Serum bile acids in term and preterm neonates: A case–control study determining reference values and the influence of early-onset sepsis

Serum bile acids (BA) reference values are lacking for neonates. Therefore, this study aimed to determine serum BA reference values in term and preterm neonates. Furthermore, as serum BA concentrations are well-known to rise in septic adults, BA values were determined in early-onset neonatal sepsis (EOS), a common and serious disease in neonates. Using high-performance liquid chromatography–high-resolution mass spectrometry (HPLC-HRMS), we profiled serum BA in 236 infants, including healthy term neonates (n = 84), premature infants (n = 101), and both term infants (n = 35) and preterm infants (n = 16) with EOS. We examined the impact of prematurity and EOS on BA concentrations. The median reference values of serum BA were 8.0 μmol/L, interquartile range (IQR): 4.6 to 12.9, in healthy term neonates and 10.1 μmol/L, IQR: 5.7 to 15.7, in preterm neonates. Neonates with EOS had significantly lower median BA values, term (4.7 μmol/L, IQR: 2.7–7.6; P < 0.01) as well as preterm (6.4 μmol/L, IQR: 3.5–8.4; P < 0.01). Furthermore, primary and conjugated BA were most abundant in all groups. Taurine-conjugated BA were predominant in all neonates; glycine-conjugated BA were significantly lower in term neonates with EOS than in controls (P < 0.05). Multivariate regression analysis results obtained for BA and inflammatory parameters revealed that BA are an independent factor associated with EOS. This is the first study to determine standard value ranges of serum BA in neonates using HPLC-HRMS. In contrast to adults with sepsis, neonates suffering from EOS exhibit significantly lower BA values than do controls of the same gestational age. These data suggest BA as a supplementary parameter within a panel of biomarkers for EOS in the future.