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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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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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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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