Hemolytic Disease of the Newborn (HDN), also known as erythroblastosis

fetalis, is a condition where maternal antibodies attack fetal red blood cells
(RBCs), causing hemolysis, anemia, and potentially severe complications in
the fetus or newborn. Below are detailed notes covering its pathophysiology,
causes, clinical features, diagnosis, management, and prevention.1.
DefinitionHDN is an alloimmune condition where maternal IgG antibodies
cross the placenta and target antigens on fetal RBCs, leading to their
destruction.It typically occurs when there is an incompatibility between
maternal and fetal blood group antigens, most commonly involving the Rh
(Rhesus) system or ABO blood group system.2.
PathophysiologyMechanism:Maternal sensitization occurs when fetal RBCs
with paternal antigens (not present in the mother) enter the maternal
circulation, triggering an immune response.Sensitization usually happens
during delivery, miscarriage, abortion, or procedures (e.g., amniocentesis),
but can occur during pregnancy if there is fetomaternal hemorrhage.Maternal
immune system produces IgG antibodies against fetal RBC antigens.These
IgG antibodies cross the placenta, bind to fetal RBCs, and cause hemolysis
via complement activation or macrophage-mediated destruction in the
spleen.Consequences:Hemolysis leads to fetal anemia.Increased bilirubin
from RBC breakdown causes jaundice in the newborn.Severe cases result in
hydrops fetalis (edema, ascites, heart failure) due to profound anemia and
hypoxia.Key Antigens Involved:Rh incompatibility: Most severe, typically
involves the D antigen (RhD). Mother is Rh-negative (D-negative), and fetus
is Rh-positive (D-positive).ABO incompatibility: Less severe, occurs when
mother is type O, and fetus is type A, B, or AB.Other antigens: Kell, Duffy,
Kidd, and other minor blood group antigens (rare).3. CausesRh
Incompatibility:Occurs when an Rh-negative mother carries an Rh-positive
fetus.Sensitization risk increases with fetomaternal hemorrhage (e.g.,
delivery, trauma, invasive procedures).First pregnancy is usually unaffected
unless prior sensitization (e.g., from transfusion or miscarriage).ABO
Incompatibility:Common in mothers with blood group O, as they naturally
produce anti-A and anti-B IgG antibodies.Can affect first pregnancies since
sensitization is not required.Other Causes:Minor blood group incompatibilities
(e.g., Kell, Duffy).Maternal autoimmune diseases or prior blood transfusions
with mismatched antigens.4. Clinical FeaturesFetal Manifestations:Mild:
Asymptomatic or mild anemia.Moderate: Anemia, hepatosplenomegaly (due
to extramedullary hematopoiesis), jaundice.Severe: Hydrops fetalis
(generalized edema, ascites, pleural/pericardial effusions, heart
failure).Neonatal Manifestations:Jaundice: Early and severe due to
unconjugated hyperbilirubinemia from hemolysis.Anemia: Pallor, tachycardia,
lethargy.Hepatosplenomegaly: From compensatory RBC
production.Kernicterus: Rare but severe, caused by high bilirubin levels
damaging the brain (leads to neurological deficits, hearing loss, or
death).Hypoglycemia: Due to islet cell hyperplasia from chronic
hypoxia.Maternal Signs: Usually none, but polyhydramnios may occur in
severe cases due to fetal hydrops.5. DiagnosisAntenatal Diagnosis:Maternal
Blood Testing:Blood group and Rh typing.Indirect Coombs test: Detects
maternal antibodies against fetal RBC antigens.Antibody titers: High or rising
titers indicate significant risk.Fetal Assessment:Ultrasound: Monitors for signs
of hydrops (edema, ascites, pericardial effusion), fetal anemia (increased
middle cerebral artery peak systolic velocity [MCA-PSV]).Amniocentesis:
Measures amniotic fluid bilirubin levels (via ΔOD450) to assess hemolysis
severity.Cordocentesis: Direct fetal blood sampling for hemoglobin,
hematocrit, and blood type.Paternal Testing: Determines if the father is
homozygous or heterozygous for the antigen (e.g., RhD), predicting fetal
risk.Postnatal Diagnosis:Newborn Blood Tests:Blood group and Rh
typing.Direct Coombs test: Positive if maternal antibodies are bound to
neonatal RBCs.Hemoglobin and hematocrit (low in anemia).Reticulocyte
count (elevated due to compensatory RBC production).Serum bilirubin
(elevated).Clinical Evaluation: Jaundice, pallor,
hepatosplenomegaly.Peripheral Smear: Shows spherocytes, polychromasia,
or nucleated RBCs.6. ManagementAntenatal Management:Monitoring:Serial
ultrasounds to assess MCA-PSV and detect hydrops.Regular maternal
antibody titers and fetal surveillance.Intrauterine Transfusion (IUT):Indicated
for severe fetal anemia (e.g., low hemoglobin or hydrops).Performed via
cordocentesis, transfusing O-negative, antigen-negative RBCs into the
umbilical vein.Risks: Fetal loss, infection, preterm labor.Early
Delivery:Considered in late preterm or term fetuses with significant
hemolysis to prevent worsening hydrops.Maternal Therapy
(Rare):Intravenous immunoglobulin (IVIG) or plasmapheresis to reduce
maternal antibody levels in severe cases.Postnatal
Management:Phototherapy:First-line for neonatal jaundice to convert
unconjugated bilirubin into water-soluble forms for excretion.Uses blue-green
light (wavelength 430–490 nm).Exchange Transfusion:Indicated for severe
anemia or hyperbilirubinemia unresponsive to phototherapy.Replaces
neonatal blood with donor blood (O-negative, antigen-negative) to remove
maternal antibodies and bilirubin.Risks: Infection, electrolyte imbalances,
thrombosis.IVIG:Used to reduce hemolysis by blocking Fc receptors on
macrophages.Adjunct to phototherapy or exchange transfusion.Supportive
Care:Correct anemia with simple RBC transfusions.Monitor and treat
hypoglycemia, respiratory distress, or heart failure.Folic acid
supplementation for increased RBC turnover.7. PreventionRh
Immunoprophylaxis:Anti-D Immunoglobulin (RhoGAM):Administered to Rh-
negative mothers to prevent sensitization.Timing:At 28 weeks gestation
(prophylactic dose).Within 72 hours post-delivery if the newborn is Rh-
positive.After events like miscarriage, abortion, amniocentesis, or
trauma.Mechanism: Neutralizes fetal Rh-positive RBCs in maternal
circulation, preventing antibody production.Kleihauer-Betke Test:Quantifies
fetomaternal hemorrhage to determine additional anti-D doses if
needed.ABO Incompatibility:No specific prophylaxis, as maternal anti-A/B
antibodies are naturally occurring.Early monitoring and phototherapy in
affected newborns.Education:Counsel Rh-negative women about the
importance of anti-D prophylaxis and avoiding unscreened blood
transfusions.8. ComplicationsFetal:Hydrops fetalis.Intrauterine fetal
demise.Neonatal:Kernicterus (bilirubin encephalopathy).Severe anemia
leading to heart failure.Infection or thrombosis from transfusions.Long-
Term:Neurological deficits (e.g., cerebral palsy, hearing loss) from
kernicterus.Developmental delays in severe cases.9. PrognosisWith
Treatment:Most cases are manageable with phototherapy, exchange
transfusion, or IUT.Prognosis is excellent for mild to moderate cases with
timely intervention.Without Treatment:Severe cases can lead to fetal death,
kernicterus, or long-term neurological damage.Prevention Impact:Routine
anti-D prophylaxis has significantly reduced Rh-related HDN incidence.10.
EpidemiologyRh Incompatibility:More common in populations with higher Rh-
negative prevalence (e.g., Caucasians, ~15% Rh-negative).Rare in African
and Asian populations (~1–5% Rh-negative).ABO Incompatibility:More
frequent but milder, occurring - affects ~1% of pregnancies with type O
mothers.Incidence:Declining due to widespread use of anti-D
immunoglobulin.11. Key Points for Quick ReferenceCause: Maternal-fetal
blood group incompatibility (Rh, ABO, or minor antigens).Pathology: Maternal
IgG antibodies destroy fetal/neonatal RBCs.Diagnosis: Maternal antibody
testing, fetal ultrasound, neonatal Coombs test, bilirubin levels.Treatment:
Phototherapy, exchange transfusion, IUT, IVIG.Prevention: Anti-D
immunoglobulin for Rh-negative mothers.Complications: Hydrops fetalis,
kernicterus, anemia, heart failure.