Obstetrics Flashcards
(43 cards)
What is FMH
Cross-placental transfer of foetal red cells into the maternal circulation
Antibodies usually associated with HDFN
Anti-K often causes erythroblastopenia and cord DAT may be negative.
Antibodies occasionally associated with HDFN
Usually IgM (do not cross placenta)
Usually cold-reacting
Often not fully developed on neonatal red cells (e.g. Lewis system)
When to test for antibodies in HDN?
First booking (8-12 weeks)
Repeat at 26-28 weeks (prior to any anti-D prophylaxis in RhD negative mothers given at 28 & 34 weeks)
For mothers with established allo-antibodies:
- 4 weekly until 28 weeks
- Then 2 weekly until delivery
Levels of concern (refer to MFM):
- Titre >=1:32
- “clinically significant rise” for non-D antibodies,
- >=1:16 or Quant >15IU/mL for D antibodies
- any level of anti-K antibodies ,
- c- antibodies= 7.5
Further testing to stratify risk once antibodies in HDFN are established
- paternal blood phenotype and genotype is determined to predict the foetal risk of inheriting the antigen the maternal antibody is directed against
- Direct foetal genotyping can establish foetal blood group expression, either by CVS or foetal DNA obtained from the maternal serum (NIPA)
- Serial testing
Monitoring once established high risk of HDFN
Maternal antibody titres: increasing antibody strength indicates ongoing and increasing antibody strength, except in cases of previously-affected pregnancies; there is no strong correlation between titre strength and degree of foetal anaemia
RCOG suggests MFM referral for non- anti-D antibodies once they reach a titre of 1:32
All new maternal allo-antibodies and doubling of titres are reportable at the RWH
Cerebral MCA Doppler velocity assessments: performed 2-weekly after 16-24/40 as a validated surrogate for foetal anaemia.
+/-Weekly CTGs may also be performed.
Invasive testing : Cordocentesis is performed to determine foetal haematocrit and determine need for IUT.
Selection of blood for IUT
group O, RhD matched, irradiated, CMV-negative, less than 5 days old, and antigen-negative for maternal red cell antibodies
Usually also Rh C, c, E, e and K matched
Risk of IUT - infection, rupture of membranes
What is NIPA testing?
Non invasive prenatal analysis for fetal RhD.
Can be performed > 12/40
Molecular blood group genotyping assay to predict RhD status of fetus in RhD negative mothers.
Uses maternal PB whoe blood for extraction of cell free fetal DNA and analysed for presence of RhD Gene.
Performed at Red Cell Reference Lab in QLD.
Specificity >98% and sensitivity >99%
Who is offered NIPA testing?
- RhD negative pregnant women who are RhD alloimmunised
- RhD negative pregnant women with obstetric indications such as severe FMH during pregnancy or IU fetal death.
- Or in non sensitised RhD women in which there is a relatiev contraindication to anti-D prophylaxis (religious beliefs, prior reaction)
Anti-D administration - principle
Risk of anti-D sensitization in a pregnancy is up to 20% if anti-D is not used when there is a post-natal FMH, leading alloimmunization and risk of neonatal jaundice and/or anemia requiring IUT in future pregnancies
Also risk of alloimmunization earlier in pregnancy with other sensitizing event eg. clinical haemorrhage or other sensitizing event
Anti-D prophylaxis in the post-natal setting reduces this risk to 1-1.5%
Anti-D prophylaxis in the post-natal and pre-natal setting further reduces this risk to 0.2%
When Anti-D is not recommended
RhD positive woman
Baby is known to be D negative
Mother is already alloimmunised
Anti-D dosing
28/40: 625 IU RhD Immunoglobulin-VF for IMI*
34/40: 625 IU RhD Immunoglobulin-VF for IMI
Delivery of baby - given atleats within 72 h
Anti-D lasts 6 weeks; count backwards from 40/40
100 IU of Rh(D) Immunoglobulin-VF protects against a FMH of 1mL of foetal Rh(D) positive red cells (2mL of whole blood)
Sensitising event
- first trimester 250IU
- second/third trimester 625IU
RhD Ig products available
Dosing of anti-D in large FMH
For FMH >15mL (designated large-volume), a follow-up FMH should be performed 48h post anti-D administration and further anti-D given if FMH is still positive and RhD Ig is not detected by IAT in maternal plasma
FMH testing and subsequent actions
What is haemolytic disease of the fetus and newborn?
haemolysis in fetus and newborn due to maternal antibody
-antigen inherited from father
-IgG implicated isotype (IgM and IgA do not cross placenta)
Not all result in clinically significant disease
-1/2 mild and deliver at term
-1/4 moderate disease (top up Tx or exchange at birth)
-1/4 severe, require intrauterine transfusion, early delivery, exchange transfusion
Incidence of clinically relevant antigens in FMH
D antigen expressed by ~6 weeks of gestation
Clinical features of FMH
Mild:
-early onset jaundice (unconjugated bilirubinaemia within 24 hours of birth)
-symptomatic anaemia without circulatory collapse (lethargy, tachycardia, poor feeding)
-thrombocytopenia (up to 25% due to suppression of thrombopoiesis, in response to increased erythropoiesis)
Severe (hydrops fetalis):
-two or more of: diffuse skin oedema, pleural/pericardial effusions and ascites
-when fetal Hb deficit 7g/dL or more below mean for gestational age (or eg// Hb <5g/dL, Hct <15%)
-concomitant thrombocytopenia and neutropenia
ABO
-usually not clinically significant disease
-hyperbilirubinaemia within 24 hours of birth if affected
Investigations of FMH
Neonatal Testing:
-maternal and infant group and maternal Ab screen
-bilirubin, retic count, FBE
-DAT
-positive: consistent with HDFN (false positives –> Wharton’s jelly if cord blood)
-negative: does not exclude HDFN esp in ABOi (poorly developed antigens), elution + IAT
-IUT can give false negative DAT
*haemolysis screen may be negative in anti-K due to erythroblastopenia
FMH treatment - postnatal considerations
-delayed cord clamping (assoc with lower incidence of anaemia and exchange transfusion)
Postnatal transfusion
-for hydrops fetalis
-volume restriction due to fluid overload state
-exchange transfusion recommended for HF, severe anaemia/hyperbilirubinaemia
-simple transfusion preferred for non-severe anaemia and hyperbilirubinaemia
Hyperbiliruinaemia (general)
-oral hydration
-phototherapy to prevent neurotoxicity
Kleihaur Betke test - principle
Relies on the fact that HbF is resistant to acid elution from the cells more than adult haemoglobin (HbA)
“Screening” test
Principle: acid-elution cytochemical method of quantifying HbF
Kleihaur Betke METHOD
After ethanol fixation, hydochloric acid at pH of 3.3 is applied to the maternal blood sample –> the HbA is denatured and the HbF remains intact
Using Shepard’s method, the smear is counterstained with eosin or erythrosin, leaving the foetal RBC pink and maternal red cells ‘ghost-like’ with absent staining
10,000 cells (using miller optical field) are counted and the % of foetal cells is determined using Mollison’s formula.
Mollisons formular assumes that the maternal red cell volume is 1800 mL, fetal cells are 22% larger than maternal cells and only 92% of fetal cells stain darkly.)
% fetal cells x 18 x 1.22 = Estimated volume of FMH in mL.
Controls in Kleihaur Betke
Positive control: fresh EDTA cord blood diluted 1:100 in adult EDTA blood
Negative control: adult EDTA blood
False positives in HbF quantification
Thalassaemias
Sickle cell anaemia
Hereditary persistence of foetal haemoglobin (HPFH)