Hemolytic disease of the fetus and newborn (HDFN), also known as erythroblastosis fetalis, is caused by maternal antibodies crossing the placenta and destroying fetal red blood cells. Rh incompatibility occurs when an Rh-negative mother has an Rh-positive baby. This can sensitize the mother's immune system and cause hemolytic anemia in subsequent Rh-positive babies. Management involves monitoring for signs of fetal anemia, performing intrauterine blood transfusions if needed, and delivering the baby when it is mature. After birth, affected babies may require phototherapy, exchange transfusions, or other treatments to prevent complications from hemolysis and jaundice. RhoGAM injections during and after pregnancy

1. WELCOME TO CPD 2ND
PART
Dr. Shamim Reza
MD Resident (Phase B)
ICMH, Dhaka.
02.01.2023

2. Hemolytic Disease of the
Fetus
and Newborn

3. Hemolytic Disease of Fetus &Newborn
• Hemolytic disease of the fetus and newborn
(HDFN ), also know as erthroblastosis fetalis,
is caused by the
• Transplacental passage of maternal antibodies
• Directed against paternally derived RBC
antigens
• Which causes increased RBC destruction
(hemolysis) in the infant

4. Hemolytic Disease of Fetus
&Newborn
• It is an important cause of anemia and
jaundice in newborn infants
• Early recognition & diagnosis are crucial for
proper management.

5. Hemolytic Disease of Fetus &Newborn cont..
• Clinically significant disease is associated
primarily with incompatibility of
ABO blood groups &
RhD antigen
• Less frequently, hemolytic disease may be
caused by differences in other antigens of the Rh
system or by other RBC antigens such as
CW, CX, DU, K(Kell),M, Duffy, S, P, MNS, Xg,
Lutheran, Diego an Kidd. Notably, anti-Lewis
maternal antibodies rarely cause HDFN.

6. Hemolytic Disease Caused by
Rh Incompatibility

7. Incidence
• RhD antigen incompatibility is approximately 3
times more common among whites than among
blacks
• ICMH Data 2021:
Total admission in neonate: 1072
Neonatal Jaundice: 211
Rh-Incompatibility: 7

8. Rh-Factor
• The Rhesus factor gets its name from
experiments conducted in 1937 by scientists
Karl Landsteiner and Alexander S. Weiner.
• Their experiments involved rabbits which,
when injected with the Rhesus monkey's red
blood cells, produced an antigen that is
present in the red blood cells of many
humans.

10. Hemolytic Disease Caused by Rh
Incompatibility
•The Rh antigenic determinants are genetically
transmitted from each parent and determine the
Rh blood type by directing the production of Rh
proteins
•The genotype is determined by the inheritance of
3 pairs of closely linked allelic genes situated on
chromosome 9 named as
C,c,
D, d (90% of HDFN caused by RhD )
E, e on the RBC surface

11. Rh Factor

12. • Blood groups are classified as Rh positive
and Rh negative
• The Rh factor , Rh+ and Rh- usually
refers specifically to the presence or
absence of antigen-D
• There are two alleles, or genetic variants ,
of this antigen: D and d.
• A person who is Rh- has two recessive
traits, dd. Anyone who has at least one D-
DD or Dd-is Rh+
Rh Blood Grouping System

13. Rh Type and Pregnancy
• A person's Rh type is generally most relevant
with respect to pregnancies
• If the pregnant woman and her husband both are
Rh negative, there is no reason to worry about
Rh incompatibility
• If wife is Rh- and her husband is Rh+ ,the baby
will inherit the father’s blood type ,
creating incompatibility between mother and
her fetus.

14. Definition
•Rh incompatibility is
a condition which
develops when there
is a difference in Rh
blood type between
that of the pregnant
mother (Rh
negative) and that
of the fetus (Rh
positive)

15. Pathophysiology
• Usually placenta acts as barrier to fetal blood
entering maternal circulation
• Sometimes during pregnancy or birth,
fetomaternal haemorrhage (FMH) can occur.
• Small quantities (usually >1mL) of Rh-positive
fetal blood, inherited from an Rh-positive father
enter the maternal circulation during pregnancy,
through spontaneous or induced abortion,or at
delivery.

16. -

19. • Once sensitization has occurred, considerably
smaller doses of antigen can stimulate an
increase in antibody titer
• Initially, a rise in IgM occurs, which is later
replaced by IgG antibody.
• Unlike IgM antibodies IgG readily crosses the
placenta to cause hemolysis of RBC

22. PATHOPHYSIOLOGY

23. Rh Incompatibility
Effect in Fetus
• Hemolytic anaemia
• Heart failure
Hydrops fetalis
• IUFD
Effect in Neonate
• Congenital anemia
of newborn
• Icterus gravis
neonatorum
• Severe growth
retardation

24. Risk factors of Rh
Isoimmunization
• Abortion
• Amniocentesis, chorionic villus
sampling(11%)
• Ante partum hemorrhage
• Fetal death
• Ectopic pregnancy
• Partial mole
• External version (2%-6%)

25. Risk factors (cont..)
• Mismatched blood transfusion
• After fetomaternal haemorrhage
• During delivery (15%-50%)
Third stage of labour
Manual removal of placenta
Caesarean section

26. The outcome for Rh-incompatible
fetuses
Not all maternal-fetal antigen incompatibility leads to
alloimmunization and hemolysis
Factors affecting the outcome:
• Differential immunogenicity (RhD antigens most
immunogenic)
• Threshold amount of fetomaternal transfusions
• IgG antibodies are more efficiently transferred across the
placenta to the fetus
• Differences in the maternal immune response

27. Sign & Symptom of Rh
Incompatibility
Rh incompatibility can cause symptoms ranging
from very mild to fatal.
• Mildest form- Rh incompatibility
1. Hemolysis (Destruction of the RBCs)
with the release of free hemoglobin into the infant's
circulation.
2. Jaundice (Hemoglobin is converted into bilirubin
which causes an infant to become yellow.

28. Fetal hemolysis
• Anaemia
• Hepatosplenomegaly

29. • Jaundice

30. Severe form of Rh Incompatibility
1.Hydrops fetalis
- An accumulation of fluid, or edema in
at least two fetal compartments
- Accumulation of fluid usually in
subcutaneous tissue on scalp, pleural
effusion, pericardial effusion, or ascitis
-In Rh incompatibility, massive fetal
red blood cell destruction causes
Severe Anemia→→ Fetal heart
Failure→→ Death of the infant shortly
after delivery.

31. 2. Total body swelling.
3. Respiratory distress (if the infant has been
delivered)
4. Circulatory collapse.
5. Kernicterus:
-Neurological syndrome in extremely jaundiced
infants
-It occurs several days after delivery and is
characterized initially by
a)Loss of the Moro reflex
b)Poor Feeding.
c) Decreased activity
Severe form of Rh Incompatibility

32. Investigations- Antenatal
• ABO blood grouping and Rh typing of mother.
• Paternal Rh type & zygosity : If father of the
baby is Rh +ve then genotype is to be
determined.
• Indirect coomb’s test:
-Detection of maternal antibody
-Degree of alloimmunization(different mem.
Of same species)

33. Coombs’ Test
The Coombs’ test looks for antibodies that may
bind to fetal blood cells and causes premature RBC
destruction (hemolysis)
Indirect Coomb’s test (Mother)- for unbound
circulating antibodies against RBC & used to
determined if the person have a reaction
to blood transfusion
Direct Coombs’ test (Baby) - to detect
antibodies that are already bound to the RBC
surface in the baby.

35. Cont..
• Estimation of IgG antibody: Some centres consider
the titre of 1:16 or antibody level >10 IU/ml as a
critical one
• If antibody titer is positive on Coomb’s test >1:16
• Detection of foetal RBC: by KB (Keilhauer Bekte)
test & Flowcytometry. It is an evidence for feto-
maternal hemorrhage

37. Cont..
• Assessment of fetal wellbeing :
1.Serial USG detects-
Fetal hydrops when oedema in the skin,
scalp and pleural or pericardial effusion and
echogenic bowel.
2.Cardiotocography-
Sinusoidal & decelerative pattern.

40. Assessment of Fetal Anaemia
Noninvasive:
Doppler ultrasound (MCA- PSV)
At 18th week
Peak systolic velocity in fetal middle cerebral artery
>1.5 MoM for the corresponding gestational age
predicts moderate to severe fetal anaemia

42. Cont..
Invasive:
• Amniocentesis and amniotic fluid
spectrophotometric analysis
• Cordocentesis

43. Amniocentesis
Indications:
■ Antibody titre reach the critical level
■ Previous history of severely affected baby
■ Father is heterozygous to determine fetal blood type
Selecction of time:
■ No history of previously affected baby –At 30 – 32
weeks and repeated after 3 to 4 weeks.
■History of previous affected baby – At least 10 wks
prior to the date of previous stillbirth or other
hemolytic manifestations on the baby.

44. Cordocentesis
Done for-
1.Fetal cord blood sampling: percutaneous
umbilical blood sampling(PUBS)
From 18th week
2. Fetal RBC transfusion
Indications:
MCA-PSV >1.5 MoM

45. Management of Hemolytic Disease of
Fetus and Neoborn(HDFN)
The main goals of therapy for HDFN are
(1)To prevent intrauterine or extrauterine death
from severe anemia and hypoxia,
(2)To prevent neurodevelopmental damage In
affected children,
(3)To avoid neurotoxicity from
hyperbilirubinemia

46. Antenatal Management

47. Antenatal visit
Blood group Rh typing
Rh negative mother
Husband’s blood group
Rh negative Rh positive
Manage as normal
pregnancy
Antibody screening at 12, 28, 36 weeks
Screen positive Screen negative
Manage as isoimmunized pregnancy
Unimmunized mother
Management of Rh negative pregnancy

48. Cont..
Screen negative
Antenatal prophylaxis at 28 weeks
Delivery at term
Cord blood of fetus
Rh negative Rh positive
No prophylaxis Post partum prophylaxis

49. Cont..
Isoimmunized
mother Obstetric history
No previous affected fetus
Previous fetus affected
Antibody titre weekly
Supervision in an equipped
center & assessment of
severity of fetal anaemia
Follow up antibody titre 4 weekly
upto 24 weeks & every 2weekly
thereafter
Neg or below
critical level(<16 )
Delivery at term
Above critical
level(>16)

50. • Rising ab titre;MCA PSV >1.5MOMs
USG- abn[fetal ascites,hydrops]
 Serial MCA PSV Doppler study every 1-2 wks from 20wks
 Serial USG every 2-3wks from 20wks
Cordocentesis to see fetal hct;if <30%
Intrauterine fetal transfusion to raise
hct upto 50%
May have to be repeated upto 34 wks
Delivery @ 34 wks
MCA PSV < 1.5
To start antenatal fetal
surveillance(NST,
BPP,Doppler study of UA)
at 32 weeks
Delivery at term

51. Fetal Blood Transfusion
Transfusions can be given through the fetal
umbilical vein.
 An intrauterine transfusion provides blood to Rh
positive fetus when fetal RBCs are being
destroyed by Rh antibodies.
 A blood transfusion is given to replace fetal RBCs
that are being destroyed by the Rh sensitized
mother's immune system.

52. Fetal Blood Transfusion(Cont…)
• This treatment given to keep the fetus healthy
Until he or she is mature enough to be
delivered .
• In a severely affected fetus, transfusions are
done every 1 to 4 weeks until the fetus is
mature enough to be delivered safely .

54. Prevention of Rh-Immunization
To prevent active immunization---
• Rh anti-D (IgG) IM given to unsensitized mother:
At 28th week of gestation – 300 µg as prophylaxis
and repeat again after delivery
• If fetomaternal bleeding --
Before 12 wks 50 µg within 72 hrs from bleeding
After 12 wks 300 µg within 72 hrs from bleeding
• After surgical evacuation - 50 µg
• Following delivery – 300 µg within 72 H

56. Prevention(cont..)
2. Amniocentesis should be done after
sonographic localization of the placenta to
prevent its injury.
3. Avoid external version.
4. To prevent hazard of transfusion
**Avoid mismatched transfusion.

57. Prevention(cont..)
To prevent or minimize feto - maternal bleed
1.Precautions during delivery—
** Prevent blood spillage during C/S.
** Quick cord clamping.
** Avoid manual removal of placenta.
** Avoid prophylactic ergometrine.

58. Postnatal Management
Diagnosis: By history and Investigation
Investigation:
a. Cord blood sampling
• S. Billirubin
• ABO grouping & Rh typing
• Coomb’s Test
• Hemoglobin
• Reticulocyte count
b. Infection screening
c. Peripheral blood film

59. Diagnosis
Obstetric history
• Rh –ve primigravida with no previous history of
blood transfusion →usually will be unaffected.
• History of prophylactic administration of anti – D
immunoglobulin following abortion or delivery

60. Diagnosis
Obstetric history (Cont..)
• History of previous fetal affection by Rh
isoimmunization
• Still born
• Severe neonatal jaundice needs exchange
transfusion
• Neonatal death due to severe jaundice

61. Postnatal Management (cont..)
Affected baby should be treated with:
• Early Phototherapy
• Early Exchange transfusion
• Intravenous immune globulin
• Metalloporphyrin

62. Early Phototherapy
• Indication • Clinical jaundice
• indirect hyperbilirubinemia
We use : broad spectrum white ,blue &
special narrow spectrum blue light
Wavelength : 420-470 nm

63. Phototherapy (cont.)
• Mechanism of action :
▪Reversible photo isomerization
▪Toxic native unconjugated 4Z,15Z bilirubin is
converted into non toxic unconjugated 4Z,15E
bilirubin which is excreted in bile without
conjugation
▪Native bilirubin is converted into lumirubin
which is excreted by kidney without conjugation

64. Phototherapy (cont.)
Complication
• Loose stool
• Macular rash
• Purpuric rash
• Transient porphyrinemia
• Overheating
• Dehydration
• Bronge Baby Syndrome

65. Exchange Transfusion
Definition :
Repetitive withdrawal of small amounts of
blood and replacement with donor blood,
until a large proportion of the original
volume has been replaced.
Mechanisms :
• Exchange transfusion removes partially
hemolyzed and antibody-coated RBCs
and also unattached antibodies
• And replaces them with donar RBCs

66. Indication of ExchangeTransfusion
• When phototherapy fails to prevent a rise in bilirubin to
toxic levels.
• Hemolytic disease of the newborn
ABO Incompatibility
Rh Incompatibility
• Severe sepsis
• DIC from multiple causes
• Metabolic disorders causing severe acidosis
• Severe fluid or electrolyte imbalance
• Polycythemia
• Severe anemia causing cardiac failure
• Acute renal and hepatic failure
• Poisoning

67. In Hemolytic Disease Immediate Exchange
Transfusion is Usually Indicated if..
• The cord bilirubin level is > 4.5 mg/dl and
the cord hemoglobin level is under 11 gm/dl
• The bilirubin level is rising > 0.5-1mg/dl/hr
despite phototherapy
• The bilirubin level is 20mg/dl or it seems
that it will reach 20mg/dl at the rate it is
rising
• Progression of anemia though adequate
control of bilirubin by phototherapy

69. Types of Exchange Transfusion
in Rh Incompetability
• Double volume exchange transfusion
• Types of blood:
-Rh of mother(Rh-ve) & ABO of the baby
-Preferably O-ve blood

71. Procedure of Exchange
Transfusion

72. Post Exchange Investigations:
• S. bilirubin (total)
• S. electrolytes
• S. calcium
• RBS
• CBC

73. Complications Related to
Exchange Transfusion
• Hypothermia
• Cardiac – arrhythmia,
arrest, failure from
hypervolemia
• Electrolyte abnormalities-
Hyperkalemia,
hypocalcemia
• Metabolic
acidosis/alkalosis
• Hypo/hyperglycemia
• Vascular complications
• Coagulopathies
• NEC
• Oxygen toxicity
• Hazards of blood
transfusion
• Portal Hypertension
• Rarely hemolysis-
Hemoglobinemia,
hemoglobinuria.

74. Intravenous Immune Globulin
• Adjunct therapy for hyper billirubinemia
caused by isoimmune hemolytic disease
• Indication :
S. Billirubin approaching exchange level
despite maximal interventions
• Dose : 0.5 – 1.0 gm/kg/dose
• Mode of action : reduces hemolysis

75. Metalloporphyrins
• Adjunct therapy
• Mode of action :
Haem is converted to biliverdin by haem
oxidase,metaloporphyrin inhibits this
conversion
• Use : Rh & ABO incompatibility,G6PD
deficiency
• Complication : Transient erythema in
patient receiving phototherapy
J Perinatol. 2012 Nov;32(11):899-900. doi: 10.1038/jp.2012.45

77. Albumin
• Albumin infusion increased plasma bilirubin-binding
capacity, mobilizing bilirubin from tissues to plasma
and transport to liver
• Albumin infusion is reported to induce a rapid
decline in unconjugated bilirubin
• Albumin infusion may be advantageous, because
an increased reserve of albumin may be protective
against bilirubin toxicity by providing more binding
sites, thereby reducing the levels of unbound
bilirubin
Arch Fr Pediatr .1993 May;50(5):399-402, Sci Rep. 2015; 5: 16203,
MD thesis by Dr Sakhawat

78. Thank You All