1. ISO-IMMUNIZATION IN
PREGNANCY
Fahad zakwan

2. RHESUS ISO-IMMUNIZATION

3. • Rhesus (Rh) factor is present on the surface of erythrocytes.
It consists of 3 pairs of genes C/c, D/d, E/e.
• The usual, but inaccurate, term " Rh+" or " Rh-" refers to the
presence or absence of the D gene.
• The D gene is dominant to "d" and therefore an " Rh+"
individual may be homozygous (DD) or heterozygous (Dd).
An " Rh-" individual has a (dd) genotype.
• Incidence: 85% of population are " Rh positive" while 15%
are " Rh negative".

4. Development of Rh-isoimmunization:
•An " Rh-" female may develop antibodies
if " Rh+" blood is passing to her
circulation via:
•Blood transfusion from " Rh+" donor.
•Pregnancy with " Rh+" foetus:

5. • When an " Rh+" father is married from an " Rh-" mother
there is a chance that the baby will be " Rh+".
• Foetal RBCs can be transmitted to the mother during delivery,
delivery, abortion, disturbed ectopic pregnancy, antepartum
antepartum haemorrhage, amniocentesis, or external cephalic
cephalic version.
• This initial stimulus produces IgM which cannot cross the placenta
the placenta again to harm the foetus due to its large molecular
molecular weight (900.000), so the first baby is escaped from the
escaped from the haemolysis.
• When the mother is exposed for a second time she will develop IgG
will develop IgG which can cross the placenta due to its low
its low molecular weight (150.000) to affect the foetus.

6. NOTE
The initial sensitization is so low that it is
not detectable by normal laboratory
testing but such patients will develop a
strong response to further stimuli.

7. • Although 15% of the population are Rh- the incidence of
Rhesus isoimmunization is 0.5-1.5% only. This is because:
• The foetus must have inherited a "D" gene from the father.
from the father. This is inevitable if the father is
is homozygous (DD), but if he is heterozygous (Dd) 50% of
(Dd) 50% of offspring will be (dd) i.e. Rh-
• ABO incompatibility between the mother and her foetus
her foetus results in the destruction of transfused foetal
transfused foetal cells before they can induce Rh antibody
Rh antibody formation.
• Individual variability of response to the stimulus.

8. PATHOLOGY
• The primary pathology in the foetus is haemolysis leading to anaemia.
• In response to the haemolytic anaemia erythropoiesis is enhanced
with an increase in blast cells.
• So the condition was called erythroblastosis foetalis.
• The haemolysis results in excessive production of bile pigments which
excreted mainly through the placenta to the mother.
• Thus, the threat during intra-uterine life is anaemia but after birth is
the accumulation of bile pigments.

9. CLINICAL VARIETIES

10. (I) Hydrops foetalis:
• The less common but most severe form in which there are:
• Severe haemolytic anaemia in utero,
• Cardiac failure,
• Gross oedema of the whole foetus and placenta,
• Hepatosplenomegaly,
• Pleural effusion and ascites,
• Polyhydramnios.
• Radiological and ultrasound features:
• "Buddha" attitude: due to abdominal distension,
• " halo" sign: due to oedema of the scalp.
• Occasionally, in severe cases a maternal syndrome develops with features
resembling pre-eclampsia plus jaundice and pruritus.

11. (II) Icterus gravis neonatorum:
It is the commonest form in which:
• The baby is anaemic at birth,
• Oedema, ascites, pleural and pericardial effusion,
• Hepatosplenomegaly.
• Jaundice not present at birth but usually develops within few hours, and is
progressive.
• Death may result during this period from heart failure, aggravated by
respiratory difficulties due to pulmonary oedema, pleural effusion and
distended abdomen.
• Kernicterus: is damage of the basal nuclei of the brain occurs if the blood
bilirubin exceeds 20 mg%. It is characterized by neck rigidity, nystagmus,
twitching and death of the neonate may occur. If survives, there is residual
spasticity and mental retardation.

12. (III) Congenital haemolytic anaemia:
•It is the mildest form in which there
is anaemia which may be evident at
birth or reveals itself up to a weak
or more postnatally

13. ANTENATAL ASESSMENT
(I) Maternal antibody level:
• It is indirect Coombs’ test hat measures specific anti-D IgG. A
concentrations above 0.5 mg/ml or titer more than 1/8 is an
indication for amniocentesis.
(2) Amniocentesis:
• The first sample from the amniotic fluid is taken at not later than 22-
24 weeks’ gestation if there is :
• a history of a previous severely affected or stillborn infant, or
• rising antibody levels.

14. • Otherwise amniocentesis is performed at 30-32
weeks.
• Repeat tests at intervals of 2-3 weeks.
• Amniotic fluid sample is examined as soon as possible
by the spectrophotometer at a wave length of 450
mm
(3) Ultrasound or X-ray:
• to diagnose hydrops foetalis

15. MANAGEMENT

16. (A) Prophylaxis:
• Rh-negative women should not receive Rh-positive blood transfusion.
• Anti - D gamma globulin should be given to:
• All Rh-negative women having Rh-positive baby in any delivery. They should
receive 500 units IM within 72 hours from delivery.
• Rh-negative women with abortion before 20 weeks should receive 250 units.
• After ectopic pregnancy, amniocentesis and abruptio placentae in Rh-negative
women.
• Women received Rh-positive blood inadvertently can receive a large dose of
anti-D globulin.

17. (B) Antenatal treatment:
1. Plasmapheresis:
• It is indicated if the foetus is severely affected (Liley zone3) before 24
weeks’ gestation.
• It aims to decrease the maternal antibody concentration by removal of 1
litre of maternal blood in each session.
• The blood is centrifuged under complete aseptic condition and the
supernatant plasma containing the antibodies is removed.
• The cells are resuspended in saline, plasma protein fraction or fresh frozen
plasma and returned to the mother.
• This is repeated five times weekly initially to be reduced to twice weekly
later on.

18. 2. Intrauterine transfusion:
• It is indicated if the foetus is severely affected between 24 and 34 weeks’
gestation.
• 80 ml of Rh-negative group O blood is injected into the peritoneal cavity of the
foetus from which the cells are rapidly absorbed.
• This is repeated every 2-3 weeks and increased to 120 ml at 33 weeks.
• The procedure is done under sonographic control and local anaesthesia.
• The rate of injection is 1.0-1.5 ml / minute.
• Cordocentesis: is intravascular transfusion into the umbilical vein under direct
vision using the fetoscope. It can be used instead of intraperitoneal injection

19. (C) Delivery:
• In severe cases, induction of labour or caesarean section is
indicated as soon as lung maturity is demonstrated by L/S
ratio.
• In milder cases, pregnancy can be allowed to continue to 37
weeks when termination is done
• The cord is not milked and immediately clamped to avoid
further passage of antibodies from the placenta. The cord is
divided 3 inches from the umbilicus to facilitate exchange
transfusion if needed

20. (D) Neonatal Management:
(I) Blood is obtained from the umbilical cord for the following
investigations:
• ABO and Rh group
• haemoglobin concentration
• serum bilirubin,
• direct Coombs’ test: detects the antibodies absorbed to the RBCs.
• Haemoglobin and bilirubin estimation is repeated every 6
hours for 36 hours.

21. (II) Exchange transfusion:
• Indications:
• Cord blood haemoglobin less than 15 gm/dl.
• Cord serum bilirubin more than 3mg% .
• Positive Coombs’ test.
• 20 ml of blood is withdrawn from the umbilical vein to be replaced by
the same amount of Rh-negative group O blood. This process is
continued till 80-90% of the foetal blood is exchanged.
• The aims are:
• Removal of bilirubin.
• Removal of some antibodies.
• Correction of anaemia.
• Replacement of Rh+ by Rh- RBCs.

22. (III) Simple transfusion:
•may be needed later on to correct anaemia.
(IV) Phototherapy:
•Exposing the baby to fluorescent light, with
protection of the eyes, reduces
bilirubinaemia.

23. ABO ISO-IMMUNIZATION

24. • Sometimes, when the mother is group O and the foetus is
group A, B or AB like his father , some anti A or anti B
antibodies pass from the mother to the foetus causing
haemolysis which can affect the first infant and usually
requires no treatment.
• Very rarely, the ABO incompatibility is severe causing marked
neonatal jaundice in the first 48 hours.
• This will indicate exchange transfusion for the newly born by
group O blood.

25. ABO incompatibility differs from Rh
incompatibility in that:
•The first baby is affected.
•It is usually mild due to the
presence of soluble A and B
antigens in the foetal tissues and
fluids in addition to the foetal
RBCs.

26. NOTE:
The natural anti-A and anti-B antibodies of group
O are IgG so it can cross the placenta to affect the
baby, whereas the natural anti-A and anti-B
antibodies of group B and A are IgM thus if the
mother is of group A or B her antibodies cannot
cross the placenta