autism and gi

8/13/2019 Autism and GI

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B R I E F R E P O R T

Brief Report: Association Between Behavioral Featuresand Gastrointestinal Problems Among Children with Autism

Spectrum Disorder

Matthew J. Maenner Carrie L. Arneson

Susan E. Levy Russell S. Kirby Joyce S. Nicholas

Maureen S. Durkin

Published online: 20 October 2011

Springer Science+Business Media, LLC 2011

Abstract Recent reports suggest certain behaviors among

children with autism spectrum disorders (ASD) may indi-cate underlying gastro-intestinal (GI) problems, and that the

presence of these behaviors may help alert primary care

providers to the need to evaluate a child with ASD for GI

problems. The purpose of this population-based study of 487

children with ASD, including 35 (7.2%) with a medically

documented history of GI problems, was to compare

behavioral features of children with and without a history of

GI problems. Unusual sleeping or eating habits and opposi-

tional behavior were significantly associated with GI prob-

lems. These behaviors, however, were frequent in both

children with and without GI problems, suggesting they may

have limited utility in a screening capacity for GI problems.

Keywords Autism spectrum disorder Gastrointestinal

Introduction

Autism spectrum disorder (ASD) encompasses a group of

developmental disorders with a range of behavioral presen-

tations and likely diverse etiologic factors (Newschaffer

et al. 2007). A number of clinical and epidemiological

studies have suggested that children with ASD are at

increased risk for gastro-intestinal (GI) problems (Ibrahim

et al. 2009), and some have suggested that certain behavioral

problems observed in children with ASD may be indicative

of a childs response to, or attempt to communicate the dis-

comfort of, an underlying GI problem (Horvath et al.1999;

Williams et al. 2010; Bauman 2010). Specific behavior

problems proposed as possible expressions of GI distress

include sleep disturbances, stereotypic or repetitive behav-

iors, self-injurious behaviors, aggression, oppositional

behavior, irritability or mood disturbances, and tantrums. A

recent pediatric consensus report called for additional

research on the association between problem behaviors

and GI problems, and for the development of a screen for GI

problems in children with ASD (Buie et al.2010).

The purpose of this brief report is to determine, in a

large, population-based sample of 8 year-old children with

ASD, whether the behavioral characteristics specified

above occur more frequently among those who have been

diagnosed with a GI problem than those without a medi-

cally documented history of GI problems. For comparison,

we also evaluate the frequency, in those with and without a

history of GI problems, of other behavioral characteristics

that are common in children with ASD but that have not

been hypothesized to be potential expressions of GI

problems.

M. J. Maenner (&)

Waisman Center and Department of Population Health Sciences,

University of Wisconsin-Madison, 1500 Highland Ave,

Madison, WI 53705, USA

e-mail: [email protected]

C. L. Arneson

Waisman Center, University of Wisconsin-Madison,

Madison, WI, USA

S. E. Levy

Childrens Hosptial of Philadelphia, Philadelphia, PA, USA

R. S. Kirby

Department of Community and Family Health, College of Public

Health, University of South Florida, Tampa, FL, USA

J. S. Nicholas

Medical University of South Carolina, Charleston, SC, USA

M. S. Durkin

Waisman Center and Departments of Pediatrics and Population

Health Sciences, University of Wisconsin-Madison, Madison,

WI, USA

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J Autism Dev Disord (2012) 42:15201525

DOI 10.1007/s10803-011-1379-6


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Methods

Study Population and Design

We implemented a cross-sectional study of children who

were 8 years of age in 2006 and met the case definition for

ASD through the Centers for Disease Control and Preven-

tions Autism and Developmental Disabilities Monitoring(ADDM) Network. The ADDM Network is a multi-site,

population-based, autism surveillance system wherein the

surveillance case definition for ASD is not entirely dependent

upon previousclinical diagnoses (Centers for Disease Control

Prevention (CDC)2009).

Although most sites participating in the ADDM Net-

work incorporate information from both medical and edu-

cational records in determining ASD case status, some

sites data collection was limited to information from

medical or clinical records. To ensure that assessment for

GI problems was possible, the study sample was restricted

to children whose records contained an evaluation from amedical doctor. The frequency of reported GI problems

varied across sites, and sites that relied heavily on educa-

tional records tended to report few to no instances of GI

problems. To minimize potential confounding by ADDM

Network site, the present analysis includes data collected

from three sites where at least 5% of eligible children were

diagnosed with a GI problem. In total, 487 out of 619

children with ASD from three sites (Alabama, Pennsylva-

nia, and Wisconsin) had been evaluated by a medical

doctor and were included in the analysis. While the ADDM

Network utilizes both healthcare and educational sources

for surveillance, the three sites included in this analysis

relied exclusively on healthcare sources for records (Cen-

ters for Disease Control Prevention (CDC) 2009).

Surveillance Ascertainment of ASD

For surveillance purposes, children were classified as

having an ASD if they displayed behaviors documented in

evaluation records that were consistent with the Diagnostic

and Statistical Manual of Mental Disorders, 4th Edition,

Text Revision (DSM-IV-TR) criteria (American Psycho-

logical Association (APA) 2000) for autistic disorder,

PDD-NOS, or Asperger disorder at any time through age

8 years. Children suspected of having ASD were identified

by screening evaluations from qualified professionals (e.g.,

including pediatricians, psychiatrists, nurses, speech ther-

apists, psychologists, occupational therapists, and others).

Children whose medical records were associated with an

International Criteria for Diagnosis, 9th Revision (ICD-9)

code for child neurodevelopmental disorders (e.g., 299.0

for autistic disorder or 314.0 for attention deficit disor-

der) were reviewed. Demographic data, descriptions of

behaviors, diagnostic summaries, psychometric test results,

and information about co-occurring disorders or disabilities

were collected and entered into a centralized composite

record and reviewed by trained clinicians according to a

specified protocol to determine case status and document

non-ASD diagnoses and associated features (e.g., abnor-

malities in sleeping). The protocol was approved by the

institutional review board at each respective surveillancesite.

Co-Occurring Characteristics

For descriptive purposes, we calculated the distribution of

the sample by sex, race or ethnicity, and ADDM autism

classification (Autistic Disorder vs. PDD-NOS). Intellectual

disability (ID) was classified when information on ID was

available and the most recent IQ score was less than 70.

Descriptions of seizure-like activity were also collected.

Cerebral palsy was monitored in two sites (Wisconsin and

Alabama).

Behavioral Features

We identified eight behavioral features cited in a recent

pediatric consensus report that may be indicative of GI

problems among children with ASD (Buie et al. 2010)

which had analogous measures in the ADDM data set:

abnormalities in sleeping; stereotyped and repetitive motor

mannerisms; self-injurious behaviors; abnormal eating

habits, abnormalities in mood or affect; argumentative,

oppositional, defiant, or destructive behaviors; aggression;and temper tantrums. These behaviors were coded accord-

ing to ADDM Network methodology, using verbatim

descriptions of the behavior from the evaluations. To

determine whether children with ASD and GI problems

simply have more documented ASD-related behaviors of

any kind, we selected an additional six behaviors that would

not seem to be related to GI discomfort: oblivious to other

children; lack of imaginative play; lack of or excessive fear;

insistence on sameness; delayed motor milestones; and

abnormal cognitive development (e.g., documentation of

uneven, scattered, or savant skills; adaptive skills with at

least one standard deviation between subtests).

GI Problems

The ADDM data include verbatim descriptions of non-

ASD diagnoses or conclusion statements made by the

examiner conducting the evaluation. We defined GI prob-

lems using many of the terms mentioned by the consensus

report (Buie et al. 2010) (constipation, abdominal pain,

diarrhea, encopresis, gastroesophageal reflux disease

J Autism Dev Disord (2012) 42:15201525 1521

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(GERD), gastritis, abdominal bloating, disaccharidase

deficiencies, inflammation of GI tract, abnormalities of the

enteric nervous system, functional abdominal pain, irritable

bowel syndrome (IBS), flatulence, Celiac disease). Addi-

tional searches were performed to identify instances of

abbreviations or misspellings, and all matches were visu-

ally inspected. All evaluations and data were thoroughly

reviewed regardless of whether a previous evaluationindicated a particular behavior.

Analysis

We performed cross-tabulations and Chi-square tests of the

significance of differences in the frequency of descriptive

and behavioral characteristics by presence of GI problems,

among the 487 children with ASD. Before combining data

from the three ADDM sites, we examined the association

within each site and found no evidence of heterogeneity

across sites. We also computed prevalence ratios with 95%confidence intervals to describe the magnitude of associa-

tions between behavioral characteristics and history of GI

problems, and estimated the overall sensitivity and positive

predictive value of the selected behavioral characteristics

as indicators of or screening items for GI problems among

children with ASD.

Results

A total of 35 children or 7.2% of this sample of childrenwith ASD had a documented history of GI problems in

their medical records. Constipation and encopresis were the

most commonly documented GI problems, followed by

gastroesophageal reflux disease (GERD). Overall, children

with GI problems were significantly more likely than those

without GI problems to have co-occurring cerebral palsy

and seizure-like activity, but did not differ in terms of sex,

race and ethnicity, frequency of co-occurring intellectual

disability, or whether they were classified as having autistic

disorder or PDD-NOS (Table 1).

As hypothesized, children with sleep abnormalities were

more likely to have a medically documented history of GIproblems (11%) than those without sleep problems (3.6%,

p\ 0.01) (Table2). Similar associations, with prevalence

ratios above 2.0, were seen for argumentative, oppositional

or destructive behavior, abnormal eating habits, mood

disturbances and tantrums, though the associations for

mood disturbances and tantrums did not reach statistical

significance (Table2). In contrast, we found no associa-

tions between the presence of GI problems and two of the

hypothesized behaviors, stereotypic/repetitive behaviors

and self-injurious behaviors (Table2). In addition, among

the ASD behaviors or variables hypothesized not to be

potential indicators of GI distress, only delayed motormilestones were significantly associated with GI problems

(Table2).

Notably, nearly all of the children with ASD, including

all 35 with a documented history of GI problems and 446

(98.7%) of others, exhibited at least one of the behavior

problems hypothesized to be potential indicators of GI

distress. For this reason, these behaviors would not be

useful as a potential screen for GI problems; though with a

cut-off ofC one item the sensitivity would be 100%, the

positive predictive value would be only 7.2% and virtually

all children with ASD would potentially be referred for GI

evaluations. Increasing the number of behaviors needed to

screen positive for GI problems from one to five

increased the positive predictive value modestly, from 7.2

to 9.4%, but only at a cost to sensitivity, which concomi-

tantly declined from 100 to 80%.

Table 1 Descriptive

characteristics of the study

sample, stratified by presence or

absence of GI problems

a Overall Chi squareb Limited to AL and WI (PA

did not monitor CP)

% With GI problems

(N= 35)

%Without GI problems

(N= 452)

v2

p Value

Male 88.6 81.0 0.13

EthnicityNon-hispanic white 68.6 62.8 0.70a

Non-hispanic black 17.1 22.8

Hispanic 2.9 5.8

Other/unknown 11.4 8.6

ASD classification

Autistic disorder 80.0 81.4 0.42

Co-occurring intellectual disability 22.9 27.0 0.53

Co-occurring cerebral palsyb 11.4 1.8 \0.01

Co-occurring seizure-like activity 54.3 29.0 \0.01

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Table 2 Percent of children

with GI problems by presence

or absence of selected

behavioral characteristics

The % with GI problems within

each behavior category can be

interpreted as positive

predictive value. The v2

p value can also be interpreted

as a test of whether the

frequency of a behavior differs

between children with and

without a history GI problemsa Fisher exact p value

Number (%)

with behavior

(out of 487)

% With GI

problems

Prevalence

ratioa

(95% CI)

v2

p Value

Behavioral characteristics hypothesized to be potential expressions of GI problems among children

with ASD

Sleep disturbance 236 (48.5) 3.1 (1.5, 6.4) \0.01

Yes 11.0

No 3.6

Stereotypic/repetitive behavior 332 (68.2) 1.4 (0.7, 2.8) 0.42

Yes 7.8

No 5.8

Self injurious behavior 194 (39.8) 1.4 (0.8, 2.7) 0.27

Yes 8.8

No 6.1

Abnormal eating habits 312 (64.1) 2.7 (1.2, 6.4) 0.02

Yes 9.3

No 3.4

Aggression 323 (66.3) 1.7 (0.8, 3.7) 0.16

Yes 8.4No 4.9

Mood disturbance 355 (72.9) 2.2 (0.9, 5.6) 0.08

Yes 8.5

No 3.8

Oppositional behaviors 344 (70.6) 2.5 (1.0, 6.3) 0.04

Yes 8.7

No 3.5

Tantrums 316 (64.9) 2.2 (1.0, 4.9) 0.05

Yes 8.9

No 4.1

Has at least 1 of the above behaviors 481 (98.8) NA 0.99a

Yes 7.3

No 0.0

Other behavioral characteristics common in children with ASD

Oblivious to other children 7 (1.4) 0 0.46a

Yes 0.0

No 7.3

Lacking imaginative play 84 (17.2) 0.6 (0.2, 1.7) 0.35

Yes 4.8

No 7.7

Lack of or excessive fear 257 (52.8) 1.5 (0.8, 2.9) 0.22

Yes 8.6

No 5.7

Insistence on sameness 72 (14.8) 0.3 (0.1, 1.4) 0.12

Yes 2.8

No 8.0

Delayed motor milestones 372 (76.4) 5.1 (1.2, 20.1) \0.01

Yes 8.9

No 1.7

Abnormal or uneven cognitive development 136 (27.9) 0.6 (0.3, 1.4) 0.28

Yes 5.2

No 8.0


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Discussion

This study provides some support for the hypothesized

association between selected behavioral characteristics in

children with ASD and the occurrence of GI problems.

Even with the relatively small size of the population-based

sample available, the study found significant positive

associations for several behaviors hypothesized to beexpressions of GI problems in children with ASD. At the

same time, it did not find such associations for most of the

control behaviors examined, suggesting that children with

ASD and GI problems were not simply more likely to be

described as having more of any type of symptoms or

behaviors than children with ASD and no history of GI

problems.

The unexpected finding of a significant positive associ-

ation between GI problems and delayed motor milestones,

which we had not hypothesized to be associated with GI

problemsor a possible expression of GI discomfortis

interesting in light of two other incidental observations inthis study, which we had not hypothesized. These two

incidental findings included the associations between GI

problems and both CP and seizure disorders. Overall, the

observed associations between GI problems and delayed

milestones, CP and seizure disorders lend support to the

idea that a sub-set of children with ASD might suffer from

underlying neurological and/or immunological dysfunction

that affects multiple organ systems and functions, including

those that are GI related. They are also consistent with

other studies showing associations between GI problems

and epilepsy (Gobbi et al. 1992) as well as the severity of

CP (Erkin et al.2010).

Perhaps the most important contribution of this study is

the finding that the behavioral characteristics hypothesized

to be expressions of GI problems are very common in

children with ASD, yet not specific to those with GI

problems. As a result, the presence of these behaviors

would not be useful on their own for screening or identi-

fying children requiring GI evaluation.

Although GI problems may contribute to selected

behaviors in some children with ASD (Ibrahim et al.2009),

most children with ASD who exhibit these behaviors did

not have a medically documented history of GI problems.

Limitations and Future Directions

The reliance of this study on information extracted from

medical records is both a strength and a limitation. It is

likely that this data source allowed accurate identification

of GI problems that were relatively persistent and severe

enough to require medical attention among children with

ASD in the populations under surveillance. At the same

time, medical records likely under-identify many of the

less severe and less persistent GI problems that are iden-

tified in studies based on parental report. In general, studies

relying on medical records to identify GI problems (Niehus

and Lord2006; Mouridsen et al. 2010; Taylor et al.2002)

report lower frequencies of GI problems than studies

relying on parental report or clinical examinations of

referred samples (Richler et al. 2006; Wang et al. 2011;

Valicenti-McDermott et al. 2008) Although studies basedon direct clinical examinations or parental report may have

better opportunities to ascertain GI problems than those

based on records, the results of such studies may be gen-

eralizable only to patients of specific academic medical

centers or to voluntary participants in an online autism

registry. In contrast, the results of the present records-based

study are generalizable to children in the population

meeting diagnostic criteria for ASD.

Although all three sites represented in this study fol-

lowed the same protocol for extracting information and

requesting records from medical sources, variability by

ADDM site is possible. The relatively small number ofchildren with GI problems limited our statistical power to

explore site differences. Without a comparison group of

children without an ASD, this study does not provide

information about whether GI problems are more frequent

in children with ASD than age-matched controls without

ASD.

The calls for population-based studies to better under-

stand the relationship between ASD and GI problems

present a methodological challenge. Population-based

studies such as ours provide greater generalizability and

representativeness of ASD in the population, yet the tasks

of measuring specific behaviors and systematically evalu-

ating GI problems are more easily accomplished in clinic-

based studies (which are likely to suffer from referral or

other biases). A strength of the ADDM Network method-

ology is that it utilizes multiple sources for ASD case

ascertainment; however, it is limited to information that

has been previously documented in records. Large, popu-

lation-based cohort studies that are both generalizable and

have strong ascertainment capabilities will provide the best

insight into the relationship between ASD and GI

problems.

Conclusion

Certain behaviors, including abnormalities in sleep pat-

terns, abnormalities in mood or affect, and argumentative,

oppositional, defiant or destructive behavior were descri-

bed significantly more often in children with ASD who also

had GI problems than in those with ASD and no history of

GI problems. These features (often described as charac-

teristics of autism) may be more common among children

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with autism who also have GI problems. However, because

these behaviors are also frequent in children with ASD and

no GI problems (nearly all children had 1 or more behav-

iors), they are unlikely to efficiently predict GI problems in

children with ASD. Consideration of medical, biological,

or physiological co-occurring conditions, genetic suscep-

tibility, diet and nutrition, and medication use are necessary

to determine whether in children with ASD both behavioralpresentation and GI problems might be associated with

other underlying factors.

Acknowledgments This work was supported by a grant from the

Autism Science Foundation and by the Centers for Disease Control

and Prevention through Cooperative Agreements UR3/CCU523235

and UR3/DD000078 as part of the Autism and Developmental Dis-

abilities Monitoring (ADDM) Network. We gratefully acknowledge

ADDM project coordinators, clinician reviewers, abstractors, ADDM

investigators who contributed to the surveillance project and data

collection. We also thank Dr. Lisa Miller for her helpful comments on

an earlier version of this manuscript.

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