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Questions and Answers
Which group of mothers is most likely to experience clinically significant ABO hemolytic disease of the fetus and newborn (HDFN)?
Which group of mothers is most likely to experience clinically significant ABO hemolytic disease of the fetus and newborn (HDFN)?
At what titer level of IgG anti-ABO antibodies is ABO HDFN more likely to occur?
At what titer level of IgG anti-ABO antibodies is ABO HDFN more likely to occur?
What is a common outcome for infants with ABO HDFN regarding their RBC antigen development?
What is a common outcome for infants with ABO HDFN regarding their RBC antigen development?
Which of the following factors has been linked to the production of high-titered IgG ABO antibodies during pregnancy?
Which of the following factors has been linked to the production of high-titered IgG ABO antibodies during pregnancy?
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What is a consequence of fetal-maternal hemorrhage (FMH)?
What is a consequence of fetal-maternal hemorrhage (FMH)?
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What is the likelihood of a Rh-negative individual forming anti-D antibodies after being transfused with Rh-positive RBCs?
What is the likelihood of a Rh-negative individual forming anti-D antibodies after being transfused with Rh-positive RBCs?
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Which of the following fetal duodenal conditions is extremely rare in ABO-induced HDFN?
Which of the following fetal duodenal conditions is extremely rare in ABO-induced HDFN?
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What genetic factor can influence an individual's ability to produce antibodies in response to antigenic exposure?
What genetic factor can influence an individual's ability to produce antibodies in response to antigenic exposure?
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What can be omitted in the initial antibody screening process?
What can be omitted in the initial antibody screening process?
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Which type of antibodies may cause mild to moderate hemolytic disease of the fetus and newborn (HDFN)?
Which type of antibodies may cause mild to moderate hemolytic disease of the fetus and newborn (HDFN)?
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What type of antibodies can be ignored in follow-up testing due to their non-pathogenic nature?
What type of antibodies can be ignored in follow-up testing due to their non-pathogenic nature?
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How can the immunoglobulin class of antibodies be established?
How can the immunoglobulin class of antibodies be established?
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Which antibodies are common in pregnant women but not known to cause HDFN?
Which antibodies are common in pregnant women but not known to cause HDFN?
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What happens when serum containing IgM antibodies is treated with a sulfhydryl reagent?
What happens when serum containing IgM antibodies is treated with a sulfhydryl reagent?
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If the antibody screen is reactive, what must be determined next?
If the antibody screen is reactive, what must be determined next?
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What causes the accumulation of unconjugated bilirubin in newborns?
What causes the accumulation of unconjugated bilirubin in newborns?
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In which trimester should Rh D-negative pregnant patients be screened for unexpected transfused antibodies?
In which trimester should Rh D-negative pregnant patients be screened for unexpected transfused antibodies?
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Which diagnostic test is considered most important for identifying ABO HDFN in newborns?
Which diagnostic test is considered most important for identifying ABO HDFN in newborns?
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What is a potential consequence of untreated high bilirubinemia in newborns?
What is a potential consequence of untreated high bilirubinemia in newborns?
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Why should cord blood samples be collected by venipuncture?
Why should cord blood samples be collected by venipuncture?
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What is the characteristic feature of unconjugated bilirubin?
What is the characteristic feature of unconjugated bilirubin?
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When jaundice appears in a newborn, what should be investigated?
When jaundice appears in a newborn, what should be investigated?
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What role does the maternal liver play in bilirubin metabolism during pregnancy?
What role does the maternal liver play in bilirubin metabolism during pregnancy?
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What signifies a positive DAT result in a newborn if anemia is not present?
What signifies a positive DAT result in a newborn if anemia is not present?
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What is the purpose of monitoring antibody titers in pregnant women with known RBC alloimmunization?
What is the purpose of monitoring antibody titers in pregnant women with known RBC alloimmunization?
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What diagnostic method is primarily used to track fetal anemia during pregnancy?
What diagnostic method is primarily used to track fetal anemia during pregnancy?
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At what gestational age is a fetal ultrasound recommended to begin monitoring fetal anemia?
At what gestational age is a fetal ultrasound recommended to begin monitoring fetal anemia?
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What is an indication for performing cordocentesis?
What is an indication for performing cordocentesis?
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What does an MCA-PSV measurement greater than 1.5 MoM indicate?
What does an MCA-PSV measurement greater than 1.5 MoM indicate?
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What has replaced amniocentesis for monitoring fetal anemia risk?
What has replaced amniocentesis for monitoring fetal anemia risk?
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When is intrauterine transfusion indicated for a fetus?
When is intrauterine transfusion indicated for a fetus?
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How is the concentration of bilirubin in amniotic fluid quantified?
How is the concentration of bilirubin in amniotic fluid quantified?
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What is the percentage reduction in the risk of an RhD-negative mother becoming allosensitized with the administration of RhIG?
What is the percentage reduction in the risk of an RhD-negative mother becoming allosensitized with the administration of RhIG?
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When is the first dose of RhIG usually administered during pregnancy?
When is the first dose of RhIG usually administered during pregnancy?
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What should be done if more than 72 hours have passed after the delivery of an RhD-positive infant regarding RhIG administration?
What should be done if more than 72 hours have passed after the delivery of an RhD-positive infant regarding RhIG administration?
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Why is RhIG not indicated for a mother if the infant is found to be D-negative?
Why is RhIG not indicated for a mother if the infant is found to be D-negative?
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What is the effect of ghod administration of RhIG on maternal sensitization from previous pregnancies?
What is the effect of ghod administration of RhIG on maternal sensitization from previous pregnancies?
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What is the half-life of IgG in the context of RhIG?
What is the half-life of IgG in the context of RhIG?
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What can happen if intramuscular RhIG is administered intravenously?
What can happen if intramuscular RhIG is administered intravenously?
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What is the purpose of screening a maternal sample using the rosette technique post-delivery?
What is the purpose of screening a maternal sample using the rosette technique post-delivery?
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Study Notes
Neonatal Manifestations of HDFN-Induced Anemia by Time of Onset
- Unconjugated bilirubin is water insoluble and travels through the bloodstream to the liver to be conjugated (water soluble) to be excreted through the GIT
- During pregnancy, indirect bilirubin is transported across the placenta and conjugated by the maternal liver and safely excreted
- After birth, the immature infant liver cannot efficiently metabolize bilirubin, causing unconjugated bilirubin to accumulate and resulting in neonatal jaundice
- Unconjugated bilirubin can lead to kernicterus or permanent brain damage.
Postnatal Diagnosis
- No single serologic test is diagnostic for ABO HDFN
- The direct antiglobulin test (DAT) is the most important diagnostic test for ABO HDFN, which can be positive even in the absence of clinical anemia
- The DAT is recommended to be done on all delivered infants, through a venipuncture to avoid contamination with maternal blood
- ABO and RhD testing should be performed to assess the results
ABO HDFN
- Group O individuals are most likely to form high-titer IgG anti-ABO antibodies, making ABO HDFN almost always limited to A or B infants of group O mothers with potent anti-A, B antibodies
- Clinically significant ABO HDFN occurs most frequently in group O mothers with group A infants in white populations and group B infants in black populations.
- ABO HDFN can occur in the first pregnancy and in any subsequent pregnancies due to it not relying on previous foreign RBC stimulation.
- Tetanus toxoid administration and helminth parasite infection during pregnancy are linked to higher levels of IgG ABO antibodies and severe HDFN.
- The typically mild course of ABO HDFN is related to the poor development of ABO antigens on fetal RBCs.
- ABO antigens are not fully developed until after the first year of life, making group A infant RBCs serologically more similar to A2 adults, and making them less susceptible to ABO HDFN.
Fetal-Maternal Hemorrhage (FMH)
- Maternal alloimmunization results from exposure to foreign red blood cells through previous or current pregnancy, previous transfusions, or organ transplant.
- During pregnancy, there is spontaneous mixing between fetal and maternal circulation, which increases throughout pregnancy.
- Any physical perturbation of a fetus or placenta in utero increases the risk of FMH, such as trauma, abortion, ectopic pregnancy, amniocentesis, or multiple pregnancies.
- The ability of individuals to produce antibodies in response to antigenic exposure varies, and is influenced by complex genetic factors.
Antibody Identification
- If antibody screening is reactive, the antibody identity must be determined.
- Cold reactive IgM antibodies, such as anti-1, anti-IH, anti-Lea, anti-Leb, and anti-P, can be ignored.
- Lewis system antibodies are common in pregnant women, but have not been reported to cause HDFN.
- Anti-M and anti-N antibodies can be IgM, IgG, or a combination of both, and can cause mild to moderate HDFN.
- The J-chain of IgM antibodies can be destroyed by treating the serum with a sulfhydryl reagent, while IgG antibodies will remain reactive.
Management of the Fetus
- During pregnancy, women with known RBC alloimmunization and/or a history of HDFN are closely monitored using antibody titers.
- The fetus is also closely monitored throughout pregnancy to check for fetal wellbeing and fetal anemia to determine the best time for delivery.
- Fetal Ultrasound: Done at about 16 to 20 weeks' gestation, every 2 weeks, to track the degree of fetal anemia.
- Invasive Monitoring:: Cordocentesis and Amniocentesis
- Intrauterine Transfusion (IUT): Indications include MCA-PSV indicating anemia (>1.5 MoM), fetal hydrops noted on ultrasound examination, and additional matching for antigens such as c and E.
- Rh Immune Globulin (RhIG)
- The risk of an RhD-negative mother becoming allosensitized can be reduced by appropriate administration of RhIG.
- The first dose is provided at 28 weeks' gestation or after trauma.
- A second dose is given after delivery of an RhD-positive infant within 72 hours after delivery, and should be given even if more than 72 hours have elapsed.
- RhIG is of no benefit once a person has formed anti-D.
- RhIG is not indicated if the infant is found to be D-negative.
- RhIG should be administered in cases of abortions, stillbirths, and ectopic pregnancies, as the blood type of the fetus cannot usually be determined.
- The mother should be D-negative, and the infant should be D-positive or D-variant to administer RhIG.
- Antibody titers are not recommended because the amount of circulating RhIG does not correlate with the effectiveness of the immune suppression or the amount of fetomaternal hemorrhage.
- The half-life of IgG is about 25 days, so only about 10% of the antenatal dose will be present at 40 weeks gestation.
- The anti-D from antenatal RhIG present at delivery should not be interpreted as active rather than passive immunization.
- RhIG can be given IV or intramuscularly.
- Intramuscular RhIG should only be given intramuscularly, as IV injections can cause severe anaphylactic reactions.
- RhIG contains IgA and may be contraindicated in patients with anti-IgA and IgA deficiency who have had anaphylactic reactions to blood products.
Key Points
- ABO HDFN is usually mild and can occur in any pregnancy.
- Fetal anemia can be diagnosed using fetal ultrasound and Doppler measurements.
- Intrauterine transfusions are used to treat severe fetal anemia.
- RhIG is effective in preventing RhD sensitization in RhD-negative mothers.
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Description
This quiz covers the neonatal manifestations of hemolytic disease of the fetus and newborn (HDFN) induced anemia, focusing on the role of bilirubin and the consequences of its accumulation after birth. It also discusses postnatal diagnostic methods, including the direct antiglobulin test (DAT) and the importance of ABO and RhD blood group testing for newborns.