1. PROF. M.C.BANSAL .
MBBS. MS . MICOG. FICOG.
FOUNDR PRINCIPAL & CONTROLLER;
JHALAWAR MEDICAL COLLEGE AND HOSPITAL, JHALWAR.
EX . PRINCIPAL & CONTROLLER;
MAHATMA GANDHI MEDICLA COLLEGE AND HOSPITAL,
SITAPURA , JAIPUR.

2. Hydrops Fetalis
 It is defined as generalized fetal edema or anasarca , which
can be detected by an Antenatal USG.
 It may be manifestation of a variety of underlying disorders.
 The condition is subdivided in to
(a) Immune hydrops .
( b) non immune hydrops.
immune variety is more common in developing countries as
Rh grouping is not an universal phenomenon .
Non immune variety is more common in the developed
countries; ratio being reported to be 9: 1 of non immune to
immune cases.
Rh –Ve persions ---India 5- 10 % 0f population –it is least in
Japan < 2% and 15 % in Europe and USA.

3. Development of Rh- D antibodies
When Rh +Ve RBCs enters the Rh-Ve mother’s blood circulation; they
stimulate the maternal immune response producing RBC antigen –
specific antibodies –isoimmunization (sensitization ) .
After few weeks , IgM antibodies ( Saline antibodies ) are produced.
IgM do not cross the placenta barrier Hence can not cause fetal
damage .
 On subsequent exposure of fetal Rh D antigen , her previously
primed B cells act swiftly to produce IgG ( albumin antibodies )
which can cross placenta ---and bounds to antigen of fetal RBCs
causing sequestration and destruction of fetal RBCs.
 Antibodies are formed in 16% of the mothers significantly after
6months of larger amount of fetomaternal bleeding and once
formed remain in circulation through the life. And each subsequent
pregnancy will have booster effect especially when fetus is Rh +Ve
fetus is in utero.

4. Schematic Diagram of antibody---Showing heavy , light chains and
antigen binding sites

6. Maternal
IgG
Fetal

8. Immune Hydrops
 The commonest cause of immune hydrops fetalis is
pregnancy in Rh negetive women with a Rh
positive fetus .
 Rh negetive mother who is already sensitized by
either by a previous pregnancy or blood
transfusion, is capable of producing
Immunogloblin G.
 These Immunoglobin G (IgG) antibodies cross the
placenta and destroy (haemolysed ) the Rh
positive RBCs of fetus.
 This phenomenon was reported by Levine in 1941.

9. Immune Hydrops Fetalis------ First pregnancy proceeds normally as Rh -ve mother is
usually not sensitized.
 Feto -placental maternal transfusion occurs at the time
of placental separation and the Rh +Ve fetal RBCs
sensitize t6he maternal immune system.
 Other procedures during pregnancy (even in first
pregnancy ) can sensitize the mother are feto- maternal
blood transfusion--- occuring in amnioscentesis ,
threatened abortion ,Ectopic pregnancy, MTP,D&E,
abruptio placenta, APH , External podalic version, IPV,
LSCS, MRP, Chorionic Villus Sampling , PIH , etc.

10. Immune Hydrops--- In subsequent pregnancy the fetal RBCs entering in
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maternal circulation may be destroyed /or some of them
may have booster effect for maternal sensitization.
Maternal Immunoglobins G cross the placenta and
destroy fetal RBCs .
In mild cases, the fetus has haemolytic disease resulting
in anaemia with mild icterus.
In severe cases fetus develops hydrops fetalis.
If IgG titers are high the disease process may start even
in early period of gestation --- resulting in IUFD.

11. Degree of Risk of Developing isoimmunisation
according to period of gestation
Gestational period
%
After 1st trimester abortion
2%
After MTP ( mid trimester )
4-5%
At term after Delivery—ABO Rh
competability
ABO incompetable
ABO incompatibility confer
substantial protection against
developing Rh (D) issoimmunisation
16%----2% at the time of delivery , 7%
willdevelopanti D antibodie by the 6
months of delivery , another 7% get
sensibilized e.g. thy develop anti D
slowly and very low titre which
becomes detactable and measurable in
next prgnancy.
1.5 -2 %

12. Why all babies are not affected in
Rh –Ve mother
 Volume of fetomaternal trnsfusion may be too low to
sensitise.
 Immunological non responders ---pregnancy
induced suppression of immune system –30%.
 ABO Major group incompetability.
 Rh set up of the fetal blood may change the Rh –
antigenicity ( stimulus )

13. Feto- maternal haemorrhage During Antenatal
Period
 O.1mlof fetal RBCs are found in 5-15 % of women’s
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circulation by 8 weeks of gestation.
75% cases it is always < 1ml .
1% show atleast 5ml fetal RBCs.
0.25% have more than 30ml of fetal RBCs hence only 1.5
% women get sensitised in Antenatal period .
It can be prevented by anti D therapy in antenatal period
---at 28 and 36 weeks of gestation and repating it after
delivery.
If any factor precipitating feto-maternal hemorrhage
need immediate anti d therapy in appropriate dose.

14. Prophylaxis---- Universal ABO Rh grouping of all girls / expactant
mother.
 Premarrital councellig regarding The Rh factor in both
life partners --- advising marriage of identical Rh factor.
 Rh Immunoglobulin (Rh-IgG) therapy within 24-48 hrs
to all Rh –Ve women after ectopic/MTP/ abortion/
delivery /amnioscentasis ,Version , APH bleeding and at
28th and 36th week of gestation in primigravida too..
 This therapy was introduced in1966 and its world wide
acceptance has remarkably reduced the incidence of
immune hydrops in developed countries , but it is still
common type of hydrops in developing world.

15. Hydrops fetalis
 Occasionally . Immune hydrops may be due to other
erythrocyte antigen apart from Rh D antigen.
 These include –major A.B.O. incopetability and
minor blood group antigens ---C D E, Kell , Jk, S, c ,
and Duffy.
 If issoimmunization occurs , then the titers of
antibodies are monitored at appropriate intervals
depending on the levels and rapidity with which they
are changing ( either every 2 or 4 weeks).

16. Rh Blood system
 Rh complex involves genetic expression of 3 separate alleles,

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namely C,D,E and small d.
Genetic locus of Rh complex is situate on short arm of
chromosome 1.
D antigen is most potent and is responsible for almost all
cases of Rh incompatibility.
The potency of immune sensitivity of antigen is in the order
of D>d >C> E>e>c.
The commonest genotypes are Cede/ cede ,Cede / cede and
cede/CDE .
Capital D is dominant and express in clinical
sympatomatology—whenever present the person is called Rh
+Ve, while one having small dd is non effective hence taken
as Rh -Ve

17. Homozygous / Heterozygous Rh- Grouping.
 Homozygous Rh + Ve = DD ( D on both sets of
antigen--- mother and father both Have contributed
D &D.
 Homologous Rh –ve = dd eg. Each of both small d
parents have contributed set of small d( Maternal d
and paternal d)
 Heterozygous means---Rh +ve when Dd( one logus
has D and another logus has d) eg. D has come from
father / mother and d has come from Mother / father
– both parents have contributed different D and d.

18. Rh +Ve
Mother
Homogyous Rh
+Ve parents
Rh +Ve
Father
DD
All children Homogygous +Ve
D D
DD
DD
DD
DD
Both parents are Rh +ve ( DD) hence all 4 children will be Rh +Ve (DD)

19. Rh –Ve
mother
Rh +Ve Father
Homozygous
dd
Dd
DD
Dd
dD
dD
All 4 Children will be Rh +Ve ( heterogygous) as D is dominant while
d is recessive

20. Rh –ve Mother
Rh –Ve father
d d
d d
d d
d d
d d
all 4 children will be Rh -ve
d d

21. fetal Rh +ve RBCs enter in Rh-ve maternal circulation---Sensitise maternal
immune system ------Mother produce saline (IgM) & albumin (IgG ) antibodies
against fetal cells– IgG antibodies cross the placental blood barrier and reach to
fetal circulation and haemolyse the fetal cells resulting in HDFN

22. Antibody Formation ( Iso immunization of Rh -ve Mother ) Haemolysis of fetal
Rh+Ve RBCs

24. Characteristics of Rh -Immunoglobins
 Saline antibodies----
 It is IgG .
 It is IgM.
 Agglutinate with Rh +Ve
 Agglutinate Rh +ve RBCs
when suspended in saline.
 It appear first –before 24
weeks– and then decline
 Larger molecule.
 Can not cross placenta
hence can not cause
Haemolytic disease of fetus
and new born.
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RBCs when suspended in
20% Albumin solution.
It appear later the saline
antibodies & continue to
increase as pregnancy
advances.
Small Molecule.
It crosses the placenta.
Causes haemolytic disease
of fetus and newborn .

25. Manifestation Of HDFN ( Erythroblastosis Fetalis
Depending upon the degree of fetal RBCs haemolysis ---It may
be -
1. Hydrops Fetalis ----Fetus is severely affected .
.
2. Icterus gravidorum neonatorum -----Relatively less
affected.
3.Congenital Anaemia ---of the newborn ; mildly affected .
Baby develops anaemia ; jaundice is not so evident or mild
, prognosis is good

26. Hydrops Fetalis
Severe form of Rh – HDFN.
2. Sever anaemia , generalised edema , ascites, and hydrothorax.
3. High cardiac output.
4. Liver damage due to fetal anoxaemia and acidosis.
5. Liver become the site of hemopoesis to compensate anemia due to
haemolysis.
6. Liver fails to produce proteins from aminoacids --hypoproteinaemia ; responsible for generalised edema.
7. Enlargement of placenta due to hyperplasia to meet the demand of
o2 transfusion to fetus.
8. USG---scalp edema ,skin edema, pericardial, pleural effusion and
ascites.
9. X-ray—buddha position __hallo around scalp—scalp edema .Limbs
apart ---due to abdominal distension.
10. Outcome  usually IUFD , sometime live birth but immediate
newborn death.
1.

27. Icterus Gravis Neonatorum
Lesser form of haemolytic disease than hydrops fetalis .
Newborn develops jaundice with in 24 hours after birth .
In uterus, most of the unconjugated bilirubin is washed
away through the placenta and thus no development of
fetal jaundice in utero.
After delivery excess of bilirubin is not excreted due to
failure of a large amount of bilirubin load by the liver of
neonate.
When serum bilirubin level rise above 20mg % it crosses
the blood brain barrier to deposit in basal ganglia
resulting in kernicterus.
This baby needs exchange transfusion.

28. Investigations
Blood in vials are sent to lab –
(a) 3ml oxalate / EDTA blood-- for Hb% and peripheral
smear.---Haemolysed RBCs, ghost cells (Maternal cells )
(b) 2ml clotted blood in another vial ---for ABO Rh
grouping , direct coomb’s test and serum bilrubin level .
DIRECT COOMB’S TEST  it is test to know , is baby is
affected by Rh –haemolytic disease or not .
If direct coomb’s test is +ve . it means baby is affected
and special management is to be done acoording to
serum bilirubin level .
As mother is already sensitized there is no role of
prophylactic anti D therapy .
If direct coomb’s test is –ve ---newborn is not affected by
Rh –iso immunizationi

29. Investigations
(a)INDIRECT COOMB’S TEST  RBC’s of specific or
mixed antigen ( KNOWN) are mixed with serum of
patient and anti human antiglobulin is added .
If agglutination of RBC’s occur ; it means antibodies
against Rh factor are present in patient’s blood.
Antibodies present in patient’s serum get attached to
RBCs and agglutination occurs.
Titer 1: 16 means agglutination occurs up to 16 times
dilution of patients serum .
(b)DIRECT COOMB’S TEST  Anti human anti globulin
are added directly to the rocs of baby.
Agglutination means anti bodies are bound to the rocs
of baby.

30. Immune Hdrops Fetalis

31. 3 D image of fetus with features of immune
hydrops

32. Rh –is0 immune –Hyderops ( aNasarca)

34. Non Immune Hydrops Fetalis( USG) Trisomy case

39. Immunoprophylaxis
Routine antenatal Rh anti therapy is recommended
to Rh negetive women married to Rh+ve partner.
300 ug ,im in deltoid muscle at 28 weeks and 36
weeks of gestation.
1 0 0 u g , i m i s g i v e n a f t e r a n y b l e e d i n g i n 1 st
trimester.
Higher dose to be given after any precipitating
factor or procedure likely to cause feto placental
hemorrhage.
300ug anti D is sufficient to neutralize 15 ml of
have fetal cell/ 30ml of whole blood.

40. Measurement of fetomaternal
Haemorrhage
KLEIHAUER- BETKE TEST - Based on acid elution
technique. Fetal and maternal rocs have different
response to KOH solution.
Maternal cells (adult Hb ) get eluded leaving behind only
cell membrane and hence appear as swollen round large
―GHOST CELLS‖ against normal fetal cells whose Hb
remain unaltered hence look as red refractile round
cells .
If in 50 low power fields of maternal peripheral blood
80 fetal RBC’s are found- it is estimated that 4ml of
fetomaternal hemorrhage has occurred.
For 1ml of fetal blood 10ug of Rh anti D is needed. Thus
300ug anti D will be sufficient for 30 ml of fetal blood
which has entered the maternal circulation.

41. Materna l Adult
Hb Get eluded with

42. Fetal Hb Is
resistant to KOH
Maternal Adult Hb
gets elude by KOH --RBCs –Swollen with
fluid

45. Rh –ve(dd) fetus rarely may be exposed
to maternal D antigen as result of
materno fetal haemorrhage and may
become sensitized in their intra uterine
life. When such girl at her adult age
has pregnancy with Rh +ve fetus , the
very first fetus may suffer from HDFN .
this mechanism of isoimmunisation is
called GRAND MOTHER THEORY .

46. Unique complication of
Hydrops Fetalis where mother
develops anasarca similar to
fetus & PIH.

47. In a previously sensitized / sensibilized
women the antibody titer may rise to
high level in subsequent pregnancy.
This may occur in d-negative fetus also.

51. Non –IMMUNE Hydrops Fetalis causes--• INFECTIONS- Parvovirus B 19, Cytomegalovirus, Toxoplasma, Syphilis,
Herpes, Rubella, Leptospirosis.
• MATERNAL CAUSE -> Diabetes Mellitus, PIH, Severe Anaemia ,
Hypopteinaemia .
• CHONDROPLASIAS  Thanatophoic dwarfism, Osteogenesis Inperfecta,
Achondrogenesis, Hypophosphatasia.
• TWIN PREGNANCY  Twin to Twin Transfusion, Acardia Twin .
• CONGENITAL TUMORS  CNS, Renal, Genital, GIT, Pulmonary Hepatic &
Placental tumors, Sacrococygeal Teratoma, Tuberus sclerosis and
Neuroblastoma.
• INBORN ERRORS OF METABOLISM --.>Mucopolyscharidosis, Gausher’s
disease, Gangliosidosis, Neuramindase deficiency, Fetal Red cell disease -Alpha thalassaemia, Sicle cell, Spherocytosis, Elliptocytosis, and Morquio’s
disease.

55. Non immune --Hyudrops fetalis with large nenigo Myelocele in neck Region