Neonatal screening for congenital adrenal hyperplasia: 17-hydroxyprogesterone levels and CYP21 genotypes in preterm infants

Objective. Neonatal screening for congenital adrenal hyperplasia (CAH) amon g preterm infants is complicated by the fact that healthy preterm infants h ave higher levels of 17-hydroxyprogesterone (17-OHP) than term infants, res ulting in a higher false-positive rate. Even when gestational age-related c utoff levels after ether extraction were used, the false-positive cases pri marily comprised preterm infants. The aim of the study was to optimize the procedure for neonatal screening for CAH in preterm infants. Methods. The 17-OHP levels in 6200 preterm infants were correlated to the g estational age. We also calculated the number of recalls for different puta tive cutoff levels of the 17-OHP by direct assay and after extraction in 12 75 preterm infants who represented the most elevated cases in a population of approximately 30 000 preterm infants. The CYP21 genotypes and screening levels were determined in the 12 preterm infants with CAH diagnosed since t he start of screening. The effect of possible interfering factors such as g estational age, neonatal stress, and prenatal glucocorticoid treatment for pulmonary maturation was studied. Results. The extraction procedure did not significantly improve the sensiti vity or specificity of the screening, whereas it delayed the day of recall from 8 to 13 days (median). We could not demonstrate any systematic influen ce of the studied stress factors or the prenatal glucocorticoid treatment o n the 17-OHP screening levels. In the patients with CAH, the 17-OHP levels correlated better with disease severity than with the degree of prematurity . Conclusions. On the basis of these results, we omitted the extraction step and changed the cutoff levels in the Swedish screening program for preterm infants. We chose to use a cutoff level of 400 nmol/L plasma in infants who were born before week 35 and 150 nmol/L for infants who were born in weeks 35 and 36. For detecting more patients, the cutoff level would have to be much lower, which would result in a number of false-positive tests that we consider to be unacceptably high. It is clear that neonatal screening canno t detect all infants with CAH. Some milder forms of the disease, just like in the past, will have to be diagnosed on the basis of clinical signs and s ymptoms.