Neonatal screening for congenital adrenal hyperplasia in Southern Brazil: a population based study with 108,409 infants

Abstract

BackgroundCongenital adrenal hyperplasia (CAH) is an autosomal recessive disorder associated with inborn errors of steroid metabolism. 21-hydroxylase enzyme deficiency occurs in 90 to 95% of all cases of CAH, with accumulation of 17 hydroxyprogesterone (17-OHP). Early diagnosis of CAH based on newborn screening is possible before the development of symptoms and allows proper treatment, correct sex assignment, and reduced mortality rates. This study describes the results obtained in the first year of a public CAH screening program in the state of Rio Grande do Sul, Brazil.MethodsWe reviewed the screening database in search of babies with suspected CAH, that is, altered birth-weight adjusted 17-OHP values at screening. The following data were analyzed for this population: screening 17-OHP values, retest 17-OHP values, serum 17-OHP values for those with confirmed CAH on retest, maternal and newborn data, and family history of CAH. For the screening program, 17-OHP levels are determined on dried blood spots obtained in filter paper with GSP solid phase time-resolved immunofluorescence.ResultsOf 108,409 newborns screened, eight were diagnosed with CAH (four males, four females). The incidence of CAH in the state was 1:13,551. Six cases were identified as classic salt-wasting CAH and two were cases of virilizing CAH. The positive predictive value (PPV) of the initial screening (before diagnostic confirmation) was 1.6%. The overall rate of false positive results was 0.47%. The number of false positive results was higher among newborns with birth weight < 2000 g.ConclusionThe present results support the need for CAH screening by the public health care system in the state, and show that the strategy adopted is adequate. PPV and false positive results were similar to those reported for other states of Brazil with similar ethnic backgrounds.

Evaluation of a Two-Tier Screening Pathway for Congenital Adrenal Hyperplasia in the New South Wales Newborn Screening Programme

“…There have been several strategies implemented by screening programs to improve the specificity of CAH screening. Improvement in the specificity was observed when the cut-off level of 17OHP was stratified based on either gestational age or birth weight and/or age of sampling [ 1 , 14 , 16 , 18 , 37 , 38 , 39 , 40 ]. Although gestational age stratification of 17OHP concentration was shown to give higher specificity, birth weight stratification has been more widely used [ 22 , 41 , 42 ].…”

“…Newborn screening for CAH began with the development of a radioimmunoassay by Pang et al, 1977 [ 10 ] measuring 17 α-hydroxyprogesterone(17OHP) using blood on microfilter paper. Since then, worldwide CAH screening or pilot studies have ensued [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ]. Newborn screening for CAH is aimed at identifying newborns with SWCAH promptly to prevent a life threatening adrenal crisis, thus reducing morbidity and mortality in affected individuals [ 23 ].…”

Early access to biological neonatal screening: coordination among child care action programs

“…An increase in early access to this test was found from 2016 to 2017, with associations between "child's age" and "place of collection" for both years, and "type of user" for 2016. Studies have highlighted the importance of early diagnosis of the diseases investigated in biological neonatal screenings, with the purpose of providing appropriate treatment in order to reduce negative repercussions on children's health (2)(3)(4)(5)(14)(15)(16) .…”

The Cost-Effectiveness of Congenital Adrenal Hyperplasia Newborn Screening in Brazil: A Comparison Between Screened and Unscreened Cohorts

“…However, the high frequency of falsepositive (FP) results remains a major issue, especially in preterm newborns. The positive predicted value (PPV) has been described to be ∼1.6-2.3% in screened Brazilian cohorts (8)(9)(10)(11). A recent pilot study conducted in Saõ Paulo found a PPV of 5.6 and 14.1% upon using the 99.8th percentile in samples collected until and after 72 h of life, respectively (3).…”