Anemia of Prematurity - Portal Neonatal

Hemolytic Disease of Newborn
Last Updated: March 14, 2003
Synonyms and related keywords: HDN, erythroblastosis fetalis, transplacental hemorrhage,
fetomaternal hemorrhage, alloimmunization, hemolysis, hyperbilirubinemia, jaundice, kernicterus,
nonimmune hydrops fetalis
AUTHOR INFORMATION Section 1 of 11
Author: Sameer Wagle, MD, Consulting Staff, Division of Neonatology, Northwest Medical Center
of Washington County
Coauthor(s): Prashant G Deshpande, MD, Consulting Staff, Department of Pediatrics, Hope
Children's Hospital
Sameer Wagle, MD, is a member of the following medical societies: Mississippi State Medical
Association
Editor(s): Oussama Itani, MD, Medical Director of Neonatology, Borgess Medical Center, Clinical
Assistant Professor, Department of Pediatrics and Human Development, Michigan State University;
Robert Konop, PharmD, Director, Clinical Account Management, Ancillary Care Management;
David A Clark, MD, Chairman, Professor, Department of Pediatrics, Albany Medical College;
Carol L Wagner, MD, Associate Professor, Department of Pediatrics, Division of Neonatology,
Medical University of South Carolina; and Neil N Finer, MD, Director, Division of Neonatology,
Professor, Department of Pediatrics, University of California at San Diego
INTRODUCTION Section 2 of 11
Background: A French midwife was the first to report hemolytic disease of the newborn (HDN) in a
set of twins in 1609. In 1932, Diamond and colleagues described the relationship of fetal hydrops,
jaundice, anemia, and erythroblasts in the circulation, a condition later called erythroblastosis fetalis.
Levine later determined the cause after Landsteiner and Weiner discovered the Rh blood group
system in 1940. In 1953, Chown subsequently confirmed the pathogenesis of Rh alloimmunization to
be the result of passage of Rh-positive fetal red blood cells after transplacental hemorrhage into
maternal circulation that lacked this antigen.
Pathophysiology: Although the Rh antibody was and still is the most common cause of severe
HDN, other alloimmune antibodies belonging to Kell (K and k), Duffy (Fya), Kidd (Jka and Jkb), and
MNSs (M, N, S, and s) systems do cause severe HDN. Rh blood group antigens are determined by
at least 2 homologous but distinct membrane-associated proteins. Two separate genes located on
chromosome 1 encode Rh proteins. Rh-negative phenotype represents absence of D protein on
RBCs and results from deletion of the RHD gene on both chromosomes. Rh antigens exist in 3 loci:
Cc, Dd, and Ee. Expression is limited to RBCs, with an increasing density during their maturation,
unlike the ABH system, which exists in a wide variety of tissues. Rh antigen is not expressed on
RBC progenitors. Of individuals who are Rh positive, 45% are homozygous and 55% are
heterozygous.
Frequency of Rh negativity is higher in whites (15%) than in blacks (5%), and it is rare in Asians. The
paternal heterozygosity determines the likelihood of an Rh-positive child being born to an Rhnegative
mother. The Kleihauer-Betke acid elution technique that determines the proportion of fetal
RBCs in maternal circulation has shown the incidence of fetomaternal hemorrhage to be 75% of all
pregnancies. Incidence and degree of such hemorrhage appears to increase with gestation. Risk is
also increased in pregnancies complicated by placental abruption, spontaneous or therapeutic
abortion, and toxemia, as well as after cesarean delivery and ectopic pregnancy.