Hemolytic Disease of the Newborn The 5 Minute Pediatric Consult


	Hemolytic Disease of the Newborn

Sadhna M. Shankar

Database
Differential Diagnosis
Data Gathering
Physical Examination
Laboratory Aids
Therapy
Follow-Up
Common Questions and Answers
Bibliography

DATABASE

DEFINITION

Hemolytic anemia occurring in the newborn due to passive transfer of maternal antibodies (IgG) against fetal red cells.

CAUSES

Most severe disease due to Rh (D) antigen sensitization
A and B antigens may also be responsible
1% of cases due to other antigens
Other antigens: Kell, Duffy, C, E, and c

PATHOPHYSIOLOGY

Rh-negative mothers may have prior sensitization due to transfusion or previous pregnancy.
Fetomaternal bleed from Rh-positive fetus across the placenta leading to maternal sensitization
Anti-D IgG produced in the maternal circulation crosses the placenta, coats fetal red blood cells (RBC) that are then destroyed in fetal spleen
May lead to severe anemia, hydrops, and hyperbilirubinemia
Extramedullary hematopoiesis in fetal liver and spleen as a response to fetal anemia leading to severe hepatosplenomegaly
ABO isoimmunization usually in case of type O mothers with type A or B fetus; clinically milder hemolysis

EPIDEMIOLOGY

15% of Caucasians are Rh-negative (dd)
48% are heterozygous (Dd)
35% are homozygous (DD)
Prevalence of Rh-positive fetus in Rh-negative mother: 15%
Incidence of Rh hemolytic disease: 6–7/1000 live births
Of all Rh-sensitized pregnancies:
- 50% require no treatment
- 31% require treatment after a full-term delivery
- 10% delivered early and require exchange transfusion
- 9% require intrauterine transfusion
Reasons for spectrum of clinical severity:
- Rh immunization rarely occurs in first pregnancy
- Many second infants may be Rh-negative
- Only fraction of women at risk develop antibodies
50% of cases of ABO disease occur in first pregnancy

GENETICS

See Epidemiology.

COMPLICATIONS

Hydrops fetalis
Still births
Neonatal hyperbilirubinemia and kernicterus
Fetal anemia

PROGNOSIS

Approximately one-half the infants have minimal anemia and hyperbilirubinemia and require either no treatment or only phototherapy.

One-fourth will require exchange transfusions.
Hydropic infants have high mortality.

DIFFERENTIAL DIAGNOSIS

Neonatal hyperbilirubinemia
- ABO incompatibility
- Galactosemia
- G6PD deficiency
- Hypothyroidism
- Pyruvate kinase deficiency
- Crigler-Najjar syndrome
- Alpha-thalassemia
- Gilbert syndrome
- Spherocytosis
- Breast milk jaundice
Hydrops fetalis
- Hematological: alpha-thalassemia, severe G6PD deficiency, twin-to-twin transfusion
- Cardiac: hypoplastic left heart syndrome, myocarditis, endocardial fibroelastosis, heart block
- Congenital infections: parvovirus, syphilis, cytomegalovirus (CMV), rubella
- Renal: renal vein thrombosis, urinary tract obstruction, nephrosis
- Placental: umbilical vein thrombosis, true knot
- Miscellaneous: trisomy 13, 18, 21, triploidy, aneuploidy, diaphragmatic hernia

DATA GATHERING

HISTORY

Previous stillbirths, abortions?
Neonatal hyperbilirubinemia requiring therapy in previous pregnancy?
Exposure of mother to blood products?
Father’s ABO and Rh type?
Rh immune globulin given after previous pregnancy or abortion?

PHYSICAL EXAMINATION

Pallor, tachycardia, tachypnea due to congestive heart failure (CHF) secondary to severe anemia
Icterus developing within 12 hours of birth
Usually no icterus at birth
Generalized edema in cases with severe anemia and hydrops
Massive hepatosplenomegaly in severe cases
Milder cases manifest with neonatal hyperbilirubinemia only
ABO incompatibility usually manifests jaundice at 24 hours

LABORATORY AIDS

ANTENATAL

ABO and Rh type of all mothers early in pregnancy
Monitor antibody titer by indirect Coombs test in Rh-negative mothers starting at 20 weeks.
Amniocentesis if maternal antibody titer more than one-eighth at any time
Spectrophotometric assessment of bilirubin concentration in amniotic fluid
Amniotic fluid values in Lileys zone 3 and high zone 2 indicative of severe fetal disease
Fetal blood sampling in severe cases to assess degree of anemia

NEONATAL

Cord blood ABO and Rh types
Cord blood hemoglobin (Hb), hematocrit (Hct), bilirubin (direct and indirect), reticulocyte count
Direct Coombs test on cord blood: positive in immune hemolytic disease
Indirect Coombs test on cord blood for passively transferred antibody
Identification of antibody after elution from RBC
Peripheral smear: nucleated RBC (spherocytes in ABO disease)

THERAPY

Neonatal resuscitation as required in severe Rh isoimmunization
Phototherapy to start as soon as possible
Exchange transfusion
- To correct anemia in severely anemic infants
- To prevent or correct hyperbilirubinemia
- To remove circulating antibodies
Indications for early exchange transfusion:
- Cord blood bilirubin more than 4.5 mg/dL and cord blood Hb less than 11 g/dL
- Bilirubin rising at rate more than 1 mg/dL/h despite phototherapy
- Birubin more than or equal to 20 mg/dL or rising to reach that level
- Hb between 11 and 13 g/dL and bilirubin rising at rate
- More than 0.5 mg/dL/h despite phototherapy
In hydropic infants, immediate partial exchange may be needed to correct anemiand CHF.
Late exchanges are needed for hyper-bilirubinemia.
Exchange transfusion removes sensitized RBC and bilirubin.
For hyperbilirubinemia double-volume exchange is indicated.
Type of blood for exchange transfusion:
- As fresh as possible (<72 hours old), CMV negative, and irradiated
- For Rh disease (if prepared before delivery): type O Rh-negative crossmatched against mother’s blood; after delivery then O negative crossmatched against infant also
- For ABO disease: type O Rh-negative or Rh-compatible crossmatched against mother and infant
Most infants with ABO incompatibility require phototherapy only.
Some infants with milder Rh isoimmunization may only have exaggerated physiologic anemia at 12 weeks.
Discontinue drugs that interfere with bilirubin metabolism (Novobiocin) or its binding to albumin (sulphonamides).

ANTENATAL MANAGEMENT

Unsensitized Rh-negative mother: Rhogam at 28 weeks
If previous stillbirth or hydrops and fetus high risk after amniocentesis plan early delivery (30 weeks)
Careful fetal monitoring and induction of pulmonary maturation
If fetus too immature for delivery, then intrauterine transfusions every 10 to 14 days

FOLLOW-UP

Watch for exaggerated physiological anemia at 12 weeks.
Assess for neurological damage.

PREVENTION

Rh hemolytic disease can be prevented by administration of Rhogam to the Rh negative women after any exposure to Rh positive blood and prophylactically during pregnancy.

COMMON QUESTIONS AND ANSWERS

Q: Does the condition become worse with each pregnancy?
A: Yes, if the mother is not treated with Rh immuglobulin after each Rh-positive pregnancy or abortion.

Q: Can maternal blood be used to transfuse the affected baby?
A: It can be used as a life-saving measure in a situation when there is no other suitable blood available for the baby.

ICD-9-CM 774.6

BIBLIOGRAPHY

Bennebroek J. Diagnosis and treatment of severe alloimmunization. Vox Sang 1994;67(Suppl 3):235–238.

Boroman JM. Antenatal suppression of Rh alloimmunization. Clin Obstet Gynecol 1991;34(2):296–303.

Nathan DG, Oski FA, eds. Hematology of infancy and childhood, 4th ed. Vol. I. Philadelphia: WB Saunders, 1993: 44–74.

Whittle MJ. Rhesus hemolytic disease. Arch Dis Child 1992;67(1 Spec No):65–68.

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