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Duration of exposure to cranial vault surgery: associations with neurodevelopment among children with single-suture craniosynostosis.

ABSTRACT: To evaluate associations between neurodevelopment and exposure to surgery and anesthetic agents in children with single-suture craniosynostosis (SSC).Young children with SSC have unexplained neurodevelopmental delays. The possible contributions of factors related to cranial vault surgery - including anesthesia - have not been previously examined.Two anesthesiologists reviewed the surgical records of 89 infants (70 had complete data). Primary exposures were duration of surgery and anesthesia and total duration of inhaled anesthesia (at age 6 months on average). Outcomes were the cognitive and motor scores from the Bayley Scales of Infant Development-II and language scores from the Preschool Language Scale, 3rd edition, given at age 36 months. Linear regression using robust standard error estimates was performed, adjusting for age at surgery and suture site.Anesthesia duration ranged from 155 to 547 min. For every 30-min increase in anesthesia duration, the estimated average decrease in developmental test scores ranged from 1.1 to 2.9 (P ranged from <0.001 to 0.30). Similar, but weaker findings were observed with surgery duration and total duration of inhaled anesthesia. Inverse relations between exposure amounts and neurodevelopment were stronger in children with nonsagittal synostosis.Average neurodevelopmental scores were lower among children experiencing longer surgeries and higher exposures to inhaled anesthesia. These associations may be due to anesthesia exposure, nonspecific effects of surgery, or unmeasured variables that correlate with surgery duration. Further study of potential causal mechanisms is warranted.

SUBMITTER: Naumann HL

PROVIDER: S-EPMC3404221 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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Duration of exposure to cranial vault surgery: associations with neurodevelopment among children with single-suture craniosynostosis.

Naumann Heather L HL Haberkern Charles M CM Pietila Kristen E KE Birgfeld Craig B CB Starr Jacqueline R JR Kapp-Simon Kathleen A KA Hopper Richard A RA Speltz Matthew L ML

Paediatric anaesthesia 20121101 11

<h4>Objective</h4>To evaluate associations between neurodevelopment and exposure to surgery and anesthetic agents in children with single-suture craniosynostosis (SSC).<h4>Background</h4>Young children with SSC have unexplained neurodevelopmental delays. The possible contributions of factors related to cranial vault surgery - including anesthesia - have not been previously examined.<h4>Methods/materials</h4>Two anesthesiologists reviewed the surgical records of 89 infants (70 had complete data). ...[more]

PMID: 22502768

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Project description:BACKGROUND: Craniosynostosis, the premature fusion of calvarial sutures, is a common craniofacial abnormality. Causative mutations in more than 10 genes have been identified, involving fibroblast growth factor, transforming growth factor beta, and Eph/ephrin signalling pathways. Mutations affect each human calvarial suture (coronal, sagittal, metopic, and lambdoid) differently, suggesting different gene expression patterns exist in each human suture. To better understand the molecular control of human suture morphogenesis we used microarray analysis to identify genes differentially expressed during suture fusion in children with craniosynostosis. Expression differences were also analysed between each unfused suture type, between sutures from syndromic and non-syndromic craniosynostosis patients, and between unfused sutures from individuals with and without craniosynostosis. RESULTS: We identified genes with increased expression in unfused sutures compared to fusing/fused sutures that may be pivotal to the maintenance of suture patency or in controlling early osteoblast differentiation (i.e. RBP4, GPC3, C1QTNF3, IL11RA, PTN, POSTN). In addition, we have identified genes with increased expression in fusing/fused suture tissue that we suggest could have a role in premature suture fusion (i.e. WIF1, ANXA3, CYFIP2). Proteins of two of these genes, glypican 3 and retinol binding protein 4, were investigated by immunohistochemistry and localised to the suture mesenchyme and osteogenic fronts of developing human calvaria, respectively, suggesting novel roles for these proteins in the maintenance of suture patency or in controlling early osteoblast differentiation. We show that there is limited difference in whole genome expression between sutures isolated from patients with syndromic and non-syndromic craniosynostosis and confirmed this by quantitative RT-PCR. Furthermore, distinct expression profiles for each unfused suture type were noted, with the metopic suture being most disparate. Finally, although calvarial bones are generally thought to grow without a cartilage precursor, we show histologically and by identification of cartilage-specific gene expression that cartilage may be involved in the morphogenesis of lambdoid and posterior sagittal sutures. CONCLUSION: This study has provided further insight into the complex signalling network which controls human calvarial suture morphogenesis and craniosynostosis. Identified genes are candidates for targeted therapeutic development and to screen for craniosynostosis-causing mutations.

Dataset Information

Duration of exposure to cranial vault surgery: associations with neurodevelopment among children with single-suture craniosynostosis.

Publications

Duration of exposure to cranial vault surgery: associations with neurodevelopment among children with single-suture craniosynostosis.

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