International Breastfeeding Journal

BioMed Central

Open Access

Research

Breastfeeding, infant formula supplementation, and Autistic

Disorder: the results of a parent survey
Stephen T Schultz*1,2,5, Hillary S Klonoff-Cohen1, Deborah L Wingard1,
Natacha A Akshoomoff3, Caroline A Macera2, Ming Ji2 and
Christopher Bacher4
Address: 1Division of Epidemiology, Department of Family and Preventive Medicine, School of Medicine, University of California, San Diego,
USA, 2Graduate School of Public Health, San Diego State University, USA, 3Department of Psychiatry, University of California, San Diego, USA,
4Autism Internet Research Survey, New Jersey, USA and 5Dental Corps, United States Navy, San Diego, USA
Email: Stephen T Schultz* - [email protected]; Hillary S Klonoff-Cohen - [email protected];
Deborah L Wingard - [email protected]; Natacha A Akshoomoff - [email protected]; Caroline A Macera - [email protected];
Ming Ji - [email protected]; Christopher Bacher - [email protected]
* Corresponding author

Published: 15 September 2006

International Breastfeeding Journal 2006, 1:16

doi:10.1186/1746-4358-1-16

Received: 19 July 2006

Accepted: 15 September 2006

This article is available from: http://www.internationalbreastfeedingjournal.com/content/1/1/16

2006 Schultz et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract
Background: Although Autistic Disorder is associated with several congenital conditions, the
cause for most cases is unknown. The present study was undertaken to determine whether
breastfeeding or the use of infant formula supplemented with docosahexaenoic acid and
arachidonic acid is associated with Autistic Disorder. The hypothesis is that breastfeeding and use
of infant formula supplemented with docosahexaenoic acid/arachidonic acid are protective for
Autistic Disorder.
Methods: This is a case-control study using data from the Autism Internet Research Survey, an
online parental survey conducted from February to April 2005 with results for 861 children with
Autistic Disorder and 123 control children. The analyses were performed using logistic regression.
Results: Absence of breastfeeding when compared to breastfeeding for more than six months was
significantly associated with an increase in the odds of having autistic disorder when all cases were
considered (OR 2.48, 95% CI 1.42, 4.35) and after limiting cases to children with regression in
development (OR 1.95, 95% CI 1.01, 3.78). Use of infant formula without docosahexaenoic acid
and arachidonic acid supplementation versus exclusive breastfeeding was associated with a
significant increase in the odds of autistic disorder when all cases were considered (OR 4.41, 95%
CI 1.24, 15.7) and after limiting cases to children with regression in development (OR 12.96, 95%
CI 1.27, 132).
Conclusion: The results of this preliminary study indicate that children who were not breastfed
or were fed infant formula without docosahexaenoic acid/arachidonic acid supplementation were
significantly more likely to have autistic disorder.

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Background
Autistic disorder (AD), also called autism, is a severe
developmental disorder defined by deficits in reciprocal
social interaction and communication, and the presence
of repetitive and ritualistic behaviors that emerge before
three years of age [1]. Some parents report regression in
their children or a loss of previously acquired skills with
the subsequent development of AD [2]. Parental report of
regression in children with AD is estimated to occur in
approximately 22% of cases [3]. Recently, parental report
of regression has been validated with the use of videotape
of children's first and second birthdays [4]. In most cases
the cause of AD is unknown [5].
A report by the California Department of Developmental
Services shows a noted increase in individuals with a diagnosis of AD receiving services [6]. The proportion (and
number) of eligible individuals with AD in their client
population of special needs children rose from 3.5%
(2,778/80,389) to 12.4% (20,377/163,792) between
1987 and 2002. Changes in case definitions, administrative and diagnostic procedures, and service-related issues
have had an effect on the number of eligible individuals
with AD in California [7]. The increase in eligible individuals with AD in California may also be due to widening of
the case definition to include children with normal or
above-normal intelligence [8] or due to diagnostic substitution of children with mental retardation [9].
A world-wide review by Fombonne of autism epidemiological surveys concluded that changes in case definition
and improved awareness account for much of the recent
increases in autism [5]. A more recent study reported a stable incidence in Midlands, UK over 15 years when study
design features were held constant [10]. It is not known
whether AD incidence is increasing or whether increases
in prevalence are the result of changing diagnostic criteria
and better case ascertainment.
The prevalence of breastfeeding in the US increased during the 1970s, decreased during the 1980s, and rose again
during the 1990s [11]. For 2002, breastfeeding in the hospital and at six months of age reached an all-time high of
70.1% and 33.2% respectively [11]. Breastfeeding is the
recommended method for infant feeding, and increasing
the number of mothers who breastfeed their children to
six months of age is a goal of Healthy People 2010 in the
US [12]. Breastfeeding has been associated with increases
in cognitive ability and academic performance [13,14].
Breastfeeding may also be important for the cognitive
ability of children at risk for AD. In a study of 145 autistic
and 224 normal children, a significantly higher proportion of autistic children (24.8%) compared to control

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children (7.5%) were weaned by the end of the first week

of life [15].
A related study examined the broader category of pervasive developmental disorder and breastfeeding. This study
found no significant difference in breastfeeding rates
between 50 children with pervasive developmental disorder and 50 control children, although both groups
reported significantly less breastfeeding than the national
average [16]. Further, the normal siblings of the children
with pervasive developmental disorder had breastfeeding
rates almost identical to the national average [16]. This
study may have been overmatched since cases and controls were matched on IQ which has been linked to breastfeeding and AD [13,14,5].
In 1994, the United Nations and the World Health Organization published a report recommending that infants
should be fed breast milk if at all possible, but if fed formula, it should be supplemented with the polyunsaturated fatty acids, docosahexaenoic acid (DHA) and
arachidonic acid (ARA) [17]. In January 2002, the first
infant formulas supplemented with DHA and ARA were
offered for sale in the US, although the older versions of
formula without supplementation also continue to be
sold [18].
DHA/ARA supplemented formula enhances weight gain
in premature infants [19] and raises the plasma and red
blood cell concentrations of DHA and ARA in full-term
infants to levels comparable to breastfed infants [20].
DHA and ARA are considered conditionally essential substrates during early life and are related to the quality of
growth and development [21]. A search of the literature
revealed no published studies that have investigated
infant formula use in relation to AD.
One study found decreased DHA in the composition of
plasma total phospholipids which resulted in significantly lower levels of total omega-3 polyunsaturated fatty
acids for autistic compared to mentally retarded subjects
[22]. Another study found a significant decrease in the
ARA composition of red blood cell polar lipids for children with regressive autism compared to control children
[23]. These decreases could be due to decreased availability of DHA and ARA in the diets of these children.
The present study was undertaken for the purpose of
determining whether breastfeeding or the use of infant
formula (with or without DHA/ARA supplementation) is
associated with AD. The hypothesis is that less breastfeeding and use of infant formula without DHA/ARA supplementation increase the likelihood of AD.

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Methods
The Autism Internet Research Survey was created by the
parent of a child with autism hoping to identify possible
causes for the rise in autism. The survey did not state
whether the rise in autism was due to a rise in incidence
or in the number of individuals registered for special education programs; however, parents who believe there is an
increase in autism incidence may have been more
inclined to take the survey. In order to quickly obtain the
number of cases required for this analysis, the internet was
used to solicit participants. Subsequently, this developed
into a New Jersey-based nonprofit organization, Autism
Internet Research Survey. Neither the organization nor the
survey is related to any commercial entity.
The Autism Internet Research Survey invited parents to
complete surveys for their children with or without AD.
Whether a child had AD was self-reported by clicking on
one of two links: "For those with autistic children who
want to take the survey click here." or "For those who want
to take the control survey (you have children, but not with
any autism spectrum disorder) click here."
Ads for the surveys were placed online using Google and
restricted to the United States. Individuals who performed
online searches containing keywords (autistic, autism
research, autism, MMR, autism education, etc.) were
shown an ad requesting their participation in a research
survey. The total number of keywords used was 306, and
they were grouped into the following categories: autism
and autistic features 262, treatment for autism 24, prominent people involved in autism 13, and possible causes of
autism 7. Participants completed the surveys from February to April 2005. The surveys included 91 questions on
breastfeeding, infant formula use, date of birth, and the
nature of their child's development. Limiting the age
range to children two to 18 years and the respondents to
parents yielded 861 case and 123 control children.
Breastfeeding data was recorded from a drop-down menu
with nine choices of duration of breastfeeding. This variable was recoded into five categories: none, less than 2
months, 26 months, more than 6 months, and
unknown. These breastfeeding categories were tested for
association with autism using logistic regression.
Infant formula use data was recorded from a drop-down
menu with 39 brand-name choices as well as "Other",
"None", and "I don't know". This variable was recoded
into three categories: None, Formula without DHA/ARA,
and Formula with DHA/ARA. Information regarding
DHA/ARA supplementation was ascertained from the
manufacturers websites. If parents chose the category
"Other" or "I don't know", no determination could be
made regarding DHA/ARA supplementation, and the data

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was excluded from further analysis (n = 38). The remaining three infant formula categories were tested for association with autism using logistic regression.
Children under two years old were excluded since AD is
rarely diagnosed before age two. For analysis of breastfeeding, the age range was limited to 218 years. Eighteen
years was chosen as the upper age for the range in an
attempt to minimize recall bias from the parents.
For analysis of infant formula, 24 years was chosen as the
age range. Four years was chosen as the upper age for this
portion of the study since supplementation with DHA/
ARA has only been available in the US since 2002. Children older than four would not have had the opportunity
to use DHA/ARA supplemented formulas during the first
year of life.
Parents of autistic children were also questioned about
the nature of their child's development. Three choices
were given in a drop-down menu: 1) My child developed
normally, then regressed (lost skills). 2) My child developed normally, then stopped. 3) My child never developed in a normal way. For the purposes of this study, if
response number 1 was chosen, the child was assumed to
have a regression in development, i.e. lost skills that had
previously been acquired.
In order to remove the effects of congenital conditions
associated with autism from the odds ratios seen in this
study, breastfeeding and infant formula use were also
tested for association with autism for the subset of children with reported regression in development.
All analyses, including characterization of the population
and logistic regression, were performed using SAS version
9.1 for Windows (SAS Institute Inc., Cary, North Carolina). This study was approved by the University of California, San Diego Human Research Protections Program
and the Institutional Review Board at San Diego State
University.

Results
Table 1 presents the characteristics of children in the
Autism Internet Research Survey. For those aged 218
years, there were 861 cases and 123 controls, and for those
aged 24 years, there were 150 cases and 38 controls.
Parental report of regression in development for these two
age groups was 25% and 23% respectively.
For children aged 218 years, the mean age of cases and
controls was similar at 7.8 and 7.4, respectively. Breastfeeding varied by group, with no breastfeeding being
reported more frequently for cases (28%) than controls
(16%) and breastfeeding for greater than six months

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Table 1: Characteristics of participants in the Autism Internet Research Survey 2005.

For children aged 218 years:

Age (years)
No breastfeeding
Breastfeeding <2 months
Breastfeeding 26 months
Breastfeeding >6 months
Unknown
Parental report of regression in their child's development
For children aged 24 years:
Age (years)
Exclusive breastfeeding (no infant formula use)
Infant formula with DHA/ARA
Infant formula without DHA/ARA
Other infant formula (DHA/ARA content unknown)
Unknown
Parental report of regression in their child's development

being reported more frequently for controls (36%) than

cases (25%).
For children aged 24 years, the mean age of cases was 3.2
and of controls was 3.0. Infant formula use varied by
group with exclusive breastfeeding (no formula use)
being reported more often for controls (16%) than cases
(8%). Use of infant formula containing DHA/ARA was
also reported more frequently for controls (58%) than
cases (26%) while use of infant formula without DHA/
ARA was reported more frequently for cases (43%) than
controls (18%). Breastfeeding for greater than six months
was reported for all children with no formula use and
23% of children with formula use (data not shown).
Age-adjusted associations of breastfeeding and AD are
presented in Table 2 for children aged 218. Decreased
breastfeeding was significantly associated with increased
likelihood of having a child with AD. No breastfeeding

Cases

Controls

N = 861
Mean (SD)
7.8 (3.9)
%
28
23
19
25
5
25
N = 150
Mean (SD)
3.2 (0.5)
%
8
26
43
17
6
23

N = 123
Mean (SD)
7.4 (4.5)
%
16
20
22
36
6
--N = 38
Mean (SD)
3.0 (0.6)
%
16
58
18
3
5
---

versus breastfeeding for more than six months was significantly associated with an increase in the odds of having
AD when all cases were considered (OR 2.48, 95% CI
1.42, 4.35) and after limiting cases to children with regression in development (OR 1.95, 95% CI 1.01, 3.78). Duration of breastfeeding showed a dose-response relationship
with AD before and after limiting cases to children with
regression in development (chi square test for trend, p =
0.0007 and p = 0.031 respectively).
Age-adjusted associations of infant formula use with AD
are presented in Table 3 for children 24 years old. Use of
infant formula without DHA/ARA supplementation versus exclusive breastfeeding was associated with a significant increase in the odds of AD when all cases were
considered (OR 4.41, 95% CI 1.24, 15.7) and after limiting cases to children with regression in development (OR
12.96, 95% CI 1.27, 132). Use of unsupplemented versus
supplemented infant formula was also associated with a

Table 2: Age-adjusted associations of breastfeeding and autistic disorder for children aged 218 years.

Variable

Odds Ratio

No Breastfeeding
2.48
Breastfeeding <2 months
1.70
Breastfeeding 26 months
1.27
Breastfeeding >6 months
reference
Limited to cases with reported regression in development
No Breastfeeding
1.95
Breastfeeding <2 months
1.84
Breastfeeding 26 months
1.59
Breastfeeding >6 months
reference

(95% Confidence Interval)

p value

(1.42 4.35)
(1.00 2.88)
(0.75 2.14)

0.001
0.050
0.373

(1.01 3.78)
(0.98 3.44)
(0.86 2.96)

0.048
0.057
0.141

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Table 3: Age-adjusted association of infant formula use with autistic disorder for children aged 24 years.

Variable

Odds Ratio

(95% Confidence Interval)

p value

Formula without DHA/ARA

Formula with DHA/ARA
Exclusive breastfeeding (no formula use)
Limited to cases with reported regression in development
Formula without DHA/ARA
Formula with DHA/ARA
Exclusive breastfeeding (no formula use)

4.41
1.02
reference

(1.24 15.7)
(0.33 3.18)

0.022
0.977

12.96
2.76
reference

(1.27 132)
(0.28 27.4)

0.031
0.387

significant increase in the odds of AD (OR 4.33, 95% CI

1.65, 11.4) when all children were considered and after
excluding children who were breastfed for more than six
months (OR 4.78, 95% CI 1.57, 14.6) (data not shown in
table). Use of infant formula with DHA/ARA compared to
exclusive breastfeeding was not significantly associated
with an increase in the odds of AD.

Discussion
The children with AD in this survey were significantly less
likely to have been breastfed and were significantly less
likely to have been fed infant formula with DHA/ARA
than typically developing children. A possible mechanism
for these associations is immune system dysfunction.
Without breast milk or infant formula supplemented with
DHA/ARA, some children's immune systems could be
compromised which could in theory lead to AD. Breast
milk provides the infant IgA and other humoral components from the mother which are important for the
immune protection of the infant. Also, use of formula
with DHA/ARA supplementation could be beneficial to
the infant immune system. DHA and ARA are discussed in
a review by Yaqoob as important for proper immune system functioning [24].
The results of this study are from an online internet survey
and should be viewed with caution. This survey was not a
random sampling of the population and has the attendant
problem of ascertainment bias. Only individuals who had
computers and were interested in taking an online survey
were participants. Also, the survey could have biased participant responses by telling them the purpose was to find
reasons for the rise in autism.
The present study relied on self-reported data regarding
the diagnosis of AD and therefore the accuracy of diagnosis was not confirmed. However, parental report of the
proportion of cases with regression in development in this
study (23% for children aged 24 and 25% for children
aged 218) was similar to that seen in a study by Siperstein and Volkmar in which 22% of parents reported
regression in their children diagnosed with AD using
DSM-IV criteria [3]. However, the present study did not
use the same question regarding regression, and the simi-

larities in the proportion with reported regression may be

due to other reasons.
The exposure data of breastfeeding and infant formula use
were of necessity also self-reported. Reliance on self-report
leads to misclassification bias; however, there is no reason
to believe that this bias is differential, especially in terms
of formula use with and without supplementation, and is
therefore assumed to be random. Non-differential misclassification would bias the results toward the null, indicating the odds ratios seen in this study could be higher in
a more rigorous study.
The internet survey was a parent-based effort and did not
include all of the demographic questions normally found
in epidemiologic surveys. The analyses in this study were
only adjusted for age. Information on gender and socioeconomic status (SES) was not obtained. SES has been
shown to not be associated with AD; however, gender is
associated with AD approximately 76% of those with
AD are male [25]. Gender could confound the association
of breastfeeding and AD if mothers are more likely to
breastfeed due to the child's gender, but child's gender has
been shown to not be associated with duration of breastfeeding [26]. The health status of the controls is unknown,
other than the parents indicating that their children had
no autism spectrum disorder. These questions will need to
be addressed in future studies.
The survey used for this study also did not address the reason why some mothers stopped or did not initiate breastfeeding. If there is a problem breastfeeding infants due to
AD, then this is a source of possible confounding; however, this would not be an issue for the infant formula
analysis. Also, the infant formula information used in this
study did not categorize the amounts of partial infant formula use. These questions will need to be addressed in a
future study.
One advantage of using this internet survey was the speed
at which the survey was administered and the results
received. This survey was completed in less than three
months. Also this survey had a large number of participants, 861 cases and 123 controls, which gives the study

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sufficient power to detect differences in breastfeeding and

infant formula use. This was an innovative study produced by concerned parents who want to find answers to
the question of what causes AD.
Another advantage is the large number of infant formula
choices in the survey's drop-down menu 39 brand name
choices were available along with "none", "other", and "I
don't know". Having this number of infant formula
choices allowed this variable to be accurately recoded into
categories with and without DHA/ARA supplementation.
Interestingly, 17% of case parents chose the "other" category compared to 3% of control parents. This indicates
that a larger percent of case parents could not find their
infant formula brand on the drop-down menu. The reason for this difference is unknown; however, if all of the
children in the "other" category used supplemented formula, then control children still used more supplemented
formula than cases, and the association between lack of
supplementation and autistic disorder remains significant
(OR 4.39, 95% CI 1.23, 15.7). Alternatively, if all of those
in the "other" category used formula not supplemented
with DHA/ARA, then the association between autistic disorder and lack of supplementation is even greater (OR
5.64, 95% CI 1.64, 19.4).

Conclusion
While Tanoue and Oda [15] found a significantly higher
number of children with autism compared to control children had already stopped breastfeeding when assessed at
the end of the first week of life, the present study is the first
to show that increased duration of breastfeeding is associated with a decreased likelihood of AD. This is also the
first study to suggest a possible link between the use of
infant formula without DHA/ARA supplementation and
AD. However, this study was based on a small group and
should be followed by a larger more rigorous study to
confirm the results.

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Competing interests
The author(s) declare that they have no competing interests.

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Authors' contributions
SS participated in the design, performed the analyses, and
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Acknowledgements
The views expressed in this article are those of the authors and do not
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