If an initial test is positive, a second blood sample (called a “repeat specimen”) is collected. The repeat blood samples for all initial positive tests for phenylketonuria and initial borderline positive for primary congenital hypothyroidism (TSH values of 25-100) are sent to the State Genetic Disease Laboratory (GDL) for testing. Repeat specimens for galactosemia are sent to the State-contracted galactosemia confirmatory laboratory at Children’s Hospital Los Angeles, while those for sickle cell disease and related hemoglobinopathies are sent to the State-contracted hemoglobin confirmatory laboratory at Children’s Hospital Oakland.
Confirmatory testing is a critical step in the screening process. There are several variables that can cause a false positive initial screening result for PKU, galactosemia, and/or hypothyroidism. The percentage of false positive test results for PKU and congenital primary hypothyroidism is much higher in specimens collected before 24 hours of age than those collected later. This is due to natural biological variation, temporary surges in hormones, and delayed functioning of enzymes in the first 24 hours. Other factors that increase the false positive rate include: prematurity/low birth weight, hyperalimentation, mother’s medications during pregnancy, and exposure of the specimen to heat. California’s screening methodology for sickle cell disease is highly accurate, resulting in virtually no false positives; however, confirmatory testing is still necessary to determine the type of sickle cell disease. In addition, confirmatory testing for significant non-sickling hemoglobin patterns is necessary to rule out Beta thalassemia and other hemoglobinopathies.