Sex differences in the neurodevelopment of school-age children with and without single-suture craniosynostosis.

PURPOSE: Previous studies have indicated that infants and school-age children with single-suture craniosynostosis (SSC, cases) score modestly but consistently lower than unaffected children (controls) on neurodevelopmental tests. However, sex differences in these functions rarely have been examined, and it is unknown whether potential sex differences vary by case status (cases vs. controls) or location of suture fusion. METHODS: We tested 182 cases and 183 demographically matched controls at a mean age of 7.4 years. We measured intellectual abilities with the Wechsler Scale of Intelligence for Children-Fourth Edition. We assessed reading, spelling, and math with a combination of the Wide Range Assessment Test-Fourth Edition, the Test of Word Reading Efficiency, and the Comprehensive Test of Phonological Processing. RESULTS: Among both cases and controls, males scored lower on all measures than females with standard score differences ranging from -1.2 to -7.8 for controls (p values from <0.001 to 0.55) and -2.3 to -8.5 for cases (p values from <0.001 to 0.33). For all but one measure, sex differences were slightly larger for cases than controls. Among cases, males were more likely than females to have learning problems (50 vs. 30%, respectively), with the highest level observed among males with unicoronal synostosis (86%). CONCLUSIONS: Sex differences in neurodevelopmental abilities among children with SSC are substantial, but not a unique correlate of this disorder as similar differences were observed among controls. Girls and those with sagittal synostosis have the lowest risk for academic problems. Boys with unicoronal synostosis warrant close developmental surveillance.

Laypersons' ratings of appearance in children with and without single-suture craniosynostosis.

BACKGROUND: Single-suture craniosynostosis (SSC) results in head shape anomalies that likely affect social perceptions of appearance. The purpose of this study was to evaluate laypersons' ratings of attractiveness in children with and without SSC. Among cases, we also examined differences by suture fused and age at surgery. METHODS: We collected photographs of 196 children with SSC and 186 children without SSC as infants (before surgery, for cases) and at ages 18 and 36 months. Photographs were rated by 8 raters, who were blinded to the population being studied. We used linear regression to compare appearance ratings for the 2 groups at each visit and to evaluate changes over time. Regression analyses were used to examine the association between age at surgery and appearance ratings. RESULTS: Children with SSC received lower appearance ratings than unaffected controls at each visit (all P < 0.001). Appearance ratings decreased over time, with a similar trajectory for children with and without SSC. Among cases, those with unicoronal and lambdoid synostosis had the lowest ratings and those with sagittal synostosis had the highest. Age at surgery was inversely associated with appearance ratings. CONCLUSIONS: Children with SSC received lower appearance ratings than unaffected controls, with minimal change after surgery. Better outcomes were associated with earlier surgery. These findings do not indicate that children with SSC failed to benefit from surgery, as without surgical intervention, asymmetrical head shape would likely have worsened over time. However, our data suggest that appearance does not fully "normalize."

Presurgical and postsurgical assessment of the neurodevelopment of infants with single-suture craniosynostosis: comparison with controls.

OBJECT: Although most infants with single-suture craniosynostosis (SSC) appear to have neurodevelopmental test scores in the average range, SSC has been associated with cognitive and motor delays during infancy. Whether and when surgery improves such deficits are not yet known. The authors aimed to compare the pre- and postsurgical neurodevelopmental status of patients with SSC with those of control infants without craniosynostosis. METHODS: The authors conducted a large, multicenter, longitudinal study of 168 infants with craniosynostosis and 115 controls without synostosis who were of similar age, race, sex, and socioeconomic status. The authors assessed participants by using the Bayley Scales of Infant Development, Second Edition (BSID-II) and the Preschool Language Scale, Third Edition (PLS-3) at enrollment, before patients' intracranial surgery, and when participants were 18 months of age (after surgery for patients). RESULTS: After adjusting for potential confounding factors in linear regression analyses, the authors found a tendency for patients to perform similarly to or slightly worse than controls on neurodevelopmental examinations at both visits. After surgery, the patients' mean scores were 0.6 to three points lower than those of controls on the five BSID-II and PLS-3 scales (p = 0.02-0.07). Compared with controls, patients had 2.3 and 1.9 times the adjusted odds of scoring in the delayed range on either BSID-II scale (Mental Development Index and Psychomotor Development Index) for the first and second visits, respectively (p = 0.001 and p = 0.015, respectively). The patients' mean adjusted test scores were nearly unrelated to the timing of their surgery. CONCLUSIONS: These findings support recommendations for neurodevelopmental screening in infants with SSC. Longer follow-up, as is being conducted with the patients in the present study, will be critical for identifying the potential longer-term correlates of SSC and its surgical correction.

Attention and executive function in children with and without single-suture craniosynostosis.

Children with single-suture craniosynostosis (SSC) have higher rates of learning disabilities and related neurocognitive problems than unaffected peers. Executive function (EF) and attention are thought to be areas of particular vulnerability, though studies to date have been limited by small sample sizes and a lack of control groups. We evaluated 179 school-aged children with SSC (cases) and 183 unaffected controls at an average age of 7 years using clinician-administered and parent and teacher report measures of EF and attention. Among children with SSC, we examined differences as a function of suture location (sagittal, metopic, unicoronal, or lambdoid) and age of corrective surgery. We used linear regression analyses, adjusted for potential confounders, to compare the two groups on all outcome measures. Cases scored lower than controls on most measures, though the magnitude of these differences was small and most were statistically insignificant. The largest relative deficit was on a measure of inhibitory control. Results changed little in sensitivity analyses adjusting for potential attrition bias and for the effects of developmental and academic interventions. Among cases, there were few differences in relation to the location of suture fusion or timing of surgery. Overall, we found limited evidence of broad deficits in EF or attention in children with SSC relative to unaffected controls. Neurocognitive development for children with SSC appears to be variable, across affected children and outcomes assessed. Further research is needed to understand the potential sources of this variability.

Intellectual and academic functioning of school-age children with single-suture craniosynostosis.

OBJECTIVE: We compared the developmental status of school-age children with single-suture craniosynostosis (case group) and unaffected children (control group). Within the case group we compared the performance of children distinguished by location of suture fusion (sagittal, metopic, unicoronal, lambdoid). METHODS: We administered standardized tests of intelligence, reading, spelling, and math to 182 case participants and 183 control participants. This sample represented 70% of those tested during infancy before case participants had corrective surgery. RESULTS: After adjustment for demographics, case participants' average scores were lower than those of control participants on all measures. The largest observed differences were in Full-Scale IQ and math computation, where case participants' adjusted mean scores were 2.5 to 4 points lower than those of control participants (Ps ranged from .002 to .09). Adjusted mean case-control differences on other measures of achievement were modest, although case deficits became more pronounced after adjustment for participation in developmental interventions. Among case participants, 58% had no discernible learning problem (score <25th percentile on a standardized achievement test). Children with metopic, unicoronal, and lambdoid synostosis tended to score lower on most measures than did children with sagittal fusions (Ps ranged from <.001 to .82). CONCLUSIONS: The developmental delays observed among infants with single-suture craniosynostosis are partially evident at school age, as manifested by lower average scores than those of control participants on measures of IQ and math. However, case participants' average scores were only slightly lower than those of control participants on reading and spelling measures, and the frequency of specific learning problems was comparable. Among case participants, those with unicoronal and lambdoid fusions appear to be the most neurodevelopmentally vulnerable.

Behavioral adjustment of toddler and preschool-aged children with single-suture craniosynostosis.

BACKGROUND: The purpose of this study was to confirm initial reports of elevated behavior problems in children with single-suture craniosynostosis, using multiple informants, longitudinal analyses, and a control group. The authors hypothesized that children with single-suture craniosynostosis would have higher levels of maladjustment than comparison children, particularly at the older age and in selected areas of previously observed vulnerability: attention and social adjustment. METHODS: The Child Behavior Checklist was completed by 436 mothers (219 with single-suture craniosynostosis) and 371 fathers (177 with single-suture craniosynostosis) when children were aged approximately 19 months, and by 361 mothers (175 with single-suture craniosynostosis) and 303 fathers (142 with single-suture craniosynostosis) when children were aged approximately 37 months. A minimum of one caregiver/teacher report was available for 169 of these children (74 with single-suture craniosynostosis) using the Caregiver-Teacher Report Form. RESULTS: Average Child Behavior Checklist/Caregiver-Teacher Report Form externalizing, internalizing, and total scores for all informants were consistently higher (worse) for children with single-suture craniosynostosis than for control group children, but most differences were small and statistically nonsignificant. No differences associated with suture site were found. At the oldest age point, both mothers and fathers (but not teachers) generated higher average scores for patients than for controls on scales measuring attention and social problems, with small to medium effect sizes (0.20 to 0.32). CONCLUSIONS: On average, toddlers/preschoolers with single-suture craniosynostosis show behavioral development that is largely indistinguishable from same-aged peers of similar socioeconomic background. The predictive significance of small group differences in attention and social adjustment will be assessed in a follow-up of this cohort at age 7.

Memory and response inhibition in young children with single-suture craniosynostosis.

Using two versions of the A-not-B task, memory and response inhibition were assessed in 17- to 24-month-old children with surgically corrected single-suture craniosynostosis (cases) and unaffected children (controls). Children's development and language were initially assessed on average at 6-7 months of age and again at this second visit. Cases and controls performed at equivalent levels on average, with cases performing slightly better than controls on several of the variables measured. However, fewer cases than controls were able to complete the more challenging of the two tasks, which may have predictive significance for later functioning. Children's age and cognitive ability were related to successful performance on the A-not-B task. Among cases, age of cranioplastic surgery was unrelated to performance. Our findings suggest that children with single-suture craniosynostosis show normal development of visual memory and response inhibition in the age range studied here.

Neurodevelopment of infants with single-suture craniosynostosis: presurgery comparisons with case-matched controls.

BACKGROUND: The hypothesized association between single-suture craniosynostosis and neurodevelopment remains unclear, given the methodologic limitations of previous studies, most notably the absence of control groups. METHODS: Standardized measures were used to assess the neurodevelopment of 125 matched case-control pairs shortly after cases were first diagnosed with isolated fusions of the sagittal, metopic, lambdoid, or right or left coronal sutures. Participants varied in age from 2 to 24 months. RESULTS: Cases had significantly lower mean standardized scores than controls on measures of cognitive ability and motor functioning (p < 0.02). These differences were unaffected by the location of synostosis, age of diagnosis, infant sex, and maternal IQ. Measures of early language functions revealed no group differences. CONCLUSIONS: Before cranioplasty, single-suture craniosynostosis is associated with modest but reliable neurodevelopmental delays that cannot be attributed to maternal intelligence and family sociodemographic variables. Follow-up of this sample will determine the predictive significance of these delays. In the meantime, routine neurodevelopmental screening of infants with isolated craniosynostosis is recommended.