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Newborn Screening for Congenital Adrenal Hyperplasia: Review of Factors Affecting Screening Accuracy
Patrice K Held1,2, Ian M Bird3, Natasha L Heather4,5
1Wisconsin State Laboratory of Hygiene, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA.
Insights
Newborn screening for 21-hydroxylase deficiency (21OHD) offers early detection but faces challenges with accuracy. This review explores limitations in current screening methods for congenital adrenal hyperplasia, impacting diagnosis and treatment.
Area of Science:
- Endocrinology
- Genetics
- Neonatal Medicine
Background:
- Newborn screening for 21-hydroxylase deficiency (21OHD), a common congenital adrenal hyperplasia, has been standard for over two decades.
- Early detection of 21OHD prevents life-threatening salt-wasting crises in newborns.
Purpose of the Study:
- To review the pathology of 21OHD and its impact on newborn screening accuracy.
- To identify factors contributing to false positive and false negative screening results.
- To discuss best practices for specimen collection in newborn screening for 21OHD.
Main Methods:
- Literature review focusing on 21OHD pathology.
- Analysis of fetal development in the hypothalamic-pituitary-adrenal axis and adrenal steroidogenesis.
- Examination of current screening methodologies and their limitations.
- Review of specimen collection practices.
Main Results:
- Current screening methods for 21OHD lack optimal specificity and sensitivity.
- False positive results lead to unnecessary follow-up, while false negatives can delay critical treatment.
- Fetal development and steroidogenesis pathways contribute to screening inaccuracies.
Conclusions:
- Limitations in current newborn screening for 21OHD necessitate further research and improved methodologies.
- Understanding screening inaccuracies is crucial for laboratorians, physicians, and endocrinologists.
- Optimizing screening protocols can enhance early diagnosis and management of congenital adrenal hyperplasia.
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.
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