Newborn screening
Newborn screening can prevent salt-wasting and adrenal crisis in those with classical 21-hydroxylase deficiency (21-OHD) by early detection and treatment. All 50 states in the US now include 17-hydroxyprogesterone (17-OHP) as a screening measure.
Screening became possible with the development of an assay for 17-OHP (a cortisol precursor that accumulates in elevated concentrations in 21-OHD), using a heel-stick capillary blood specimen absorbed on to filter paper.
Screening serves several important purposes:
A number of newborn screening programs have been developed in the US, Europe, and Japan. As of 2018, all 50 states in the US screen newborns for CAH.[14]Speiser PW, Arlt W, Auchus RJ, et al. Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018 Nov 1;103(11):4043-88.
https://academic.oup.com/jcem/article/103/11/4043/5107759
http://www.ncbi.nlm.nih.gov/pubmed/30272171?tool=bestpractice.com
Cost-benefit analysis has indicated that newborn screening for classical 21-OHD is cost-effective and has been recommended by expert consensus.[14]Speiser PW, Arlt W, Auchus RJ, et al. Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018 Nov 1;103(11):4043-88.
https://academic.oup.com/jcem/article/103/11/4043/5107759
http://www.ncbi.nlm.nih.gov/pubmed/30272171?tool=bestpractice.com
The neonatal screening method is highly sensitive for the salt-wasting form. The sensitivity is lower in the milder simple virilizing and nonclassical forms.[22]Gidlöf S, Wedell A, Guthenberg C, et al. Nationwide neonatal screening for congenital adrenal hyperplasia in Sweden: a 26-year longitudinal prospective population-based study. JAMA Pediatr. 2014 Jun;168(6):567-74.
http://www.ncbi.nlm.nih.gov/pubmed/24733564?tool=bestpractice.com
Samples taken in the first 24 hours of life are elevated in all infants and may give false-positive results.[23]Allen DB, Hoffman GL, Fitzpatrick P, et al. Improved precision of newborn screening for congenital adrenal hyperplasia using weight-adjusted criteria for 17-hydroxyprogesterone levels. J Pediatr. 1997 Jan;130(1):128-33.
http://www.ncbi.nlm.nih.gov/pubmed/9003862?tool=bestpractice.com
[24]Therrell BL Jr, Berenbaum SA, Manter-Kapanke V, et al. Results of screening 1.9 million Texas newborns for 21-hydroxylase-deficient congenital adrenal hyperplasia. Pediatrics. 1998 Apr;101(4 Pt 1):583-90.
http://www.ncbi.nlm.nih.gov/pubmed/9521938?tool=bestpractice.com
False-positive results may also be observed in low birth-weight, sick or premature infants.[23]Allen DB, Hoffman GL, Fitzpatrick P, et al. Improved precision of newborn screening for congenital adrenal hyperplasia using weight-adjusted criteria for 17-hydroxyprogesterone levels. J Pediatr. 1997 Jan;130(1):128-33.
http://www.ncbi.nlm.nih.gov/pubmed/9003862?tool=bestpractice.com
[25]Al Saedi S, Dean H, Dent W, et al. Screening for congenital adrenal hyperplasia: the Delfia Screening Test overestimates serum 17-hydroxyprogesterone in preterm infants. Pediatrics. 1996 Jan;97(1):100-2.
http://www.ncbi.nlm.nih.gov/pubmed/8545200?tool=bestpractice.com
False-negative results may be observed in neonates receiving dexamethasone for management of unrelated problems, maternal steroid use, immaturity of the adrenal axis or other laboratory error.[26]Rohrer TR, Gassmann KF, Pavel ME, et al. Pitfall of newborn screening for congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Biol Neonate. 2003;83(1):65-8.
http://www.ncbi.nlm.nih.gov/pubmed/12566686?tool=bestpractice.com
[27]Saroufim R, Nebesio TD, Eugster EA. Characteristics of patients with classic congenital adrenal hyperplasia missed on the newborn screen. Horm Res Paediatr. 2024;97(5):470-6.
https://karger.com/hrp/article/97/5/470/870188/Characteristics-of-Patients-with-Classic
http://www.ncbi.nlm.nih.gov/pubmed/37992692?tool=bestpractice.com
Newborn screening results need to be confirmed with serum 17-OHP measurements.