Delirium prevalence and associated factors in critically ill neonates hospitalized in the NICU and their neurodevelopmental implications

Abstract Despite the vulnerability of the developing neonatal brain, delirium remains a largely unrecognized complication in the NICU, with its prevalence and associated factors still poorly characterized. This condition is increasingly recognized as a potential indicator of acute brain dysfunction. However, evidence regarding its neurodevelopmental consequences remains speculative and requires longitudinal investigation. Accordingly, this study aimed to identify factors associated with the development of delirium in neonates admitted to the NICU and to explore their neurodevelopmental implications. This prospective observational study with a cross-sectional analytical design was conductedin three Level III NICUs between November 2023 and January 2025. A total of 243 neonates were included. Data were collected using a demographic questionnaire and the Cornell Assessment of Pediatric Delirium (CAPD) scale. Statistical analysis included descriptive statistics. A multivariable logistic regression model was developed, with covariates selected a priori based on a Directed Acyclic Graph (DAG) to minimize bias. The model’s quality was assessed using the Hosmer-Lemeshow test, Area under the Curve (AUC), and Nagelkerke R 2 . The final multivariable logistic regression model identified several independent factors: Corrected Age (OR 0.964, 95% CI 0.941–0.989, p = 0.004) and Birthweight (OR 0.872 per 100 g increase, 95% CI 0.815–0.933, p < 0.001) were protective factors, with higher values decreasing the odds of delirium. Being a first-born neonate significantly increased the odds of delirium (OR 18.834, 95% CI 6.152–57.662, p < 0.001). Jaundice (OR 5.221, 95% CI 1.559–17.485, p = 0.007), Sepsis (OR 5.615, 95% CI 2.092–15.069, p = 0.001), and Respiratory Distress Syndrome (RDS) (OR 8.558, 95% CI 2.061–35.538, p = 0.003) were strongly associated with increased odds of delirium compared to prematurity. Conversely, Transient Tachypnea of the Newborn (TTN) was associated with significantly lower odds of delirium (OR 0.126, 95% CI 0.027–0.599, p = 0.009) compared to other diagnoses. Delirium is prevalent among NICU neonates and is significantly associated with factors related to brain development, including lower corrected age, lower birth weight, first-born status, sepsis, RDS, and jaundice, while TTN appears protective. These cross-sectional findings highlight a high prevalence of delirium in the NICU and identify several associated factors. While the results support the need for systematic screening, causal relationships and the clinical utility of screening for improving neurodevelopmental outcomes require confirmation through prospective interventional studies.