1025 Intravenous Immune Globulin (IVIG): neonatal indications

IVIG has FDA approval for use in adults and children for primary immunodeficiency, paediatric HIV infection, idiopathic thrombocytopaenic purpura (ITP), Kawasaki disease, chronic lymphatic leukaemia and bone marrow transplantation. Off-label use is not uncommon for the management of a number of neonatal conditions, and it is appropriate to review literature and current opinion on such use since there are potential adverse effects such as thromboembolic complications due to hyperviscosity, renal failure, neutropaenia, aseptic meningitis, skin reactions, haemolytic anaemia, and arthritis. IVIG is prepared from pooled plasma from a minimum of 1000 healthy donors, but often many more are used (up to 100 000), giving the product broad immune specificity. Adverse effects are inter alia related to manufacturing techniques, and whereas previously contaminants and IgG aggregates (which formed high molecular weight complexes) were a problem, modern techniques have eliminated the risk and the consequent inadequate activation of complement and possibility of anaphylaxis. In the full term neonate, as a result of active placental transport, the IgG concentration in the last month of gestation approaches 1g/dL and in fact may exceed maternal concentrations at term. These concentrations contribute to the pathophysiology of immune-mediated conditions such as haemolytic disease of the newborn and neonatal alloimmune thrombocytopaenia. IgG levels in the preterm neonate are far lower, usually ≤500mg/dL. The osmolarity of IVIG may exceed 1000mOsm/L, and the optimal pH for stability is 4.0-4.5. The former characteristic may introduce risk of thromboembolic events, while addition of stabilizers to adjust to physiologic pH may be associated with adverse events. Off-label uses in neonatology include administration for Rh and ABO haemolytic disease, alloimmune thrombocytopaenia and alloimmune neutropaenia, neonatal sepsis, parvovirus B19 infection, neonatal haemochromatosis and neonatal Kawasaki disease. Most research has been done in neonates with haemolytic disease, and results have shown a reduced need for exchange transfusion; however there have been several reports of necrotizing enterocolitis following IVIG administration, possibly related to microthrombi in mesenteric vessels. Evidence for use in the other conditions is sparse, and with the exception of neonatal haemochromatosis, IVIG does not appear to substantially alter outcomes.

Read more:
NeoReviews 2010; 11: e370-378
Autoimm Rev 2007; 6: 257-9
Pediatrics 2010; 125: 139-44