Phenobarbital is Associated with Cholestasis in low birth weight Infants with Hemo-dynamically Significant Patent Ductus Arteriosus

Abstract

Objectives: This retrospective cohort study aimed to assess whether phenobarbital was associated with cholestasis in low birth weight (LBW) infants with hemo-dynamically significant patent ductus arteriosus (hsPDA).Methods: This study included 148 LBW infants (24~34 weeks, birth weight<2000 g) diagnosed with hsPDA, admitted to neonatal intensive care unit (NICU) from September 2016 to September 2019. Of the 148 infants, twenty infants were diagnosed with cholestasis. To assess the independent association with cholestasis or direct bilirubin, binary logistic or multivariable linear regression was done, adjusting for major confounders (birth weight, gestational age, critical risk index for babies, invasive mechanical ventilation, any sepsis onset in 28 days and etc). Result: Binary logistic regression analysis was done adjusting for 12 related confounders. After adjustment, the “delay of full enteral feeding” was still associated with “duration of phenobarbital” (DOP) (OR: 1.571; P = 0.015) or “duration of phenobarbital before cholestasis onset” (DOPBCO) (OR: 1.662; P = 0.014); Cholestasis was still associated with “DOP” (OR: 1.553; P = 0.005) or “DOPBCO” (OR: 1.353; P = 0.088); “High direct bilirubin summit” (>1.5 mg/dl) was still associated with “DOP” (OR: 1.686; P = 0.003) or “DOPBCO” (OR: 1.511; P = 0.021). Multivariate linear regression revealed that “persist time of cholestasis” was associated with “DOB” (B: 2.254; P = 0.050) after adjustment of “delay of full enteral feeding”.Conclusion: This study found that phenobarbital was associated with neonatal cholestasis in LBW infants with hsPDA. Phenobarbital should be used cautiously in this population.