Newborn Screening for Congenital Adrenal Hyperplasia: Review of Factors Affecting Screening Accuracy

Patrice K Held; Ian M Bird; Natasha L Heather

doi:10.3390/ijns6030067

Newborn Screening for Congenital Adrenal Hyperplasia: Review of Factors Affecting Screening Accuracy

Int J Neonatal Screen. 2020 Aug 23;6(3):67. doi: 10.3390/ijns6030067. eCollection 2020 Sep.

Authors

Patrice K Held^{1

2}, Ian M Bird³, Natasha L Heather^{4

5}

Affiliations

¹ Wisconsin State Laboratory of Hygiene, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA.
² Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA.
³ Department of Obstetrics and Gynecology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53715, USA; imbird@wisc.edu.
⁴ Newborn Screening, LabPlus, Auckland City Hospital, Auckland 1023, New Zealand; NHeather@adhb.govt.nz.
⁵ Liggins Institute, University of Auckland, Auckland 1010, New Zealand.

Abstract

Newborn screening for 21-hydroxylase deficiency (21OHD), the most common form of congenital adrenal hyperplasia, has been performed routinely in the United States and other countries for over 20 years. Screening provides the opportunity for early detection and treatment of patients with 21OHD, preventing salt-wasting crisis during the first weeks of life. However, current first-tier screening methodologies lack specificity, leading to a large number of false positive cases, and adequate sensitivity to detect all cases of classic 21OHD that would benefit from treatment. This review summarizes the pathology of 21OHD and also the key stages of fetal hypothalamic-pituitary-adrenal axis development and adrenal steroidogenesis that contribute to limitations in screening accuracy. Factors leading to both false positive and false negative results are highlighted, along with specimen collection best practices used by laboratories in the United States and worldwide. This comprehensive review provides context and insight into the limitations of newborn screening for 21OHD for laboratorians, primary care physicians, and endocrinologists.

Keywords: congenital adrenal hyperplasia; newborn screening.

Publication types

Review