medwireNews: Using increased 17-hydroxyprogesterone (17-OHP) cutoffs that are specific to both birthweight and age at sample collection reduces the number of false-positive congenital adrenal hyperplasia (CAH) cases identified by newborn screening, research shows.
Tânia Bachega (Faculdade de Medicina da Universidade de São Paulo, Brazil) and co-researchers studied samples collected from 271,810 newborns in São Paulo state, with 214,092 of these samples being collected within 72 hours of birth.
They found that median 17-OHP levels fell with increasing birthweight, and were significantly lower for all birthweight categories except the highest (>2500 g) in samples collected less than 72 hours after birth compared with samples collected later, “highlighting the need to create specific [neonatal 17-OHP] cut-offs for each age at sample collection.”
Among babies in the lowest birthweight category (≤1500 g), median 17-OHP levels were 38.7 nmol/L for samples collected at less than 72 hours versus 40.2 nmol/L for those collected later. The same pattern was seen for babies in the 1501–2000 g and 2001–2500 g birthweight categories, but it was reversed for those in the highest birthweight category, with corresponding values of 15.6 versus 11.7 nmol/L.
For all birthweight categories and for both collection times, using the 99.8th percentile, rather than the 99.5th, achieved a lower rate of false-positive results. Overall, the false-positive rates were 0.53% and 0.21% using the 99.5th and 99.8th percentiles, respectively, for samples collected within 72 hours, and a corresponding 0.50% and 0.20% for samples collected later.
“To prevent late diagnosis and the development of salt wasting crises, we recommend that the sample collection should be performed between 48 h–72 h”, the researchers note in Clinical Endocrinology.
They stress that the higher cutoff identified all patients with salt-wasting CAH. There were no cases of CAH following negative screening reported in the study region and period, and the higher cutoff successfully identified a patient with salt-wasting CAH who had received antenatal glucocorticoid therapy.
The 99.8th percentile cutoff also identified all five patients with the simple virilising form of CAH. The team notes, however, that patients with either form could have been missed because they died before diagnosis, moved out of the study area or remain undiagnosed.
Among the 591 false-positive cases remaining when using the 99.8th percentile cutoff were eight with “extremely increased” 17-OHP levels. Four of these were due to sample collection error and three of the remaining four cases were in the intensive care unit at the time of collection due to sepsis.
Other false-positive cases included patients whose 17-OHP levels normalised at follow-up, and those in whom genetic analysis confirmed non-classic forms of CAH.
By Eleanor McDermid
Clin Endocrinol 2016; Advance online publication
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