Wisconsin Newborn Screening Laboratory Newsletter:

Increase in False Positive 17-OHP newborn screening results

Newborn Screening Newsletter               No. 60

March 2006         

Increase in false positive 17-OHP newborn screening results

In testing for congenital adrenal hyperplasia, 17- a -hydroxyprogesterone (17-OHP) is the major analyte. A recent increase in false positive results has been reported by the newborn screening program. Although the increase affects all 4 birth weight categories, it is most problematic in low birth weight babies.

The measurement of 17-OHP depends upon a rabbit-derived antibody. Although this antibody has a high sensitivity to 17-OHP, it has sub-optimal specificity for other adrenal gland steroids --- giving rise to a higher number of false positive 17-OHP results. In the past we have minimized false positives by establishing birth weight related 17-OHP cutoffs. Recently the reagent manufacturer began using a new lot of antibody (the previous supply had been exhausted), which is apparently more reactive to the interfering steroids and is the cause for the increase in the false positives.

Response: Although our preliminary evaluation of the "new" antibody indicated a possible increase in false positives, the endocrine advisory committee approved using the previously established cutoffs until enough data had been collected to assure that no salt-losing forms of CAH would be missed if we made adjustments to the 17-OHP cutoffs. A review of the recent data has led us to the following changes: (1) combine the two lowest weight categories (< 1300 g and 1300-1700 g); (2) increase the 17-OHP cutoffs for "Definite" and "Possible" abnormal reports for the other two weight categories. The "follow-up" guidelines, which are included with the abnormal reports, have been updated to reflect these changes and are enclosed with this letter for your review. The new 17-OHP cutoffs and the revised follow-up guidelines will be implemented on March 6, 2006.

Assessment: We are confident these changes will reduce the number of false positives reported without increasing the risk of missing a baby with a true salt-losing form of CAH. Keep in mind that CAH screening in Wisconsin is designed to detect severe salt-losing forms of CAH and that variants such a simple virilizing CAH and non-classical CAH may not be detected through screening. You, as the treating physician, should remain cognizant of the possible presence of the other CAH variants as indicated by clinical signs and symptoms. Likewise, even though the presence of false positives is an additional burden to you, an elevated 17-OHP result still serves as an important reminder to consider the possibility of salt-losing CAH in your patient.

Comment: The issue of non-specific antibody screening tests is not unique to Wisconsin . Unfortunately, there is essentially one supply of antibody for the newborn screening market. In addition to seeking a better source of antibody, we and our laboratory colleagues across the country are working on alternative methods.

We thank those of you who have expressed concern about the increase in false positives and to everyone for your patience while we work to resolve this issue. Since this letter is being sent primarily to hospital staff (nurses, laboratory staff, etc), we request that you share it with your medical staff colleagues.

Sincerely