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Molecular Autism
Published in: Molecular Autism 1/2017

Open Access 01-12-2017 | Research

No evidence of early head circumference enlargements in children later diagnosed with autism in Israel

Authors: Ilan Dinstein, Shlomi Haar, Shir Atsmon, Hen Schtaerman

Published in: Molecular Autism | Issue 1/2017

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Abstract

Background

Large controversy exists regarding the potential existence and clinical significance of larger brain volumes in toddlers who later develop autism. Assessing this relationship is important for determining the clinical utility of early head circumference (HC) measures and for assessing the validity of the early overgrowth hypothesis of autism, which suggests that early accelerated brain development may be a hallmark of the disorder.

Methods

We performed a retrospective comparison of HC, height, and weight measurements between 66 toddlers who were later diagnosed with autism and 66 matched controls. These toddlers represent an unbiased regional sample from a single health service provider in the southern district of Israel. On average, participating toddlers had >8 measurements between birth and the age of two, which enabled us to characterize individual HC, height, and weight development with high precision and fit a negative exponential growth model to the data of each toddler with exceptional accuracy.

Results

The analyses revealed that HC sizes and growth rates were not significantly larger in toddlers with autism even when stratifying the autism group based on verbal capabilities at the time of diagnosis. In addition, there were no significant correlations between ADOS scores at the time of diagnosis and HC at any time-point during the first 2 years of life.

Conclusions

These negative results add to accumulating evidence, which suggest that brain volume is not necessarily larger in toddlers who develop autism. We believe that conflicting results reported in other studies are due to small sample sizes, use of misleading population norms, changes in the clinical definition of autism over time, and/or inclusion of individuals with syndromic autism. While abnormally large brains may be evident in some individuals with autism and more clearly visible in MRI scans, converging evidence from this and other studies suggests that enlarged HC is not a common etiology of the entire autism population. Early HC measures, therefore, offer very limited clinical utility for assessment of autism risk in the general population.
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Literature
1.
Courchesne E, Redcay E, Kennedy DP. The autistic brain: birth through adulthood. Curr Opin Neurol. 2004;17:489–96.CrossRefPubMed
2.
Courchesne E, Pierce K, Schumann CM, Redcay E, Buckwalter JA, Kennedy DP, et al. Mapping early brain development in autism. Neuron. 2007;56:399–413.CrossRefPubMed
3.
Courchesne E, Karns CM, Davis HR, Ziccardi R, Carper RA, Tigue ZD, et al. Unusual brain growth patterns in early life in patients with autistic disorder An MRI study. Neurology. 2001;57:245–54.
4.
Haar S, Berman S, Behrmann M, Dinstein I. Anatomical abnormalities in autism? Cortex: Cereb; 2014.
5.
Bartholomeusz HH, Courchesne E, Karns CM. Relationship between head circumference and brain volume in healthy normal toddlers, children, and adults. Neuropediatrics. 2002;33:239–41.CrossRefPubMed
6.
Courchesne E, Carper R, Akshoomoff N. Evidence of brain overgrowth in the first year of life in autism. JAMA. 2003;290:337–44.CrossRefPubMed
7.
Dementieva YA, Vance DD, Donnelly SL, Elston LA, Wolpert CM, Ravan SA, et al. Accelerated head growth in early development of individuals with autism. Pediatr Neurol. 2005;32:102–8.CrossRefPubMed
8.
Dawson G, Munson J, Webb SJ, Nalty T, Abbott R, Toth K. Rate of head growth decelerates and symptoms worsen in the second year of life in autism. Biol Psychiatry. 2007;61:458–64.CrossRefPubMed
9.
Webb SJ, Nalty T, Munson J, Brock C, Abbott R, Dawson G. Rate of head circumference growth as a function of autism diagnosis and history of autistic regression. J Child Neurol. 2007;22:1182–90.CrossRefPubMedPubMedCentral
10.
Elder LM, Dawson G, Toth K, Fein D, Munson J. Head circumference as an early predictor of autism symptoms in younger siblings of children with autism spectrum disorder. J Autism Dev Disord. 2008;38:1104–11.CrossRefPubMed
11.
Courchesne E, Mouton PR, Calhoun ME, Semendeferi K, Ahrens-Barbeau C, Hallet MJ, et al. Neuron number and size in prefrontal cortex of children with autism. JAMA. 2011;306:2001–10.CrossRefPubMed
12.
Hazlett HC, Poe M, Gerig G, Smith RG, Provenzale J, Ross A, et al. Magnetic resonance imaging and head circumference study of brain size in autism: birth through age 2 years. Arch Gen Psychiatry. 2005;62:1366–76.CrossRefPubMed
13.
Schumann CM, Bloss CS, Barnes CC, Wideman GM, Carper RA, Akshoomoff N, et al. Longitudinal magnetic resonance imaging study of cortical development through early childhood in autism. J Neurosci. 2010;30:4419–27.CrossRefPubMedPubMedCentral
14.
Shen MD, Nordahl CW, Young GS, Wootton-Gorges SL, Lee A, Liston SE, et al. Early brain enlargement and elevated extra-axial fluid in infants who develop autism spectrum disorder. Brain. 2013;136:2825–35.CrossRefPubMedPubMedCentral
15.
Courchesne E, Campbell K, Solso S. Brain growth across the life span in autism: age-specific changes in anatomical pathology. Brain Res. 2011;1380:138–45. Elsevier B.V.CrossRefPubMed
16.
Hazlett HC, Gu H, Munsell BC, Kim SH, Styner M, Wolff JJ, et al. Early brain development in infants at high risk for autism spectrum disorder. Nature. 2017;542:348–51.CrossRefPubMed
17.
18.
Raznahan A, Wallace GL, Antezana L, Greenstein D, Lenroot R, Thurm A, et al. Compared to what? Early brain overgrowth in autism and the perils of population norms. Biol Psychiatry. 2013;74:563–75.CrossRefPubMedPubMedCentral
19.
Zwaigenbaum L, Young GS, Stone WL, Dobkins K, Ozonoff S, Brian J, et al. Early head growth in infants at risk of autism: a baby siblings research consortium study. J Am Acad Child Adolesc Psychiatry. 2014;53:1053–62.CrossRefPubMedPubMedCentral
20.
Constantino JN, Majmudar P, Bottini A, Arvin M, Virkud Y, Simons P, et al. Infant head growth in male siblings of children with and without autism spectrum disorders. J Neurodev Disord BioMed Central. 2010;2:39–46.CrossRef
21.
Barnard-Brak L, Sulak T, Hatz JKI. Macrocephaly in children with autism spectrum disorders. Pediatr Neurol. 2011;44:97–100.CrossRefPubMed
22.
Surén P, Stoltenberg C, Bresnahan M, Hirtz D, Lie KK, Lipkin WI, et al. Early growth patterns in children with autism. Epidemiology. 2013;24:660–70.CrossRefPubMedPubMedCentral
23.
Gray KM, Taffe J, Sweeney DJ, Forster S, Tonge BJ. Could head circumference be used to screen for autism in young males with developmental delay? J Paediatr Child Health. 2012;48:329–34.CrossRefPubMed
24.
Nordahl CW, Lange N, Li DD, Barnett LA, Lee A, Buonocore MH, et al. Brain enlargement is associated with regression in preschool-age boys with autism spectrum disorders. Proc Natl Acad Sci U S A. 2011;108:20195–200.CrossRefPubMedPubMedCentral
25.
Nordahl CW, Braunschweig D, Iosif A-M, Lee A, Rogers S, Ashwood P, et al. Maternal autoantibodies are associated with abnormal brain enlargement in a subgroup of children with autism spectrum disorder. Brain Behav Immun. 2013;30:61–5.CrossRefPubMedPubMedCentral
26.
27.
Chaste P, Klei L, Sanders SJ, Murtha MT, Hus V, Lowe JK, et al. Adjusting head circumference for covariates in autism: clinical correlates of a highly heritable continuous trait. Biol Psychiatry. 2013;74:576–84.CrossRefPubMedPubMedCentral
28.
Sacco R, Gabriele S, Persico AM. Head circumference and brain size in autism spectrum disorder: a systematic review and meta-analysis. Psychiatry Res. 2015;234:239–51.CrossRefPubMed
29.
Davidovitch M, Golan D, Vardi O, Lev D, Lerman-Sagie T. Israeli children with autism spectrum disorder are not macrocephalic. J Child Neurol. 2011;26:580–5.CrossRefPubMed
30.
Lord C, Risi S, Lambrecht L, Cook EH, Leventhal BL, DiLavore PC, et al. The autism diagnostic observation schedule-generic: a standard measure of social and communication deficits associated with the spectrum of autism. J Autism Dev Disord. 2000;30:205–23.CrossRefPubMed
31.
Lord C, Rutter M, Di Lavore P, Risi S, Gotham K, Bishop S. Autism and Diagnostic Observation Schedule, Second Edition (ADOS-2) Manual (Part I): Modules 1-4. Western Psychological Services: Torrance, CA; 2012.
32.
Gotham K, Pickles A, Lord C. Standardizing ADOS scores for a measure of severity in autism spectrum disorders. J Autism Dev Disord. 2009;39:693–705.CrossRefPubMed
33.
Fombonne E, Rogé B, Claverie J, Courty S, Frémolle J. Microcephaly and macrocephaly in autism. J Autism Dev Disord. 1999;29:113–9.CrossRefPubMed
34.
Lainhart JE, Piven J, Wzorek M, Landa R, Santangelo SL, Coon H, et al. Macrocephaly in children and adults with autism. J Am Acad Child Adolesc Psychiatry. 1997;36:282–90.CrossRefPubMed
35.
Davidovitch M, Patterson B, Gartside P. Head circumference measurements in children with autism. J Child Neurol. 1996;11:389–93.CrossRefPubMed
36.
37.
Fombonne E. Epidemiology of pervasive developmental disorders. Pediatr Res. 2009;65:591–8. Nature Publishing Group.CrossRefPubMed
38.
39.
Croen LA, Grether JK, Hoogstrate J, Selvin S. The changing prevalence of autism in California. J Autism Dev Disord. 2002;32:207–15.CrossRefPubMed
40.
Teller IC, Embleton ND, Griffin IJ, van Elburg RM. Post-discharge formula feeding in preterm infants: A systematic review mapping evidence about the role of macronutrient enrichment. Clin. Nutr. 2016;35:791–801.
41.
Morse NL. Benefits of docosahexaenoic acid, folic acid, vitamin D and iodine on foetal and infant brain development and function following maternal supplementation during pregnancy and lactation. Nutrients. 2012;4(7):799–840.
42.
Pedersen M, Von Stedingk H, Botsivali M, Agramunt S, Alexander J, Brunborg G, et al. Birth weight, head circumference, and prenatal exposure to acrylamide from maternal diet: the European prospective mother-child study (NewGeneris). Environ Health Perspect. 2012;120:1739–45.PubMedPubMedCentral
43.
Koubaa S, Hällström T, Brismar K, Hellström PM, Hirschberg AL. Biomarkers of nutrition and stress in pregnant women with a history of eating disorders in relation to head circumference and neurocognitive function of the offspring. BMC Pregnancy Childbirth. 2015;15:318.CrossRefPubMedPubMedCentral
44.
Roak BJO, Vives L, Fu W, Egertson JD, Stanaway IB, Phelps IG, et al. Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders. Science (80-). 2012;338:1619–22.CrossRef
45.
Gu H, Ph D, Gerig G, Elison JT, Styner M, Botteron KN, et al. Differences in white matter fiber tract development present from 6 to 24 months in infants with autism. Am J Psychiatry. 2012;169:589–600.CrossRefPubMedPubMedCentral
46.
Fingher N, Dinstein I, Ben-Shachar M, Haar S, Dale AM, Eyler L, et al. Toddlers later diagnosed with autism exhibit multiple structural abnormalities in temporal corpus callosum fibers. Cortex. 2017. (in press)
47.
Stoner R, Chow ML, Boyle MP, Sunkin SM, Mouton PR, Roy S, et al. Patches of disorganization in the neocortex of children with autism. N Engl J Med. 2014;370:1209–19.CrossRefPubMedPubMedCentral
48.
Jeste SS, Geschwind DH. Disentangling the heterogeneity of autism spectrum disorder through genetic findings. Nat Rev Neurol. 2014;10:74–81. Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.CrossRefPubMedPubMedCentral
49.
Happé F, Ronald A, Plomin R. Time to give up on a single explanation for autism. Nat Neurosci. 2006;9:1218–20.CrossRefPubMed
Metadata
Title
No evidence of early head circumference enlargements in children later diagnosed with autism in Israel
Authors
Ilan Dinstein
Shlomi Haar
Shir Atsmon
Hen Schtaerman
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Molecular Autism / Issue 1/2017
Electronic ISSN: 2040-2392
DOI
https://doi.org/10.1186/s13229-017-0129-9

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