Rh negative mothers need proper management to reduce the complications in pregnancy.

1. ISO-IMMUNIZATION PREGNANCY
RHESUS
ISO-IMMUNIZATION
MS LIPI MONDAL
SENIOR TUTOR,JCN

2. RHESUS ISO-IMMUNIZATION
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
POSITIVE” OR “RH NEGATIVE” REFERS TO THE
PRESENCE OR ABSENCE OF THE D GENE.
THE D GENE IS DOMINANT TO “D” AND THEREFORE AN
“RH POSITIVE” INDIVIDUAL MAY BE HOMOZYGOUS (DD)
OR HETEROZYGOUS (DD).
AN “RH NEGATIVE “ INDIVIDUAL HAS A (DD) GENOTYPE.

3. Incidence: 85% of population are “Rh positive” while
15% are “Rh negative”.
Development of Rh-isoimmnization:
An “Rh negative” female may develop antibodies if
“Rh positive” blood is passing to her circulation via:
Blood transfusion from “Rh positive” donor.
Pregnancy with “Rh positive” foetus:
When an “Rh positive” father is married from an “Rh
negative” mother there is a chance that the baby will
be “Rh positive”.

4. Foetal RBCs can be transmitted to the mother during;
delivery,
abortion,
disturbed ectopic pregnancy,
antepartum haemorrhage,
amniocentesis, or
external cephalic version.
This initial stimulus produces IgM which cannot cross
the placenta again to harm the foetus due to its large
molecular weight (900.000) so the first baby is
escaped from the haemolysis.

5.  When the mother is exposed for a second time she will develop IgG which can
cross the placenta due to its low molecular weight (150.000) to affect the foetus.
 Sensibilization: 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.

6.  Although 15% of the population are Rh negative 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.
 This is inevitable if the father is homozygous (DD), but if he is heterozygous (Dd)
50% of offsprings will be (dd) i.e. Rh negative.

7.  ABO incompatibility between the mother and her foetus results in the destruction
of transfused foetal cells before they can induce Rh antibody formation.
 Individual variability of response to the stimulus.
Clinical varieties:
 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.

8.  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. 1. Hydrops foetalis:
The less common but most severe form in which there are;
Cardiac failure,
Gross oedema of the whole foetus and placenta,
Hepatosplenomegaly,
Pleural effusion and ascitis
Polyhydramnios.
Large, pale, edematous placenta with fluid oozing from it
Radiological and ultrasound features;
Budda 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.

10. Anemia, tissue anoxaemia, metabolic acidosis
Adverse effect on fetal heart, brain and placenta
Hyperplasia of placental tissues to inc. the amount of oxygen
But RBCs reduce due to progressive hemolysis
Liver damage leading to hypernatremia which leads to generalised
edema, ascities, hydrothorax
Cardiac failure
Stillbirth/macerated/ dies soon after birth

11. HYDROPS FOETALIS

12. 2. Icterus gravis neonatorum:
It is the commonest form in which;
The baby is anaemic at birth,
Oedema, ascitis, pleural and pericardial effusion,
Hepatosplenomegaly,
Jaundice not present at birth but usually develops
within 24 hours, and is progressive.
Death may result during this period from
heart failure,
aggravated by respiratory difficulties due to
plulmonary oedema, pleural effusion and distended
abdomen.

13.  Kernicterus: is damage of the basal nuclei of the brain occurs if the blood bilirubin
exceeds 20mg%.
 It is characterised by
 neck rigidity,
 nystagmus,
 twitching and
 death of the neonate may occur.
 If survives, there is residual spasticity and
 mental retardation.

14. 3. Congenital haemolytic anaemia:
 It is the mildest form in which there is anaemia which may be evident at birth or
reveals itself upto 6 weeks or postnatally. Liver and spleen enlarged

15. Antenatal assessment:
1. Maternal antibody level:
indirect Coombs’ test that 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.
3. Ultrasound or X-ray:
To diagnose hydrops foetalis.

16. Management:
I. Prophylaxis:
Rh – negative women should not receive Rh-positive
blood transfusion.
Anti – D gammaglobulin 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.

17.  Women received Rh-positive blood inadvertently can receive a large dose of anti-D
globulin -
 Trials were made for prophylaxis with 1500 units given at 28 weeks or 500 units at 28
weeks and another one at 34 weeks’ gestation.
II. Antenatal treatment:
a) Plasmapheresis:
 It is indicated if the foetus is severely affected before 24 weeks’ gestation.

18.  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 supermatant
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.

19. b) Intrauterine transfusion:
It is indicated if the foetus is severely affected between
24 and 34 weeks’ gestation.
80ml 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
120ml at 33 weeks.
The procedure is done under sonographic control and
local anaesthesia.
The rate of injection is 1.0-1.5 ml/minute.
c) Cordocentesis: is intravascular transfusion into the
umbilical vein under direct vision using the fetoscope.
It can be used instead of intraperitoneal injection.

20. III. 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 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.

21. IV. Neonatal Management:
 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.

22.  Exchange transfusion:
Indications:
 Cord blood haemoglobin less than 15gm/dl.
 Cord serum bilirubin more than 3mg%.
 Positive Coombs’ test.
 20ml 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.

23. The aims are;
Removal of bilirubin.
Removal of some antibodies.
Correction of anaemia.
Replacement of Rh-positive by Rh-negative RBCs.
Simple transfusion:
May be needed later on to correct anaemia.
Phototherapy:
Exposing the baby to fluorescent light, with
protection of the eyes, reduces bilirubinaemia.