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Surgical Timing And Neurocognitive Development Among Patients With Craniosynostosis: Analysis Of Confounding Variables And Selection Bias
Jeremy V. Lynn, BS, Lauren K. Buchman, N/A, Christopher J. Breuler, MD, Steven R. Buchman, MD.
University of Michigan, Ann Arbor, MI, USA.

Purpose: Among patients with craniosynostosis, the relationship between surgical timing and neurocognitive development remains controversial. In 1988, Renier et al described a cause (delayed cranial vault remodeling) and effect (delayed neurocognitive development) relationship, stating that "mental deficiency is more frequent after one year of age" and therefore "the younger the patient at the time of surgery, the better the [neurocognitive] result." The purpose of this study is to identify factors potentially confounding the relationship between surgical timing and neurocognitive development. We hypothesize that children with socioeconomic disadvantages or comorbid conditions are more likely to undergo delayed cranial vault remodeling and may represent a selection bias toward delayed neurocognitive development.
Methods: A retrospective review study was designed, and IRB approval was obtained. All patients with craniosynostosis who underwent cranial vault remodeling between 2009 and 2020 at a single institution were included. Patients with syndromic or multi-suture craniosynostosis were excluded. Demographic, socioeconomic, and clinical variables were documented. The sample was dichotomized to compare patients who underwent cranial vault remodeling before (Early) and after (Late) 12 months of age. Differences between the Early and Late groups were determined using chi-square analysis at p<0.05 significance.
Results: A total of 227 patients met inclusion criteria. The sample consisted of patients diagnosed with sagittal (53.7%), metopic (28.2%), coronal (15.5%), and lambdoid (2.6%) synostosis. The Early and Late groups contained 157 patients (69.2%) and 70 patients (30.8%), respectively. Compared to the Early group, the Late group contained a significantly larger proportion of patients who identified as non-white (p=0.03), qualified for need-based financial assistance from the hospital (p=0.03), were born preterm (p<0.01), or carried a comorbid diagnosis (p<0.01). Notably, based on pre-operative neurocognitive testing with the Bayley Scales for Infant and Toddler Development, the Late group contained a significantly larger proportion of patients with baseline cognitive delays relative to the Early group (p = 0.011).
Conclusion: This study identifies characteristic differences between patients with craniosynostosis who underwent cranial vault remodeling before and after 12 months of age. Race, socioeconomic status, and comorbid conditions may separately impact both access to timely surgical care and long-term neurocognitive development. This study supports our hypothesis that the cause (delayed cranial vault remodeling) and effect (delayed neurocognitive development) relationship described by Renier et al may be confounded by selection bias. Future studies evaluating the relationship between surgical timing and neurocognitive development must consider the potential for these and other confounding factors.




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