Overview
Definition:
Hemolytic disease of the fetus and newborn (HDFN) is a condition where maternal antibodies cross the placenta and attack fetal red blood cells, leading to hemolysis
ABO incompatibility is the most common cause, occurring when there is a blood group mismatch between mother and fetus, typically a group O mother with an AB or B fetus
Rh hemolytic disease, historically more severe, arises from Rh antigen incompatibility, usually an Rh-negative mother with an Rh-positive fetus.
Epidemiology:
ABO HDFN accounts for approximately 75% of HDFN cases
Its incidence has decreased with improved antenatal care
Rh HDFN incidence has dramatically reduced due to routine Rh immune globulin (RhoGAM) prophylaxis
Mild ABO HDFN is common and often asymptomatic
Severe HDFN, more typical of Rh disease, can lead to hydrops fetalis and stillbirth.
Clinical Significance:
Understanding the differences between ABO and Rh HDFN is crucial for accurate diagnosis, timely management, and prevention of severe neonatal complications
Early recognition and intervention can prevent severe anemia, hyperbilirubinemia, kernicterus, and even fetal demise, thereby improving long-term neurological outcomes and reducing healthcare burden.
Clinical Presentation
Symptoms:
Jaundice appearing within the first 24 hours of life
Increasing lethargy
Poor feeding
Pallor
Enlarged spleen and liver (hepatosplenomegaly)
Signs of anemia such as rapid breathing or fast heart rate
In severe cases, hydrops fetalis (generalized edema) and signs of fetal distress.
Signs:
Generalized icterus
Pale or jaundiced skin
Hepatosplenomegaly
Signs of anemia: tachycardia, tachypnea
Neurological signs of hyperbilirubinemia (if untreated): lethargy, poor suck, hypotonia, opisthotonos, seizures, coma
Kernicterus is a late manifestation.
Diagnostic Criteria:
Diagnosis is suspected in neonates with unexplained jaundice appearing early and progressing rapidly
Confirmatory criteria include: evidence of hemolysis (anemia, reticulocytosis, elevated unconjugated bilirubin), presence of maternal antibodies against fetal red blood cell antigens, and demonstration of these antigens on the infant's red blood cells (positive direct antiglobulin test - DAT) or in maternal serum.
Diagnostic Approach
History Taking:
Maternal blood group and Rh type
Previous pregnancies complicated by HDFN
History of Rhogam administration
Family history of jaundice or anemia
Any maternal illness or medications during pregnancy
Infant's gestational age and birth weight
Onset and progression of jaundice
Presence of fever or poor feeding.
Physical Examination:
Thorough assessment of vital signs including temperature, heart rate, and respiratory rate
Careful examination for jaundice, noting the cephalocaudal progression
Palpation for hepatosplenomegaly
Neurological assessment for signs of hyperbilirubinemia
Assessment for edema and signs of hydrops fetalis.
Investigations:
Complete blood count (CBC) with differential and reticulocyte count: confirms anemia and hemolysis
Peripheral blood smear: shows spherocytes (more common in ABO HDFN), nucleated red blood cells, and polychromasia
Serum bilirubin levels: unconjugated and conjugated, to assess severity and pattern of jaundice
Direct antiglobulin test (DAT): detects antibodies or complement on infant's RBCs
If DAT is positive, antibody identification should be performed on infant's eluate and maternal serum
Blood typing of infant and mother
Cord blood studies: maternal and infant blood type, DAT, CBC, bilirubin.
Differential Diagnosis:
Physiological jaundice: typically appears after 24 hours of life and resolves within 7-10 days
Breastfeeding jaundice: due to decreased intake or increased enterohepatic circulation
Breast milk jaundice: due to substances in breast milk affecting bilirubin conjugation
Neonatal sepsis: can cause conjugated hyperbilirubinemia and hemolysis
Inherited hemolytic anemias (e.g., hereditary spherocytosis, G6PD deficiency): typically present without maternal antibody involvement
Polycythemia: can cause jaundice.
Management
Initial Management:
Assessment of gestational age, clinical status, and laboratory findings
Immediate phototherapy for significant hyperbilirubinemia
Close monitoring of bilirubin levels and clinical signs
Adequate hydration and nutrition.
Medical Management:
Phototherapy: uses specific wavelengths of light to convert indirect bilirubin to less toxic water-soluble compounds
Exchange transfusion: indicated for severe anemia, failure of phototherapy to lower bilirubin, or very high bilirubin levels threatening kernicterus
IV immunoglobulin (IVIG): may be used to reduce the need for exchange transfusion, especially in Rh HDFN, by blocking antibody binding to RBCs.
Surgical Management:
Not directly applicable to HDFN itself
However, in cases of hydrops fetalis due to severe HDFN, intrauterine transfusions or even preterm delivery might be considered, though with significant risks.
Supportive Care:
Nursing care: vigilant monitoring of vital signs, hydration status, and signs of complications
Nutritional support: adequate feeding to promote gut motility and reduce enterohepatic circulation
Phototherapy management: ensuring adequate exposure and eye protection
Monitoring for signs of neurological impairment.
Complications
Early Complications:
Severe anemia, hyperbilirubinemia leading to kernicterus, hydrops fetalis, heart failure, disseminated intravascular coagulation (DIC), sepsis
Severe hemolysis can lead to acute kidney injury.
Late Complications:
Chronic bilirubin encephalopathy (kernicterus), leading to auditory neuropathy, visual impairment, motor deficits (cerebral palsy), and cognitive impairment
Post-hemorrhagic anemia requiring long-term management.
Prevention Strategies:
For Rh HDFN: routine antenatal screening of Rh-negative women and administration of Rh immune globulin (RhoGAM) at 28 weeks gestation and postpartum if the infant is Rh-positive
For ABO HDFN: close monitoring of infants born to group O mothers, especially if previous ABO HDFN occurred
Early recognition and prompt initiation of phototherapy can prevent severe hyperbilirubinemia.
Prognosis
Factors Affecting Prognosis:
Gestational age at birth
Severity of anemia and hyperbilirubinemia
Promptness and effectiveness of treatment
Development of kernicterus or other neurological sequelae
Presence of hydrops fetalis at birth.
Outcomes:
Most infants with mild ABO HDFN have an excellent prognosis with supportive care and phototherapy
Infants with severe HDFN requiring exchange transfusion or who develop kernicterus have a poorer prognosis with potential for long-term neurodevelopmental deficits
Rh HDFN, when prevented by RhoGAM, has an excellent outcome.
Follow Up:
Infants treated for HDFN require follow-up to monitor for delayed anemia and assess neurodevelopmental progress
Auditory brainstem response (ABR) testing is recommended for all infants who experienced significant hyperbilirubinemia or HDFN
Developmental assessments should be done periodically.
Key Points
Exam Focus:
ABO HDFN is typically milder, with spherocytes on smear and positive DAT
Rh HDFN can be severe, with more dramatic anemia and potential for hydrops
Rhogam prophylaxis is key for Rh HDFN prevention
Jaundice appearing within 24 hours and rising rapidly suggests HDFN.
Clinical Pearls:
Always check maternal blood type
A direct Coombs test (DAT) positive in the infant is highly suggestive of immune-mediated hemolysis
Exchange transfusion is a life-saving intervention for severe cases
Kernicterus is preventable!
Common Mistakes:
Misinterpreting a weakly positive DAT
Delaying phototherapy or exchange transfusion in severe hyperbilirubinemia
Not considering HDFN in any neonate with early onset jaundice and anemia
Failing to administer Rhogam to eligible mothers.