doi:10.1016/j.jpedsurg.2008.10.101
Copyright © 2009 Published by Elsevier Inc.
BAPS papers

Results from a pediatric surgical centre justify early intervention
in disorders of sex development

Jennifer M. Crawforda, 1, , Garry Warneb, Sonia Grovera, b, c,
Bridget R. Southwellc and John M. Hutsona, b, c, ,
aSchool of Medicine, University of Melbourne, Parkville, Victoria
3052, Australia
bRoyal Children's Hospital, Parkville, Victoria 3052, Australia
cMurdoch Childrens Research Institute, Parkville, Victoria 3052,
Australia

Received 3 October 2008; accepted 23 October 2008. Available online
20 February 2009.

Abstract
Background

Controversy persists surrounding early management of disorders of sex
development. We assessed genital appearance, gender identity, and
quality of life in prepubertal children who have had early surgical
intervention.

Methods
Children treated for disorders of sex development who were 5 to 10
years of age were eligible (n = 54). Children were scored (modified
Creighton scale) for anatomical and cosmetic outcome, and both
patients and parents completed PedsQL quality-of-life and gender
identity questionnaires, with ethics approval.

Results
Of 54 patients, 41 presented for review. Treatment began at 13.2 (1.8-
250.1) months (median; range) and were reviewed at 7.5 ± 2.1 (mean ±
SD) years of age. Nineteen were raised as girls and 22 as boys. Girls
had good (85%) or satisfactory (15%) anatomical/cosmetic outcome,
whereas 52% boys had good, 38% satisfactory, and 10% poor cosmetic
outcomes. On gender identity questionnaire, boys scored 3.9 ± 0.4
(mean ± SD) and girls 3.6 ± 0.5; 1 of 19 boys and 3 of 19 girls had
lower scores, suggesting risk of gender identity disorder. Quality-of-
life scores were 80+ for physical and 65 to 80 for psychosocial
scores.

Conclusions
Early intervention is generally associated with positive outcomes for
patients and parents. Girls had better anatomical outcomes than boys,
and gender dysphoria risks were low in both sexes.

Key words: Disorders of sex development (DSD); Quality of life (QOL);
Gender identity; Health care satisfaction; PedsQL

Article Outline
1. Methods
2. Results
3. Discussion
References

Disorders of sex development (DSD) occur when an individual's
chromosomal, gonadal, or anatomical sex develops atypically [1].
Children affected by these disorders can present in a number of
different ways and at almost any age. However, most commonly,
children are noted to have a DSD at birth when their genitalia are
sufficiently ambiguous that immediate sex assignment is difficult.
This is a distressing situation and necessitates a multidisciplinary
team approach at a centre specialised in the management of these
patients [1].

Most tertiary centres specialising in DSD management advocate early
surgical intervention for patients with DSD. Biological reasons for
operating early include the maternal oestrogenic effect on infant
tissues, satisfactory results, and reduced risk of urinary tract
infections [1], [2] and [3]. Early surgery is also thought to be
psychologically beneficial to the child because normally appearing
genitalia allow for appropriate gender development and less stigma
associated with DSD while also minimising parental anxiety, allowing
for better bonding. Another assumed psychological benefit of early
surgery is the infant's inability to form long-term memories [2],
preventing the child from remembering traumatic hospital experiences.

Presently, there is controversy surrounding early intervention in
DSD, although at the Royal Children's Hospital (RCH), Melbourne, the
Australian and New Zealand referral centre for DSD management, its
multidisciplinary management team continues to offer early surgical
intervention as part of a holistic treatment plan. Some patient
advocacy groups, most notably, the Intersex Society of North America,
are calling for the practice to be abandoned. They claim that
performing such an operation that is not readily reversible and has
profound life-long effects without an individual's informed consent
is unethical. It is possible, however, that members of the Intersex
Society of North America only represent the end of the spectrum of
patients with DSD who experienced poor outcomes and are not
representative of all patients with DSD. Poor outcomes of feminising
genital surgery reported in the UK in 2001 [4] further contributed to
the argument against early intervention in DSD. As long as
controversy persists surrounding DSD management, evaluation of short-
and long-term outcomes is imperative for those centres who practise
early intervention to ensure that current practice is also best
practice.

This study aimed to determine the results of early intervention in
the RCH patient population aged 5 to 10 years. Outcomes measured
included anatomical and cosmetic result, quality of life, and gender
identity. Overall, we found that early intervention yielded
acceptable cosmetic results while producing minimal impairment in
quality of life and gender identity development.

1. Methods
The records of children born between 1997 and 2003 (aged 5-10 years
at time of study) who were treated for a DSD at the RCH were
retrospectively evaluated. Diagnoses, date of birth, and dates of
surgical intervention were noted. Those patients who had not
undergone surgery for ambiguous genitalia were excluded. At the time
of their review appointments, the study was explained to children and
their parents. After obtaining informed consent, children were
examined and genitalia scored on a modified scale by Creighton et al
[4] and completed the PedsQL Pediatric Quality of Life Inventory 4.0.
Parents also completed the Parent Report version of the quality of
life inventory as well as the Gender Identity Questionnaire for
Children (GIQC).

The anatomical and cosmetic evaluation included the following
criteria for females: genital symmetry, clitoral size, clitoral
position, number of perineal openings, size of labia majora and
minora. Males were evaluated for stretched penile length (SPL),
testicular volume, genital symmetry, urethral position, presence of
chordee, scrotal fusion, scrotal position, and position of testes in
the scrotum. Both males and females were given an overall cosmetic
score of good (genitalia appear normal; no abnormal features),
satisfactory (up to 2 minor abnormalities; unlikely to be judged
abnormal by a nonmedically trained person), or poor (genitalia appear
abnormal; 3 or more abnormal features).

The PedsQL Generic Core Scales 4.0 for children and parents are
validated questionnaires, consisting of 23 items [5], [6] and [7].
Items are divided into physical (8 items) and psychosocial (15 items)
domains. Each question asks the child (or parent) to rate how often
an item has been a problem for them in the past 1 month. Possible
responses include the following: 0 = never a problem, 1 = almost
never a problem, 2 = sometimes a problem, 3 = often a problem, and 4
= almost always a problem. Each item was then reverse-scored and
linearly transformed to a scale of 0 to 100 so that 0 = 100, 1 = 75,
2 = 50, 3 = 25, and 4 = 0. The mean scores for each domain were then
calculated. Higher scores indicate better quality of life.

The GIQC is a validated parent-report questionnaire designed to
screen for gender identity disorder in the paediatric population [8].
This 16-item questionnaire encompasses a range of sex-typed
behaviours, and each is rated on a 5-point scale for frequency of
occurrence. Three items also include a response of not applicable.
The score of each item is averaged to obtain a score between 1 and 5
on the questionnaire. Higher scores indicate more same-gender
behaviour and lower scores indicate more cross-gender behaviour.

This project was approved by the institutional ethics committee.

For statistical analysis and descriptive statistics, GraphPad Prism
(Graph Pad, LaJolla, CA) was used.

2. Results
After review of medical records, 54 children were identified as being
eligible for participation in the study. Ten of these patients were
lost to follow-up. Of 44 patients, 41 participated in 1 or more
component of the study. Diagnoses of female participants included 16
congenital adrenal hyperplasia, 2 ovotesticular DSD, and 1 XX
virilisation of unclear cause, and diagnoses of males included 5
mixed gonadal dysgenesis, 3 partial androgen insensitivity syndrome,
3 ovotesticular DSD, 1 5á-reductase deficiency, 1 17â-hydroxysteroid
deficiency, 1 Klinefelter syndrome, 1 placental insufficiency, 1
vanishing testes syndrome, and 6 XY undervirilisation of unclear
cause. The median age of patients at their first surgical
intervention was 13.2 months (range, 1.8-250.1) and the mean age at
the time of study was 7.5 ± 2.1 (mean ± SD) years.

Thirteen females underwent anatomical evaluation. Eleven (85%)
received a cosmetic score of good and 2 (15%) scored satisfactory
(Fig. 1). Of the 21 males who were examined, 11 (52%) scored good, 8
(38%) satisfactory, and 2 (10%) poor. Short SPL was a commonly found
abnormal feature that contributed to the poorer outcomes in the male
population. Only 3 of 21 males had a SPL within 1 SD of normal and
only 10 of 21 were within 2 SD of normal [9].

Full-size image (30K)
Fig. 1. Cosmetic results of early surgery by sex in 5- to 10-year
olds.

View Within Article



Quality-of-life inventories were completed by both patients and
parents. Both parents and children rated physical quality of life as
being close to published values for healthy children [5], with the
exception of male children who rated their physical quality of life
lower (79.06), although this was not significantly lower than that
reported by female children or by parents of male children (Fig. 2
and Fig. 3). In terms of psychosocial quality of life, both parents
and children scored quality of life lower than healthy children [5].
Boys reported a lower psychosocial quality of life than girls as
reported by parents (66.85 vs 75.90, not significantly different) and
children (70.06 vs 78.96, not significantly different).

Full-size image (32K)
Fig. 2. Parent-reported PedsQL scores: healthy children (Varni et al
[5]) (solid black bar), male DSD group (striped bar), and female DSD
group (cross-hatched bar).

View Within Article

Full-size image (32K)

Fig. 3. Child-reported PedsQL scores: healthy children (Varni et al
[5]) (solid black bar), male DSD group (striped bar), and female DSD
group (cross-hatched bar).

View Within Article



Mean scores on the GIQC were significantly different for males and
females (3.95 vs 3.56; P = .0051). One of 19 males and 3 of 19
females had a score of 3 or less, suggesting that they may be at risk
of gender identity disorder or gender dysphoria (Fig. 4).

Full-size image (18K)

Fig. 4. Gender Identity Questionnaire for Children by sex. Data
points within circles represent those children at risk of gender
dysphoria or gender identity disorder.

View Within Article


3. Discussion
This study found that acceptable cosmetic results can be achieved by
early genital surgery, as 100% of females and 90% of males had
satisfactory or better outcomes. Also, when practised in concert with
appropriate psychological care as part of a holistic management plan,
early intervention results in minimal impairment in quality of life
or gender development.

The finding that most patients in our cohort at the RCH had
acceptable cosmetic results agrees with other reports in the
literature that rate cosmetic appearance after genitoplasty. In
addition, we have shown previously that long-term outcomes (at mean
age of 18 years) in our patients undergoing feminising genitoplasty
are excellent, with only 6% with poor cosmetic outcome and a very low
rate of redosurgery required in adolescence [3]. All patients in a
series evaluated by Bocciardi et al [10] were found to have good
cosmetic appearance, although the cosmetic criteria used were not
stated. Similarly, Roll et al [11] found that 13 of 19 patients had
excellent and 6 of 19 had good cosmetic appearance when scored on a
scale of excellent, good, satisfactory, or poor.

However, our results contrast sharply with those reported by
Creighton et al in 2001. They found that 41% of their patients had a
poor cosmetic result, which led to their conclusion that genital
surgery should be delayed until adolescence [4]. The subject
selection methods may explain the differing results of these studies.
In the Creighton study, patients were selected from an adult
gynaecology clinic based on having a history of feminising genital
surgery, whereas the RCH cohort consisted of all patients who
underwent genital surgery at our institution. The patients in
Creighton's cohort may represent the minority of patients with DSD
who are affected by worse outcomes that require adult gynaecological
treatment. Patients whose outcomes had been better may not see the
need for this type of specialised care and therefore may not be
included in their sample.

There is a paucity of information regarding quality of life in
paediatric patients with DSD. Physical quality of life, as reported
by both parents and children, was in the same range as those reported
by healthy children in other studies [5], [6] and [7], with the
exception of male children who rated their physical quality of life
lower (79.06). However, this was not statistically significantly
lower than the physical quality of life reported by female children
or by parents of male children. On the psychosocial quality of life
domain, female children and their parents reported that quality of
life was only slightly lower (78.96 and 75.90) than that reported by
healthy children (79.37) and their parents (80.58) [7]. Conversely,
both male children and their parents rated psychosocial quality of
life as being low at 70.06 and 66.85, respectively. This may be
because of the poorer cosmetic results related to micropenis in the
male patient group.

This study also found that children in the RCH cohort display more
cross-gender behaviour than normal children but that most were not at
serious risk of gender dysphoria or gender identity disorder. This is
not particularly surprising as similar cross-gender behaviour has
been found in boys with partial androgen insensitivity syndrome [12]
and in girls with congenital adrenal hyperplasia [13] and [14]
because of their aberrant prenatal hormone exposure. However, results
from a study by Zucker et al [14] suggest that although children with
congenital adrenal hyperplasia display more tomboyish behaviour, they
do not experience higher levels of gender dysphoria as adults.

The main limiting factor of this study was sample size and
participation rate, which were 41 (34 for anatomical/cosmetic
evaluation) and 76% (63%), respectively. Most nonparticipants were
lost to follow-up. This raises the concern of whether those lost to
follow-up experienced poorer outcomes than participants. However,
those lost to follow-up underwent fewer operations and were slightly
older than those studied, suggesting that nonparticipants actually
experienced better outcomes than those studied, and that they
subsequently lost contact with the hospital as they no longer
required specialised care.

In conclusion, results of this study support continuation of early
intervention in DSD. When practised in concert with a holistic
management plan, surgery yields positive outcomes in terms of
cosmesis, minimal impairment in quality of life, and appropriate
gender identity development.

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Presented at the 55th Annual Congress of the British Association of
Paediatric Surgeons, Salamanca, Spain, July 2-5, 2008.

Corresponding author. Department of Surgical Research, Royal
Children's Hospital, Parkville, VIC 3052, Australia. Tel.: +61 3 9345
5805; fax: +61 3 9345 7997.
1 Presenting author.


Journal of Pediatric Surgery Volume 44, Issue 2, February 2009, Pages
413-416