Presenter Status
Student
Abstract Type
Research
Primary Mentor
Keith Feldman
Start Date
3-5-2022 11:30 AM
End Date
3-5-2022 1:30 PM
Presentation Type
Poster Presentation
Description
Background: A life-sustaining therapy, use of total parenteral nutrition (TPN) allows for meeting nutritional needs of low birth weight, premature, or otherwise complex infants with conditions that prevent feeding through the GI tract. However, 40-60% of infants on long-term TPN have been shown to develop parenteral nutrition-associated liver disease (PNALD)1 , a serious condition characterized by cholestatic jaundice, steatosis, and hepatic fibrosis. Given these risks, providers must account for risk of hepatic injury when prescribing TPN, including attributes of gestational age, infection, surgical and diagnosis history2-6 . Yet with a multifactorial pathogenesis, significant heterogeneity in PNALD incidence still occurs. Looking to additional factors implicated in development of infant liver disease, we find diagnoses of congenital heart disease (CHD). Cardiac hepatopathy and hepatic fibrosis are prone to develop in children with CHD7 . Yet, there is limited literature on the relationship between CHD and direct hyperbilirubinemia. Quantifying an association between the two may serve to guide evidence-based practice for future PNALD risk-screening and TPN prescription guidelines.
Objective: The objective of this study was to test the hypothesis that CHD may place neonatal patients receiving TPN at higher risk for developing PNALD. A secondary objective aimed to quantify the association between more specific CHD diagnoses and development of direct hyperbilirubinemia.
Methods & Design: Demographic, diagnosis, and laboratory information along with pharmacy TPN data were drawn from records of infants admitted to Children’s Mercy Level-IV NICU 1/1/2010-1/1/2020. Infants were required to have received a minimum of 14 TPN-days over a 21-day window during first 8 weeks of life. Direct bilirubin (DBili) values were gathered from day-14 of TPN exposure through 28-days following final TPN administration. All infants with congenital or acquired conditions known to be associated with conjugated hyperbilirubinemia were excluded. CHD diagnoses were classified as defined by Norman et. al8 : Category-A (defects compromising systemic output), Category-B (defects creating sustained cyanosis), and Category-C (CHF and pulmonary overcirculation). To assess if infants with CHD were at an increased risk for developing PNALD, a time-varying cox-survival model was fit with a binary indicator for CHD, culminative time-varying parameter for days of TPN exposure, adjusted for demographics (GA, Sex, Birthweight), and stratified by DOL TPN was initiated. A follow-up analysis refined the CHD indicator to adjust for co-morbid CHD diagnoses of each infant. Models were estimated using a 10,000- iteration bootstrap and 95% confidence intervals around model coefficients. Sensitivity analysis of the PNALD definition was performed, spanning DBili >[2-5]mg/dL and requiring the value in [1-3] labs.
Results: After exclusion, 758 infants were used for analysis. Figure-1(A) presents the hazard-ratio between infants with CHD diagnosis vs. those without, indicating a clear increase in risk, becoming more produced at higher DBili levels, even when 3 labs above a threshold were required. Results by diagnosis can be found in Figure-1(B).
Conclusions: This work offers a first step to understanding how CHD diagnoses can be factored into clinical algorithms for TPN prescription in infants. Future work will explore lipid profiles and timing as routes to mitigate TPN risk in patients with CHD.
Additional Files
Increased Prevalence of Parenteral Nutrition-Associated Liver Disease in Neonates With Congenital Heart Disease.pdf (605 kB)Abstract
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Increased Prevalence of Parenteral Nutrition-Associated Liver Disease in Neonates With Congenital Heart Disease
Background: A life-sustaining therapy, use of total parenteral nutrition (TPN) allows for meeting nutritional needs of low birth weight, premature, or otherwise complex infants with conditions that prevent feeding through the GI tract. However, 40-60% of infants on long-term TPN have been shown to develop parenteral nutrition-associated liver disease (PNALD)1 , a serious condition characterized by cholestatic jaundice, steatosis, and hepatic fibrosis. Given these risks, providers must account for risk of hepatic injury when prescribing TPN, including attributes of gestational age, infection, surgical and diagnosis history2-6 . Yet with a multifactorial pathogenesis, significant heterogeneity in PNALD incidence still occurs. Looking to additional factors implicated in development of infant liver disease, we find diagnoses of congenital heart disease (CHD). Cardiac hepatopathy and hepatic fibrosis are prone to develop in children with CHD7 . Yet, there is limited literature on the relationship between CHD and direct hyperbilirubinemia. Quantifying an association between the two may serve to guide evidence-based practice for future PNALD risk-screening and TPN prescription guidelines.
Objective: The objective of this study was to test the hypothesis that CHD may place neonatal patients receiving TPN at higher risk for developing PNALD. A secondary objective aimed to quantify the association between more specific CHD diagnoses and development of direct hyperbilirubinemia.
Methods & Design: Demographic, diagnosis, and laboratory information along with pharmacy TPN data were drawn from records of infants admitted to Children’s Mercy Level-IV NICU 1/1/2010-1/1/2020. Infants were required to have received a minimum of 14 TPN-days over a 21-day window during first 8 weeks of life. Direct bilirubin (DBili) values were gathered from day-14 of TPN exposure through 28-days following final TPN administration. All infants with congenital or acquired conditions known to be associated with conjugated hyperbilirubinemia were excluded. CHD diagnoses were classified as defined by Norman et. al8 : Category-A (defects compromising systemic output), Category-B (defects creating sustained cyanosis), and Category-C (CHF and pulmonary overcirculation). To assess if infants with CHD were at an increased risk for developing PNALD, a time-varying cox-survival model was fit with a binary indicator for CHD, culminative time-varying parameter for days of TPN exposure, adjusted for demographics (GA, Sex, Birthweight), and stratified by DOL TPN was initiated. A follow-up analysis refined the CHD indicator to adjust for co-morbid CHD diagnoses of each infant. Models were estimated using a 10,000- iteration bootstrap and 95% confidence intervals around model coefficients. Sensitivity analysis of the PNALD definition was performed, spanning DBili >[2-5]mg/dL and requiring the value in [1-3] labs.
Results: After exclusion, 758 infants were used for analysis. Figure-1(A) presents the hazard-ratio between infants with CHD diagnosis vs. those without, indicating a clear increase in risk, becoming more produced at higher DBili levels, even when 3 labs above a threshold were required. Results by diagnosis can be found in Figure-1(B).
Conclusions: This work offers a first step to understanding how CHD diagnoses can be factored into clinical algorithms for TPN prescription in infants. Future work will explore lipid profiles and timing as routes to mitigate TPN risk in patients with CHD.
