Longitudinal comparison between male

and female preschool children with autism

spectrum disorder

Valentina Postorino, Laura Maria Fatta,

Lavinia De Peppo, Giulia Giovagnoli,
Marco Armando, Stefano Vicari & Luigi
Mazzone
Journal of Autism and
Developmental Disorders

ISSN 0162-3257

J Autism Dev Disord

DOI 10.1007/s10803-015-2366-0

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 Author's personal copy
J Autism Dev Disord
DOI 10.1007/s10803-015-2366-0
ORIGINAL PAPER
Longitudinal comparison between male and female preschool
children with autism spectrum disorder
Valentina Postorino • Laura Maria Fatta •
Lavinia De Peppo • Giulia Giovagnoli •
Marco Armando • Stefano Vicari • Luigi Mazzone
Ó Springer Science+Business Media New York 2015
Abstract Epidemiological studies have highlighted a
strong male bias in autism spectrum disorder (ASD),
however few studies have examined gender differences in
autism symptoms, and available findings are inconsistent.
The aim of the present study is to investigate the longitu-
dinal gender differences in developmental profiles of 30
female and 30 male age-matched preschool children with
ASD. All the children underwent a comprehensive evalu-
ation at T0 and at T1. Our results have shown no significant
interaction between time and gender for predicting autism
symptoms, developmental quotient, parental stress, chil-
dren’s adaptive skills and behavior problems. Shedding
light on the developmental trajectories in ASD could help
clinicians to recognize children with ASD at an earlier age
and contribute to the development of appropriate
treatments.
Keywords Autism spectrum disorder
Preschoolers

Males
Females
Longitudinal
V. Postorino
L. M. Fatta
L. De Peppo
G. Giovagnoli

M. Armando
S. Vicari
L. Mazzone (&)
Child Neuropsychiatry Unit, Department of Neuroscience,
I.R.C.C.S. Children’s Hospital Bambino Gesù, Piazza S.
Onofrio, 4, 00165 Rome, Italy
e-mail: gigimazzone@yahoo.it
L. M. Fatta
I.R.C.C.S. Centro Neuolesi ‘‘Bonino-Pulejo’’ Via Provinciale
Palermo, S.S.113 Contrada Casazza, 98124 Messina, Italy
L. De Peppo
G. Giovagnoli
Psychology Department, Libera Universita’ Maria Ss. Assunta,
Rome, Italy
Introduction
Autism spectrum disorder (ASD) is a broad category
characterized by persistent deficits in social communication
and social interaction, and restricted and repetitive patterns
of behavior. According to the Diagnostic and Statistical
Manual of Mental Disorders—fifth edition (DSM-5), due to
the heterogeneity of this diagnostic classification, ASD is
better differentiated by severity of autism symptoms, and
association with language impairment and intellectual dis-
ability (American Psychiatric Association 2013).
Recent epidemiological studies on ASD show a signif-
icantly higher prevelence of the disorder in males
(Fombonne 2009). These studies found a male: female
(M:F) ratio ranging from 1.33:1 to 16:1, with a mean of 4:1
(Fombonne 2009; Baird et al. 2006; Nygren et al. 2012a,
2012b; CDC 2014). This M:F ratio rises to 10:1 in
Asperger syndrome and ‘‘high functioning autism’’,
whereas it drops to 2:1 in subjects with a comorbid intel-
lectual disability (Fombonne 1999, 2009; Nicholas et al.
2008; Bryson et al. 2008).
Some studies have observed that this gender disparity
could be due to a strong social gender bias that causes
parents and clinicians to have different perceptions and
expectations for boys compared to girls, with diagnosis of
ASD being made at a later age in the latter group, even
when symptom severity is constant across genders (Carter
et al. 2007; Holtmann et al. 2007; McLennan et al. 1993;
Shattuck et al. 2009; Mandell et al. 2009; Russell et al.
2011; Mondschein et al. 2000). Furthermore, it has been
hypothesized that these epidemiological data could reflect a
bias in diagnostic criteria, probably due to a different
behavioral phenotype in males and in females, and it is
therefore possible that girls either go undiagnosed or are
misdiagnosed (Kopp and Gillberg 1992; Attwood 2007).
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Another possible explanation is the widely cited
‘‘extreme male brain’’ theory of Baron-Cohen et al. (2003),
that assumes a neuropsychological difference between
genders, with males predominating in the systemizing
domain, whereas females are superior in the empathizing
domain. According to this theory, in ASD there is a stronger
drive to systemize independent of gender compared to
normal subjects and this hypothesis seems to be associated
to biological and genetic factors (i.e., fetal testosterone,
epigenetic effect on X chromosome genes and the male-
limited expression of genes on the Y chromosome) (Baron-
Cohen et al. 2014; Baron-Cohen Baron-Cohen 2003b;
Baron-Cohen et al. 2003, 2005, 2011; Chapman et al. 2006;
Chura et al. 2010; Ingudomnukul et al. 2007).
In order to understand the sex bias in ASD the hypothesis
of a female protective effect against autistic behavior was
empirically tested by Robinson et al. (2013) in a study on
two nationally-representative samples of dizygotic twins.
The results of this study provide the strongest evidence to
date that female sex protects girls from autistic impairments
and suggest that girls require a greater etiological load to
manifest an autistic phenotype (Werling et al. 2013b).
Although gender disparity in prevalence rates has been
extensively studied, only a few studies examined gender
differences in autistic symptoms, and available findings are
inconsistent. Most studies failed to find any differences in
the core symptoms of ASD between males and females
(Carter et al. 2007; Banach et al. 2009; Andersson et al.
2013; Mayes and Calhoun 2011; Zwaigenbaum et al. 2012;
Mandy et al. 2012; Szatmari et al. 2012; Donna et al. 2013).
On the other hand, a meta-analysis of 20 studies investi-
gating gender differences in ASD reported few differences
in symptom severity between males and females. Specifi-
cally, there were no gender differences in social behaviors
or communication, but girls showed less restricted, repeti-
tive and stereotyped behaviors (RRB) than boys (Van
Wijngaarden-Cremers et al. 2013). It is worth noting that
female with ASD and an average or above average intel-
lectual ability may be undiagnosed or misdiagnosed due to a
different clinical manifestation, and therefore differences in
symptom severity between genders may be affected by this
diagnostic bias (Shattuck et al. 2009; Mandell et al. 2009;
Baron-Cohen 2003b; Kirkovski et al. 2013).
Regarding co-occurring comorbid psychopathology
among samples with ASD, the majority of studies failed to
identify any gender differences (Hofvander et al. 2009; Lu-
gnegard et al. 2011; Matson and Nebel-Schwalm 2007; Park
et al. 2012; Simonoff et al. 2008; Lai et al. 2011; Mazzone
et al. 2013). However, some studies reported that girls with
ASD appeared to be at greater risk than boys for internalizing
psychopathology (Solomon et al. 2012; Mazzone et al. 2012).
Indeed, recent studies report that parents of children
with ASD experience higher levels of stress than parents of
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J Autism Dev Disord
typically developing children (Mugno et al. 2007; May
et al. 2012; Zaidman-Zait et al. 2011; Bauminger et al.
2010). Moreover, parental stress was found to be positively
correlated with autism symptoms and severity, as well as
with internalizing and externalizing behavior problems
(Bauminger et al. 2010; Herring et al. 2006). However,
none of these studies has focused on gender differences in
parenting stress reported by parents of children with ASD.
Longitudinal studies investigating the differences
between genders with regard to symptom severity, devel-
opmental changes in symptoms presentation and course
may have significant implications for the development of
adequate assessment and treatment strategies for patients
with ASD. Shedding light on gender differences in devel-
opmental trajectories is crucial for both clinical and
research purposes with regard to diagnosis and treatment.
However, to our knowledge, no previous study has
addressed this issue. Therefore, the aim of the present study
was to investigate the longitudinal gender differences in
developmental profiles in a sample of preschool children
suffering from ASD with particular focus on the relation-
ship between children’s behavior problems and experi-
enced stress in the parenting role reported by parents.
Participants and methods
Participants and procedure
A total of 60 preschool children suffering from ASD were
enrolled in this study. Of these, 30 females were age-matched
with 30 males (aged 2–5.4 years; Mean age ± SD: 3.55 ±
0.9). All the children were referred to the Child Neuropsy-
chiatry Unit of the Bambino Gesu’ Children’s Hospital in
Rome (Italy) between December 2010 and December 2012.
All the participants’ parents provided a written informed
consent. Exclusion criteria included the presence of specific
genetic disorders, other medical disorders or epilepsy. On
entry into the study, autism had to be diagnosed by an expert
clinician using DSM-IV-TR criteria (American Psychiatric
Association 2000). All the subjects underwent a comprehen-
sive developmental profile evaluation at the time of admission
(Time 0, T0) and at follow-up (Time 1, T1).
Developmental quotient assessment
All the children were assessed using the Griffiths Mental
Development Scale-Extend Revised (GMDS-ER) (Griffiths
2006). GMDS-ER I and II assess a child’s strengths and
weaknesses in all developmental areas, and can be used to
measure the rate of development of children from birth to
8 years of age. The six areas of development measured by the
scales are: (A) Locomotor, measuring the gross motor
 Author's personal copy
J Autism Dev Disord
development; (B) Personal-Social, examining the social and
daily living skills; (C) Hearing and Speech, measuring
receptive and expressive language; (D) Eye-Hand Coordina-
tion, focusing on fine motor skills, manual dexterity and visual
monitoring skills; (E) Performance, focusing on manipulation
of objects; (F) Practical Reasoning, measuring mathematic
ability and abstract reasoning. Each subscale provides a dif-
ferent developmental quotient and a diagnostic indication of
individual problems in early childhood. In the present study,
all the children were unable to perform GMDS-ER practical
reasoning scale either at T0 or T1. Griffith’s six subscales are
expressed as quotients constituting the general developmental
quotient (GDQ). The GDQ is derived from the average of
quotients resulting from the six subscales. The test scores are
transformed into developmental ages (D.A.) and then into
quotients according to the following equation: developmental
quotient (DQ) = Developmental age 9 100/chronological
age (CA). Developmental quotients rather than mental age are
used to make it possible to compare children of different
chronological ages and to compare a child’s performance at
different time periods.
Evaluation of autism symptoms
All the children were assessed for the presence of autism
symptoms using the Autism Diagnostic Observation Sche-
dule-Generic (ADOS-G) performed by a licensed clinician
(Lord et al. 2000). The ADOS-G is a semi-structured, stan-
dardized, play-based assessment measure evaluating current
autistic behaviors. The ADOS-G is divided into four separate
modules. Each module is aimed at a specific level of expres-
sive language ability (ranging from pre-verbal to fluent
speech). The choice of modules is based on the subject’s
expressive language level. The use of different modules
reduces possible biasing effects of differences in language
skills. Scoring is done immediately after administration of the
ADOS-G. Each item is scored on a 0–3 scale (0 = no evi-
dence of abnormal behavior to 3 = markedly abnormal
behavior) and each module has a specific diagnostic algo-
rithm. Items used in the algorithms are divided into four areas:
communication, social interaction, play/creativity, and
restricted/repetitive behaviors or interests (RRB). The total
score for communication and social interaction provides a cut-
off for diagnosis at various ‘‘levels of ASD’’. In the present
study, at T0 all children performed module 1 (cut-off for
autism = 12 and ASD = 7), whereas, at T1, 54 children (28
males and 26 females) performed module 1 and 6 children (2
males and 4 females) performed module 2 (cut-off for aut-
ism = 12 and ASD = 8). The ADOS-G has good to excellent
psychometric properties, and satisfactory ability to differen-
tiate individuals with and without ASD. However, the ADOS-
G algorithm does not include RRB and literature studies have
suggested that if RRB are included it may help to increase
ADOS-G diagnostic stability (Lord et al. 2006). Therefore, the
ADOS-G has been revised (Gotham et al. 2007). In the revised
version, module 1 is split into ‘‘No words’’ and ‘‘Some
words’’, and module 2 into ‘‘Younger than 5’’ and ‘‘5 or
older’’. The revised algorithm is divided into two new
domains, social affect (SA) and RRB. To calculate the total
cut-off, SA and RRB are combined into one score. An ASD
severity scale has been developed basing on 18 narrowly
defined age and language cells, and the total raw scores have
been divided into a 10-point severity score (1 = fewer prob-
lems and 10 = more severe problems) (de Bildt et al. 2011;
Gotham et al. 2009).
Assessment of adaptive skills, behavior problems
and parental stress
All the parents of the participating children performed the
Vineland Adaptive Behavior Scale-Survey Form (VABS-
SF) with a trained and experienced clinician, in order to
measure the children’s adaptive skills (Sparrow et al. 1984;
Balboni and Pedrabissi 2003). Moreover, they completed
the Child Behavior Checklist version 1‘–5 (CBCL) and
the Parent Stress Index-Short Form (PSI-SF) to rate chil-
dren’s emotional and behavior problems and levels of
stress experienced in the parenting role (Achenbach and
Eofbrock 1983; Achenbach and Rescorla 2000, 2001;
Abidin 1990, 1995; Guarino et al. 2008).
The VABS-SF is a standardized parent interview of
everyday adaptive functioning, designed to measure adap-
tive behaviors in children from birth to 18 years. It consists
of 297 items falling into four general functioning domains:
communication skills, daily living skills, social skills and
motor skills.
The communication domain assesses receptive, expressive, and
written skills according to age level. The daily living skills domain
taps personal, domestic, and community skills. For the socialization
domain, the child is rated on interpersonal relationship skills,
socialization during play and leisure time, and coping skills. The
motor skills domain includes development of gross and fine motor
skills. An adaptive behavior composite score for each of the four
domains was attained for all participants and transformed into
equivalent ages based on published Italian norms (Balboni and
Pedrabissi 2003).
The CBCL version 1‘–5 is an extensively used tool of
99 items on a three point Likert scale, that provides scores
for seven syndrome scales, five different DSM-oriented
scales and three broad-brand scales (i.e., internalizing
symptoms, externalizing symptoms and total behavior
problems). Raw scores for each clinical factor were
transformed into T-scores based on published norms:
T-scores[63 were considered indicative of clinical impair-
ment for the three broad-band scales, whereas T-scores C70
were considered indicative of clinical impairment for
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syndrome and DSM-oriented scales (Achenbach and Eof-
brock 1983; Achenbach and Rescorla 2000, 2001). The
psychometric properties of the CBCL show good validity
and reliability (Achenbach and Eofbrock 1983; Achenbach
and Rescorla 2000, 2001).
The PSI-SF is a 36-item questionnaire that measures
different aspects of experienced stress in the parenting role
using three subscales: parental distress (PD), measuring an
impaired sense of parental competence and depression,
parent–child dysfunctional interaction (P-CDI), intended to
measure unsatisfactory parent–child interactions, and dif-
ficult child (DC), measuring behavioral characteristics of
the child that make him/her easy or difficult to manage.
The total PSI-SF score is seen as an indicator of the par-
ent’s overall experience of parenting stress (Abidin 1990,
1995; Guarino et al. 2008). Parents rate each of the 36
items on a 5-point scale. The 90th percentile of the total
PSI-SF score represents a ‘‘clinically significant’’ level of
parenting stress. The PSI-SF has been shown to be a valid
and reliable measure (Abidin 1995; Guarino et al. 2008;
Zaidman-Zait et al. 2011).
Data Analysis
Data analyses were performed using the Statistical Package
for Social Sciences (SPSS 20.0 for Windows). Independent
samples t-tests, at T0 and T1, were performed to evaluate
differences between gender and ADOS severity score,
GMDS-ER, VABS-SF, CBCL and PSI-SF. Mixed
ANOVA analysis were performed between time (within-
group variable) and gender (between-group variable) on
GMDS-ER, VABS-SF, ADOS severity score, CBCL and
PSI-SF (dependent variables). The strength of the rela-
tionship between independent variables (time and gender)
and dependent variables was assessed by calculating the
F test and the corresponding P value. Mixed ANOVA
analysis showed that the assumption of sphericity had been
violated for all the variables tested (ADOS severity score:
p \ .001, GMDS-ER: p \ .001, VABS-SF: p = .001,
CBCL: p \ .001 and PSI-SF: p \ .001) therefore degrees
of freedom were corrected using Greenhouse-Geisser
estimates of sphericity. Furthermore, paired samples t-tests
were applied to the data in order to evaluate differences
within gender between each time assessment and autism
symptoms, developmental quotient, parental stress, chil-
dren’s adaptive skills and behavior problems. An alpha
level of 0.05 was set for statistical significance.
Results
Comparisons between male and female groups at T0, using
independent samples t-tests, showed significantly higher
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scores in the male group on GDQ (t = 2.213, p = .033),
eye–hand coordination (t = 2.618, p = .013) and perfor-
mance (t = 2.901, p = .005) GMDS-ER scales and CBCL
anxiety problems subscale (t = 2.640, p = .012; Table 1
and 2). Whereas, comparison between male and female
groups at T1, using independent samples t-tests, showed
significantly higher scores in the male group on eye-hand
coordination (t = 2.016, p = .049) GMDS-ER scale and
CBCL sleep problems subscale (t = 2.044, p = .047;
Tables 1 and 2). Evaluating differences between time (T0
and T1) and gender on developmental quotient (GMDS-
ER), mixed ANOVA analysis indicated a main effect of
time (F:21.702; p \ .001) and this effect was not modified
by gender (F:1.627; p for the effect modification = .208).
Moreover, mixed ANOVA analysis between time (T0 and
T1) and gender on children’s adaptive skills (VABS-SF)
indicated a main effect of time (F:46.7; p \ .001) that
again was not modified by gender (F:0.585; p for the effect
modification = .448). Furthermore, mixed ANOVA ana-
lysis between time (T0 and T1) and gender on autism
symptoms (ADOS severity score), children’s behavior
problems (CBCL) and parental stress (PSI-SF) revealed no
statistically significant main effect or interaction. More-
over, within the female group, paired samples t-tests
between T0 and T1 showed significantly higher scores at
T1 on GDQ (t = -4.271, p \ .001), locomotor (t =
-2.805, p = .009), personal–social (t = -4.495, p \ .001)
and performance (t = -4.148, p \ .001) GMDS-ER scales,
communication skills (t = -3.342, p = .002), daily living
skills (t = -5.580, p \ .001), social skills (t = -2.529,
p = .018) and motor skills (t = -8.260, p \ .001) VABS-
SF domains (Fig. 1). On the other hand, within the male
group, paired samples t-tests between T0 and T1 indicated
higher scores at T1 on GDQ (t = -2.588, p = .016), per-
sonal–social (t = -2.881, p = .008) GMDS-ER scale,
communication (t = -2.452, p = .023), daily living skills
(t = -2.227, p = .037), social skills (t = -3.215, p = .004)
and motor skills (t = -2.853, p = .009) VABS-SF
domains (Fig. 1).
Discussion
Epidemiological data have shown a significantly higher
prevalence of ASD in males and recent evidence suggests
that the observed gender ratio may be influenced by sex
differences in symptomatology of ASD (Fombonne 2009).
However, there is a great deal of literature concerning the
varying profile of autism as expressed by gender differ-
ences and the vast majority of studies have been conducted
with predominantly male samples (Bell et al. 2005). Fur-
thermore, the available findings on the differences in
clinical profiles between males and females with ASD have
 J Autism Dev Disord

Table 1 ADOS severity score, GMDS-ER and VABS-SF at T0 and T1

T0 T1
All participants Females Males t P All participants Females Males t P
(N = 60) (N = 30) (N = 30) (N = 60) (N = 30) (N = 30)
Mean ± SDa Mean ± SD Mean ± SD Mean ± SD Mean ± SD Mean ± SD

ADOSb Severity score 6.42 ± 1.734 6.66 ± 1.696 6.20 ± 1.769 -1.008 NSc 6.27 ± 1.552 6.48 ± 1.37 6.07 ± 1.701 -1.030 NS
d
GMDS-ER
GDQe 63.81 ± 20.33 58.20 ± 13.78 70.04 ± 24.53 2.213 .033 72.09 ± 20.98 70.11 ± 21.14 74.00 ± 21.01 0.697 NS
Locomotor 83.11 ± 24.01 80.87 ± 17.94 85.59 ± 29.51 0.739 NS 90.56 ± 25.20 95.21 ± 25.99 86.07 ± 24.01 -1.380 NS
Personal-social 63.04 ± 24.16 57.07 ± 17.76 69.67 ± 28.62 1.971 NS 74.95 ± 26.56 72.32 ± 25.46 77.48 ± 29.69 0.703 NS
Hearing and speech 40.98 ± 25.79 35.86 ± 17.36 46.48 ± 31.97 1.559 NS 45.21 ± 27.85 38.75 ± 25.88 51.45 ± 28.69 1.752 NS
Eye–hand coordination 59.81 ± 22.34 52.60 ± 13.06 67.81 ± 27.53 2.618 .013 65.00 – 22.84 58.96 ± 21.50 70.83 ± 22.93 2.016 .049
Performance 71.58 ± 27.27 62.07 ± 20.30 82.15 ± 30.37 2.901 .005 84.09 ± 26.58 82.82 ± 28.90 85.31 ± 24.59 0.351 NS
VABS-SFf
Communication skills 1.80 ± 0.81 1.62 ± 0.39 2.02 ± 1.09 1.833 NS 2.25 ± 1.09 2.05 ± 0.89 2.46 ± 1.24 1.436 NS
Daily living skills 2.12 ± 0.77 1.99 ± 0.43 2.27 ± 1.04 1.326 NS 2.55 ± 0.70 2.50 ± 0.62 2.61 ± 0.78 0.575 NS
Social skills 1.88 ± 0.45 1.83 ± 0.29 1.93 ± 0.59 0.801 NS 2.18 ± 0.55 2.08 ± 0.49 2.29 ± 0.59 1.454 NS
Motor skills 2.48 ± 0.84 2.28 ± 0.55 2.72 ± 1.07 1.917 NS 3.17 ± 0.88 3.25 ± 0.79 3.09 ± 0.97 -0.715 NS
Author's personal copy

Bold values are statistically significant

a
Standard Deviation
b
Autism Diagnostic Observation Schedule
c
Not significant P [ 0.05
d
Griffiths Mental Development Scale-Extended Revised
e
General Developmental Quotient
f
Vineland Adaptive Behavior Scale-Survey Form

123
 Table 2 CBCL and PSI-SF at T0 and T1
T0 T1

123
All participants Females Males t P All participants Females Males t P
(N = 60) (N = 30) (N = 30) (N = 60) (N = 30) (N = 30)
Mean ± SDa Mean ± SD Mean ± SD Mean ± SD Mean ± SD Mean ± SD

CBCL 1‘–5b
Syndrome scales
Emotionally reactive 55.08 ± 6.43 54.22 ± 5.39 55.96 ± 7.36 0.984 NSc 56.00 ± 7.54 54.67 ± 5.42 57.43 ± 9.18 1.406 NS
Anxious/depressed 53.79 ± 5.10 52.85 ± 3.91 54.77 ± 6.02 1.378 NS 53.74 ± 6.10 52.33 ± 3.81 55.25 ± 7.64 1.857 NS
Somatic complaints 53.68 ± 5.12 53.37 ± 5.23 54.00 ± 5.09 0.443 NS 54.67 ± 5.68 54.17 ± 5.09 55.21 ± 6.31 0.698 NS
Withdrawn 70.28 ± 10.06 70.00 ± 10.64 70.58 ± 9.62 0.207 NS 67.76 ± 9.88 68.17 ± 10.11 67.32 ± 9.81 0.323 NS
Sleep problems 52.68 ± 4.67 52.30 ± 4.13 53.08 ± 5.23 0.604 NS 53.49 ± 5.18 52.14 ± 3.39 54.89 ± 6.30 2.044 .047
Attention problems 59.34 ± 7.34 59.96 ± 7.04 58.69 ± 7.74 0.626 NS 59.86 ± 7.80 59.20 ± 7.29 60.57 ± 8.38 0.666 NS
Aggressive behavior 52.81 ± 4.47 53.04 ± 4.83 52.58 ± 4.15 0.371 NS 52.76 ± 4.87 52.03 ± 3.82 53.54 ± 5.77 1.176 NS
Int, Ext, Tot, Otherd
Internalizing Problems 57.67 ± 8.15 57.19 ± 7.98 58.15 ± 8.44 0.431 NS 56.95 ± 8.57 55.76 ± 6.92 58.18 ± 9.97 1.067 NS
Externalizing problems 51.98 ± 6.97 51.81 ± 6.46 52.15 ± 7.56 0.174 NS 52.05 ± 8.15 51.62 ± 7.38 52.50 ± 8.99 0.404 NS
Total problems 57.78 ± 10.08 57.56 ± 10.44 58.00 ± 9.89 0.160 NS 56.91 ± 10.02 57.07 ± 10.28 56.75 ± 9.93 0.119 NS
DSM-oriented scales
Affective problems 56.02 ± 6.65 55.70 ± 5.07 56.35 ± 7.61 0.349 NS 56.76 ± 7.61 56.00 ± 6.10 57.57 ± 9.00 0.783 NS
Anxiety problems 54.08 ± 5.87 52.07 ± 3.32 56.15 ± 7.17 2.640 .012 54.24 ± 6.85 52.63 ± 4.35 55.96 ± 8.54 1.890 NS
Perv dev problemse 66.74 ± 8.80 66.93 ± 7.38 66.54 ± 10.21 -0.159 NS 65.60 ± 9.23 63.33 ± 7.76 68.04 ± 10.16 1.988 NS
ADHDf problems 54.75 ± 6.81 55.07 ± 6.42 54.42 ± 7.31 -0.345 NS 54.33 ± 5.74 52.83 ± 4.94 55.93 ± 6.18 2.112 NS
Opp def problemsg 53.40 ± 5.57 53.74 ± 6.34 53.04 ± 4.74 0.455 NS 53.09 ± 5.54 52.60 ± 5.29 53.61 ± 5.85 0.688 NS
PSI-SFh
PDi percentile 56.13 ± 34.05 59.04 ± 33.15 52.67 ± 35.58 0.628 NS 56.33 ± 32.50 54.73 ± 30.95 58.33 ± 34.91 0.401 NS
P-CDIj percentile 72.83 ± 21.41 74.40 ± 23.15 70.95 ± 19.53 -0.540 NS 67.24 ± 27.38 71.17 ± 22.65 62.33 ± 32.18 -1.182 NS
Author's personal copy

DCk percentile 72.61 ± 23.70 74.60 ± 24.82 70.24 ± 22.66 0.617 NS 69.44 ± 23.19 69.00 ± 20.81 70.00 ± 26.31 0.156 NS
Total percentile 72.74 ± 26.44 73.24 ± 28.73 72.14 ± 24.11 0.139 NS 66.19 – 28.11 68.00 ± 24.37 63.92 ± 32.60 -0.527 NS

Bold values are statistically significant

a
Standard Deviation
b
Child Behavior Checklist version 1‘–5
c
Not significant P [ 0.05
d
Internalizing, Externalizing, Total and Other Problems
e
Pervasive developmental problems
f
Attention Deficit/Hyperactivity problems
g
Oppositional defiant problems
h
Parent Stress Index-Short Form
i
Parental Distress
j
Parent–Child Dysfunctional Interaction
k
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Difficult Child
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J Autism Dev Disord
Fig. 1 Trajectories of changes in the male and female groups
shown contrasting results (Carter et al. 2007; Banach et al.
2009; Andersson et al. 2013; Van Wijngaarden-Cremers
et al. 2013; Hofvander et al. 2009; Lugnegard et al. 2011;
Matson and Nebel-Schwalm 2007; Park et al. 2012; Si-
monoff et al. 2008; Lai et al. 2011; Mayes and Calhoun
2011; Zwaigenbaum et al. 2012; Mandy et al. 2012;
Szatmari et al. 2012; Donna et al. 2013). On the one hand,
most studies found no gender differences on social
behaviors or communication nor on RRB (Carter et al.
2007; Banach et al. 2009; Andersson et al. 2013; Hof-
vander et al. 2009; Lugnegard et al. 2011; Matson and
Nebel-Schwalm 2007; Park et al. 2012; Simonoff et al.
2008; Lai et al. 2011; Mayes and Calhoun 2011; Zwai-
genbaum et al. 2012; Mandy et al. 2012). For instance,
Andersson et al. (2013), in a cross-sectional study aimed at
investigating gender differences in clinical and develop-
mental profiles in 20 preschool girls and 20 age-matched
preschool boys with suspected ASD, found no significant
differences on communication and RRB. On the other
hand, some literature data have reported girls to be less
impaired than boys with regard to RRB: this result does not
suggest that females with ASD report no deficits in this
area, but instead that females may not exhibit the same
behavioral pattern of RRB as that presented by males, and
it is possible therefore that RRB of females can be masked
and less clinically identifiable (Van Wijngaarden-Cremers
et al. 2013; Szatmari et al. 2012; Donna et al. 2013).
In our study, in order to compare children performing
different modules of ADOS-G, we used the ADOS-G
severity score which combines SA and RRB scores into
one total cut-off score. Therefore, we could not detect the
gender differences on RRB in our sample. However, in line
with the results of other reports, we found no differences in
severity of autism symptoms between males and females
either across time or at a specific time assessment (nor at
T0 or at T1; Carter et al. 2007; Banach et al. 2009; An-
dersson et al. 2013; Mayes and Calhoun 2011; Zwaigen-
baum et al. 2012; Mandy et al. 2012; Szatmari et al. 2012;
Donna et al. 2013). Furthermore, our results have shown no
significant interaction between time and gender for pre-
dicting cognitive ability, parental stress, children’s adap-
tive skills or behavior problems. Indeed, confirming
123
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previous studies reporting that a lower cognitive ability is
found more frequently in females with ASD than in males,
in our population, at admission, females showed signifi-
cantly lower scores on generalized developmental quotient
(Fombonne 1999, 2009; Nicholas et al. 2008; Bryson et al.
2008). However, at follow-up, in our study, this gender
difference was not confirmed. This result could be
explained taking into account the trajectories of changes in
cognitive ability of males and females separately. Specifi-
cally, even though both male and female groups showed a
statistically significant improvement on cognitive ability
over time, gains in cognitive ability made between T0 and
T1 assessments in the male group were of small effect size
(d = 0.2), whereas females presented considerably devel-
opments, of large effect size (d = 0.9), on cognitive ability
between time of admission and time of follow-up. These
findings could support the hypothesis that clinical symp-
toms may be masked in higher functioning autism females
with the result that they are undiagnosed or misdiagnosed,
or that girls, particularly that girls recognized at an early
age, require a greater etiological load to manifest an
autistic phenotype (Shattuck et al. 2009; Mandell et al.
2009; Baron-Cohen 2003a; Robinson et al. 2013; Werling
et al. 2013a; Kirkovski et al. 2013).
Besides these results, the present study has some
important limitations that should to be taken into account.
First, due to the limited number of girls referred for
screening, we could only collect a small sample. Second,
the sample was clinically referred and not intended to be
representative of children with ASD in the general popu-
lation; we did not include control groups of males and
females without ASD, which is important given the
increasing evidence for the presence of autistic traits in the
general population (Ruta et al. 2012). Although, to our
knowledge there are no previous longitudinal studies
investigating gender differences regarding symptomatol-
ogy in preschoolers with ASD, the span of the assessments
in our study is not wide.
Epidemiological studies have highlighted a strong male
bias in ASD and further research is needed on the preva-
lence estimates of this disorder between genders. Several
studies have highlighted the benefits of early identification
and intervention for children with ASD (Dawson 2008;
Cangialose and Allen 2014). Therefore, shedding light on
the developmental trajectories in ASD could increase cli-
nicians’ diagnostic sensitivity and lead to an earlier iden-
tification of children with ASD. Furthermore, defining the
presentation and course of symptom domains and severity
in patients with ASD would contribute to the development
of appropriate early intervention and treatment strategies.
Indeed, given that sex hormone levels change during a
lifetime and may modulate the presentation of the autism
phenotype, studies on the mechanism by which these
123
J Autism Dev Disord
factors may be a risk for males and females are crucial.
Finally, our findings suggest that male and female pre-
school children with ASD present similar clinical profiles
over time, but, given the lack of longitudinal controlled
studies on this issue, further studies are essential.
Acknowledgments Authors would like to thank Giovanni Tripepi
for his valuable guidance in the statistical analysis of data, interpre-
tation of results and discussion on the themes addressed in this
manuscript.
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