Neonatal immunoglobulin levels. Maternal IgG can cross the placenta, but IgA or IgM cannot. Chronic infections involving the fetus, such as congenital syphilis, toxoplasmosis, rubella, and cytomegalic inclusion disease, induce IgM production by the fetus. Increased IgM levels in cord blood at birth or in neonatal blood during the first few days of life suggest chronic intrauterine infection. Infection near term or subsequent to birth results in an IgM increase beginning 6-7 days postpartum. Unfortunately, there are pitfalls when such data are interpreted. Many cord blood samples become contaminated with maternal blood, thus falsely raising IgM values. Normal values are controversial; 20 mg/dl is the most widely accepted upper limit. Various techniques have different reliabilities and sensitivities. Finally, some investigators state that fewer than 40% of rubella or cytomegalovirus infections during pregnancy produce elevated IgM levels before birth.

Agammaglobulinemia. This condition may lead to frequent infections. Electrophoresis displays decreased gamma-globulin levels, which can be confirmed by quantitative measurement of IgG, IgA, and IgM. There are several methods available to quantitatively measure IgG, IgA, and IgM such as radial immunodiffusion, immunonephelometry, and immunoassay. Immunoelectrophoresis provides only semiquantitative estimations of the immunoglobulins and should not be requested if quantitative values for IgG, IgA, or IgM are desired.

Nitroblue tetrazolium test. Chronic granulomatous disease of childhood is a rare hereditary disorder of the white blood cells (WBCs) that is manifested by repeated infections and that ends in death before puberty. Inheritance is sex-linked in 50% of cases and autosomal recessive in about 50%. Polymorphonuclear leukocytes are able to attack high-virulence organisms, such as streptococci and pneumococci, which do not produce the enzyme catalase, but are unable to destroy staphylococci and certain organisms of lower virulence such as the gram-negative rods, which are catalase producers. Normal blood granulocytes are able to phagocytize yellow nitroblue tetrazolium (NBT) dye particles and then precipitate and convert (reduce) this substance to a dark blue. The test is reported as the percentage of granulocytes containing blue dye particles. Monocytes also ingest NBT, but they are not counted when performing the test. Granulocytes from patients with chronic granulomatous disease are able to phagocytize but not convert the dye particles, so that the NBT result will be very low or zero, and the NBT test is used to screen for this disorder. In addition, because neutrophils increase their phagocytic activity during acute bacterial infection, the nitroblue tetrazolium test has been used to separate persons with bacterial infection from persons with leukocytosis of other etiologies. In general, acute bacterial infection increases the NBT count, whereas viral or tuberculous infections do not. It has also been advocated as a screening test for infection when the WBC count is normal and as a means to differentiate bacterial and viral infection in febrile patients. Except for chronic granulomatous disease there is a great divergence of opinion in the literature on the merits of the NBT test, apportioned about equally between those who find it useful and those who believe that it is not reliable because of unacceptable degrees of overlap among patients in various diagnostic categories. Many modifications of the original technique have been proposed that add to the confusion, including variations in anticoagulants, incubation temperature, smear thickness, method of calculating data, and use of phagocytosis “stimulants,” all of which may affect test results.

Some conditions other than bacterial infection that may elevate the NBT score (false positives) include normal infants aged less than 2 months, echovirus infection, malignant lymphomas (especially Hodgkin’s disease), hemophilia A, malaria, certain parasitic infestations, Candida albicans and Nocardia infections, and possibly the use of oral contraceptives. Certain conditions may (to varying degree) induce normal scores in the presence of bacterial infection (false negatives); these include antibiotic therapy, localized infection, systemic lupus erythematosus, sickle cell anemia, diabetes mellitus, agammaglobulinemia, and certain antiinflammatory medications (corticosteroids, phenylbutazone).