role of ivig in the management of neonatal isoimmune hemolytic jaundice
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‘ROLE OF IVIG IN THE MANAGEMENT OF NEONATAL ISOIMMUNE HEMOLYTIC JAUNDICE’
MEETA SACHDEV G.MALINI, P.N.AGRAWAL, S.M.DEWANGAN
DEPTT. OF PEDIATRICS JLN HOSPITAL & RESEARCH CENTRE BHILAI
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INTRODUCTION
Neonatal jaundice: Common in 1st wk of life
60% of term & 80% of preterm infants.
Clinical jaundice: Bilirubin >7 mg/dl.
Mostly physiologic
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NONPHYSIOLOGIC JAUNDICE IN WELL INFANT
Hemolytic disease of newborn (ABO/Rh)
Incidence of ABO incompatibility : 25%
significant jaundice : 2.5%
Incidence of Rh incompatibility : 4.8%
significant jaundice : 0.17 – 0.31%
Gupte et al. Natl Med J India 1994; 7: 65-66
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WHY WORRY
Clinically indistinguishable
Bilirubin rises to toxic
levels
Acute bilirubin
encephalopathy
Left with sequelae-
KERNICTERUS
Athetosis, sensorineural
deafness, intellectual
deficits
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CONVENTIONAL MANAGEMENT
Intensive phototherapy (excretion by alternative pathways)
Maintain hydration & increase feeds
(decreases enterohepatic circulation)
Exchange transfusion (mechanical removal)
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EXCHANGE TRANSFUSION Prerequisites
Invasive procedure
Trained personnel
Well-equipped setup
Sepsis screen & blood
culture
Parentral fluids &
prophylactic antibiotics
Near- fatal
complications(5%) &
mortality (1%)
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COMPLICATIONS OF EXCHANGE TRANSFUSION
RISK OF EXPOSURE TO BLOOD COMPLICATIONS OF UVC Hypocalcaemia , hypomagnesaemia, hyperkalemia Hypoglycemia, acid-base disturbances Cardiovascular, apnea, seizures Bleeding, hemolysis Infection Misc- hypo/hyperthermia, NEC. Etc.
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Slide 8
IVIG IN HDN -AAP GUIDELINES
Indication: Hemolytic disease of newborn with
significant
hyperbilirubinemia
Dose: 0.5-1gm/kg
Mode of administration: Infusion given over 2-4
hrs.
Monitoring: For adverse reactions
(Pediatrics 2004;114:297-316)
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YY
Y
YYY
YY Y
Y
Y
Y Y
Y
Y
Y
Y
Y Y
YYY Y Y
Y
Y
Y Y
Y
Fetal RBC
Maternal Antibodies
Y
RE cell
Lysis of RBC
IVIG
BlockadeMECHANISM OF IVIG
ImmunoglobulinFc
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WHY THIS STUDY
After publication of AAP guidelines,
IVIG is being used more frequently in HDN.
Is IVIG useful only to bring down the bilirubin
level ?
Are there any more advantages?
What is our experience?
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AIMS & OBJECTIVES
To evaluate the efficacy of IVIG in HDN
To compare the stay, cost of treatment
& complications between IVIG & Exchange group
Which is safer?
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Slide 12
MATERIAL & METHODS
TYPE OF STUDY : OBSERVATIONAL
TIME FRAME : JAN 2010 – DEC 2011
NO. OF SUBJECTS : 16(16) INCLUSION CRITERIA : Healthy neonates (>35wks),
HDN & significant
hyperbilirubinemia EXCLUSION CRITERIA : Sick neonates & gestation
<35 wks.
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MATERIAL & METHODS
Blood grouping of infants whose mother’s blood
group is O/Rh negative
Close monitoring for clinical jaundice
Measurement of serum bilirubin levels
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MATERIAL & METHODS
INTENSIVE PHOTOTHERAPY & Maintain hydration
INTRAVENOUS IMMUNOGLOBULIN INFUSION : Rising bilirubin level despite intensive phototherapy OR bilirubin levels were within 2-3 mg % of exchange
levels
EXCHANGE TRANSFUSION : Bilrubin level >5mg% of exchange threshold
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AAP GUIDELINES FOR PHOTOTHERAPY(Pediatrics 2004;114:297-316)
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AAP GUIDELINES FOR EXCHANGE TRANSFUSION
(Pediatrics 2004;114:297-316)
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OBSERVATIONS
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SEX DISTRIBUTION
Female : male = 1.28: 1
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GESTATION
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WEIGHT
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INCOMPATIBILITY
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BIRTH ORDER
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Slide 23
H/O JAUNDICE IN SIBLING
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SERUM BILIRUBIN LEVELS
Peak bilirubinMean value
(Age in days)
After 24 hrs
After 48 hrs
After 72 hrs
IVIG19.53
(2.5 Days)
16.31 13.16 9.95
p < 0.005Significant
p< 0.001Highly
significant
p < 0.001Highly
significant
Exchange transfusion
25.09 (3.75 Days)
18.82 13.23 9.68
p < 0.001Highly
significant
p < 0.001Highly
significant
p < 0.001Highly
significant
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CULTURE-POSITIVE SEPSIS
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PARENTRAL FLUIDS & ANTIBIOTICS
ANCILLARY TREATMENT IVIG EXCHANGE
TRANSFUSION
IV FLUIDS 3 (19%) 16 (100%)
ANTIBIOTICS
First line 3 (19%) 0
Broad spectrum 2 (13%) 9 (56%)
Extended spectrum 0 7 (44%)
DURATION OF ANTIBIOTICS
2-5 D 5 (31%) 4 (25%)
6-10 D 0 4 (25%)
11-14 D 0 8 (50%)
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MEAN VALUES IVIG group Blood exchange group
p value(Unpaired T
test) Significance
DURATION OF PHOTOTHERAPY 5.5 Days 4.5 Days p > 0.05
Not significant
HOSPITAL STAY 7.2 Days 9.6 Days p < 0.05Significant
COST ( Rs) 13,500 22,200 p < 0.005Highly significant
DURATION & COST OF T/T
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Slide 28
ADVERSE EFFECTS IN EXCHANGE TRANSFUSION
Hypoc
alce
mia
Throm
bocy
tope
nia
Prove
n se
psis
Seizu
res
Anem
ia
Hyper
sens
itivity
0%
20%
40%
60%
80%
100%
44%
25%19% 19%
13%
0%
%
of
pa
tien
ts
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CONCLUSION
Predicting the risk of severe jaundice, close
monitoring & follow-up is crucial in ABO & Rh
incompatibility
Early intervention with intensive phototherapy &
IVIG is helpful in averting exchange transfusion, its
associated risks & complications significantly
Duration of stay & cost of treatment is significantly
reduced
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Slide 30
REFERENCES Alcock GS, Liley H. Immunoglobulin infusion for isoimmune
hemolytic jaundice in neonates (review). Cochrane Database Syst Rev 2001;(4)
Vinayaka G et al. role of intravenous immunoglobulin in the management of hemolytic disease of newborn. Pediatrics Today Vol XII No. 6,2009
Alpay F et al. High dose intravenous immunoglobulin therapy in neonatal immune hemolytic jaundice. Acta Pediatr 1999;88:216-119
Patra K. Adverse effects associated with neonatal exchange transfusion in the 1990s. J Pediatr 2004;144:626-31
Mukhopadhyay K et al.Intravenous immunoglobuin in rhesus hemolytic disease. Indian J Pediatr 2003;70:697-9
Miqdad AM et al. IVIG therapy for significant hyperbilirubinemia in ABO hemolytic disease of newborn. J Matern Fetal Neonatal Med 2004;16:163-6
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Slide 31
HOUR-SPECIFIC BILIRUBIN NOMOGRAM(Bhutani VK, et al.Pediatrics 1999;103:6-14)
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TIMING OF FOLLOW-UP (Pediatrics 2004;114:297-316)
Infant discharged
Before age 24 h
Between 24 & 48 h
Between 48 & 72 h
follow-up by
72 h
96 h
120 h
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Slide 33
THANK YOU