Intravenous Immunoglobulin (IVIG) is a specialized treatment used for severe hyperbilirubinemia in newborns, commonly known as severe newborn jaundice. This condition involves an excessive buildup of the yellow pigment bilirubin in the bloodstream, often causing a yellowish discoloration of the skin and eyes. While most newborn jaundice is mild and self-resolving, high concentrations of bilirubin can be harmful. IVIG is reserved for infants when standard phototherapy is insufficient to control rapidly rising bilirubin levels, or when there is a high risk of complications due to a specific underlying cause.
Understanding Severe Newborn Jaundice
Bilirubin is a byproduct of the normal breakdown of red blood cells (RBCs) that the newborn’s liver must process and clear. Newborns naturally have higher bilirubin levels because their red blood cells have a shorter lifespan and their immature livers are less efficient at clearance. Severe hyperbilirubinemia is concerning because unconjugated bilirubin can cross the blood-brain barrier.
If levels become excessively high, bilirubin can deposit in brain tissue, potentially causing a neurological injury known as acute bilirubin encephalopathy. The most severe, chronic form of this brain damage is called kernicterus, which can lead to permanent neurological impairments, including cerebral palsy and hearing loss. IVIG treatment is often necessitated by severe hemolytic disease of the newborn (HDN), where the infant’s red blood cells are destroyed rapidly. HDN is typically caused by an incompatibility between the mother’s and the baby’s blood types, such as Rh or ABO incompatibility, where maternal antibodies cross the placenta and target the infant’s red blood cells.
The Substance: What is Intravenous Immunoglobulin (IVIG)?
Intravenous Immunoglobulin (IVIG) is a therapeutic blood product derived from the pooled plasma of thousands of healthy human donors. This pooling ensures the final product contains a broad spectrum of antibodies, primarily Immunoglobulin G (IgG). IgG makes up over 90% of the active components in the sterile solution.
The primary function of IVIG is to modulate or support the immune system in various disorders. In newborns, IVIG provides a concentrated supply of pre-formed antibodies delivered directly into the infant’s vein. The product is manufactured using processes like cold ethanol precipitation to enrich the IgG content and includes steps for virus inactivation to ensure safety.
Mechanism of Action Against Hemolytic Disease
IVIG targets the immune-mediated destruction of red blood cells that occurs in HDN. The core problem is that maternal IgG antibodies attach to the infant’s red blood cells, tagging them for destruction. These antibody-coated cells are then rapidly cleared and destroyed in the spleen and liver by the newborn’s immune cells, specifically macrophages.
The mechanism involves the saturation and blockade of Fc receptors on these immune-clearing cells. Fc receptors are the binding sites on macrophages that recognize and attach to the maternal IgG antibodies coating the red blood cells. By flooding the newborn’s system with a large dose of donor-derived IgG, IVIG effectively occupies these Fc receptors. This competitive binding blocks the macrophages from destroying the infant’s antibody-coated red blood cells, slowing the rate of hemolysis and reducing bilirubin production.
Treatment Administration and Safety
IVIG is administered when total serum bilirubin (TSB) levels are rising despite intensive phototherapy, or when they approach the level requiring an exchange transfusion. The recommended dosage typically ranges from 0.5 to 1 gram per kilogram of the infant’s weight, given as a slow intravenous infusion. This infusion is generally delivered over about two hours, though the rate may be adjusted based on the infant’s tolerance.
Close monitoring of the infant’s vital signs, including heart rate and blood pressure, is necessary throughout the infusion to detect adverse reactions. A second dose may be given 12 hours later if bilirubin levels remain high or continue to rise rapidly. Potential side effects include mild, transient reactions such as fever, chills, or headache. More serious, though rare, risks include allergic reactions, fluid overload, or hypotension. The primary goal of using IVIG is to reduce the need for an exchange transfusion, an invasive procedure used to quickly lower bilirubin levels.