Autoimmune conditions of pregnancy

Question 1

what is a maternal isoantibody/alloantibody and give some clinical examples?

Answer 1

antibodies against an antigen that the mother DOES NOT have
–> Implication= No deleterious effects to the mother but may be lethal to the foetus

Red cell iso-immunisation
Perinatal allo immune thrombocytopenia
perinatal allo-immune neutropenia

Question 2

what is a maternal auto-antibody and give some clinical examples?

Answer 2

auto-antibody against an antigen the mother HAS herself

thyroid autoimmune disease–> congenital hyperthyroidism
SLE–> lupus like rash in child and FTT
ITP–> thrombocytopenia in the fetus
Sjogren’s disease–> congenital heart block and cardiomyopathy

Question 3

what are the sites of spontaneous haemorrhage in a fetus with alloimmune thrombocytopenia?

Answer 3

intracranial haemorrhage

GIT

Question 4

what is the main squelae of alloimmune neutopenia in a baby?

Answer 4

overwhelming bacterial sepsis

Question 5

what happens if you give WCC to a baby with alloimmune neutropenia?

Answer 5

graft vs host disease

Question 6

Which red cell antigens can be potentially harmful?

Answer 6

Rhesus D d etc
kell
kid
duffy
MNS

presence of anti-duffy/kid antibodies etc will result in haemolysis

Question 7

how might severe haemolysis result in neonatal cardiac failure?

Answer 7

rate of haemolysis exceeds> EPO production–> anaemia–> hydrops (cardiac failure)

Question 8

how might we predict the severity of red cell isoimmunisation reaction?

Answer 8

look at the level of antibody (titre)

the lower the titre, the less severe
the higher the titre, the more severe

so this is a good tool for risk assessment

Question 9

when do we give prophylactic anti-D antibodies?

Answer 9

administered routinely at 28 and 34 weeks of gestation

And at other times of sensitisation:
Before 20 wks= miscarriage/abortion, ectopic pregnancy, amniocentesis/CVS
After 20 weeks= antepartum haemorrhage, DELIVERY!!!

or spontaneous occult bleeding and trauma such as MVA at any time during pregnancy

Question 10

how might a mother obtain auto-antibodies from antigen exposure from fetus?

Answer 10

blood transfusion

maternal-fetal transfusion

Question 11

what is the most sensitive way of detecting hypovolemia in a child?

Answer 11

postural hypotension

Question 12

what is the basic pathophysiology of rhesus isoimmunisation?

Answer 12

Rh-ve mother is exposed to blood from Rh+ve fetus –> produces antibodies to rhesus antigens (IgM to IgG)–> IgG crosses the placenta and contact the RBC of Rh+ve fetus

Question 13

what is the percentage of pregnant women screened at their first antenatal visit who are found to be Rh-ve?

Answer 13

1%

Question 14

what percentage of Rh-ve pregnant women have anti-D antibodies?

Answer 14

85%

Question 15

what are the two extremes of red cell isoimmunisation reaction?

Answer 15

mild jaundice (mildest form)

hydrops foetalis secondary to anaemia causing cardiac failure (most severe form)

Question 16

what does isoimmunisation refer to?

Answer 16

Where an antibody crosses the placenta and is directed against an antigen that the fetus possesses but not the mother

Question 17

what potential effect does maternal Sjogren’s syndrome have on the fetus?

Answer 17

fetal heart block

Question 18

what antibody is associated with anti-phospholipid syndrome?

Answer 18

anti-cardiolipin

Question 19

what type of antibody (IgM or IgG) can cross the placenta?

Answer 19

IgG

Question 20

how many babies get mild/moderate/severe forms of red cell isoimmunisation reactions?

Answer 20

mild= 50%

moderate = 25%

severe = 25%

Question 21

a woman with duffy negative blood urgently requires blood and receives duffy positive blood. what happens?

Answer 21

nothing.

but sensitisation will occur causing antibody production to duffy antigen, so next time she receives duffy positive blood she will have a massive transfusion reaction

Question 22

how might a pregnant mother become sensitised to a foriegn antigen? (i.e. how might a maternal isoantibody form?)

Answer 22

blood transfusions and IVDU

maternal fetal haemorrhage/mixing of blood from previous pregnancies

Question 23

at the first antenatal visit, you do a screen for red cell antibodies and find the pregnant woman is Rh D negative. what must you do ix-wise?

Answer 23

1. Look at the anti-D antibody titre to assess risk/severity
2. Screen the partner!!!

If also Rh-negative then fetus NOT at risk of isoimmunisation reaction.
If Rh-positive, may either be homozygous DD or heterozygous Dd.

Question 24

what type of blood do we ideally give ALL women of child bearing age during a blood transfusion to avoid future red cell isoimmunisation complications?

Answer 24

should give D negative, Kell negative blood!

Question 25

how long do we have post delivery to give anti-D antibodies if required to the mother?

Answer 25

up to 72 hours! so three days

Question 26

which is more common; ABO or rhesus incompatibility between mother and child? what is the prognosis of both?

Answer 26

ABO is 3 x more common than rhesus incompatibility.

ABO incompatibility usually results in mild jaundice but almost never in anaemia or fetal death. so much better prognosis than rhesus incompatibility

Question 27

what is your antenatal management of low risk red cell immunised pregnancies?

Answer 27

1. Antibody titre level at each visit to monitor for maternal-fetal haemorrhage (look for rising titre)
2. Continue with current model of care.
3. Deliver no later than 38 weeks to prevent prolonged jaundice

Question 28

what is your antenatal management of moderate risk red cell immunised pregnancies?

Answer 28

1. Antibody titre level at each antenatal visit.
2. Refer to specialist maternal service!
3. Measure the ultrasound flow through the MCA (middle cerebral artery) from 20 weeks. If anaemia is present, then blood systolic velocity through MCA will increase.
4. CTG from 32 weeks.
5. Deliver at 38 weeks or earlier if fetal anemia present

Question 29

what is your antenatal management of high risk red cell immunised pregnancies?

Answer 29

1. U/s screening from 17 weeks
2. Refer to specialist maternal service
3. Fetal blood Sampling-if partner is heterozygous to determine whether baby has offending antigen
4. Intrauterine transfusions if fetal anaemia present (can give maternal RBC minus the plasma bc it contains the antibodies but not ideal as you can’t keep on bleeding the woman during pregnancy)
5. Delivery is indicated when risk of fetal transfusions outweighs the benefits

Question 30

how might we determine whether the fetus has the D antigen if the partner of a rhesusD negative woman is heterozygous for D antigen (i.e. Dd)?

Answer 30

via aminocentesis (prefer not due to risk of sensitisation event) or

fetal DNA sourced from maternal blood (preferred for DNA analysis)

Question 31

what blood test do we do to test for fetal maternal haemorrhage?

Answer 31

Kleihauer–Betke test - measures the amount of foetal blood in maternal blood

Question 32

how might we assess for anaemia in a fetus at high risk of anaemia?

Answer 32

continuous CTG or measurement of MCA (middle cerebral artery) fortnightly and then weekly during the 3rd trimester

Question 33

at what anti-D antibody titre in the maternal blood is concerning for increased risk of fetal anaemia?

Answer 33

> 1:16 titre

or 4 fold increases in antibody titre such as 1:16 to 1:64

Question 34

what is the significance of maternal anti-kell antibodies?

Answer 34

any titre of anti-kell antibodies in maternal blood –> risk of fetal anemia in kell +ve babies

Question 35

why is it important to quantify the amount of foetal maternal haemorrhage in a sensitising event for a rhesus-negative mother?

Answer 35

important to quantify bc higher levels of FMH requires higher doses of passive anti-D immunisation for the mother

Question 36

how frequent should we be checking the anti-D antibody levels in a rhesus-negative mother during her pregnancy?

Answer 36

monthly blood tests watching for any change in titre levels as titre levels often dictate risk of foetal anaemia

Question 37

what are the anti-d titre cut off levels for mild/moderate/high risk rhesus disease pregnancies?

Answer 37

mild= > 16

moderate= >64

high risk= > 512

Question 38

when do we begin to monitor MCA waveforms on fetal uss doppler for pregnancies at risk of rhesus disease?

Answer 38

from 20 weeks gestation

Question 39

what are the doses of anti-D immunoglobulin that we administer to rhesus negative women?

Answer 39

First trimester (dose 250 IU)

• Chorionic Villus Sampling;
• Miscarriage;
• Termination of pregnancy (either medical or surgical);
• Ectopic pregnancy

Second and third trimester (basic dose 625 IU)

• Obstetric haemorrhage;
• Amniocentesis, cordocentesis;
• External cephalic version of a breech presentation, whether successful
• Abdominal trauma, or any other suspected intra-uterine bleeding or sensitising event.

All Rh (D)-negative women (who have not actively formed their own Anti-D) should be offered a prophylactic dose of 625 IU at approximately 28 weeks gestation and again at approximately 34 weeks gestation.

All women who deliver an Rh (D)-positive baby should have quantification of fetomaternal haemorrhage to guide the appropriate dose of anti-D prophylaxis, and the dose should be given within 72 hours if possible.