Background: The paradigm of pediatric intestinal failure management has changed during the last decade. The objective of this study was to explore this process and quantify the independent effect of new treatment options.

Methods: Patients were derived from the prospective registry of our intestinal rehabilitation program (IRP).  Change over time was analyzed using multivariate Box-Jenkins-method based autoregressive integrative moving average models (ARIMA), which allow accounting for time delay of exposure and effect. Model selection was driven by clinical reasoning and goodness-of-fit. Post-estimation assessment of residuals and over-fitting was performed. Quarterly time periods were applied. Secondary analyses included non-parametric trend and cumulative exposure analysis.

Results: 196 patients with neonatal/infantile short bowel syndrome born between 07/1996 and 12/2011 were identified. Disease-specific mortality from liver failure and sepsis decreased significantly (p<0.001; Figure). Introduction of IRP and Omega-3 lipid emulsions were independently associated with decreased disease-specific mortality by 68.6% and 42.4% (p<0.001; p<0.001) when adjusted for small bowel length, gestational age and development of intestinal failure associated liver disease (IFALD). Gestational age and IFALD were significant predictors of disease-specific mortality (-95% risk per gestational week, p<0.001; 9.3% risk increase, p<0.001). Other mortality was unchanged and affected by IFALD only (24.6% risk increase, p=0.001). Parenteral nutrition weaning remained stable and was increased by 2.3% per 1% of small bowel and 62.5% with IFALD (p<0.001; p<0.001). Development of IFALD was predicted by persistent conjugated bilirubin >50µmol/L and male sex (51.4%, p<0.001; 24.8%, p=0.007). Progression into liver failure, sepsis and catheter complication rates decreased significantly over time (p=0.001; p<0.001; p<0.001).

Conclusions: Introduction of IRP and Omega-3 lipid emulsions independently decreased disease-specific mortality when adjusted for disease severity and progression. For the first time, time series analysis was applied to evaluate the independent impact of treatment options on patient outcomes over the evolution of an intestinal rehabilitation program.