LECTURE OF

1. Guidelines for IVIG in the
treatment of neonatal jaundice
By
Dr . Magdy Shafik Ramadan
Senior Pediatric and Neonatology consultant
M.S, Diploma, Ph.D of Pediatrics

2. What Is
IVIG
• Intravenous Immunoglobulin (IVIG) is a
solution of highly purified immunoglobulin
G, derived from large pools of human plasma
that contain antibodies against a broad
spectrum of bacterial and viral agents

3. • 4 Things About
IVIG
1
• It can be given Intravenously (IV
through the vein or subcutaneously
(under the skin).
• MOST IMPORTANTLY IVIG CAN BE
GIVEN SAFELY IN THE
CONVENIENCE OF YOUR HOME.

4. 2
• Some home Infusion companies will
send a nurse to your home

5. 3
• Some companies will even help you
and your doctor complete all necessary
documents.

6. 4
• Insurance companies can be
challenging to deal with in the IVIG
treatment approval process.

7. IVIG is used to treat primary and secondary
immune deficiencies, autoimmune,
infections and neuroimmunological
disorders.
• Patients with primary immune
deficiencies usually receive treatment
therapy for life.

8. IVIG Therapy has been used extensively in
the treatment and prevention of a variety of
infectious and inflammatory diseases.
• Patients with compromised Immune systems
who have these conditions often benefit from
the passive immunity provided by IVIG
therapy.

9. IVIG is used in patients with primary
immunodeficiency's and certain conditions
associated with B-cell Chronic Lymphocytic
Leukemia, Pediatric HIV, and Bone Marrow
Transplant.
• IVIG is also utilized to raise platelet counts in
patients with Idiopathic Thrombocytopenic
Purpura and to treat the symptoms related to
other clinical conditions such as Kawasaki
Syndrome.

10. Various Other Diseases and Immune Disorders
where IGIV Is Used:
• Chronic Sinusitis
• Chronic Inflammatory
• Demyelinating Polyneuropathy
• Multiple Sclerosis (MS)
• Myasthenia Gravis (MG
• Systenic Lupus Erythematosus (SLE)
• Guillain-Barre Syndrome (GBS)
• Autoimmune Diabetic Neuropathy
• Polymyositis
• Multifocal Motor Neuropathy (MMN)
• Dermatomyositis
• Rheumatoid Arthritis (RA)

11. • Common Variable Immunodeficiency (CVID)
• Hypogammaglobulinemia
• Severe Combined Immunodeficiency (SCID)
• Wiskott-Aldrich Syndrome (WAS)
• X-Linked Agammaglobulinemia (XLA)

12. Uses of IVIG (cont.)
Immunomodulatory effect
(High dose therapy)
Replacement therapy
(Low dose therapy)
Off-labelLicensed
•Autoimmune neutropenia
•Autoimmune hemolysis
•Anti Factor VIII inhibitor
•Multiple sclerosis
•Myasthenia gravis
•Stiff person syndrome
•ANCA associated
vasculitis
•Polymyositis/Dermatomyo
sitis
•RA
•SLE – APS
•GVHD
•Sepsis syndrome
•TEN
•Graves opthalmopathy
•Immune
thrombocytopenic
purpura
•GBS
•CIDP
•Kawasaki disease
•Multifocal motor
neuropathy
•Primary mmunodeficiency
•HIV infection
•BMT
•B-cell lymphocytic
leukemia
•Multiple myeloma

13. Preparation of IVIG

14. Forms available
• Dosage Forms & Strengths
• injectable solution
• 10% (100mg/mL)
• 5% (50mg/mL)

15. • Contraindications
Hypersensitivity to gamma globulin
Isolated IgA deficiency
Hyperprolinemia (with some products)
Serum sickness like reaction.
Hemolytic anemia can develop
subsequent to IGIV therapy due to
enhanced RBC sequestration

16. IVIG Administration
• Clinical trials of IVIG administration to treat hemolytic
anemia have been promising.
• The immune process involves the formation of an
antibody-antigen complex between the maternal
antibody and the antigen of the fetal or neonatal RBC.
• The lower portion of the maternal antibody is termed the
Fc regionThe lower portion of the maternal antibody is
termed the Fc region
• This portion of the antibody attaches to the Fc receptors
on specific immune system cells, such as macrophages,
stimulating the ingestion and destruction of the antigen-
antibody complex and the RBC.

17. • administration of IVIG blocks the Fc
receptors of the immune cells.17 This
subsequently stops the destruction of
RBCs and the progression of hemolytic
anemia.

18. • Infusion Rates:
• 0.5 ml/kg/hour for the first fifteen (15) minutes
If no problems occur, increase infusion to
• 1 ml/kg/hour for the next fifteen (15) minutes
If no problems occur, increase infusion to
• 2 ml/kg/hour for the next fifteen (15) minutes
If no problems occur, increase infusion to
• 4 ml/kg/hour for the remainder of the infusion
• The maximum rate of infusion for IVIG is 4
ml/kg/hour.
• Stop the infusion or decrease the infusion rate if side
effects occur.
• Potential side effects are:
Hypotension -Tachycardia-Flushing

19. • ABO Incompatibility
• ABO incompatibilities can occur in the following
situations:
• (1) the mother’s blood type is O, and the
neonate’s blood type is A or B;
• (2) the mother’s blood type is B, and the
neonate’s blood type is A or AB;
• (3) the mother’s blood type is A, and the
neonate’s blood type is B or AB

20. • Indication of use in isoimmune heamoltic anemia :
• Rh and ABO incompatibility.
• Not indicated unless Direct Antibody Test (DAT)
is positive.
• Other isoimmune haemolytic disease (no
systematic reviews available).
• Difficulties in obtaining appropriate blood for
ET or parental refusal for ET.
• Do not give if exchange transfusion imminent.

21. Strength of recommendation
RecommendationGrade
ESCMID strongly suport
recommondation for use
A
ESCMID moderately suport
recommendation for use
B
ESCMID marginally suport
recommendation for use
C
ESCMID suport recommendation (weak )
against use
D

22. Guidelines for treatment of neonatal jaundice
• 1- All pregnant women should be tested for ABO and
Rh (D) blood types and have a serum screen for
unusual isoimmune antibodies (evidence quality B:
benefits exceed harms)
• 2- If a mother has not had prenatal blood grouping
or is Rh-negative, a direct antibody test (or Coombs’
test), blood type, and an Rh (D) type on the infant’s
(cord) blood are strongly recommended (evidence
quality B:

23. • 3-Sick infants and those who are jaundiced at or
beyond 3 weeks should have a measurement of
total and direct or conjugated bilirubin to identify
cholestasis (evidence quality D:.
The results of the newborn thyroid and
galactosemia screen should also be checked in these
infants (evidence quality D
• 4- Measurement of the glucose-6-phosphate
dehydrogenase (G6PD) level is recommended for a
jaundiced infant who is receiving phototherapy
and whose family history or ethnic or geographic
origin suggest the likelihood of G6PD deficiency or
for an infant in whom the response to
phototherapy is poor (evidence quality C

24. • G6PD deficiency is widespread and frequently
unrecognized, and although it is more common in
the populations around the Mediterranean and in
the Middle East.
• G6PD deficiency occurs in 11% to 13% of African
Americans.
• In a recent report, G6PD deficiency was
considered to be the cause of hyperbilirubinemia
in 19 of 61 (31.5%) infants who developed
kernicterus

25. • 5-All hospitals should provide written and verbal
information for parents at the time of discharge,
which should include an explanation of jaundice,
the need to monitor infants for jaundice, and
advice on how monitoring should be done
(evidence quality D

26. 6-Infants with a positive DAT(Direct Antbody
Reaction) who have predicted severe disease based
on antenatal investigation or an elevated risk of
progressing to exchange transfusion based on the
postnatal progression of TSB concentration should
receive IVIG at a dose of 1 g/kg (recommendation
grade A).
7.1.4: In isoimmune hemolytic disease, administration
of intravenous γ-globulin (0.5-1 g/kg over 2 hours) is
recommended if the TSB is rising despite intensive
phototherapy or the TSB level is within 2 to 3 mg/dL
(34-51 μmol/L) of the exchange level If necessary,
this dose can be repeated in 12 hours (evidence
quality B: benefits exceed harms

27. • Intravenous γ-globulin has been shown to reduce
the need for exchange transfusions in Rh and ABO
hemolytic disease.
• Although data are limited, it is reasonable to
assume that intravenous γ-globulin will also be
helpful in the other types of Rh hemolytic disease
such as anti-C and anti-E.

28. • 8-It is an option to measure the serum albumin
level and consider an albumin level of less than 3.0
g/dL as one risk factor for lowering the threshold
for phototherapy use (evidence quality D.

29. Guidelines for exchange transfusion in infants 35 or more
weeks’
Subcommittee on Hyperbilirubinemia Pediatrics
2004;114:297-316
©2004 by American Academy of Pediatrics

30. • High bilirubin/albumin (B/A) ratios increase the
risk of bilirubin neurotoxicity.
• The B/A ratio may be a valuable measure, in
addition to the total serum bilirubin (TSB), in the
management of hyperbilirubinemia
• In preterm infants of 32 weeks' gestation or less
with hyperbilirubinemia we found no significant
effect of the additional use of B/A ratio compared
to TSB-based treatment on the composite motor
score at 18 to 24 months' corrected age.

31. • Bilirubin/albumin ratio (B/A) may provide a
better estimate of free bilirubin than total serum
bilirubin (TSB).
• Both TSB and B/A are strong predictors of
neurotoxicity, but B/A does not improve prediction
over TSB alone.
• Bilirubin/albumin ratio —
The bilirubin/albumin (B/A) ratio can be used as
an additional factor in determining the need for
exchange transfusion; it should not be used alone
but in conjunction with TB values

32. • Guidelines 9:
If an exchange transfusion is being considered, the
serum albumin level should be measured and the
bilirubin/albumin (B/A) ratio used in conjunction
with the TSB level and other factors in determining
the need for exchange transfusion (evidence quality
D.
10-Immediate exchange transfusion is
recommended in any infant who is jaundiced and
manifests the signs of the intermediate to advanced
stages of acute bilirubin encephalopathy
(hypertonia, arching, retrocollis, opisthotonos, fever,
high-pitched cry) even if the TSB is falling (evidence
quality D

33. • For infants ≥38 weeks gestation, consider
exchange transfusion when
TB (mg/dL)/albumin (g/dL)ratio is >8.0
• For infants 35 to 37 6/7 weeks and well or ≥38
weeks with high risk (eg, isoimmune hemolytic
disease or G6PD deficiency), consider exchange
transfusion when
TB (mg/dL)/albumin (g/dL) ratio is >7.2
• For infants 35 to 37 6/7 weeks with high risk (eg,
isoimmune hemolytic disease or G6PD deficiency),
consider exchange transfusion when
TB (mg/dL)/albumin (g/dL) ratio is >6.8

34. Additional Albumin
• this is the rationale for the recommendation to
administer 25% albumin either 1 hour before an
exchange ( 1 gr / kg )
• No evidence shows that this practice is of practical
value in neonates with normal albumin levels.
• Side effects of this practice( congestive heart
failure)

35. • Intravenous immunoglobulin in isoimmune
haemolytic disease of newborn: an updated systematic review
and meta-analysis.Review articleLouis D, et al. Arch Dis Child Fetal
Neonatal Ed. 2014.Show full citation
• Abstract
• BACKGROUND: Intravenous immunoglobulin (IVIg) is used in neonates
with isoimmune haemolytic disease to prevent exchange transfusion (ET).
However, studies supporting IVIg had methodological issues.
• OBJECTIVE: To update the systematic review of efficacy and safety of IVIg
in neonates with isoimmune haemolytic disease.
• METHODS: MEDLINE, Embase databases and Cochrane Central
Register of Controlled Trials (Cochrane Library) were searched (from
inception to May 2013) for randomised or quasi-randomised controlled
trials comparing IVIg with placebo/controls in neonates with isoimmune
haemolytic disease without any language restriction. Three investigators
assessed methodological quality of included trials. Meta-analyses were
performed using random effect model and risk ratio (RR)/risk difference
(RD) and mean difference with 95% CI

36. • calculated.
• MAIN RESULTS: Twelve studies were included, ten trials
(n=463) of Rh isoimmunisation and five trials (n=350) of
ABO isoimmunisation (three studies had both population).
Significant variations in risk of bias precluded an overall
meta-analysis of Rh isoimmunisation. Studies with high risk
of bias showed that IVIg reduced the rate of ET in Rh
isoimmunisation (RR 0.23, 95% CI 0.13 to 0.40), whereas
studies with low risk of bias that also used prophylactic
phototherapy did not show statistically significant difference
(RR 0.82, 95% CI 0.53 to 1.26). For ABO isoimmunisation,
only studies with high risk of bias were available and meta-
analysis revealed efficacy of IVIg in reducing ET (RR 0.31,
95% CI 0.18 to 0.55).

37. • CONCLUSIONS: Efficacy of IVIg is not
conclusive in Rh haemolytic disease of
newborn with studies with low risk of bias
indicating no benefit and studies with high
risk of bias suggesting benefit. Role of IVIg
in ABO disease is not clear as studies that
showed a benefit had high risk of bias.

40. A new therapy in treatment of neonatal
jundice
• 1-A new therapy currently under
development consists of inhibition of
bilirubin production through blockage of
heme oxygenase.
mesoporphyrins and protoporphyrins
(Stannsoporfin).
2-Supplementation of probiotics appears to
show promise for newborns with pathologic
neonatal jaundice.

41. • 3-Zinc sulfate supplementation is a
controversial potential approach for
treating neonatal jaundice.

42. THANK YOU