Efficacy of Intravenous Immunoglobulin in Management of Rh and ABO Incompatibility Disease

Study Overview
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Brief Summary
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hemolytic disease of newborn is an important cause of hyperbilirubinemia with significant morbidity and mortality in neonatal period. intravenous immunoglobulin has widely used in management of hemolytic disease of new born

Detailed Description
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Hemolytic disease of the newborn (HDN) due to red cell alloimmunisation is an important cause of hyperbilirubinemia with significant morbidity in the neonatal period . Hemolytic disease of the newborn has unfortunately continued to contribute to perinatal and neonatal morbidity and mortality in developing countries . The degree to which the fetus is affected correlated with the amount of maternal antibody that cross the placenta . Hemolysis from ABO incompatibility is one of the most common cause of isoimmune hemolytic disease during neonatal period. Infants with blood group type A or B , carried by blood group type O mother, will have a positive antibody because of maternal anti-A or anti-B transfer in to the fetal circulation. Ten percent of these infants will present with hemolytic disease . Most of the infant presents with unconjugated hyperbilirubinemia in the first 24 h of life and it is rarely a cause in patients who are discharged from nursery and readmit with severe hyperbilirubinemia. Rh incompatibility can occur when an Rh-negative pregnant mother is exposed to Rh-positive fetal red blood cells secondary to fetomaternal hemorrhage during the course of pregnancy from spontaneous or induced abortion , trauma, invasive obstetric procedures, or normal delivery. As a consequence, blood from the fetal circulation, and, after a significant exposure, sensitization occurs leading to maternal antibody production against the foreign Rh antigen. Once produced, maternal Rh immunoglobulin G (IgG) antibodies may cross freely from the placenta to the fetal circulation, where they form antigen-antibody complexes with Rh- positive fetal erythrocytes and eventually are destroyed, resulting in a fetal alloimmune-induced hemolytic anemia and Jaundice. Traditional neonatal treatment of HDN consists of intensive phototherapy and exchange transfusion (ET). However, ET is a high-risk invasive procedure associated with a significant rate of adverse effects .Although the mortality rate associated with ET is currently reported to be less than 0.3% in term infants , the morbidity rates can reach 74% and includes catheter-related complications, sepsis, thrombocytopenia and hypocalcemia Intravenous Immunoglobulin G (IVIG) therapy has been widely used for a variety of indications in newborn period such as alloimmune neonatal thrombocytopenia and an adjunctive treatment of neonatal infections. American Academy of Pediatrics, recommends high dose IVIG (0.5_1 g/kg) as an additional treatment of Rh and ABO hemolytic disease and its use however there is no consensus on its routine use in ABO hemolytic disease yet . IVIG contains a spectrum of antibodies capable of interacting with and altering the activity of cells of the immune system as well as antibodies capable of reacting with cells such as erythrocytes. When hemolytic disease occurs, maternal antibodies present in the infant's blood attach to the antigen receptors on the infant's red blood cells. Specifically, the maternal antibody attaches its Fc region, the lower portion of the antigen, to specific immune system cells , such as machrophages, stimulating the destruction of the antigen-antibody complex and the red blood cell. It has been proposed that IVIG blocks the Fc receptor and therefore blocks the binding of the antibody to the antigen. With this blockade, hemolysis no longer occurs. Neonatal treatment with intravenous immunoglobulin (IVIG) has been suggested as an altenative therapy to ET for isoimmune hemolytic jaundice to reduce the need for exchange transfusion and duration of phototherapy and hospitalization in isoimmune hemolytic disease of the newborn.

Official Title
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Efficacy of Intravenous Immunoglobulin in Management of RH and ABO Incompatibility Disease of Newborn and Its Effect in Decrease Duration of Hospital Stay and Need for Exchange Transfusion

Conditions
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Haemolysis Neonatal

Intervention / Treatment
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* Drug: intravenous immunoglobulin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1)Gestational age more than or equal 37 weeks and postnatal age from 48hr-72hr. 2)Anemia with Reticulocytic count 10% 3)Serum total bilirubin around 18mg/dl . Exclusion Criteria: 1)perinatal asphyxia. 2)Congenital malformation. 3)Severe respiratory distress. 4)Sepsis during hospital stay. 5)Metabolic problems . 6)Gestational age less than 37 weeks

Ages Eligible for Study
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Minimum Age: 48 Hours
Maximum Age: 30 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: intervention group will recieve intravenous immunoglobulin and phototherapy and control group that will receive phototherapy only
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Intervention group<br>Use of single dose of intravenous immunoglobulin in a dose 0.5_1gm /kg to intervention group | Drug: intravenous immunoglobulin<br>* giving intravenous immunoglobulin to neonates included in inclusion criteria in a dose of 0.5-1 gm<br>* Other names: gammaglobulin;|
| Other: Control group<br>Control group will recieve phototherapy only | Drug: intravenous immunoglobulin<br>* giving intravenous immunoglobulin to neonates included in inclusion criteria in a dose of 0.5-1 gm<br>* Other names: gammaglobulin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To measure duration of phototherapy | to measure how many neonate need for exchange transfusion after one dose of intravenous immunoglobulin and reduction of haemolysis rate which is estimated by reduction in reticulocytic count | Two days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| duration of hospital stay | neonates with intravenous immunoglobulin is expected to stay less in hospital and decrease duration of phototherapy | Four days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hemolysis,newborn