Impact of Neonatal Body (Dis)Proportionality Determined by the Cephalization Index (CI) on Gross Motor Development in Children with Down Syndrome: A Prospective Cohort Study

Background: Children with Down syndrome (DS) lag behind typical children in the acquisition of developmental milestones, which could differ depending on body proportionality. We aimed to determine the difference in the acquisition of developmental milestones in children with DS with a disproportionate cephalization index (CI) compared to a proportionate CI. We created a motor development model that predicted milestone acquisition times. Methods: In this 20-year prospective cohort study, 47 children with DS aged 3 months to 5 years, followed up to 2020, were grouped according to the ratio of head circumference to birth weight (HC/BW) or CI into proportionate (CI < 1.1) and disproportionate (CI >= 1.1). We used a modified Munich Functional Developmental Diagnostic Scale that was assessed for reliability and content validity (Levene's test and discriminant analysis) to determine 28 motor milestones. Linear regression was used to predict time to milestone acquisition, controlling for sex, maternal age, and birth weight. Results: Compared to proportionate CI, children with disproportionate CI were delayed in the milestone acquisition of a prone position by 2.81 months, standing before walking by 1.29 months, and a supine position by 1.61 months. Both groups required more time to reach standing after the acquisition of independent walking, but children with disproportionate CI reached those milestones later (4.50 vs. 4.09 months, p < 0.001). Conclusion: Children with disproportionate CI acquired milestones in a predictable order but slower than those with a proportionate CI. Our findings support the need to classify the degree of motor developmental delay in children with DS into unique functional groups rather than rely on clinicians' arbitrary descriptions of the timing of developmental delays in children with DS.