Association between congenital heart disease and parenteral nutrition-associated liver disease in neonates: A retrospective cohort study

JPEN J Parenter Enteral Nutr. 2023 May;47(4):501-510. doi: 10.1002/jpen.2484. Epub 2023 Mar 5.


Objective: Infants receiving parenteral nutrition (PN) are at increased risk of PN-associated liver disease (PNALD), which can lead to hepatic fibrosis. Congenital heart disease (CHD) represents a risk factor for hepatic fibrosis, so this study sought to better understand whether infants with CHD were at elevated risk of PNALD when receiving long-term PN.

Study design: This study includes a retrospective cohort of infants at a level IV neonatal intensive care unit from 2010 to 2020 who received long-term PN during the first 8 weeks of life. A time-varying Cox survival model was used to model risk of PNALD between infants with and without CHD, adjusted for demographics, surgical intervention, and PN exposure, using a 5000-iteration bootstrap estimation. Secondary analyses evaluated risk against discrete CHD diagnoses, and sensitivity analysis was performed on the magnitude and quantity of direct bilirubin laboratory measurements making up the PNALD definition.

Results: Neonates with CHD were found to be at higher risk for PNALD during or soon after long-term PN exposure. A pattern of increasing association strength with increasing bilirubin threshold suggests infants with CHD may also experience higher degrees of injury.

Conclusions: This work offers a step in understanding how diagnoses can be factored into neonate PN prescription. Future work will explore modifications in lipid profiles and timing to mitigate risk in patients with CHD.

Keywords: liver disease; neonates; outcomes research/quality; parenteral nutrition.

MeSH terms

  • Bilirubin
  • Heart Defects, Congenital* / complications
  • Humans
  • Infant
  • Infant, Newborn
  • Liver Cirrhosis / complications
  • Liver Diseases* / etiology
  • Parenteral Nutrition / adverse effects
  • Retrospective Studies


  • Bilirubin