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Questions and Answers
What is the purpose of monitoring antibody levels during pregnancy?
What is the purpose of monitoring antibody levels during pregnancy?
Which antibody is primarily responsible for causing Hemolytic Disease of the Fetus and Newborn (HDFN)?
Which antibody is primarily responsible for causing Hemolytic Disease of the Fetus and Newborn (HDFN)?
What is a method used to predict the risk of HDFN regarding antibody levels?
What is a method used to predict the risk of HDFN regarding antibody levels?
Why might maternal sensitization occur in Rh D negative pregnancies despite anti-D prophylaxis?
Why might maternal sensitization occur in Rh D negative pregnancies despite anti-D prophylaxis?
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Which method is NOT mentioned as a diagnostic tool for HDFN?
Which method is NOT mentioned as a diagnostic tool for HDFN?
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What characterizes the impact of Anti-K in HDFN?
What characterizes the impact of Anti-K in HDFN?
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What antibody level indicates a mild risk of HDFN related to Anti-D?
What antibody level indicates a mild risk of HDFN related to Anti-D?
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What policy regarding blood transfusion does the Welsh Blood Service implement for c negative women?
What policy regarding blood transfusion does the Welsh Blood Service implement for c negative women?
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Study Notes
Haemolytic Disease of the Fetus and Newborn (HDFN) - Detection and Treatment
- HDFN is a condition where maternal antibodies attack fetal red blood cells
- All pregnant women are screened for ABO and RhD blood groups and red blood cell antibodies during early and late pregnancy
- Antibody specificity is identified
- Antibody levels are monitored to detect sudden changes indicating fetal concerns
- Antibody levels are measured by quantification (anti-D, -c) and antibody titration for other antibodies
- Paternal phenotype and zygosity testing is done when appropriate
Diagnostic Testing - Laboratory Based
- Pregnant women are screened for red blood cell antibodies
- Antibody specificity is determined
- Antibody levels are monitored; sudden changes signal fetal problems
- Antibody levels are measured by quantitation and titration
Alternative Methods
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Fetal blood type:
- Chorionic villus sampling (CVS)
- Maternal blood cell-free fetal DNA (cffDNA)
- Amniotic fluid sampling: used for rising bilirubin levels in the amniotic fluid
- Ultrasound: used to assess hydrops and mid-cerebral velocity (MCV)
Anti-D in HDFN
- Anti-D continues to be the main cause of HDNF, due to high immunogenicity
- Even with anti-D prophylaxis introduced in 1969, maternal sensitization still happens annually in roughly 1000 Rh-negative pregnancies
- Effects on first pregnancies are rare
Anti-K in HDFN
- Anti-K is the second most common cause of severe HDNF
- Characterised by severe HDN at low antibody levels
- Affects haemolysis of red blood cells and erythroblasts affecting compensatory erythropoiesis
- Over 50% of antibodies are produced due to multiple transfusions &/or previous pregnancies
Anti-c in HDFN
- Anti-c is the third most common cause of severe HDNF
- A policy is in place to provide R1R1 blood to women of childbearing age with C-negative blood groups
How to Predict HDFN Risk - Antibody Levels
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Quantitation:
- Anti-D: Mild (<4 IU/mL), Severe (>15 IU/mL)
- Anti-c: Mild (<7 IU/mL), Severe (>20 IU/mL)
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Titration:
- Anti-K: No specific cut-off but increasing titres are important
- Other antibodies: No issues if titres are <32; scores above that may need further investigation
NHSBT HDFN Database Data (12-month period)
- Data on antibody types, frequency of occurrence, and number of cases treated (table of data)
Invasive Procedures for Detection
- Amniocentesis: Measure OD450 (a measure of bilirubin in amniotic fluid) to detect fetal bilirubin levels, but carries a risk of miscarriage, premature labour, and fetal demise
- Fetal blood sampling: Direct measurement of fetal anemia, but associated with a risk of fetal loss, or higher risk with hydropic fetuses
Non-invasive Procedures for Detection
- Ultrasonography: Early signs of hydrops (excess fluid buildup), pleural/pericardial effusions, etc
- Velocimetry: to measure blood flow in fetal arteries and detect signs of anemia
Treatment
-
Transfusion:
- Inter-uterine transfusion: corrects severe anaemia in the womb
- Exchange transfusion: Reduce bilirubin levels rapidly
- Top-up transfusion: corrects anaemia if bilirubin levels are not high
Alternate Treatments
- Intravenous immunoglobulin (IVIg): Treatment for severe cases of RhD incompatibility
- Early delivery: Potentially administering antenatal steroids for lung maturity in the fetus
- UV light: Breakdown of unconjugated bilirubin deposited in the skin for less severe cases
Prevention
- Anti-D prophylaxis: Pre-1969 introduction has greatly reduced the incidence of HDFN, along with improved cause of death percentages (per 2,200 births)
- Blood provision: Antigen-negative blood to women of childbearing age, particularly RhD-negative or K-negative blood
Non-invasive Prenatal Testing (NIPT)
- CffDNA detection: Maternal plasma/serum testing began in 1997
- cffDNA analysis: Cells in maternal blood
- Characteristics of cffDNA: Fragmented, derived from apoptosis, removed after delivery
Application of NIPT
- Sequencing and genotyping of fetal DNA in maternal plasma
- Fetal DNA levels: 3% in early pregnancy, and rising to 6% in the third trimester
NICE Approved NIPT Testing
- Individual tests for fetal genotyping (many RH genotypes, RHD, Kell), fetal gender, aneuploidy, hemoglobinopathies, single or gene disorders
- High-throughput NIPT for fetal RHD genotyping to guide antenatal prophylaxis with anti-D immunoglobulin for RhD-negative women
RhD Fetal Genotyping from Maternal Plasma
- Manage sensitized pregnant women, avoids invasive procedures (and reduced risk of miscarriage), less need for RhD-negative blood products, and thus cost savings
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Description
Explore the crucial aspects of Haemolytic Disease of the Fetus and Newborn (HDFN), including its detection and treatment methods. This quiz covers the screening processes for maternal antibodies, the importance of antibody specificity, and alternative diagnostic tests that can be utilized. Gain a deeper understanding of how these components impact fetal health.
