Phenobarbital is Associated with Cholestasis in Preterm Infants with Hemo-dynamically Significant Patent Ductus Arteriosus

Abstract Objectives: This retrospective study aimed to assess whether phenobarbital was associated with cholestasis in preterm infants with hemo-dynamically significant patent ductus arteriosus (hsPDA).Methods: This study included 151 preterm infants (24~34 weeks, birth weight<2000 g) diagnosed with hsPDA, admitted to a level III neonatal intensive care unit (NICU) from September 2016 to September 2019. Of the 151 infants, twenty-seven infants were diagnosed with cholestasis. To assess the independent association of phenobarbital with cholestasis, binary logistic regression was done, adjusting for major confounders (birth weight, gestational age, critical risk index for babies and etc).Result: To explore whether the risk of cholestasis was independently increased by duration of phenobarbital, binary logistic regression analysis was done adjusting for significant confounders (p<0.05). After adjustment with confounders “critical risk index for babies”, “invasive mechanical ventilation”, “any sepsis onset in 28 days” and “duration of cimetidine”, cholestasis was still associated with “duration of phenobarbital” (OR: 1.350; 95% CI: 1.064, 1.714; P = 0.014) and “CMV infection” (OR: 10.818; 95% CI: 0.915, 127.914; P = 0.059). Furthermore, “duration of phenobarbital” might independently delay the time to reach full enteral feeding (OR: 1.479; 95% CI: 1.088, 2.011; P = 0.013), causing parenteral nutrition associated cholestasis.Conclusion: This study found that duration of phenobarbital was associated with neonatal cholestasis in premature infants with hsPDA. Phenobarbital should be used cautiously in preterm infants with hsPDA or cholestasis.