Primary care physicians are often in the unique position of not only acting as the first point of contact for families with concerns about children’s development or behavior but also then being able to provide ongoing guidance, support, and care to youth with autism spectrum disorder (ASD) and their families over time.1,2  In this capacity, providers increasingly find themselves fielding questions related to the safety and efficacy of a wide variety of interventions.

A growing evidence base supports the benefits of specific behavioral, educational, and, to a limited extent, certain pharmacologic interventions for individuals with ASD.35  Unfortunately, because of the difficulty in obtaining effective treatments (because of factors such as limited availability, high cost, or extensive waiting lists), the modest benefit of available interventions, the lack of medications that address core symptoms, and the chronic, sometimes significant impairments associated with ASD itself, families often search for more widely available and more powerful ways of helping their children.6 

It should not be surprising that many, if not a substantial majority of families, not only have questions about but actually pursue and implement a wide variety of complementary and alternative interventions, including dietary and nutritional approaches.610  For some of these complementary and alternative interventions, there is clear and substantial evidence of no benefit (eg, secretin).11,12  For other interventions, there is clear evidence of potential harm in the absence of evidence of benefit (eg, chelation).13  However, for most purported interventions, there is little research into efficacy or outcomes, which leaves providers and families in the challenging position of struggling to understand the safety and potential benefits of such approaches.6 

In this issue of Pediatrics, Fraguas et al14  present results on their meta-analysis of nutritional and dietary interventions in an attempt to synthesize evidence of their potential effects. The authors extracted data from 27 studies that varied dramatically in terms of the interventions themselves, quality and risk of bias, the extreme number of clinical measures and outcomes evaluated, and characteristics of the populations studied. In an attempt to address this profound heterogeneity, the authors create categories of interventions as well as clinical domains and symptom categories. The authors suggest, via 37 separate meta-analyses of this aggregated outcome data, that dietary supplementation may play a role in the management of some symptoms, functions, and clinical domains for individuals with ASD. The authors themselves interpret this finding with caution, given the above noted methodologic limits and the fact that even via their categorization method interventions revealed small effect sizes relative to the placebo. Ultimately, they rightly conclude that their analysis of the data does not support nonspecific dietary interventions as current treatments for ASD.

However, even more caution may be needed when interpreting findings. Significant questions remain regarding the internal validity of the methods used to accomplish the meta-analyses themselves. The limits and quality of the existing studies included within the meta-analyses present a fundamental barrier that even complex, sophisticated data analyses may not overcome. In addition, the categorization performed by the authors ended up combining different types of nutritional and vitamin supplementation into single categories, raising questions regarding what, in fact, comprised the aggregated intervention under study. The authors combined 206 different outcome measures and their varied subscale domains, which were not clearly specified as primary or secondary outcomes in primary studies and were not designed to measure change during the time frame postulated (if at all). These measures and domains may in fact not create valid or understandable categories for the purpose of making clinical judgments or recommendations. Unfortunately, this suggests that there are fundamental questions regarding the defined interventions (which supplements, what dosages, what duration) and outcomes examined in the current work and that any interpretation of such findings as revealing evidence of benefit may not be well aligned with the data. Moreover, the populations studied are so varied and poorly described in primary studies that additional questions remain regarding who might benefit on the basis of factors such as age, level of functioning, or co-occurring medical and/or behavioral conditions.

It is clear that we need more high-quality data for parents and providers regarding a wide variety of interventions for children with ASD, including dietary interventions and nutritional supplementation. In a field in which children present with complex phenotypes and genotypes and yet service access and benefit can be limited, offering families a low-intensity, off-the-shelf treatment may hold tremendous appeal. Although high-quality trials of specific interventions are available, we should be cautious when interpreting preliminary results or risk continuing to support intervention choices, some of which hold potential for harm, on the basis of anecdotal evidence. Ultimately, Fraguas et al14  best support the assertion that there is little evidence to support the use of nutritional supplements or dietary therapies for children with ASD, which has been the conclusion of other reviews and analyses.6 

Opinions expressed in these commentaries are those of the authors and not necessarily those of the American Academy of Pediatrics or its Committees.

COMPANION PAPER: A companion to this article can be found online at www.pediatrics.org/cgi/doi/10.1542/peds.2018-3218.

FUNDING: No external funding.

     
  • ASD

    autism spectrum disorder

1
Committee on Children With Disabilities
.
American Academy of Pediatrics: the pediatrician’s role in the diagnosis and management of autistic spectrum disorder in children
.
Pediatrics
.
2001
;
107
(
5
):
1221
1226
2
Carbone
PS
,
Behl
DD
,
Azor
V
,
Murphy
NA
.
The medical home for children with autism spectrum disorders: parent and pediatrician perspectives
.
J Autism Dev Disord
.
2010
;
40
(
3
):
317
324
3
Williamson
E
,
Sathe
NA
,
Andrews
JC
, et al
.
Medical Therapies for Children With Autism Spectrum Disorder—An Update. Comparative Effectiveness Reviews, No. 189
.
Rockville, MD
:
Agency for Healthcare Research and Quality
:
2017
4
Weitlauf
AS
,
McPheeters
ML
,
Peters
B
, et al
.
Therapies for Children With Autism Spectrum Disorder: Behavioral Interventions Update. Comparative Effectiveness Reviews, No. 137
.
Rockville, MD
:
Agency for Healthcare Research and Quality
;
2014
5
Weitlauf
AS
,
Sathe
NA
,
McPheeters
ML
, et al
.
Interventions Targeting Sensory Challenges in Children With Autism Spectrum Disorders—An Update. Comparative Effectiveness Reviews, No. 186
:
Rockville, MD
:
Agency for Healthcare Research and Quality
;
2017
6
Sathe
N
,
Andrews
JC
,
McPheeters
ML
,
Warren
ZE
.
Nutritional and dietary interventions for autism spectrum disorder: a systematic review
.
Pediatrics
.
2017
;
139
(
6
):
e20170346
7
Perrin
JM
,
Coury
DL
,
Hyman
SL
, et al
.
Complementary and alternative medicine use in a large pediatric autism sample
.
Pediatrics
.
2012
;
130
(
2
suppl 2
):
S77
S82
8
Owen-Smith
AA
,
Bent
S
,
Lynch
FL
, et al
.
Prevalence and predictors of complementary and alternative medicine use in a large insured sample of children with autism spectrum disorders
.
Res Autism Spectr Disord
.
2015
;
17
:
40
51
9
Höfer
J
,
Hoffmann
F
,
Bachmann
C
.
Use of complementary and alternative medicine in children and adolescents with autism spectrum disorder: a systematic review
.
Autism
.
2017
;
21
(
4
):
387
402
10
Winburn
E
,
Charlton
J
,
McConachie
H
, et al
.
Parents’ and child health professionals’ attitudes towards dietary interventions for children with autism spectrum disorders
.
J Autism Dev Disord
.
2014
;
44
(
4
):
747
757
11
Williams
K
,
Wray
JA
,
Wheeler
DM
.
Intravenous secretin for autism spectrum disorders (ASD)
.
Cochrane Database Syst Rev
.
2012
;(
4
):
CD003495
12
Krishnaswami
S
,
McPheeters
ML
,
Veenstra-Vanderweele
J
.
A systematic review of secretin for children with autism spectrum disorders
.
Pediatrics
.
2011
;
127
(
5
). Available at: www.pediatrics.org/cgi/content/full/127/5/e1322
13
James
S
,
Stevenson
SW
,
Silove
N
,
Williams
K
.
Chelation for autism spectrum disorder (ASD) [published online ahead of print May 11, 2015]
.
Cochrane Database Syst Rev
.
2015
;(
5
):
CD010766
14
Fraguas
D
,
Diaz-Caneja
CM
,
Pina-Camacho
L
, et al
.
Dietary interventions for autism spectrum disorder: a meta-analysis
.
Pediatrics
.
2019
;
144
(
4
):
e20183218

Competing Interests

POTENTIAL CONFLICTS OF INTEREST: Dr Weitlauf has been a consultant for and received fees from Adaptive Technology Consulting. Dr Warren has been a consultant for and received fees from Adaptive Technology Consulting and Hoffman La Roche; his institution received funding from Autism Speaks to support efforts related to the Autism Speaks Autism Treatment Network. Dr Goode has indicated he has no potential conflicts of interests to disclose.

FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.