Neurodevelopmental Disorders and the Inverse Metabolic Profile: A Nationwide Propensity-Matched Analysis

Background Adults with neurodevelopmental disorders (NDD) may exhibit a distinct metabolic and nutritional risk profile compared to the general population. Although pediatric studies have reported higher obesity rates in certain neurodevelopmental disorder subtypes, particularly autism spectrum disorder, findings are heterogeneous, and national-level data in adults remain limited. This study assessed the association between NDD and three key metabolic outcomes in hospitalized adults: obesity, non-alcoholic fatty liver disease (NAFLD), and protein-calorie malnutrition. Methods This retrospective study utilized the National Inpatient Sample (2016-2020) and included adults aged 18 years and older. NDD was identified using diagnostic codes for autism spectrum disorder, intellectual disability, and related developmental disorders. The primary outcomes were obesity, NAFLD, and protein-calorie malnutrition. All hospitalizations involving NDD were included. To ensure an adequate pool of potential controls for matching, a 20:1 random sample of non-NDD hospitalizations was initially selected, followed by 1:4 nearest-neighbor propensity score matching based on age, sex, race, primary payer, and income quartile. Survey-weighted multivariable logistic regression models were used to estimate adjusted odds ratios (aORs). Results The final matched cohort comprised 856,315 weighted hospitalizations, including 171,263 adults with NDD and 685,052 matched controls. Propensity score matching achieved excellent covariate balance, with all standardized mean differences <0.10, indicating clinically similar baseline characteristics between groups. Adults with NDD demonstrated an inverse metabolic profile, with lower odds of obesity (aOR 0.76) and NAFLD (aOR 0.56), but higher odds of protein-calorie malnutrition (aOR 1.25).  Conclusions Hospitalized adults with neurodevelopmental disorders exhibit an inverse metabolic profile, characterized by lower odds of obesity and NAFLD but higher odds of malnutrition. These findings contrast with the pediatric literature and indicate that metabolic risk patterns in NDD may shift with age. Recognition of this distinct profile may inform targeted metabolic screening and nutritional interventions for this vulnerable population.