Updated: 8/12/2021

Rh Hemolytic Disease of the Newborn

Review Topic
  • A 32-year-old G1P0 woman presents to the emergency room with contractions. She was found to be Rh-negative and her husband’s Rh status is unknown. Fetal ultrasound shows no signs of edema or ascites. After the Kleihauer-Betke test, she is given the appropriate dose of Rh IgG.
  • Overview
    • Rh hemolytic disease of the newborn is caused by Rh incompatibility
    • maternal anti-Rh IgG antibodies cross the placenta and destroy fetal Rh-positive red blood cells
  • Epidemiology
    • incidence
      • 15% of the population is Rh-negative
    • risk factors
      • history of prior blood transfusion
      • previous pregnancy
      • mother is Rh-negative, and father is Rh-positive or unknown
      • prior administration of Rh IgG (RhoGam)
      • history of invasive obstetric procedures
  • Pathogenesis
    • mechanism    
      • Rh factor is a red blood cell antigen
      • when an Rh-negative mother is pregnant with an Rh-positive fetus, the mother is exposed to Rh-positive red blood cells and leads to maternal antibody production (IgG) against the foreign Rh antigen
      • as IgG can cross the placenta, subsequent pregnancy with Rh-positive fetus will result in fetal alloimmune-induced hemolytic anemia
      • development of antibody depends on volume of transplacental crossover of red blood cells, concurrent presence of ABO incompatibility, and extent of maternal immune response
      • breakdown of red blood cells causes elevation of bilirubin
  • Symptoms
    • hemolytic anemia
  • Physical exam
    • inspection
      • jaundice
      • pallor
  • Fetal ultrasound
    • indication
      • suspected Rh incompatibility
    • findings
      • fetal ascites and edema
  • Serum labs
    • hyperbilirubinemia
    • low hematocrit
    • elevated reticulocyte count
    • positive direct Coombs test in fetus; positive indirect Coombs test in the mother
  • Rosette test
    • initial test to test for fetal-maternal hemorrhage
  • Kleihauer-Betke test
    • measures fetal red blood cells in utero in maternal circulation to determine dose of RhoGAM
  • ABO incompatibility
    • key distinguishing factor
      • typically less severe
  • Medical
    • maternal anti-D immune globulin (Rh IgG or RhoGAM) administration
      • indication
        • if mother is Rh-negative and has not been sensitized previously, given at 28th week of pregnancy, if possible, and 72 hours after birth
        • external cephalic version
        • amniocentsis
        • ectopic pregnancy
        • any suspected / known exposure of Rh-positive blood 
    • exchange transfusion
      • indications
        • erythroblastosis fetalis
        • hydrops fetalis
        • kernictus
  • Kernicterus secondary to hyperbilirubinemia
    • loss of Moro reflex
    • posturing
    • poor feeding
    • seizures
  • Erythroblastosis fetalis
    • most severely, can manifest as hydrops fetalis with high output cardiac failure, edema, and death
    • indication for immediate delivery and exchange transfusion

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