Diversity of disorders causing neonatal cholestasis - the experience of a tertiary pediatric center in Germany

Abstract

Background and objective: Rapidly establishing the cause of neonatal cholestasis is an urgent matter. The aim of this study was to report on the prevalence and mortality of the diverse disorders causing neonatal cholestasis in an academic center in Germany.

Methods: Clinical chemistry and cause of disease were retrospectively analyzed in 82 infants (male n = 42, 51%) that had presented with neonatal cholestasis to a tertiary medical center from January 2009 to April 2013.

Results: Altogether, 19 disorders causing neonatal cholestasis were identified. Biliary atresia was the most common diagnosis (41%), followed by idiopathic cases (13%), progressive familial intrahepatic cholestasis (PFIC, 10%), cholestasis in preterm infants (10%), α1AT deficiency, Alagille syndrome, portocaval shunts, mitochondriopathy, biliary sludge (all 2%), and others. Infants with biliary atresia were diagnosed with a mean age of 62 days, they underwent Kasai portoenterostomy ~66 days after birth. The majority of these children (~70%) received surgery within 10 weeks of age and 27% before 60 days. The 2-year survival with their native liver after Kasai procedure was 12%. The time span between Kasai surgery and liver transplantation was 176 ± 73 days. Six children (7%), of whom three patients had a syndromic and one a non-syndromic biliary atresia, died prior to liver transplantation. The pre- and post-transplant mortality rate for children with biliary atresia was ~12 and ~17%, respectively.

Conclusion: Neonatal cholestasis is a severe threat associated with a high risk of complications in infancy and it therefore requires urgent investigation in order to initiate life saving therapy. Although in the last 20 years new causes such as the PFICs have been identified and newer diagnostic tools have been introduced into the clinical routine biliary atresia still represents the major cause.

Keywords: ERCP; Kasai procedure; biliary atresia; neonatal cholestasis; neonatal jaundice.

Figure 1

The various disorders that led to neonatal cholestasis and the proportion of patients of each entity (%) of a cohort of 82 infants at a single tertiary medical center.

Figure 2

The causes of neonatal cholestasis and the proportion of patients of each entity (%) of a cohort of 37 infants that were initially referred with unclear cholestasis to the University Children’s Hospital Essen.

Figure 3

Mortality pre- and post-LTX in biliary atresia (BA) and other disorders causing neonatal cholestasis. The bar graph shows the proportion of deceased children before and after liver transplantation (%). Absolute patient numbers are printed in bold inside the bar graph segments.