Cholestasis In Infants With Down Syndrome Is Not Due To Extrahepatic Biliary Atresia: A Ten-Year Single Egyptian Centre Experience

Abstract

Purpose

We aimed to define the clinical presentations, course and outcome of cholestasis in infants with Down syndrome (trisomy 21) who presented to the Pediatric Hepatology Clinic, New Children Hospital, Cairo University, Egypt.

Methods

Retrospective analysis of data of cohort of infants with Down syndrome and cholestasis who followed up during 2005–2015.

Results

Among 779 infants with cholestasis who presented during 2005–2015, 61 (7.8%) had Down syndrome. Six dropped out. Among the 55 who followed-up for a mean duration +SD = 12.1 ± 16.7 months, none had extrahepatic biliary atresia (EHBA), 37 (63.3%) had neonatal hepatitis and 18 (32.7%) had non-syndromic paucity of intrahepatic biliary radicals. Fourteen (25.4%) had associated congenital heart disease. Only 35 (63.3%) cleared the jaundice. Twenty-nine (52.7%) received ursodeoxycholic acid (UDCA); of them, 13 cleared the jaundice, one improved, 14 progressed and one died, compared to 22 who cleared the jaundice of the 26 who did not receive UDCA. Only three of those who did not receive UDCA progressed and none died. UDCA carried a 3.4-fold risk of poor prognosis (p= 0.001). UDCA use was associated with more complications (p= 0.016) in those with Down syndrome and cholestasis.

Conclusion

We did not come across EHBA among neonates and infants with Down syndrome in 10 years. Non-syndromic paucity is associated with favorable outcome in infants with Down syndrome. UDCA use in cholestasis with Down syndrome is associated with poor outcome.

Keywords:

• cholestasis
• extrahepatic biliary atresia
• EHBA
• neonatal hepatitis
• Down syndrome
• trisomy 21
• ursodeoxycholic acid
• UDCA

Acknowledgments

We acknowledge all Pediatric Hepatology Team Members and archiving secretaries of the Pediatric Hepatology Clinic, New Children Hospital, Cairo University Hospital, Cairo University. There was no funding source for this study. The trial was approved by the Pediatric Department Committee for Post-Graduate Studies and Research, and by Post-Graduate Studies and Research Administration, Faculty of Medicine, Cairo University, Cairo, Egypt. The corresponding author had full access to all of the data and takes full responsibility for the veracity of the data and statistical analysis.

Abbreviations

ALT, alanine aminotransferase; AST, aspartate aminotransferase; CHD, congenital heart disease; D.Bil, direct bilirubin; EHBA, extrahepatic biliary atresia; SD, standard deviation; T.Bil, total bilirubin; UDCA, ursodeoxycholic acid.

Compliance With Ethical Statements

This article does not contain any studies with human participants or animals performed by any of the authors. It is a retrospective study including all files of neonates and infants who presented with cholestasis and clinical features of Down syndrome (trisomy 21) during 2005–2015. The study was approved by The Pediatric Department Committee for Post-Graduate Studies and Research, and by Post-Graduate Studies and Research Administration, Faculty of Medicine, Cairo University, Egypt.

What Is Known?

1. Exclusion of surgical causes of cholestasis is invasive, yet it is part of workup in every neonate with cholestasis as surgical portoenterostomy should not be delayed beyond 3 months of age to halt the march of biliary cirrhosis.

2. Cholestasis associated with trisomy 21 (Down syndrome) has been reported previously.

What Is New?

1. Cholestasis in Down syndrome was never found to be due to biliary atresia; we did not come across a single obstructive cholestasis in Down syndrome in 10 years of practice.

2. Generally, the outcome of cholestasis is favorable in Down syndrome, especially if the etiology of cholestasis is non-syndromic paucity, unless they receive ursodeoxycholic acid, as its' use is associated with poor outcome, complications and fatality.

Disclosure

The authors report no conflicts of interest in this work.