AUTHOR=Santos Silva Ermelinda , Almeida Alexandra , Frutuoso Simão , Martins Esmeralda , Valente Maria João , Santos-Silva Alice , Lopes Ana Isabel 

TITLE=Neonatal Cholestasis Over Time: Changes in Epidemiology and Outcome in a Cohort of 154 Patients From a Portuguese Tertiary Center

JOURNAL=Frontiers in Pediatrics

VOLUME=Volume 8 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2020.00351

DOI=10.3389/fped.2020.00351

ISSN=2296-2360

ABSTRACT=management of neonatal cholestasis, which may have changed its epidemiology, diagnostic accuracy, outcomes and survival. Our goal was to characterize these changes over time in our setting.

Methods: Retrospective cohort study in a tertiary center, enrolling patients born between January 1985 and October 2019. The cohort was divided into two periods, before (A; n=67) and after (B; n=87) the year 2000; and in two groups, according to patient´s outcome (favourable, unfavourable). Overall survival and survival without orthotopic liver transplant (OLT) were evaluated in the two periods (A and B) and in different subgroups of underlying entities.

Results: We found that the age of cholestasis recognition decreased significantly from period A to period B [median 43 days and 22 days, respectively, p<0.001)]; the changes in epidemiology were relevant, with a significant decrease in alpha-1-antitrypsin deficiency (p<0.001) and an increase in transient cholestasis (p=0.004). A next-generation sequencing (NGS) panel available since mid-2017 was applied to 13 patients with contributory results in 7, but, so far, only in 2 patients led to conclusive diagnosis of underlying entities. The number of cases of idiopathic cholestasis did not vary significantly. Over time there was no significant change in the outcome (p=0.116). Overall survival and survival without OLT had no significant improvement during the period of observation (in periods A and B, 86% versus 88%, and 85% versus 87%, respectively). However, in period B, with OLT we achieved the goal of 100% of survival rate.

Conclusions: Our data suggest that transient cholestasis became a very important subset of neonatal cholestasis, requiring specific guidance. The NGS panels can provide important inputs on disease diagnosis but, if applied without strict criteria and expertise, they can open a Pandora's box due to misinterpretation. Despite all the advances in accurate diagnosis and timely management – including early recognition of cholestasis - the improvement in patient outcomes and survival were still not significant.