Retrospective Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Sep 18, 2017; 9(26): 1108-1114
Published online Sep 18, 2017. doi: 10.4254/wjh.v9.i26.1108
Conjugated hyperbilirubinemia presenting in first fourteen days in term neonates
Fang Kuan Chiou, Christina Ong, Kong Boo Phua, Fares Chedid, Ajmal Kader
Fang Kuan Chiou, Christina Ong, Kong Boo Phua, Gastroenterology Service, Paediatric Medicine, KK Women’s and Children’s Hospital, Singapore 229899, Singapore
Fares Chedid, Neonatal Medicine, Al Jalila Children’s Specialty Hospital, Dubai, United Arab Emirates
Ajmal Kader, Pediatric Gastroenterology, Dubai Hospital, Dubai, United Arab Emirates
Author contributions: Chiou FK and Kader A contributed equally to this work; Chiou FK contributed to study design, collected and analyzed the data, and drafted and revised the manuscript; Kader A is the principal investigator who designed and supervised the study, provided direction and guidance in data analysis, and reviewed and revised the manuscript; Ong C and Phua KB contributed to study design and reviewed the manuscript for intellectual content; Chedid F contributed to data analysis and provided expertise in statistical analysis; all authors have read and approved the final version of the manuscript.
Institutional review board statement: The study was reviewed and approved by Singhealth Centralised Institutional Review Board.
Informed consent statement: Singhealth Centralised Institutional Review Board has approved waiver of informed consent based on ethical considerations, that the study involved only a retrospective review of medical records, did not require any additional visit, procedure or intervention for study patients, involved minimal risk to study patients, and no risk of breach in patient confidentiality as all data were anonymized with no patient identifier.
Conflict-of-interest statement: The authors have no conflict of interest to declare.
Data sharing statement: Dataset is available from the corresponding author at Consent for data sharing from study participants was not obtained as presented data are anonymized and risk of identification is low.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Ajmal Kader, MBBS, MD, FRCPCH, Consultant, Pediatric Gastroenterology, Dubai Hospital, Al Khaleeja Street, PO Box 7272, Dubai, United Arab Emirates.
Telephone: +97-15-59886975
Received: March 20, 2017
Peer-review started: March 23, 2017
First decision: June 30, 2017
Revised: July 6, 2017
Accepted: September 5, 2017
Article in press: September 7, 2017
Published online: September 18, 2017

To describe the etiology and characteristics of early-onset conjugated hyperbilirubinemia (ECHB) presenting within 14 d of life in term neonates.


Retrospective review was performed of term infants up to 28-d-old who presented with conjugated hyperbilirubinemia (CHB) at a tertiary center over a 5-year period from January 2010 to December 2014. CHB is defined as conjugated bilirubin (CB) fraction greater than 15% of total bilirubin and CB greater or equal to 25 μmol/L. ECHB is defined as CHB detected within 14 d of life. “Late-onset” CHB (LCHB) is detected at 15-28 d of life and served as the comparison group.


Total of 117 patients were recruited: 65 had ECHB, 52 had LCHB. Neonates with ECHB were more likely to be clinically unwell (80.0% vs 42.3%, P < 0.001) and associated with non-hepatic causes (73.8% vs 44.2%, P = 0.001) compared to LCHB. Multifactorial liver injury (75.0%) and sepsis (17.3%) were the most common causes of ECHB in clinically unwell infants, majority (87.5%) had resolution of CHB with no progression to chronic liver disease. Inborn errors of metabolism were rare (5.8%) but associated with high mortality (100%) in our series. In the subgroup of clinically well infants (n = 13) with ECHB, biliary atresia (BA) was the most common diagnosis (61.5%), all presented initially with normal stools and decline in total bilirubin but with persistent CHB.


Secondary hepatic injury is the most common reason for ECHB. BA presents with ECHB in well infants without classical symptoms of pale stools and deep jaundice.

Keywords: Conjugated hyperbilirubinemia, Biliary atresia, Cholestasis, Direct hyperbilirubinemia, Neonatal jaundice

Core tip: Conjugated hyperbilirubinemia (CHB) is not routinely checked before 14-21 d of life, hence incidence and etiology of early-onset CHB (ECHB) before 14 d are not well-documented. Nearly three-quarters of ECHB have non-hepatic cause and are expected to recover with supportive treatment, while biliary atresia and metabolic disorders are important etiologies associated with significant morbidity. In our study, BA presenting before 14 d were detected solely from low levels of CHB without pale stools or worsening jaundice. Further studies are needed to determine if CHB screening before 14 d would lead to improved detection and outcome in neonatal liver disorders.