Change of Outcomes in Pediatric Intestinal Failure: Use of Time-Series Analysis to Assess the Evolution of an Intestinal Rehabilitation Program

Abstract

The clinical picture of pediatric intestinal failure has changed over the past 15 years, while effectiveness evolving treatment options remains unclear. This study explored evolution in care and quantified independent effects of new treatment options. Consecutive patients (n= 196) with neonatal or infantile intestinal failure, born between July 1996 and December 2011, were derived from an intestinal rehabilitation program (IRP) patient registry. Change over time was analyzed using multivariable Box-Jenkins method-based autoregressive integrative moving average models (ARIMA), robust linear regression, and nonparametric trend analysis. Four systematically introduced treatment options (IRP, serial transverse enteroplasty, omega-3 lipid emulsions, and ethanol locks) were evaluated. Analyses were adjusted for patient characteristics and disease severity. The primary outcome was disease-specific mortality from liver failure and sepsis. Secondary outcomes included parenteral nutrition weaning, transplantations, catheter complications, and liver disease. Patient characteristics remained unchanged over time, except for decreasing small bowel length (-0.5%/quarter; 95% CI-0.85,-0.16) and ICU admission time (-0.6 days/quarter; 95% CI-1.03,-0.18). Disease-specific mortality diminished significantly over time (-0.02 deaths/quarter; 95% CI-0.03,-0.01) by IRP and omega-3 lipids introduction (-0.6 deaths/quarter each, 95% CI-1.23,-0.02 and-0.77,-0.45, respectively). Serial transverse enteroplasty and ethanol locks had no significant impact. Parenteral nutrition weaning and transplantations remained unchanged, while catheter sepsis and complication rates decreased by 0.3 episodes/1,000 catheter-days each (95% CI-0.43,-0.2 and-0.45,-0.24, respectively). Introduction of IRP and omega-3 lipids independently decreased disease-specific mortality. For the first time, time series analysis was applied to evaluate effectiveness of treatment options in intestinal rehabilitation.