler P, Melnyk S, et al. Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. Am J Clin Nutr. 2004;80(6):1611-1617.

James SJ, Melnyk S, Jernigan S, et al. Metabolic endophenotype and related genotypes are associated with oxidative stress in children with autism. Am J Med Genet B Neuropsychiatr Genet. 2006;141B(8):947-956.

James SJ, Melnyk S, Fuchs G, et al. Efficacy of methylcobalamin and folinic acid treatment on glutathione redox status in children with autism. Am J Clin Nutr. 2009;89(1):425-430.

Townsend DM, Tew KD, Tapiero H. The importance of glutathione in human disease. Biomed Pharmacother. 2003;57(3-4):145-155.

Vojdani A, Mumper E, Granpeesheh D, et al. Low natural killer cell cytotoxic activity in autism: The role of glutathione, IL-2 and IL-15. J neuroimmunol. 2008;205(1):148-154.

Schultz ST, Klonoff-Cohen HS, Wingard DL, Akshoomoff NA, Macera CA, Ji M. Acetaminophen (paracetamol) use, measles-mumps-rubella vaccination, and autistic disorder: the results of a parent survey. Autism. 2008;12(3):293-307.

Cox AR, McDowell S. A response to the article on the association between paracetamol/acetaminophen: use and autism by Stephen T. Schultz. Autism. 2009;13(1):123-124. [author reply 124-125]

Schultz S, Desilva M, Gu TT, Qiang M, Whang K. Effects of the Analgesic Acetaminophen (Paracetamol) and its para-Aminophenol Metabolite on Viability of Mouse-Cultured Cortical Neurons. Basic Clin Pharmacol Toxicol. 2011. [Epub ahead of print]

Good P. Did acetaminophen provoke the autism epidemic? Altern Med Rev. 2009;14(4):364-372.

DeStefano F. Vaccines and autism: evidence does not support a causal association. Clin Pharmacol Ther. 2007;82(6):756-759.

Madsen KM, Hviid A, Vestergaard M, et al. A population-based study of measles, mumps, and rubella vaccination and autism. N Engl J Med. 2002;347(19):1477-1482.

Destefano F, Price CS, Weintraub ES. Increasing Exposure to Antibody-Stimulating Proteins and Polysaccharides in Vaccines Is Not Associated with Risk of Autism. J Pediatr. 2013;163(2):561-567.

Gust DA, Strine TW, Maurice E, et al. Underimmunization among children: effects of vaccine safety concerns on immunization status. Pediatrics. 2004;114(1):e16-e22.

Kimmel SR, Burns IT, Wolfe RM, Zimmerman RK. Addressing immunization barriers, benefits, and risks. J Fam Pract. 2007;56(2 Suppl Vaccines):S61-S69.

Summary of Recommendations for Child/Teen Immunization (Age birth through 18 years). http://www.immunize.org/catg.d/p2010.pdf. Accessed on 5/27/13, 2013.

Miller NZ, Goldman GS. Infant mortality rates regressed against number of vaccine doses routinely given: is there a biochemical or synergistic toxicity? Hum Exp Toxicol. 2011;30(9):1420-1428.

Anderson GF, Hussey PS, Frogner BK, Waters HR. Health spending in the United States and the rest of the industrialized world. Health Aff (Millwood). 2005;24(4):903-914.

Werner E, Dawson G. Validation of the phenomenon of autistic regression using home videotapes. Arch Gen Psychiatry. 2005;62(8):889-895.

Lu CY, Chiang BL, Chi WK, et al. Waning immunity to plasma-derived hepatitis B vaccine and the need for boosters 15 years after neonatal vaccination. Hepatology. 2004;40(6):1415-1420.

Peltola H, Patja A, Leinikki P, Valle M, Davidkin I, Paunio M. No evidence for measles, mumps, and rubella vaccine-associated inflammatory bowel disease or autism in a 14-year prospective study. Lancet. 1998;351(9112):1327-1328.

Kaye JA, del Mar Melero-Montes M, Jick H. Mumps, measles, and rubella vaccine and the incidence of autism recorded by general practitioners: a time trend analysis. BMJ. 2001;322(7284):460-463.

Imani F, Kehoe KE. Infection of human B lymphocytes with MMR vaccine induces IgE class switching. Clin Immunol. 2001;100(3):355-361.

Ozonoff S. Recurrence Risk for Autism Spectrum Disorders: A Baby Siblings Research Consortium Study. Pediatrics. 2011;128(3):e488-e495.

Siegel RM, Kiely M, Bien JP, et al. Treatment of otitis media with observation and a safety-net antibiotic prescription. Pediatrics. 2003;112(3 Pt 1):527-531.

Dowell SF, Marcy SM, Phillips WR, Gerber MA, Schwartz B. Otitis media-principles of judicious use of antimicrobial agents. Pediatrics. 1998;101(Suppl 1):165-171.

Finkelstein JA, Davis RL, Dowell SF, et al. Reducing antibiotic use in children: a randomized trial in 12 practices. Pediatrics. 2001;108(1):1-7.

del Campo R, Bravo D, Canton R, et al. Scarce evidence of yogurt lactic acid bacteria in human feces after daily yogurt consumption by healthy volunteers. Appl Environ Microbiol. 2005;71(1):547-549.

Fernandez-Checa JC, Garcia-Ruiz C, Colell A, et al. Oxidative stress: role of mitochondria and protection by glutathione. Biofactors. 1998;8(1-2):7-11.

Filipek PA, Juranek J, Nguyen MT, Cummings C, Gargus JJ. Relative carnitine deficiency in autism. J Autism Dev Disord. 2004;34(6):615-623.

Gargus JJ, Imtiaz F. Mitochondrial Energy-Deficient Endophenotype in Autism. Am J Biochem Biotechnol. 2008;4:198-207.

Holtzman D. Autistic spectrum disorders and mitochondrial encephalopathies. Acta Paediatr. 2008;97(7):859-860.

Oliveira G, Diogo L, Grazina M, et al. Mitochondrial dysfunction in autism spectrum disorders: a population-based study. Dev Med Child Neurol. 2005;47(3):185-189.

Rossignol DA, Frye RE. Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis. Mol Psychiatry. 2012;17(3):290-314.

Poling JS, Frye RE, Shoffner J, Zimmerman AW. Developmental regression and mitochondrial dysfunction in a child with autism. J Child Neurol. 2006;21(2):170-172.

Herbert MR, Buckley JA. Autism and Dietary Therapy: Case Report and Review of the Literature. J Child Neurol. 2013. 28(8):975-982.

Aguilar F. Combination Vaccines are Key to Achieving Complete On-Time Childhood Immunization Coverage. Curr Pediatr Rev. 2007;3(4):289-292.

Comi AM, Zimmerman AW, Frye VH, Law PA, Peeden JN. Familial clustering of autoimmune disorders and evaluation of medical risk factors in autism. J Child Neurol. 1999;14(6):388-394.

Molloy CA, Morrow AL, Meinzen-Derr J, et al. Familial autoimmune thyroid disease as a risk factor for regression in children with Autism Spectrum Disorder: a CPEA Study. J Autism Dev Disord. 2006;36(3):317-324.

Mouridsen SE, Rich B, Isager T, Nedergaard NJ. Autoimmune diseases in parents of children with infantile autism: a case-control study. Dev Med Child Neurol. 2007;49(6):429-432.

Silva SC, Correia C, Fesel C, et al. Autoantibody repertoires to brain tissue in autism nuclear families. J Neuroimmunol. 2004;152(1-2):176-182.

Singer HS, Morris CM, Williams PN, Yoon DY, Hong JJ, Zimmerman AW. Antibrain antibodies in children with autism and their unaffected siblings. J Neuroimmunol. 2006;178(1-2):149-155.

Singer HS, Morris CM, Gause CD, Gillin PK, Crawford S, Zimmerman AW. Antibodies against fetal brain in sera of mothers with autistic children. J Neuroimmunol. 2008;194(1-2):165-172.

Ashwood P, Van de Water J. Is autism an autoimmune disease? Autoimmun Rev. 2004;3(7-8):557-562.

Zimmerman AW, Connors SL, Matteson KJ, et al. Maternal antibrain antibodies in autism. Brain Behav Immun. 2007;21(3):351-357.

Pasca SP, Dronca E, Kaucsar T, et al. One carbon metabolism disturbances and the C677T MTHFR gene polymorphism in children with autism spectrum disorders. J Cell Mol Med. 2009;13(10):4229-4238.

Ueland PM, Hustad S, Schneede J, Refsum H, Vollset SE. Biological and clinical implications of the MTHFR C677T polymorphism. Trends Pharmacol Sci. 2001;22(4):195-201.

Persico AM, Militerni R, Bravaccio C, et al. Adenosine deaminase alleles and autistic disorder: case-control and family-based association studies. Am J Med Genet. 2000;96(6):784-790.

Williams TA, Mars AE, Buyske SG, et al. Risk of autistic disorder in affected offspring of mothers with a glutathione S-transferase P1 haplotype. Arch Pediatr Adolesc Med. 2007;161(4):356-361.

Brimacombe M, Xue M, Parikh A. Familial risk factors in autism. J Child Neurol. 2007;22(5):593-597.

Folstein SE, Rutter ML. Autism: familial aggregation and genetic implications. J Autism Dev Disord. 1988;18(1):3-30.

Gregg JP, Lit L, Baron CA, et al. Gene expression changes in children with autism. Genomics. 2008;91(1):22-29.

Herbert MR, Russo JP, Yang S, et al. Autism and environmental genomics. Neurotoxicology. 2006;27(5):671-684.

O'Hara NH, Szakacs GM. The recovery of a child with autism spectrum disorder through biomedical interventions. Altern Ther Health Med. 2008;14(6):42-44.

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Published

2013-07-31

How to Cite

Mumper, MD, FAAP, E. (2013). Can Awareness of Medical Pathophysiology in Autism Lead to Primary Care Autism Prevention Strategies?. North American Journal of Medicine and Science, 6(3). Retrieved from https://www.najms.com/index.php/najms/article/view/191

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Original Research