Neurodevelopmental Outcomes in Infants and Children With Single-Suture

This article was downloaded by: [Texas A & M International University]
On: 04 October 2014, At: 14:31

Publisher: Routledge
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Developmental Neuropsychology
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/hdvn20
Neurodevelopmental Outcomes in
Infants and Children With Single-Suture
Craniosynostosis: A Systematic Review
abcd acde af
Sarah J. Knight , Vicki A. Anderson , Megan M. Spencer-Smith
acg
& Annette C. Da Costa
a
Clinical Sciences, Murdoch Childrens Research Institute,
Melbourne, Australia
b
Department of Paediatrics, The University of Melbourne,
c
Psychological Sciences, The University of Melbourne, Melbourne,
Australia
d
Victorian Paediatric Rehabilitation Service, Monash Children’s,
e
Psychology Department, The Royal Children’s Hospital, Melbourne,
Australia
f
Department of Neuroscience, Karolinska Institutet, Stockholm,
Sweden
g
Department of Plastic and Maxillofacial Surgery, The Royal
Children’s Hospital, Melbourne, Australia
Published online: 17 Apr 2014.
To cite this article: Sarah J. Knight, Vicki A. Anderson, Megan M. Spencer-Smith & Annette
C. Da Costa (2014) Neurodevelopmental Outcomes in Infants and Children With Single-Suture
Craniosynostosis: A Systematic Review, Developmental Neuropsychology, 39:3, 159-186, DOI:
10.1080/87565641.2014.886690
To link to this article: http://dx.doi.org/10.1080/87565641.2014.886690
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the
“Content”) contained in the publications on our platform. However, Taylor & Francis,
our agents, and our licensors make no representations or warranties whatsoever as to
the accuracy, completeness, or suitability for any purpose of the Content. Any opinions
and views expressed in this publication are the opinions and views of the authors,
and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content
should not be relied upon and should be independently verified with primary sources
of information. Taylor and Francis shall not be liable for any losses, actions, claims,
proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or
howsoever caused arising directly or indirectly in connection with, in relation to or arising
out of the use of the Content.
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden. Terms &
Conditions of access and use can be found at http://www.tandfonline.com/page/terms-
and-conditions
Downloaded by [Texas A & M International University] at 14:31 04 October 2014
DEVELOPMENTAL NEUROPSYCHOLOGY, 39(3), 159–186
Copyright © 2014 Taylor & Francis Group, LLC
ISSN: 8756-5641 print / 1532-6942 online
DOI: 10.1080/87565641.2014.886690
Neurodevelopmental Outcomes in Infants and Children

With Single-Suture Craniosynostosis: A Systematic Review
Sarah J. Knight
Clinical Sciences, Murdoch Childrens Research Institute, Melbourne, Australia,

Department of Paediatrics, The University of Melbourne, Melbourne, Australia,
Psychological Sciences, The University of Melbourne, Melbourne, Australia, and
Victorian Paediatric Rehabilitation Service, Monash Children’s, Melbourne, Australia
Vicki A. Anderson
Psychological Sciences, The University of Melbourne, Melbourne, Australia,
Victorian Paediatric Rehabilitation Service, Monash Children’s, Melbourne, Australia, and
Psychology Department, The Royal Children’s Hospital, Melbourne, Australia
Megan M. Spencer-Smith
Clinical Sciences, Murdoch Childrens Research Institute, Melbourne, Australia, and
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden
Annette C. Da Costa
Psychological Sciences, The University of Melbourne, Melbourne, Australia, and
Department of Plastic and Maxillofacial Surgery, The Royal Children’s Hospital, Melbourne,
Australia
Children with single-suture craniosynostosis (SSC) are increasingly considered to be at high risk
of adverse neurodevelopmental outcomes. This systematic review aimed to synthesise and critically
appraise the existing literature on the neurodevelopmental features of SSC, with particular attention
to methodological quality. A total of 33 articles based on 27 cohorts met inclusion criteria. In the
context of variable methodological design and quality, most neurodevelopmental studies indicated
that children with SSC are at increased risk for difficulties in cognitive, language, and motor domains
during infancy (both pre- and post-surgery) and childhood. Limited information exists on factors
influencing outcome.
Correspondence should be addressed to Sarah J. Knight, Developmental Disability and Rehabilitation Research,
Clinical Sciences, Murdoch Childrens Research Institute, Royal Children’s Hospital, Flemington Road, Parkville, VIC
3052, Australia. E-mail: sarah.knight@mcri.edu.au
160 KNIGHT, ANDERSON, SPENCER-SMITH, DA COSTA
Craniosynostosis is a developmental craniofacial disorder affecting approximately 1 in 2,500 live

births (Cohen & MacLean, 2000; Singer, Bower, Southall, & Goldblatt, 1999). It is character-
ized by premature, pathological fusion of one or more of the fibrous connections, or sutures,
that normally separate the bony plates of the skull during early development. Of typically pre-
natal onset, this condition produces anomalous skull growth and may have consequences for the
developing brain as a result of compromised brain growth, risk of raised intracranial pressure
(ICP) and primary brain dysmorphology. Skull phenotype is dependent on the particular suture
fused (Figure 1). Craniofacial and brain development is a complex and highly integrated pro-
cess involving several gene families, cell populations and tissue types that is not well understood
(Richtsmeier et al., 2006). While craniosynostosis appears to reflect disruption to these complex
processes, its aetiology and pathophysiology remain largely unclear. Craniosynostosis may occur
as part of a syndrome occurring in association with other congenital abnormalities, but most cases
are isolated and affect a single suture. In single-suture craniosynostosis (SSC), surgery is usually
indicated and preferentially performed in early infancy, to release the fused suture, reshape the
deformed skull and improve brain growth potential (Cohen & MacLean, 2000).
Two published narrative reviews (Kapp-Simon, Speltz, Cunningham, Patel, & Tomita, 2007;
Speltz, Kapp-Simon, Cunningham, Marsh, & Dawson, 2004) have concluded that SSC is associ-
ated with an increased risk for mild but persistent neuropsychological deficits. The mechanisms
by which neurodevelopment could be disrupted in SSC are unknown. Morphological differences
between the brains of children with SSC and typically developing children have been reported
both prior to and following cranial vault reconstruction surgery (Aldridge et al., 2005; Aldridge,
Marsh, Govier, & Richtsmeier, 2002). According to popular developmental neuroscience models
the developing brain is vulnerable to disruption and a range of factors will determine a child’s
neurodevelopmental outcome (Anderson, Spencer-Smith, & Wood, 2011; Dennis, Yeates, Taylor,
& Fletcher, 2007). First, certain biological risk factors may contribute to functional reorganiza-
tion of the brain and associated neurological and developmental processes. In SSC, these might
include the diagnostic subtype (metopic, sagittal, coronal, lambdoid), presence and duration of
raised ICP, associated brain abnormalities, and severity of cerebral malformation. Intrinsic factors
such as presence of a gene mutation should also be considered. Second, the child’s environment,
including sociodemographic characteristics and family function, can have a major influence on a
child’s development throughout life. Lastly, developmental factors, including age at surgery and
age at testing, may influence research findings and child outcomes (Dennis et al., 2007). In par-
ticular, suggestions from the broader child neuropsychology literature support the view that an
earlier age at “insult” (that is, cranial abnormality, surgery) may result in poorer cognitive out-
come (Anderson et al., 2011), while later age at testing is more likely to provide a fuller account
of the child’s neurodevelopmental weaknesses (Ballantyne, Spilkin, & Trauner, 2007; Dennis,
Spiegler, Hetherington, & Greenberg, 1996; Dennis et al., 2007; Taylor, Minich, Klein, & Hack,
2004; H. G. Taylor et al., 2002; Westmacott, MacGregor, Askalan, & deVeber, 2009).
We conduct the first systematic review of the existing literature on the neurodevelopmental
features of SSC, with particular attention to the robustness of the specific methodological tech-
niques applied. This work further builds on previous review papers by including 11 recent articles
published since the time of last narrative review (2007). We have used a theoretical framework,
which incorporates factors associated with functional outcome, to provide a richer understanding
of the developmental implications of these conditions, and to identify areas warranting further
research inquiry.
NEURODEVELOPMENT IN SINGLE-SUTURE CRANIOSYNOSTOSIS 161
A
FIGURE 1 Skull phenotype for the three most common forms of

single-suture craniosynostosis: (A) sagittal, (B) coronal, and (C) metopic
synostosis. (color figure available online)
METHOD
Literature Search and Eligibility Criteria
Literature searches were performed in June 2012 using Medline (1990–2012), PsycINFO
(1990–2012), and CINAHL (1990–2012). The searches were restricted to peer-reviewed jour-
nal articles published in English. The Medical Subject Headings (MeSH) or key words included
[craniosynostosis] AND [motor OR language OR neuropsychology OR cognition].
Abstracts of all articles retrieved from the searches were independently reviewed by two
authors (SK and ADC) for inclusion, and potentially relevant papers were retrieved in full. Two
reviewers (SK and ADC) independently assessed these studies for inclusion, using the follow-
ing pre-defined criteria: (a) studies of infants, children and/or adolescents (≤18 years of age)
with SSC who have or have not undergone surgical intervention for the condition; and (b)
studies reporting neurodevelopmental/ neurocognitive/educational outcomes (e.g., developmen-
tal, motor, language, cognitive). Additional potentially relevant journal articles were sought by
searching citation lists of the articles that met inclusion criteria.
Data Extraction and Synthesis
All articles were reviewed and data extracted by a single reviewer (SK) using a standardized
extraction form designed for this review. Information extracted pertained to study design, partici-
pant characteristics, method of diagnosis, inclusion/exclusion criteria, outcome measures, sample
ascertainment procedures, recruitment/attrition rates, examiner characteristics and study find-
ings. Extracted data were double-checked for accuracy by a second reviewer (ADC). Outcomes of
included studies were divided into three categories: pre-surgical outcome, postsurgical outcome
during infancy, and childhood outcome. Meta-analysis was precluded due to wide variability in
methodological design including comparison of clinical sample to test norms rather than a control
group, variation in tests used, inclusion of heterogeneous subgroups, wide age variations, possi-
ble sample ascertainment biases and varied exclusion criteria. Thus, we performed a descriptive
review which we conducted rigorously and systematically.
RESULTS
Of 508 papers retrieved from the search, the final sample included 33 papers examining
neurodevelopmental status in 27 cohorts of infants and/or school-aged children with SSC
(Figure 2). A list of excluded papers is available from the corresponding author on request.
Study Characteristics and Quality
Overall, aspects of methodological design were extremely variable across the 33 included
research papers, with a preponderance of cross-sectional studies, variations in surgical status,
and limited use of matched control groups (sTable 1 and 2). The age ranges at each assessment
point tended to be broad and varied widely across studies. One-third of studies reported partici-
pation rate, with varying rates reported (M = 75%, range: 23–100%). Attrition rates were clearly
stated in 3 (Bellew, Chumas, Mueller, Liddington, & Russell, 2005; Cohen et al., 2004; Speltz,
Endriga, & Mouradian, 1997) of the 12 longitudinal studies, with one of these studies conducting
statistical comparisons between those whose data were included in the study to those who did
not participate in all assessments (Speltz et al., 1997). Diagnoses other than SSC that may have
affected outcome assessment findings were included in the exclusion criteria by 18/33 studies.
Reported exclusionary diagnoses varied widely across these studies and consisted of prematurity
(Kapp-Simon, Leroux, Cunningham, & Speltz, 2005; Ruiz-Correa et al., 2007; Speltz et al., 2007;
References (duplicates removed)

from electronic search and screened
n = 508
Excluded based on review of titles

and abstracts n=460
Full copies retrieved

and assessed for

eligibility n = 48 Excluded n = 19
Not SSC only n = 10; not a data paper (e.g.,

Studies identified from review or letter) n = 4; no developmental
searching reference outcome assessment n = 4; conference
lists n = 4 proceedings n = 1
Publications included in
the review n = 33
FIGURE 2 Flow diagram of literature search.
Starr et al., 2007, 2010; Toth et al., 2008), presence of major medical or neurological conditions
(Bottero, Lajeunie, Arnaud, Marchac, & Renier, 1998; Da Costa et al., 2006, 2012; Kapp-Simon
et al., 2005; Korpilahti, Saarinen, & Hukki, 2012; Magge, Westerveld, Pruzinsky, & Persing,
2002; Ruiz-Correa et al., 2007; Speltz et al., 2007; Starr et al., 2007 2010; Toth et al., 2008), intra-
operative or postoperative complications (Da Costa et al., 2006; Speltz et al., 1997), sensorineural
hearing impairment (Shipster et al., 2003), birth defects (Speltz et al., 1997), presence of major or
minor malformations (Kapp-Simon et al., 2005; Korpilahti et al., 2012; Ruiz-Correa et al., 2007;
Speltz et al., 2007; Starr et al., 2007, 2010; Toth et al., 2008), extracranial pathologic condition
(Mendonca et al., 2009), genetic disorder (Chieffo et al., 2010) and various syndromes (Becker
et al., 2005; Bottero et al., 1998; Magge et al., 2002; Mathijssen, Arnaud, Lajeunie, Marchac, &
Renier, 2006; Mendonca et al., 2009). One-third of studies described examiner qualifications and
measures used to ensure examiner reliability were seldom reported.
Participant Characteristics
Participant characteristics for each study are displayed in Table 2. The number of participants in
each trial ranged from 16 to 396 (Md = 49). With the exception of two studies (Arnaud et al.,
2002; Mathijssen et al., 2006) reporting on a sample of children with coronal synostosis, a prepon-
derance of male participants characterized study samples (Md = 76%, range 30–86%), reflecting
general trends in the epidemiology of SSC. Gender distributions were not reported in five studies
TABLE 1
Summary Statistics of the Methodological Design of Included Studies
Design I Cross-sectional (21/33) Longitudinal (12/33)
Age at assessment Infancy Childhood Both infancy & Infancy only Infancy to
(9/21) (9/21) childhood or (7/12) childhood (5/12)
unknown (3/21)
Surgery status Pre-surgery Post-surgery Mixed∗ Pre- to Mixed∗
(7/21) (10/21) (4/21) post-surgery (2/12)
(10/12)
Design II Retrospective (10/33) Prospective (23/33)

Comparison sample Matched control group (9/33) Normative data from psychometric
measure (23/33)
Radiographic Reported (15/33) Not reported (18/33)
confirmation of
SSC diagnosis
Sample Clinic-referred source Medical record review Not reported

ascertainment (16/33) (10/33) (7/33)
Subtype of SSC Mixed (14/33) Sagittal (10/33) Metopic (7/33) Coronal (2/33)
Note. SSC = single-suture craniosynostosis.

∗ Mixed: only a proportion of the sample underwent reconstructive surgery.
(Da Costa et al., 2006; Gewalli et al., 2001; Magge et al., 2002; Nejad & Nikoobakhat, 2010;
Panchal et al., 2001). Over half of the studies focused on a particular subtype of SSC, and the
remaining included mixed subtypes of SSC (Table 1 and 2).
Studies investigating post-surgical functioning (n = 28) documented age at surgical interven-
tion in 60% of cases. Surgery ages varied extensively both within and between study samples
(Table 2). Family socioeconomic status (SES) (Da Costa et al., 2012; Kapp-Simon et al., 2005;
Panchal et al., 2001; Speltz et al., 2007; Starr et al., 2007, 2010; Toth et al., 2008), maternal edu-
cation (Da Costa et al., 2012; Speltz et al., 2007; Warschausky et al., 2005), and parental stress
(Kapp-Simon et al., 2005) were not commonly reported. Participant ethnicity was indicated in
7/33 studies (Kapp-Simon et al., 2005; Korpilahti et al., 2012; Ruiz-Correa et al., 2007; Speltz
et al., 2007; Starr et al., 2007, 2010; Toth et al., 2008). Few studies (n = 7) reported on varied
potential medical risk factors for developmental outcome, such as pre- and perinatal characteris-
tics (e.g., Apgar score, birth complications) (Virtanen, Korhonen, Fagerholm, & Viljanto, 1999),
surgical complications (Da Costa et al., 2012), gestational age (Da Costa et al., 2012; Korpilahti
et al., 2012; Warschausky et al., 2005), or birth weight (Virtanen et al., 1999; Warschausky et al.,
2005).
Study Findings
Pre-Surgical Infant Neurodevelopment
Various outcome measures were employed across studies (Table 3). Most of the infant studies
(n = 14) used a version of the Bayley Scales of Infant Development (BSID, BSID–II) to assess
TABLE 2
Methodological and Participant Characteristics of Included Studies
First Author Number of Surgery Age in % Surgery Age at Evaluation in

(Year) Cases of SSC Months∗ male Statusb Monthsa Neurobehaviorial Measures
Da Costa (2012) 56 SSC N/A 80 Pre 8.9 (2.9) [4–16] BSID-II: MDI, PDI
Korpilahti (2012) 32 SSC 10.6 (6.6) 66 Post 40.8 (3.6) Reynell Developmental Language Scales III;
Renfrew Naming Task; MacArthur
Communicative Developmental Inventories +
informal assessment + parent report
Bellew (2011) 32 sagittal 8.5 (7.3) [2.8-39.9] 81 Pre T1: 7.4 (6.3) [2.4–35.1] Griffiths Mental Development Scales
Post T2: 15.5 (7.9) [5.7–46.3]
T3: 64.2 (3.3)
[58.6–71.3]
Chieffo (2011) 35 sagittal 7.2 [4-12] 74 Post Sagittal: 13.4 WISC-R, Purdue Pegboard, Developmental Test
[9.2–16.1] years of Visual Motor and Perceptual Integration,
Rey Complex Figure, Bells Cancellation Test,
Tower of London
30 unicoronal Unicoronal: 14.9
[9.9–16.11] years
Nejad (2010) 24 SSC 8.9 NR Pre 8.9 [4–16] BSID-II: MDI, PDI
Post
Starr (2010)∗ 49 metopic NR 69 Pre T1 Md = 7 BSID-II, PLS-3, quantified measure of severity
based on CT
Post T2 Md = 19, T3 Md =
37
Ruiz-Correa 75 sagittal N/A 83 Pre Md = 4.5 BSID-II, PLS-3, quantified measure of severity
(2007)∗ based on CT
Toth (2008)∗ 200 SSC NR 66 Post [17–24] A-not-B task
Mendonca (2008) 20 metopic 16 [11–26] 65 Post NR Speech and language assessment (see Shipster,
2003); Quantified measure of severity based on
CT
Starr (2007)∗ 168 SSC NR 64 Pre Md = 18.1 [17–31] BSID-II; PLS-3
Post
Speltz (2007)∗ 125 SSC N/A 61 Pre 6.5 (3.9) BSID-II; PLS-3
(Continued)
165
166
TABLE 2
(Continued)
First Author Number of Surgery Age in % Surgery Age at Evaluation in

(Year) Cases of SSC Months∗ male Statusb Monthsa Neurobehaviorial Measures
Da Costa (2006) 18 SSC NR NR Post 10.9 (2.5) [7–16] years WISC-III

Mathijssen (2006) 220 unicoronal 13 [4 – 192] 30 Pre T1: n = 85 < 1 year Brunet-Lezine test, Nonverbal Brunet-Lezine
Scale, New Metric Intelligence Scale, WISC-R
Post T2: n = 59 ≥ 1 year
Kelleher (2006) 63 metopic Md=12 [4-144] 76 Mixed NR Parent questionnaire
Kapp-Simon 100 SSC N/A 64 Pre 7.3 [1.7–30.6] BSID-II; PLS-3; maternal IQ; parenting stress
(2005)∗ index
Warschausky 22 metopic 11.6 (4.8) 86 Pre 10.6 (6.4) [3.6–25.3] BSID or BSID-II (MDI only)
(2005)
Becker (2005) 214 SSC NR 58 Post 6.3 [2.0–10.6] years Diagnosis of speech, language, cognitive or
behavioral abnormalities (assessed using
informal & sometimes standardized assessment
[CBCL, BSID I & II, VABS, Cattel scale])
Bellew (2005) 43 sagittal 8.0 (7.16) [2.8-39.7] 84 Mixed T1: surgery, no surgery Griffiths Mental Development Scales
(28 surgery, = 7 T2: surgery = 15,
13 no no surgery = 35
surgery)
Cohen (2004) 22 SSC 5.9 [2.5-10] 55 Pre T1: 5.9 [2.5-10] BSID-II
Post T2: 1 year post-surgery
(n = 15)
Boltshauser 30 sagittal N/A 77 Pre No surgery 9.3 Formal neuropsychology assessment (tests varied
(2003) [2.5–25.5] according to age)
Shipster (2003) 76 sagittal NR 80 Mixed Mixed surgery status BSID-II; WPPSI-R; WISC-III, standardized and
[9 months – 15 years] non-standardized speech and language tests
Arnaud (2002) 99 bicoronal 11 [1-69] 39 Pre NR Brunet-Lezine test, Nonverbal Brunet-Lezine
Post NR
Magge (2002) 16 sagittal 10 [1-26] NR Post [6–16] years WISC-III, WRAT-R, Connor’s CPT, Wisconsin
Card Soring Task, Developmental Test of
Visual-Motor Integration, VABS
Gewalli (2001) 26 sagittal 6.9 (2.3) [4-16] NR Pre T1: [4–16] Griffith Mental Development Scales
Post T2: [9–40]
Panchal (2001) 21 SSC N/A NR Pre T1: 10.9 BSID
Virtanen (1999) 18 sagittal 2.8 [0.2-7.5] 72 Post [7.8–16.3] years WISC-R
Bottero (1998) 76 metopic 11.5 [2-74] 82 Post 6.5 [3.0–16.5] years Brunet-Lezine test, Nonverbal Brunet-Lezine
Kapp-Simon 84 SSC 7.9 (3.8) [<12] n=47 78 Mixed T1: 8.1 (4.3), T2: 18.4 T1 & T2: BSID MDI, T3: McCarthy Scales of
(1998) (6.2), T3: 50.2 (11.7) Children’s Abilities
20.9 (3.8)
[>12] n=16
Lajeunie (1998) 127 metopic NR 77 Mixed 4.8 [0.5–16.5] years NR
Speltz (1997) 19 sagittal 4.7 (2.0) [1.5-8.6] 82 Pre T1:4.1 (1.7) [1.5–8.0] BSID
Post T2: 12.4 (0.9)
[11.1–15.9]
T3: 24.4 (1.7)
[15.5–27.2]
Sidoti (1996) 36 metopic NR 75 Mixed 7.1 [0.5–22.2] years Research designed questionnaire
Arnaud (1995) 396 sagittal NR 77 Pre T1: 12 Brunet-Lezine test, Nonverbal Brunet-Lezine
100 were Post T2: 6.4 years Scale, New Metric Intelligence Scale, WISC-R
tested twice
(41 without
surgical
correction)
Kapp-Simon 45 SSC NR 76 Pre T1: 8.1 BSID or BSID-II at T1 and T2 (MDI only)
(1993) Post T2: 18.4 T3: Direct assessment or chart review
Note. T1 = first assessment; T2 = second assessment; T3 = third assessment; NR = Not reported; N/A = Not applicable; BSID-II = Bayley Scale of Infant Development, 2nd
Edition; CBCL = Child Behavior Checklist; CPT = Continuous Performance Task; CT = computerized tomography; MDI = Mental Development Index (from BSID/BSID-II);
PDI = Psychomotor Development Index (from BSID/BSID-II); PLS-3 = Preschool Language Scale, 3rd Edition; SSC = single-suture craniosynostosis; VABS = Vineland
Adaptive Behavior Scales; WISC-III = Wechsler Intelligence Scales for Children–Third Edition; WISC-R = Wechsler Intelligence Scales for Children–Revised; WPPSI-R =
Wechsler Preschool and Primary Scales of Intelligence–Revised; WRAT-R = Wide Range Achievement Test Revised.
∗ part of a larger study
a M (SD) [range] unless otherwise specified. b Pre = no craniofacial reconstructive surgery at the time of developmental assessment; Post = participants had undergone craniofacial
reconstructive surgery at the time of developmental assessment; Mixed = some participants in the sample had undergone craniofacial reconstructive surgery at the time of
developmental assessment, others had not.
167
168
TABLE 3
Summary of Results, Strengths, and Limitations of Included Studies
First Author (Year) Summary of Outcome Results Strengths Limitations
Da Costa (2012) Lower MDI, M = 97.7 (6.7), and PDI, M = 87.7 Prospective Cross-sectional
(13.0). No association between SSC subtype and Medium sample size No control group
MDI or PDI Excluded other diagnoses that may affect outcome Surgery age not reported
Reported high participation rate Variable age at assessment
Radiographic confirmation of SSC reported
Korpilahti (2012) Deficient language skills in all patients with SSC. Prospective Small sample size
Better language skills for sagittal synostosis Excluded other diagnoses that may affect outcome No control group
compared with other types of SSC Radiographic confirmation of SSC reported Participation and attrition rates not
reported
Bellew (2011) Pre-surgery: poorer gross motor function than other Prospective Small sample size
areas Longitudinal No control group
Post-surgery: deficit resolved and improvement at Attrition rate reported Variable age at assessment
5-year follow-up Did not exclude comorbidities that may
The children with non-surgical SS (no surgery) affect outcome
showed no improvement in development and Participation rate not reported
deterioration in fine motor control Limited sample characteristics reported
Chieffo (2011) All children started school at a normal age and Prospective Cross-sectional
attended regular classes. Sagittal: 7% visuospatial Medium sample size Variable age at assessment
and constructional ability defects and visual Control group Did not exclude comorbidities that may
memory recall deficits; 17% selective and affect outcome (with the exception of
sustained attention deficits. Unicoronal: 30% genetic disorder)
processing and planning speech deficits Participation rate not reported
Limited sample characteristics reported
Nejad (2010) Reduced pre-surgery BSID-II scores; MDI: M = Prospective Small sample size
84.3 (2.1); PDI: M = 80.5(4.2). Improvements Longitudinal No control group
postoperatively on BSID-II; MDI: M = 91.3 (0.1); Attrition rate reported Did not report gender
PDI: M = 91.3(0.2) but below controls. Mixed surgical status
Improvements in performance level from pre- to Variable age at assessment
post-surgery Did not exclude comorbidities that may
affect outcome
Participation rate not reported
Starr (2010) Little association between neurodevelopmental Prospective Did not report surgery age
scores and severity and no associations that Medium sample size Variable age at assessment
persisted at age 3 years Control group
Excluded other diagnoses that may affect outcome
Participation rate reported
Ruiz-Correa (2007) No association between neurodevelopmental level Prospective Variable age at assessment
and severity Medium-large sample size
Control group
Excluded other diagnoses that may affect outcome
Toth (2008) No difference between cases and controls for visual Prospective Did not report age at surgery
memory and response inhibition. No difference in Large sample size Variable age at assessment
performance between metopic and sagittal Control group
synostosis Excluded other diagnoses that may affect outcome
(Continued)
169
170
TABLE 3
(Continued)
Medonca (2008) 6/20 had speech and language impairments. Excluded other diagnoses that may affect outcome Retrospective
No association between severity or surgery age Cross-sectional
with speech and language performances Small sample size
No control group
No standardised outcome measures used
Did not report age at assessment
Starr (2007) Lower scores on MDI (M = 92.1), PDI Prospective Did not report surgery age
(M = 84.9) and PLS-AC, but not on PLS-EC, than Large sample size Variation in age at assessment
controls [MDI (M = 95.0), PDI (M = 88.9)]. Control group
Scores unrelated to timing of surgery Excluded other diagnoses that may affect outcome
Speltz (2007) Lower scores on MDI (M = 91.1) and PDI Prospective Variation in age at assessment
(M = 84.1) than controls (MDI:M = 94.9), PDI Large sample size
(M = 88.8). Scores on PLS-3 were not different Control group
from controls. Excluded other diagnoses that may affect outcome
No effect of location of synostosis, age at Radiographic confirmation of diagnosis reported
diagnosis, gender, maternal intelligence on test Participation rate reported
scores
Da Costa (2006) IQ in average range: M = 104.7 (15.8). No age or Prospective Cross-sectional
gender effect on outcome Excluded other diagnoses that may affect outcome Small sample size
No control group
Surgery age and gender distribution not
reported
Variation in age at assessment
Participation rate not reported
Mathijssen (2006) Preoperative performance not associated with Prospective No control group
surgery age. Longitudinal Age at assessment not clearly specified
No difference in mean postoperative IQ between Large sample size Wide variation in age at surgery
surgery before 1 year and after 1 year. Increased Did not exclude comorbidities that may
incidence of elevated ICP, but no effect on affect outcome
cognitive outcome. Participation rate not reported
No correlation between the presence of the
FGFR3 mutation and postoperative IQ
Kelleher (2006) 34% speech and/or language delay, 47% receiving Medium sample size Retrospective
remedial or resource hours, 20% required a Cross-sectional
special needs classroom assistant because of No control group
behavioral issues. Mixed surgical status
No differences between children treated with Age at assessment not reported
surgery and those treated conservatively No objective assessment
37% of parents expressed concerns about their Did not exclude comorbidities that may
child’s behavior affect outcome
Kapp-Simon (2005) Lower scores on MDI (M = 91.9), PDI (M = Prospective Cross-sectional
83.5) and PLS-AC (M = 90.4) but not on PLS-EC Large sample size No control group
(M = 95.8). Excluded other diagnoses that may affect outcome Surgery age not reported
Maternal IQ and SES not correlated with MDI, Radiographic confirmation of diagnosis reported Variation in age at assessment
PDI, or PLS. Participation rate reported
Gender unrelated to developmental status.
Infant age negatively correlated with PLS-AC
MDI scores for sagittal and right unicoronal
synostosis were lower than in the other diagnostic
subtypes
(Continued)
171
172
TABLE 3
(Continued)
Warschausky (2005) MDI: M = 96.0 (SD = 14.5). No difference in MDI Radiographic confirmation of SSC reported Retrospective
scores by severity Cross-sectional
MDI positively correlated with maternal education Small sample size
No control group
2 versions of test used
Did not exclude comorbidities that may
affect outcome
Becker (2005) Speech, cognitive, and/or behavioral abnormalities Large sample size Retrospective
in 49% (right unilateral coronal, 61 %; bilateral Radiographic confirmation of SSC reported Cross-sectional
coronal, 55%; multi, 47%; metopic, 57%; left No control group
unilateral coronal, 52%; lambdoid, 44%; and Surgery age not reported
sagittal, 39%). Wide variation in age at assessment
As patient age increased, percentage of speech, Variation in assessment used for
cognitive and behavioural difficulties also diagnosis of abnormality (sometimes
increased not standardised assessment)
affect outcome
Bellew (2005) Lower motor scores (M = 89.4, SD = Prospective Variation in age at assessment
23.1) compared to controls (M = 101.8, SD = Longitudinal Small sample sizes when divided into
15.6) and increase in motor scores for patients Control group surgery versus no surgery
post-surgery (M = 108.8, SD = 13.9). Reported participation and attrition rates Did not exclude comorbidities that may
No difference between controls and patients on all affect outcome
other scales. Increase in motor scores following
surgery
All scales within normal limits for infants that did
not undergo surgery. T1: DGQ M = 98.6 (SD =
8.6); T2: DGQ M = 99.8 (SD = 21.0)
Cohen (2004) Preoperative: MDI M = 81.1, PDI M = 78.3 Prospective Small sample size
Postoperative: MDI M = 79.3, PDI M = 89.53 Longitudinal Variation in age at assessment
Post-surgery improvement in PDI scores, but not Did not exclude comorbidities that may
MDI scores affect outcome
Low participation rate
Boltshauser (2003) Average IQ. 6 patients: below average learning and Prospective Cross-sectional
memory. 12 children below average attention Control group Small sample size
Radiographic confirmation of SSC reported Variation in age at assessment
Participation rate reported Did not exclude comorbidities that may
affect outcome
Shipster (2003) No increased prevalence of global cognitive Medium sample size Retrospective
impairment but high rate of speech and/or Radiographic confirmation of SSC reported Cross-sectional
language impairment (37%). Participation rate reported No control group
Raised intracranial pressure, peri-neonatal risk Surgery age not reported
factors, otitis media, or being operated unrelated Mixed surgery status
to impairment. Wide variation in age at assessment
Older surgery age and family history of speech Did not exclude comorbidities that may
and language impairment both associated with affect outcome
impairments
Arnaud (2002) Pre-surgery mental status better in the patients tested Prospective Age at assessment not reported
before 1 year of age. Pre-surgery operative mental Longitudinal No control group
assessment correlated with postoperative Large sample size Did not exclude comorbidities that may
assessment. Postoperative mental outcome better Participation rate reported affect outcome
when surgery performed before 1 year of age.
Functional outcomes better in the subgroup of
noncarriers of the FGFR mutation, but differences
were not statistically significant
(Continued)
173
174
TABLE 3
(Continued)
Magge (2002) Average FSIQ, VIQ, significantly better than PIQ; Excluded other diagnoses that may affect outcome Retrospective
Increased. 50% had a reading and/or spelling Participation rate reported Cross-sectional
disability. No association between surgery age and Small sample size
outcome No control group
Participation rate low
Gewalli (2001) No difference in pre- and post-surgery Prospective Small sample size
developmental scores. Longitudinal No control group
No association between pre- and post-surgical Gender distribution not reported
scores and ICP Variation in age at assessment
Pre-surgery: GDQ M = 104.5 (SD=12.4), Did not exclude comorbidities that may
Post-surgery: GDQ M = 101.4 (SD=13.6) affect outcome
Participation and attrition rate not
reported
Panchal (2001) Pre-surgery PDI, but not MDI scores, were Prospective Cross-sectional
significantly lower than test norms. Radiographic confirmation of SSC reported Small sample size
No association between age at assessment and No control group
MDI or PDI scores. PDI distribution: 0% Gender distribution not reported
accelerated, 43% normal, 48% mild delay, 9% Did not exclude comorbidities that may
significant delay. affect outcome
No association between SES (as referenced by Participation rate not reported
health coverage status) and developmental
outcome
Virtanen (1999) Mild deficiencies in immediate memory capacity and Prospective Control group Radiographic Cross-sectional
language development. Other performances equal confirmation of SSC reported Small sample size
to controls. Severity at time of surgery not Wide variation in age at assessment
associated with neuropsychological performance. Did not exclude comorbidities that may
No association between surgery age and test affect outcome
performance Participation and attrition rates not
reported
Bottero (1998) 32% of sample with reported or observed Medium-Large sample size Retrospective
developmental problem. Excluded some comorbidities that may affect Cross-sectional
Problem status associated with severity, surgery outcome No control group
prior to one year of age and extracranial Participation rate reported No standardised outcome measures used
abnormality Wide variation in age at assessment
Kapp-Simon (1998) Base rate of mental retardation at T1 was consistent Prospective No control group
with normative data; however, the incidence of Longitudinal Variation in age at assessment
retardation was two to three times the expected Medium-large sample size Surgical status mixed
rate at T2 and T3. Did not exclude comorbidities that may
Learning disorders were present in 47% of affect outcome
school-age children who were not retarded. Participation and attrition rates not
Subtype or surgical status not related to outcome reported
Lajeunie (1998) IQ M = 103 (12) [69–140] Retrospective
Cross-sectional
No control group
Measures used not reported
Surgery status mixed
Wide variation in age at assessment
affect outcome
Speltz (1997) No group differences at any age Prospective Small sample size
MDI: T1: M = 105, SD = 14; T2: M = 112, SD = Longitudinal Variation in age at assessment
14; T3: M = 107, SD = 21 Control group Participation and attrition rates not
PDI: T1: M = 104, SD = 10; T2: M = 102, SD = Excluded other diagnoses that may affect outcome reported
13; T3: M = 103, SD = 12. MDI scores and
surgery age inversely correlated
Sidoti (1996) 20 = normal development without apparent Radiographic confirmation of SSC Retrospective
disability. 8 = mild to moderate learning reportedParticipation rate reported Cross-sectional
disabilities or behavioral problems, 4 = significant Small sample size
mental impairment. No control group
Impaired cognitive development not limited to No standardised measures
children with abnormal karyotype or central Surgery status mixed
nervous system anomaly Surgery age not reported
affect outcome
(Continued)
175
176
TABLE 3
(Continued)
Arnaud (1995) No surgery: T1: M = 105, SD = 8, T2: M = 106, Longitudinal Retrospective

SD = 12 Large sample size No control group
Surgery: T1: M = 106, SD = 12, T2: M = 101, Participation rate reported Surgery status mixed
SD = 12. Surgery age not reported
No effect of age at surgery. No differences by Variation in age not reported (mean
surgery status (treatment vs non-treatment only)
affect outcome (with the exception of
hydrocephalus)
Kapp-Simon (1993) T1: M = 100, SD = 13; T2: M = 95, SD = 15. Prospective No control group
No association between severity of cranial Longitudinal Surgery age not report
malformation and neurodevelopmental status. Medium sample size Variation in age not reported (mean
Pre- and post-surgery MDI scores unrelated to Radiographic confirmation of SSC reported only)
surgery age Did not exclude comorbidities that may
affect outcome
Participation rate and attrition rates not
reported
Note. BSID = Bayley Scale of Infant Development; BSID-II = Bayley Scale of Infant Development, 2nd Edition; ICP=Intracranial pressure; MDI = Mental Development
Index (from BSID/BSID-II); PDI = Psychomotor Development Index (from BSID/BSID-II); PLS-3 = Preschool Language Scale, 3rd Edition; PLS-AC = Preschool Language
Scale-3, auditory comprehension; PLS-EC = Preschool Language Scale-3, expressive language; GDQ = Global Development Quotient (from Griffith’s Mental Development
Scales); WISC-R = Wechsler Intelligence Scale for Children - Revised; WISC-III= Wechsler Intelligence Scale for Children–Third Edition; WPPSI-R = Wechsler Preschool
and Primary Scales of Intelligence–Revised.
mental and motor developmental level. The Griffith Mental Development Scales was employed
in two studies (Bellew, Liddington, Chumas, & Russell, 2011; Gewalli et al., 2001) and the
Brunet-Lezine Test in four studies (Arnaud et al., 2002; Bottero et al., 1998; Dennis et al., 2007;
Mathijssen et al., 2006). Language development was assessed using the Preschool Language
Scales–Third Edition in five studies (Kapp-Simon et al., 2005; Ruiz-Correa et al., 2007; Speltz
et al., 2007; Starr et al., 2007, 2010) from the same multisite project. Korpilahti et al. (2012)
used a range of standardized speech and language measures to assess pre-school language func-
tioning. Other studies report the results of less standardized language assessments (i.e., clinical
observation by a speech pathologist) (Becker et al., 2005; Mendonca et al., 2009; Shipster et al.,
2003).
The results of three older and less rigorously designed studies, suggest that the pre-surgical
developmental level of infants with craniosynostosis does not differ from normative population
averages (Gewalli et al., 2001; Kapp-Simon, Figueroa, Jocher, & Schafer, 1993) or controls
(Speltz et al., 1997). However, the majority of studies (n = 10), including a number of recent
high quality studies, have reported a heightened risk of pre-surgical developmental delay in both
cognitive and motor domains (Bellew et al., 2005, 2011; Bottero et al., 1998; Cohen et al., 2004;
Da Costa et al., 2012; Kapp-Simon et al., 2005; Nejad & Nikoobakhat, 2010; Panchal et al.,
2001; Speltz et al., 2007; Starr et al., 2007). Two studies (Da Costa et al., 2012; Panchal et al.,
2001) describe an over-representation of infants at the lower end of the developmental spectrum
and under-representation of children displaying advanced development compared with normative
estimates.
Post-Surgical Infant Neurodevelopment
Poorer performance on measures of early cognitive and motor development persisted at post-
surgical assessment in most studies (Cohen et al., 2004; Nejad & Nikoobakhat, 2010; Speltz et al.,
2007). Reduced post-operative language functioning during the infancy and pre-school periods
has also been reported (Korpilahti et al., 2012; Starr et al., 2007). Post-surgical resolution of early
motor delays in studies on sagittal synostosis has been reported by one study group (Bellew et al.,
2005, 2011); however, several methodological limitations including lack of control group, small
sample size and limited information about participant characteristics, suggest that these findings
should be interpreted cautiously.
Childhood Outcomes
Intellectual ability has been an area of particular focus in children with SSC. The majority
of the childhood studies employed a version of the Wechsler Intelligence Scales for Children
(WISC–R, WISC–III) to measure general intellectual functioning (n = 10). Other aspects of
cognitive functioning (e.g., memory, attention, executive function) were not commonly examined
during the infancy or childhood periods (Boltshauser, Ludwig, Dietrich, & Landolt, 2003; Chieffo
et al., 2010; Korpilahti et al., 2012; Magge et al., 2002; Toth et al., 2008).
While group means for IQ are generally within the average range, studies have demonstrated
that the distribution of IQ scores for children with SSC is shifted downward compared to norma-
tive data, with more children than expected falling in the below average ranges, and, conversely,
less than expected falling in the above average categories (Da Costa et al., 2006). Studies of older
children with SSC show an increased prevalence of learning, behavioral and language difficul-
ties based on parent report or retrospective review of the medical records (Becker et al., 2005;
Kelleher et al., 2006; Sidoti, Marsh, Marty-Grames, & Noetzel, 1996). On formal assessment,
school-aged children with SSC have been shown to display age-appropriate general intellectual
functioning (Boltshauser et al., 2003; Da Costa et al., 2006; Lajeunie, Le Merrer, Marchac, &
Renier, 1998; Magge et al., 2002; Shipster et al., 2003). Higher rates of speech and language
impairments are evident (Becker et al., 2005; Kelleher et al., 2006; Mendonca et al., 2009;
Shipster et al., 2003; Virtanen et al., 1999). The few studies that have examined other aspects of
cognitive function have demonstrated deficits in visuospatial skills (Chieffo et al., 2010), memory
and attention (Boltshauser et al., 2003; Chieffo et al., 2010; Virtanen et al., 1999) and academic
performance (Magge et al., 2002).
Intrinsic Factors Associated With Neurodevelopmental Outcomes in SSC
Brain imaging. One study older retrospective study used a direct measure of brain struc-
ture and/or functioning to investigate its correlates with neurobehavioral outcome. Bottero
et al. (1998) found no association between presence of gross indicators of intracranial abnor-
mality on brain computerized tomography (CT) with long-term “mental outcome” (determined
by parent/teacher report and in some cases, psychometric testing). No convincing relationship
between presence or severity of increased intracranial pressure (ICP) and developmental level
has been demonstrated (Bottero et al., 1998; Dennis et al., 2007; Gewalli et al., 2001; Mathijssen
et al., 2006; Shipster et al., 2003). There are no published studies combining contemporary,
sophisticated neuroimaging techniques (e.g., magnetic resonance imaging [MRI], diffuse tensor
imaging) with functional developmental outcome measures.
Severity of skull deformity. Seven studies have investigated the relationship between sever-
ity of skull deformity and neurodevelopmental performance using clinician-rated (Bottero et al.,
1998; Kapp-Simon et al., 1993; Warschausky et al., 2005) and quantitative measures based on
CT scans (Mendonca et al., 2009; Ruiz-Correa et al., 2007; Starr et al., 2010; Virtanen et al.,
1999). With the exception of the study by Bottero et al. (1998) (a retrospective study that did not
use standardized measures to assess developmental outcome), no relationship between degree
of craniofacial deformity and neurodevelopmental outcome was identified (Kapp-Simon et al.,
1993; Mendonca et al., 2009; Ruiz-Correa et al., 2007; Starr et al., 2010; Virtanen et al., 1999;
Warschausky et al., 2005).
Subtype of craniosynostosis. Seven studies have addressed differences in

neurodevelopment in SSC subtypes. Becker et al. (2005) retrospectively investigated speech,
cognition and behavior (with variable use of standardized tools and informal assessment) in
214 children with an average age of 6 years and 4 months. They illustrated that the different
affected suture groups were similar in terms of the likelihood of an abnormality, although there
was a non-significant trend for children with sagittal synostosis to display better neurocognitive
function. Consistent with this, in a prospective study with a relatively smaller sample, Korpilahti
et al. (2012) demonstrated that children aged 3 years with sagittal synostosis managed better in
all language areas compared with other types of SSC. Infancy studies to date, including the high
quality, multi-site study have not elicited a statistically significant difference in developmental
profiles across the diagnostic subtypes (Kapp-Simon, 1998; Kapp-Simon et al., 2005; Speltz
et al., 2007; Starr et al., 2007; Toth et al., 2008).
Genetics. Two studies (Arnaud et al., 2002; Mathijssen et al., 2006) have investigated
genetic contributions to developmental functioning in bicoronal and unicoronal synostosis,
respectively. While neither found a statistically significant relationship, Arnaud et al. (2002)
reported a trend toward poorer performance on age-appropriate developmental or intellectual
assessment in patients with bicoronal synostosis testing positive for a candidate gene mutation
for craniosynostosis (Fibroblast Growth Factor Receptor 3) compared to non-carriers with the
condition.
Gender. Da Costa et al. (2006) found no association with gender on intellectual function-
ing in school-aged children with varying forms of craniosynostosis. Likewise, no association
with gender was found in a large-scale, high quality study of pre-operative neurodevelopmental
functioning (Kapp-Simon et al., 2005; Speltz et al., 2007).
Extrinsic Factors Associated With Neurodevelopmental Outcomes in SSC
The few studies that have investigated the contribution of extrinsic variables including SES,
maternal education, or maternal intelligence upon infant development in SSC have yielded
inconsistent findings. Warschausky et al. (2005) demonstrated a positive correlation between pre-
surgical BSID scores and maternal education in a retrospective review of 22 infants with untreated
metopic synostosis. Family environment has been found to influence “mental” outcome estimated
in older children based on retrospective medical record review (Bottero et al., 1998). In compari-
son, no association between pre-surgical BSID–II scores and maternal intelligence or family SES
was found in a large prospectively studied cohort (Kapp-Simon et al., 2005; Speltz et al., 2007).
Developmental Factors Associated With Neurodevelopmental Outcomes in SSC
Age at surgery. Studies used various methods for analysing the impact of surgery age. Six
studies used dichotomous variables (i.e., surgery before or after a particular age) and five studies
used a continuous variable for surgery age. Three older and less methodologically rigorous studies
using dichotomous variables reported that surgery before 1 year of age was associated with better
outcome than surgery after 1 year of age (Arnaud et al., 2002; Bottero et al., 1998; Speltz et al.,
1997), while two studies found no difference in outcome scores when comparing surgery before
and after 1 year of age (Kapp-Simon, 1998; Mathijssen et al., 2006). Shipster and colleagues
(2003) showed that surgery at a later age (after 4 years of age) was associated with greater risk
of speech, language and cognitive impairments. Two more recent studies stemming from a large
and well-designed multi-site project found no correlation between surgery age and post-surgical
developmental level during late infancy (Starr et al., 2007; Toth et al., 2008). Further, no such
relationship was evident in studies investigating neuropsychological outcomes in school-aged
children (Da Costa et al., 2006; Magge et al., 2002) or in a study by Mendonca and colleagues
(2009) who did not find a significant relationship between age at surgery and the speech and
language development. Descriptively, the pattern of positive and null findings with respect to
the influence of surgery age did not appear to be explained by the subtype of craniosynostosis
included in the particular cohorts.
Age at evaluation. Two retrospective cross-sectional chart reviews analysed age at evalu-
ation. Mendonca and colleagues (2009) reported an increase in speech and language difficulties
in children with metopic synostosis assessed at age 5 years compared with at 3 years. In a
mixed subtype SSC cohort, Becker et al. (2005) revealed that as age at evaluation increased,
the percentage of speech-language, cognitive and behavioral abnormalities also increased.
DISCUSSION
This is the first systematic review of neurodevelopmental outcomes of SSC in children.

Thirty-three peer-reviewed, empirical papers that examined neurodevelopmental functioning in
27 cohorts of infants and/or school-aged children with SSC were identified. Taken together, the
weight of findings from this systematic review indicates that, at a group level, children with
SSC are at elevated risk for developmental difficulties during the infancy and childhood. Overall,
while the range of methodological weaknesses described should be considered when interpreting
these findings, the elevated risk for adverse developmental functioning during infancy and early
childhood in SSC is strengthened by a recent and more rigorously conducted multi-site cohort-
comparison study yielding results that support this notion (Kapp-Simon et al., 2005; Ruiz-Correa
et al., 2007; Speltz et al., 2007; Starr et al., 2007, 2010; Toth et al., 2008). The developmental tra-
jectory and the nature of the neurodevelopmental difficulties and factors contributing to outcome
are not yet clear.
The majority of studies evaluating presurgical cognitive and motor performances using stan-
dardized measures showed an overall reduction in presurgical cognitive and motor skills in
children with SSC compared to normative population estimates. There was a tendency for
more recent and higher quality studies (with larger sample sizes and control groups) to report
reduced neurodevelopmental scores on standardized measures. There is some evidence that
neurodevelopmental problems in cognitive, motor and language domains persist following sur-
gical intervention in the infancy and pre-school periods. Studies have shown that school-aged
children with SSC perform as a group within the age-appropriate range on measures of general
intellect. While seldom studied, these children have also been found to display specific areas of
cognitive deficit affecting language, visuospatial skills, memory and attention. In general, the
literature on school-aged outcomes is much less comprehensive and subject to a range of signif-
icant methodological challenges such as low participation rate, small sample sizes and limited
use of control groups when compared to the infancy studies. Improving our understanding of
the long-term developmental implications of CFS using high quality methodological approaches
represents a research priority.
Factors Influencing Neurodevelopmental Outcomes in SSC
The current review used a neuropsychological framework to summarise current research findings
on factors that may moderate or mediate developmental outcome in SSC. For the purposes of this
review, these factors were grouped into intrinsic (brain imaging, severity of deformity, subtype of
craniosynostosis, genotype, gender), extrinsic (environmental) and developmental (age at surgery,
age at evaluation) factors.
Intrinsic Factors
There has been limited empirical investigation into intrinsic factors that may contribute to
neurodevelopmental outcome (e.g., brain structure and function, genetics). On the basis of the
reviewed literature, there appears no convincing evidence that presence of intracranial malforma-
tion, increased ICP or severity of craniofacial deformity are associated with neurodevelopmental
level. It is important to note that techniques for quantifying alterations in craniofacial and brain
structure and function have been reasonably limited. Recent advances in technology may how-
ever lead to advances in our understanding of these sequelae. For example, recent MRI work
by Aldridge and colleagues (Aldridge et al., 2002, 2005) reported morphological differences
between the brains of children with SSC and typically developing children. Furthermore, fol-
lowing surgical intervention, while changes were noted in brain structure, their brains remained
abnormal compared to typically developing children (Aldridge et al., 2002, 2005). As yet, the
relationship between brain structure and functional neurobehavioral outcome in SSC has not
been examined in detail using sophisticated brain imaging techniques.
In a range of developmental conditions, such as spina bifida meningomyelocele and congen-
ital heart disease, the presence of a genetic mutation has been associated with increased risk of
neurodevelopmental difficulties (Fletcher et al., 2005; Gaynor et al., 2003; Zeitser et al., 2008).
While for many cases of SSC the underlying cause remains largely unknown, a number of candi-
date gene mutations have recently been identified to occur in a sizable minority of cases (Lattanzi
et al., 2012). Few studies have however systematically addressed whether the identified gene
mutations are associated with greater risk for neurodevelopmental sequelae. Integrating contem-
porary neuroimaging, genetic, and neuropsychological evaluations will help to better understand
the interplay between these factors.
It has been proposed that particular subtypes of SSC may be associated with particular neu-
robehavioral phenotypes (Kapp-Simon et al., 2007). The current review found no clear evidence
that a particular subtype of SSC is associated with a particular phenotype; nor that a spe-
cific subtype is associated with lower or at higher risk for poor neurodevelopmental outcome.
Although there was a suggestion in two studies that children with sagittal synostosis tended
to have better outcomes, the methodological quality of these studies was reasonably low and
the trends were non-significant. Small subgroup sizes may have precluded the capacity for
detection of subtle subgroup differences; however, it is noteworthy that subtype differences in
neurodevelopment have not been elicited in the large multi-site study.
Extrinsic Factors
The few studies that have investigated extrinsic variables, such as SES, maternal education,
or maternal intelligence on developmental outcome in SSC have yielded inconsistent find-
ings (Bottero et al., 1998; Kapp-Simon et al., 2005; Panchal et al., 2001; Speltz et al., 2007;
Warschausky et al., 2005). Distal environmental factors such as family resources, SES, and fam-
ily function are important contributors to outcome in other developmental conditions influencing
brain development, such as spina bifida (Fletcher et al., 2005; Lomax-Bream, Barnes, Copeland,
Taylor, & Landry, 2007). Future analysis of the impact of social risk on the development of these
children during different developmental stages will help clarify the potential moderating role of
social and environmental factors in SSC. Investigating the relevance of more “proximal” factors,
such as maternal mental health, parenting style, and attachment for infants with craniosynostosis
is of particular significance for this patient group, due to its diagnosis early in infancy.
Previous research has found high levels of stress and poor mother–child bonding in infants
with early medical illnesses (Treyvaud et al., 2009), providing a potential target area for early
intervention.
Developmental Factors
Age at surgery. Exploring an association between neurodevelopmental outcome and sur-

gical age has been of major interest in the literature because it allows indirect testing of the
hypothesis that later surgeries are associated with more prolonged risk of increased intracranial
pressure and consequently, compromised brain development. Timing of surgery in SSC can be
affected by a number of systematic factors including timing of initial patient presentation, general
risk of performing surgery in a young infant, malleability of cranial bones, waiting lists, severity
of the condition, the type of surgery being performed and psychosocial considerations, which
should be taken into consideration by researchers when exploring the influence of surgery age
on neurodevelopment. Consideration of these factors is particularly relevant when surgery age is
delayed beyond the infancy period. In other clinical populations, age at surgery has been noted to
be an important determinant of functional outcome (Limperopoulos et al., 2002; Loddenkemper
et al., 2007). To date, equivocal findings exist in the SSC literature, with some studies finding an
inverse relationship between surgery age and test performance in infants with SSC, but several
others have not found an association. Wide variation in surgery ages, methodological approaches
and quality within and between studies has likely contributed to the variable findings. Children
undergoing surgery at ages beyond the infancy period were included in many of these studies and
so it remains unclear whether smaller differences in age at surgery are associated with differences
in functional outcome.
Age at evaluation. Specific functions emerge at different ages in typically developing

children; therefore, even healthy children vary in their ability to perform tasks at different devel-
opmental stages. For example, high-level language and executive function are only assessable in
older children when these skills are sufficiently developed. Dennis et al. (2007) highlights that
while insult in infancy appears to be associated with comparatively few immediate issues, with
ongoing development children appear to “grow into” their deficits or “fail to acquire” expected
skills (Anderson, Northam, Hendy, & Wrennall, 2001). Therefore, the effects of age at evalua-
tion may be reflected in latent or delayed sequelae occurring due to a difficulty in meeting new
developmental demands (Dennis et al., 2007). This pattern has been demonstrated in a number of
other clinical populations (A. N. Taylor et al., 2002; Taylor et al., 2004; Westmacott et al., 2009).
Support for this notion has been demonstrated in SSC by two retrospective cross-sectional stud-
ies (Becker et al., 2005; Mendonca et al., 2009). However, these studies did not use standardized
measures to document outcomes and nor did they investigate the same children at different devel-
opmental stages. Longitudinal studies that incorporate standardized neurocognitive assessment
of children from infancy to school-age will help to elucidate whether deficits emerge with age in
SSC.
Limitations and Future Directions
This review employed a detailed systematic and theoretically driven approach to examine the cur-
rent literature on neurodevelopmental outcomes in SSC. It is acknowledged that limiting inclusion
to peer-reviewed published studies in English language may have introduced a potential publi-
cation bias. The scope of this review permitted by the published literature is also limited by
methodological flaws and inconsistencies which caution the interpretation of results. Despite
common strengths with respect to adequate sample size and use of standardized measurement
tools for the most part, shared weaknesses were apparent. The most notable limitations identified
by the current review were: (1) biased or unclear sample ascertainment procedures; (2) absence
of appropriate comparison groups; (3) broad ranges for surgery and assessment age; (4) limited
details regarding participant characteristics and/or inclusion of some patients with complex med-
ical problems; (5) overrepresentation of cross-sectional studies and retrospective medical chart
reviews; (6) mixed samples of SSC subtypes; (7) mixed pre- and post-surgical samples; (8) lim-
ited attention to neurocognitive skills beyond general intellectual or developmental assessment;
and (9) few studies that have examined key predictive factors or considered them in an integrated
manner.
Neurodevelopmental trajectories are likely to be reasonably heterogeneous for children with
craniosynostosis and thus it will be important for future research to identify those at most risk
for targeted intervention. Future research adopting a theory-driven analysis of craniosynostosis,
which integrates state-of-the-art genetic, neurobiological, and neurodevelopmental methods,
as well as incorporating comprehensive age-related and environmental considerations, should
enhance our understanding of a variety of brain-behavior questions and prompt new research
directions. Longitudinal studies with follow-ups beyond early childhood adopting this approach
will help to delineate the specific genetic, medical, neural, environmental, and age predictors of
good and poor neurobehavioral outcomes in children and adolescents with SSC and to better tar-
get limited resources to those children most at risk for poor outcomes. Such studies may also
lead to better decision making for surgery, and its timing and in ensuring appropriate and timely
referrals for educational or early intervention services.
REFERENCES
Aldridge, K., Kane, A. A., Marsh, J. L., Panchal, J., Boyadjiev, S. A., Yan, P., Richtsmeier, J. T. (2005). Brain morphology
in nonsyndromic unicoronal craniosynostosis. The Anatomical Record: Part A, Discoveries in Molecular, Cellular and
Evolutionary Biology, 285(2), 690–698.
Aldridge, K., Marsh, J., Govier, D., & Richtsmeier, J. T. (2002). Central nervous system phenotypes in craniosynostosis.
Journal of Anatomy, 201(1), 31–39.
Anderson, V., Northam, E., Hendy, J., & Wrennall, J. (2001). Developmental neuropsychology: A clinical approach. New
York, NY: Psychology Press.
Anderson, V., Spencer-Smith, M., & Wood, A. (2011). Do children really recover better? Neurobehavioural plasticity
after early brain insult. Brain, 134(8), 2197–2221.
Arnaud, E., Meneses, P., Lajeunie, E., Thorne, J. A., Marchac, D., & Renier, D. (2002). Postoperative mental and
morphological outcome for nonsyndromic brachycephaly. Plastic and Reconstructive Surgery, 110(1), 6–12.
Ballantyne, A. O., Spilkin, A. M., & Trauner, D. A. (2007). Language outcome after perinatal stroke: Does side matter?
Child Neuropsychology, 13(6), 494–509. doi:10.1080/09297040601114878
Becker, D. B., Petersen, J. D., Kane, A. A., Cradock, M. M., Pilgram, T. K., & Marsh, J. L. (2005). Speech, cognitive,
and behavioral outcomes in nonsyndromic craniosynostosis. Plastic and Reconstructive Surgery, 116(2), 400–407.
doi:http://dx.doi.org/10.1097/01.prs.0000172763.71043.b8
Bellew, M., Chumas, P., Mueller, R., Liddington, M., & Russell, J. (2005). Pre- and postoperative
developmental attainment in sagittal synostosis. Archives of Disease in Childhood, 90(4), 346–350.
doi:http://dx.doi.org/10.1136/adc.2003.035824
Bellew, M., Liddington, M., Chumas, P., & Russell, J. (2011). Preoperative and postoperative developmental attain-
ment in patients with sagittal synostosis: 5-year follow-up. Journal of Neurosurgery: Pediatrics, 7(2), 121–126.
doi:http://dx.doi.org/10.3171/2010.11.PEDS10216
Boltshauser, E., Ludwig, S., Dietrich, F., & Landolt, M. A. (2003). Sagittal craniosynostosis: Cognitive
development, behaviour, and quality of life in unoperated children. Neuropediatrics, 34(6), 293–300.
doi:http://dx.doi.org/10.1055/s-2003-44667
Bottero, L., Lajeunie, E., Arnaud, E., Marchac, D., & Renier, D. (1998). Functional outcome after surgery for
trigonocephaly. Plastic and Reconstructive Surgery, 102(4), 952–960. doi:http://dx.doi.org/10.1097/00006534-
199809040-00002
Chieffo, D., Tamburrini, G., Massimi, L., Di Giovanni, S., Giansanti, C., Caldarelli, M., & Di Rocco, C. (2010). Long-term
neuropsychological development in single-suture craniosynostosis treated early. Journal of Neurosurgery: Pediatrics,
5(3), 232–237. doi:10.3171/2009.10.peds09231
Cohen, M. M., & MacLean, R. (2000). Craniosynostosis: diagnosis, evaluation, and management. New York, NY: Oxford
University Press.
Cohen, S. R., Cho, D. C., Nichols, S. L., Simms, C., Cross, K. P., & Burstein, F. D. (2004). American
Society of Maxillofacial Surgeons outcome study: Preoperative and postoperative neurodevelopmental
findings in single-suture craniosynostosis. Plastic and Reconstructive Surgery, 114(4), 841–847.
doi:http://dx.doi.org/10.1097/01.PRS.0000132854.14237.A8
Da Costa, A. C., Anderson, V., Savarirayan, R., Wrennall, J. A., Chong, D. K., Holmes, A. D., Meara, J. G. (2012).
Neurodevelopmental functioning of infants with untreated single-suture craniosynostosis during early infancy. Child’s
Nervous System, 28(6), 869–877. doi:10.1007/s00381-011-1660-1
Da Costa, A. C., Walters, I., Savarirayan, R., Anderson, V., Wrennall, J. A., & Meara, J. G. (2006). Intellectual outcomes
in children and adolescents with syndromic and nonsyndromic craniosynostosis. Plastic and Reconstructive Surgery,
118(1), 175–181. doi:http://dx.doi.org/10.1097/01.prs.0000221009.93022.50
Dennis, M., Spiegler, B. J., Hetherington, C. R., & Greenberg, M. L. (1996). Neuropsychological sequelae of the treatment
of children with medulloblastoma. Journal of Neurooncology, 29(1), 91–101.
Dennis, M., Yeates, K. O., Taylor, H. G., & Fletcher, J. M. (2007). Brain reserve capacity, cognitive reserve capacity,
and age-based functional plasticity after congenital and acquired brain injury in children. In Y. Stern (Ed.), Cognitive
reserve: Theory and applicatons (pp. 53–83). Philadelphia, PA: Taylor & Francis.
Fletcher, J. M., Copeland, K., Frederick, J. A., Blaser, S. E., Kramer, L. A., Northrup, H., Dennis, M. (2005). Spinal
lesion level in spina bifida: A source of neural and cognitive heterogeneity. Journal of Neurosurgery, 102(3 Suppl),
268–279. doi:10.3171/ped.2005.102.3.0268
Gaynor, J. W., Gerdes, M., Zackai, E. H., Bernbaum, J., Wernovsky, G., & Clancy, R. R. (2003). Apolipoprotein E geno-
type and neurodevelopmental sequelae of infant cardiac surgery. Journal of Thoracic and Cardiovascular Surgery,
126, 1736–1745.
Gewalli, F., Guimarães-Ferreira, J. P., Sahlin, P., Emanuelsson, I., Horneman, G., Stephensen, H., & Lauritzen, C. G.
(2001). Mental development after modified pi procedure: Dynamic cranioplasty for sagittal synostosis. Annals of
Plastic Surgery, 46(4), 415–420.
Kapp-Simon, K. A. (1998). Mental development and learning disorders in children with single suture
craniosynostosis. Cleft Palate-Craniofacial Journal, 35(3), 197–203. doi:http://dx.doi.org/10.1597/1545-
1569%281998%29035%3C0197:MDALDI%3E2.3.CO;2
Kapp-Simon, K. A., Figueroa, A., Jocher, C. A., & Schafer, M. (1993). Longitudinal assessment of mental develop-
ment in infants with nonsyndromic craniosynostosis with and without cranial release and reconstruction. Plastic and
Reconstructive Surgery, 92(5), 831–839.
Kapp-Simon, K. A., Leroux, B., Cunningham, M., & Speltz, M. L. (2005). Multisite study of infants with single-suture
craniosynostosis: Preliminary report of presurgery development. Cleft Palate-Craniofacial Journal, 42(4), 377–384.
doi:http://dx.doi.org/10.1597/04-044.1
Kapp-Simon, K. A., Speltz, M. L., Cunningham, M. L., Patel, P. K., & Tomita, T. (2007). Neurodevelopment of children
with single suture craniosynostosis: A review. Child’s Nervous System, 23(3), 269–281. doi:10.1007/s00381-006-
0251-z
Kelleher, M. O., Murray, D. J., McGillivary, A., Kamel, M. H., Allcutt, D., & Earley, M. J. (2006). Behavioral, devel-
opmental, and educational problems in children with nonsyndromic trigonocephaly. Journal of Neurosurgery, 105(5
Suppl), 382–384.
Korpilahti, P., Saarinen, P., & Hukki, J. (2012). Deficient language acquisition in children with single
suture craniosynostosis and deformational posterior plagiocephaly. Child’s Nervous System, 28(3), 419–425.
doi:http://dx.doi.org/10.1007/s00381-011-1623-6
Lajeunie, E., Le Merrer, M., Marchac, D., & Renier, D. (1998). Syndromal and nonsyndromal primary trigonocephaly:
Analysis of a series of 237 patients. American Journal of Medical Genetics, 75(2), 211–215.
Lattanzi, W., Bukvic, N., Barba, M., Tamburrini, G., Bernardini, C., Michetti, F., & Di Rocco, C. (2012). Genetic basis of
single-suture synostoses: Genes, chromosomes and clinical implications. Child’s Nervous System, 28(9), 1301–1310.
doi:10.1007/s00381-012-1781-1
Limperopoulos, C., Majnemer, A., Shevell, M. I., Rohlicek, C., Rosenblatt, B., Tchervenkov, C., & Darwish, H. Z.
(2002). Predictors of developmental disabilities after open heart surgery in young children with congenital heart
defects. Journal of Pediatrics, 141(1), 51–58. doi:10.1067/mpd.2002.125227
Loddenkemper, T., Holland, K., Stanford, L., Kotagal, P., Bingaman, W., & Wyllie, E. (2007). Developmental outcome
after epilepsy surgery in infancy. Pediatrics, 119(5), 930–935.
Lomax-Bream, L. E., Barnes, M., Copeland, K., Taylor, H. B., & Landry, S. H. (2007). The impact of spina bifida on
development across the first 3 years. Developmental Neuropsychology, 31(1), 1–20. doi:10.1207/s15326942dn3101_1
Magge, S. N., Westerveld, M., Pruzinsky, T., & Persing, J. A. (2002). Long-term neuropsychological effects of sagittal
craniosynostosis on child development. Journal of Craniofacial Surgery, 13(1), 99–104.
Mathijssen, I., Arnaud, E., Lajeunie, E., Marchac, D., & Renier, D. (2006). Postoperative cognitive outcome for synostotic
frontal plagiocephaly. Journal of Neurosurgery, 105, Pediatrics(Suppl. 1), 16–20.
Mendonca, D. A., White, N., West, E., Dover, S., Solanki, G., & Nishikawa, H. (2009). Is there a relationship between the
severity of metopic synostosis and speech and language impairments? Journal of Craniofacial Surgery, 20(1), 85–88.
doi:http://dx.doi.org/10.1097/SCS.0b013e3181955244
Nejad, E. A, & Nikoobakhat, M. (2010). Post-operative neurodevelopmental findings in syndromic and non-syndromic
craniosynostosis. Iranian Journal of Child Neurology, 3(4), 45–50.
Panchal, J., Amirsheybani, H., Gurwitch, R., Cook, V., Francel, P., Neas, B., & Levine, N. (2001). Neurodevelopment
in children with single-suture craniosynostosis and plagiocephaly without synostosis. Plastic and Reconstructive
Surgery, 108(6), 1492–1498.
Richtsmeier, J. T., Aldridge, K., DeLeon, V. B., Panchal, J., Kane, A. A., Marsh, J. L., Cole, T. M., III. (2006). Phenotypic
integration of neurocranium and brain. Journal of Experimental Zoology. Part B, Molecular and Developmental
Evolution, 306(4), 360–378. doi:10.1002/jez.b.21092
Ruiz-Correa, S., Starr, J. R., Lin, H. J., Kapp-Simon, K. A., Cunningham, M. L., & Speltz, M. L. (2007). Severity of
skull malformation is unrelated to presurgery neurobehavioral status of infants with sagittal synostosis. Cleft Palate-
Craniofacial Journal, 44(5), 548–554. doi:10.1597/06-190.1
Shipster, C., Hearst, D., Somerville, A., Stackhouse, J., Hayward, R., & Wade, A. (2003). Speech, language, and cogni-
tive development in children with isolated sagittal synostosis. Developmental Medicine and Child Neurology, 45(1),
34–43.
Sidoti, E. J., Jr., Marsh, J. L., Marty-Grames, L., & Noetzel, M. J. (1996). Long-term studies of metopic synostosis:
Frequency of cognitive impairment and behavioral disturbances. Plastic and Reconstructive Surgery, 97(2), 276–281.
Singer, S., Bower, C., Southall, P., & Goldblatt, J. (1999). Craniosynostosis in Western Australia, 1980–1994: A
population-based study. American Journal of Medical Genetics, 83(5), 382–387.
Speltz, M. L., Endriga, M. C., & Mouradian, W. E. (1997). Presurgical and postsurgical mental and psychomotor devel-
opment of infants with sagittal synostosis.. presented at the annual meeting of the American Cleft Palate-Craniofacial
Association, San Diego, California, April 1996. Cleft Palate-Craniofacial Journal, 34(5), 374–379.
Speltz, M. L., Kapp-Simon, K., Collett, B., Keich, Y., Gaither, R., Cradock, M. M., Cunningham, M. L. (2007).
Neurodevelopment of infants with single-suture craniosynostosis: presurgery comparisons with case-matched con-
trols. Plastic and Reconstructive Surgery, 119(6), 1874–1881. doi:10.1097/01.prs.0000259184.88265.3f
Speltz, M. L., Kapp-Simon, K. A., Cunningham, M., Marsh, J., & Dawson, G. (2004). Single-suture
craniosynostosis: A review of neurobehavioral research and theory. Journal of Pediatric Psychology, 29(8), 651–668.
doi:10.1093/jpepsy/jsh068
Starr, J. R., Kapp-Simon, K. A., Cloonan, Y. K., Collett, B. R., Cradock, M. M., Buono, L., Speltz, M. L. (2007).
Presurgical and postsurgical assessment of the neurodevelopment of infants with single-suture craniosynostosis:
comparison with controls. Journal of Neurosurgery, 107(2 Suppl), 103–110. doi:10.3171/PED-07/08/103
Starr, J. R., Lin, H. Jill, Ruiz-Correa, S., Cunningham, M. L., Ellenbogen, Richard G., Collett, B. R.,. . . Speltz, M. L.
(2010). Little evidence of association between severity of trigonocephaly and cognitive development in infants with
single-suture metopic synostosis. Neurosurgery, 67(2), 408–415. doi:10.1227/01.NEU.0000371992.72539.8B
Taylor, A. N., Romeo, H. E., Beylin, A. V., Tio, D. L., Rahman, S. U., & Hovda, D. A. (2002). Alcohol consump-
tion in traumatic brain injury: Attenuation of TBI-induced hyperthermia and neurocognitive deficits. Journal of
Neurotrauma, 19(12), 1597–1608. doi:10.1089/089771502762300256
Taylor, H. G., Minich, N. M., Klein, N., & Hack, M. (2004). Longitudinal outcomes of very low birth weight:
Neuropsychological findings. Journal of the International Neuropsychological Society, 10(2), 149–163.
Taylor, H. G., Yeates, K. O., Wade, S. L., Drotar, D., Stancin, T., & Minich, N. (2002). A prospective study of short-
and long-term outcomes after traumatic brain injury in children: Behavior and achievement. Neuropsychology, 16(1),
15–27.
Toth, K., Collett, B., Kapp-Simon, K. A., Cloonan, Y. K., Gaither, R., Cradock, M. M., Speltz, M. L. (2008). Memory and
response inhibition in young children with single-suture craniosynostosis. Child Neuropsychology, 14(4), 339–352.
doi:http://dx.doi.org/10.1080/09297040701594888
Treyvaud, K., Anderson, V., Howard, K., Bear, M., Hunt, R. W., Doyle, L. W., Anderson, P. J. (2009). Parenting behaviour
is associated with the early neurobehavioual development of very preterm children. Pediatrics, 123, 555–561.
doi:10.1542/peds.2008-0477
Virtanen, R., Korhonen, T., Fagerholm, J., & Viljanto, J. (1999). Neurocognitive sequelae of scaphocephaly. Pediatrics,
103(4 I), 791–795. doi:http://dx.doi.org/10.1542/peds.103.4.791
Warschausky, S., Angobaldo, J., Kewman, D., Buchman, S., Muraszko, K. M., & Azengart, A. (2005). Early develop-
ment of infants with untreated metopic craniosynostosis. Plastic and Reconstructive Surgery, 115(6), 1518–1523.
doi:http://dx.doi.org/10.1097/01.PRS.0000160270.27558.64
Westmacott, R., MacGregor, D., Askalan, R., & deVeber, G. (2009). Late emergence of cognitive deficits after unilateral
neonatal stroke. Stroke, 40(6), 2012–2019. doi:10.1161/STROKEAHA.108.533976
Zeitser, I., Jarvick, G. P., Bernbaum, J., Wernovsky, G., Nord, A. S., Gerdes, M., Gaynor, J. W. (2008). Genetic factors
are important determinants of neurodevelopmental outcome after repair of tetralogy of Fallot. Journal of Thoracic
and Cardiovascular Surgery, 135(1), 91–97. doi:10.1016/j.jtcvs.2007.04.074

Neurodevelopmental Outcomes in Infants and Children With Single-Suture

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Neurodevelopmental Outcomes in Infants and Children With Single-Suture

Uploaded by

Copyright:

Available Formats

This article was downloaded by: [Texas A & M International University]

On: 04 October 2014, At: 14:31

To link to this article: http://dx.doi.org/10.1080/87565641.2014.886690

PLEASE SCROLL DOWN FOR ARTICLE

Neurodevelopmental Outcomes in Infants and Children

Clinical Sciences, Murdoch Childrens Research Institute, Melbourne, Australia,

Craniosynostosis is a developmental craniofacial disorder affecting approximately 1 in 2,500 live

FIGURE 1 Skull phenotype for the three most common forms of

Literature Search and Eligibility Criteria

Data Extraction and Synthesis

Study Characteristics and Quality

References (duplicates removed)

Excluded based on review of titles

Full copies retrieved

and assessed for

Not SSC only n = 10; not a data paper (e.g.,

FIGURE 2 Flow diagram of literature search.

Design I Cross-sectional (21/33) Longitudinal (12/33)

Design II Retrospective (10/33) Prospective (23/33)

Sample Clinic-referred source Medical record review Not reported

Note. SSC = single-suture craniosynostosis.

Pre-Surgical Infant Neurodevelopment

First Author Number of Surgery Age in % Surgery Age at Evaluation in

First Author Number of Surgery Age in % Surgery Age at Evaluation in

Da Costa (2006) 18 SSC NR NR Post 10.9 (2.5) [7–16] years WISC-III

First Author (Year) Summary of Outcome Results Strengths Limitations

First Author (Year) Summary of Outcome Results Strengths Limitations

First Author (Year) Summary of Outcome Results Strengths Limitations

First Author (Year) Summary of Outcome Results Strengths Limitations

First Author (Year) Summary of Outcome Results Strengths Limitations

Arnaud (1995) No surgery: T1: M = 105, SD = 8, T2: M = 106, Longitudinal Retrospective

Post-Surgical Infant Neurodevelopment

Intrinsic Factors Associated With Neurodevelopmental Outcomes in SSC

Subtype of craniosynostosis. Seven studies have addressed differences in

Extrinsic Factors Associated With Neurodevelopmental Outcomes in SSC

Developmental Factors Associated With Neurodevelopmental Outcomes in SSC

This is the first systematic review of neurodevelopmental outcomes of SSC in children.

Factors Influencing Neurodevelopmental Outcomes in SSC

Age at surgery. Exploring an association between neurodevelopmental outcome and sur-

Age at evaluation. Specific functions emerge at different ages in typically developing

Limitations and Future Directions

You might also like