Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Original Paper Neonatology 2012;101:306–310 DOI: 10.1159/000335333 Cholestasis in Neonates with Red Cell Alloimmune Hemolytic Disease: Incidence, Risk Factors and Outcome Vivianne E.H.J. Smits-Wintjens a Mirjam E.A. Rath a Irene T.M. Lindenburg b Dick Oepkes b Erik W. van Zwet c Frans J. Walther a Enrico Lopriore a a Division of Neonatology, Department of Pediatrics, b Division of Fetal Medicine, Department of Obstetrics, and c Department of Biostatistics, Leiden University Medical Center, Leiden, The Netherlands were independently associated with cholestasis: treatment with at least one IUT (OR 5.81, 95% CI 1.70–19.80, p = 0.005) and rhesus D type of alloimmunization (OR 4.66, 95% CI 1.05– 20.57, p = 0.042). Additional diagnostic tests to investigate possible causes of cholestasis were all negative. In 5 infants (12%), supportive medical and nutritional therapy was start- ed, and one neonate required iron chelation therapy. Conclu- sion: Cholestasis occurs in 13% of neonates with HDN due to red cell alloimmunization, and it is independently associated with IUT treatment and rhesus D type of alloimmunization. Copyright © 2012 S. Karger AG, Basel Introduction Hemolytic disease of the newborn (HDN) due to red cell alloimmunization may lead to excessive unconjugat- ed hyperbilirubinemia, anemia and iron overload [1]. A few studies have reported an association between HDN and the development of conjugated hyperbilirubinemia, i.e. cholestasis [2–5]. Some of these studies (mostly case reports) describe that cholestasis in neonates with HDN is uncommon and usually mild and transient [3–5]. Oth- er reports however detail severe and protracted courses of cholestasis [2, 4, 6, 7]. The etiology of cholestatic liver disease in neonates with HDN has been associated with Key Words Hemolytic disease of the newborn  Cholestasis  Hyperbilirubinemia  Intrauterine blood transfusion  Iron overload Abstract Background: Etiology of cholestatic liver disease in neonates with hemolytic disease of the newborn (HDN) has been as- sociated with iron overload due to intrauterine red cell trans- fusions (IUTs). Data on the incidence and severity of cholesta- sis in neonates with HDN are scarce, and little is known about pathogenesis, risk factors, neonatal management and out- come. Objective: To evaluate incidence, risk factors, manage- ment and outcome of cholestasis in neonates with red cell alloimmune hemolytic disease. Methods: All (near-) term ne- onates with HDN due to red cell alloimmunization admitted to our center between January 2000 and July 2010 were in- cluded in this observational study. Liver function tests (in- cluding conjugated bilirubin) were routinely performed in the neonatal period. We recorded the presence of cholesta- sis, investigated several potential risk factors and evaluated the management and outcome in affected neonates. Re- sults: A total of 313 infants with red cell alloimmune hemo- lytic disease treated with or without IUTs were included. The incidence of cholestasis was 13% (41/313). Two risk factors Received: September 12, 2011 Accepted after revision: November 24, 2011 Published online: February 18, 2012 V.E.H.J. Smits-Wintjens, MD Division of Neonatology, Department of Pediatrics, J6-S Leiden University Medical Center, PO Box 9600 NL–2300 RC Leiden (The Netherlands) Tel. +31 71 526 2909, E-Mail v.smits  @  lumc.nl © 2012 S. Karger AG, Basel 1661–7800/12/1014–0306$38.00/0 Accessible online at: www.karger.com/neo Downloaded by: Leiden University 145.88.209.33 - 9/26/2014 9:11:25 AM