Neonatal Immune Neutropenia (NIN)
Clinical findings. NIN can occur in the first pregnancy which might be the result of a transplacental passage of the mobile neutrophils into the maternal circulation. Allo- and isoimmunization to neutrophil antigens occur in about 0.4 %, but the incidence of NIN is below 0.1%. In utero the fetus is protected against bacterial infections. After birth, NIN has a diverse clinical presentation, ranging from no infections to reported fatalities of up to 5% associated with overwhelming septicaemia. However, infections of the navel (omphalitis) and the skin predominate. Typically, affected neonates present absolute neutrophil counts of less than 500 per µl, and neutropenia resolves within 11 weeks, but can persist as long as 28 weeks. In a few cases, immaturity of the phagocytic system and/or depletion of the storage pool during birth can result in overt neutropenia not until the second day of life. Bone marrow examination reveals a normal or hypercellular marrow with a more or less pronounced shift to the left. Occasionally the marrow is hypocellular and/or mature and band forms are absent giving the marrow the appearance of a maturational arrest, although this not the case.
Therapy. Since NIN is a self-limited disorder, symptomatic and prophylactic treatment with antibiotics is usually sufficient. In severe cases, the granulocyte colony-stimulating factor (G-CSF) has been successfully used to increase the neutrophil counts although resistance to G-CSF has occurred due to anti-HNA-2 isoantibodies (2). On the one hand G-CSF resistance can be the result of reduced neutrophil production in the bone marrow as HNA-2 expression begins very early in myelopoiesis, on the other hand, G-CSF causes increased HNA-2 expression on the neutrophil surface promoting antibody binding and phagocytosis by macrophages. In these cases high doses of intravenous immunoglobulin (IVIG) might be an alternative although ineffective IVIG treatment of NIN has been repeatedly reported.
2.Maheshwari A, Christensen RD, Calhoun D. Resistance to recombinant human granulocyte colony-stimulating factor in neonatal alloimmune neutropenia associated with anti-human neutrophil antigen-2 (NB1) antibodies. Pediatrics 2002;109:e64