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Selected Publication:
Zöhrer, E.
The influence of prematurity and early-onset sepsis on typical and atypical bile acids in neonates
Doktoratsstudium der Medizinischen Wissenschaft; Humanmedizin; [ Dissertation ] Graz Medical University; 2016. pp.
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- Authors Med Uni Graz:
- Advisor:
- Hoffmann Karl Martin
- Jahnel Jörg
- Scharnagl Hubert
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- Abstract:
- Background: Bile acids (BA) are essential for intestinal lipid absorption. Although BA mainly circulate between liver and gut, extraportal serum BA concentrations correlate with total BA quantity. Of note is that total serum BA levels and the composition of the BA pool (the “BA profile”) differ in healthy adults and neonates. In adults, the typical BA, cholic and chenodeoxycholic acids, are the predominant BA species. In both term and preterm neonates, these typical BA predominate as well; however, “atypical” BA - otherwise mainly found in rodents – such as alpha-, beta-, gamma-, or omega-muricholic acid also are synthesized. This study initially aimed to determine standard value ranges of total BA levels including both typical and atypical BA in term and preterm neonates. Secondly, because serum BA concentrations rise in septic adults, BA values were determined in early-onset neonatal sepsis (EOS), a common and serious disease in neonates, to learn if monitoring serum BA values in neonates could identify sepsis at its onset. Methods: The total BA profile – serum levels and composition of typical and atypical BA - was determined in 102 neonates using high-performance liquid chromatography – high-resolution mass spectrometry: 67 term neonates (47 healthy and 20 with EOS) and 35 preterm neonates (22 healthy and 13 with EOS) were included. Results: In healthy term neonates, the median reference value of total BA was 8.7 µmol/L (interquartile range [IQR]: 5.0 – 13.5), higher than in healthy adults (0.3 – 6.5 µmol/L). In contrast to healthy term neonates, term neonates with EOS had significantly lower median BA values (6.2 µmol/L, IQR: 3.8 – 8.6; p<0.01). In healthy preterm neonates, the median reference value of total BA was 11.2 µmol/L (IQR: 5.6 – 16.9). Preterm neonates with EOS did not have significantly altered BA values (7.4 µmol/L, IQR: 4.0 – 10.0). Independently of gestational age and state of health of the neonate, the BA pool consisted primarily of taurine-conjugated BA: the most abundant BA was a typical BA, tauro-chenodeoxycholic acid. The most common atypical BA in healthy term and preterm neonates were tauro-gamma-muricholic acid and tauro-alpha-muricholic acid, respectively. In EOS (equal term and preterm), tauro-omega-muricholic acid (TOMCA) was the most predominant atypical BA species, present in quantities significantly higher than those in healthy subjects (p<0.01). Conclusion: This is the first study to determine standard value ranges of total BA levels in neonates including both typical and atypical BA. We propose that “atypical” BA are common in early infancy. Additionally, in contrast to adults with sepsis, total BA values in term neonates suffering from EOS are significantly lower than in healthy controls. Hence, we suggest serum BA in general – and TOMCA specifically - as an EOS biomarker with potential clinical value.