Hemolytic disease of the fetus and newborn

Question 1

ethiology

Answer 1

ABO incompatibility: present in ∼ 20% of all pregnancies; however, only 5–10% of newborns from these pregnancies are symptomatic
Rh incompatibility
Risk factors: maternal exposure to fetal blood during pregnancy [1]
Antenatal procedures (e.g., amniocentesis, cesarean section, termination of pregnancy)
Pregnancy-related complications (e.g., ectopic pregnancy, placental abruption)
Trauma

Question 2

pathophysiology

Answer 2

ABO incompatibility
Highest risk: mother with blood group O; newborn with blood group A or B
Maternal antibodies (anti-A and/or anti-B) against nonself antigens of the ABO system are present even if sensitization has not occurred ;, so fetal hemolysis may occur during the first pregnancy
Rh incompatibility
In an Rh-negative mother and Rh-positive newborn: maternal exposure to fetal blood (fetomaternal hemorrhage) → production of maternal IgM antibodies against the Rh antigen → over time, seroconversion to Rh-IgG (able to cross the placenta)
In a subsequent pregnancy with an Rh-positive newborn: rapid production of maternal IgG anti-D antibodies to fetal RhD antigens → Rh-IgG agglutination of fetal RBCs with hemolytic anemia → risk of HDFN with possible hydrops fetalis

Question 3

clinical features prenatal and postnatal

Answer 3

Prenatal
Hydrops fetalis (only expected in cases of Rh incompatibility
Postnatal
Neonatal anemia
Hepatosplenomegaly
Neonatal jaundice
Usually present at birth or manifests within the first 24 hours of life
In Rh incompatibility, unconjugated bilirubin levels may be dangerously high, causing kernicterus
Hypoxia

Question 4

diagnosis prenatal and postnatal

Answer 4

Prenatal diagnosis
Imaging
Ultrasound: to determine hydrops fetalis
Doppler sonography of fetal blood vessels: Increased flow rate indicates fetal anemia.
Postnatal diagnosis
If the newborn has signs of hemolysis, conduct a Coombs test (either direct or indirect).
Rh incompatibility: positive
ABO incompatibility: weak positive or negative

Question 5

treatment

Answer 5

Prenatal
Intrauterine blood transfusion
Postnatal
Anemia: iron supplementation and, if necessary, RBC transfusion
Hyperbilirubinemia: phototherapy; if necessary, exchange transfusion with red blood cells
See “Treatment” in neonatal jaundice
In severe cases, IV immunoglobulin (IVIG)

Question 6

prevention

Answer 6

Screening
ABO and Rh typing of the mother
Rh-positive mothers do not need further screening.
Rh-negative mothers: screening for anti-D antibodies
No anti-D antibodies (unsensitized mothers): antibody screening repeated at 28 weeks’ gestation and at delivery. See “Anti-D immunoglobulin (RhoGAM)” below.
Anti-D antibodies manifest with an anti-D antibody titer > 1:8, which indicates maternal sensitization to fetal Rh antigens (sensitized mothers). Further monitoring with amniocentesis and imaging is required for evidence of hemolysis.
Fetomaternal hemorrhage in Rh-negative mother
Conduct a rosette test (initial test of choice). This is a qualitative test that assesses whether fetomaternal hemorrhage has occurred.
If the rosette test is positive, conduct a Kleihauer-Betke test.
The amount of fetal hemoglobin determines the amount of RhoGam necessary.
Anti-D immunoglobulin (RhoGAM)
Background
Pathophysiology: See “Rhesus incompatibility” under pathophysiology above
Anti-D prophylaxis protects newborns in subsequent pregnancies.
Only indicated in unsensitized mothers
Indication and implementation
Anti-D prophylaxis should be administered during the 28th week of gestation and within 72 hours following the birth of an Rh-positive baby.
The efficacy of anti-D prophylaxis relies on antibody-mediated immunosuppression.
Further indications in Rh negativity
miscarriage, ectopic pregnancy
Bleeding during pregnancy
amniocentesis, chorionic villus sampling