Congenital Adrenal Hyperplasia (CAH) in Newborn Screening
Yes, Congenital Adrenal Hyperplasia (CAH) is included in the core panel of disorders recommended for newborn screening in the United States. 1
Evidence and Recommendations
CAH is one of the high-scoring conditions identified by the American College of Medical Genetics (ACMG) as appropriate for inclusion in newborn screening programs:
- CAH was among the top scoring conditions in the ACMG evaluation system, following medium-chain acyl CoA dehydrogenase (MCAD) deficiency, congenital hypothyroidism (CH), phenylketonuria (PKU), biotinidase deficiency (BIOT), and sickle cell anemia (Hb SS) 1
- It is officially designated as part of the core panel of disorders recommended for universal newborn screening 1
- The screening is performed using tandem mass spectrometry (MS/MS) which measures 17α-hydroxyprogesterone (17-OHP) levels in dried blood spots 1
Screening Effectiveness and Limitations
The effectiveness of CAH screening varies by disease subtype:
- Newborn screening is highly effective for detecting the salt-wasting (SW) form of CAH, which is the most severe and potentially life-threatening form 2
- Studies have shown that all salt-wasting CAH patients would be detected using recommended cut-off limits for 17-OHP (30 nmol/l) 2
- However, approximately one-third of children with the moderate (simple virilizing) form of CAH may be missed by screening, resulting in a significant false-negative rate 2, 3
- False-positive rates remain relatively high compared to other newborn screening disorders, particularly in premature and low birth weight infants 3, 4
Screening Improvements
Several approaches have been implemented to improve CAH screening:
- Some states have implemented two-tier screening protocols with second-tier steroid profiling to reduce false positives 3
- Establishing normative reference levels based on birth weight or gestational age may help minimize false-positive rates, particularly in low birth weight newborns 4
- Molecular analysis (CYP21A2 gene sequencing) has been found valuable as a confirmatory test for children with persistently elevated 17-OHP levels 5
Clinical Implications
Healthcare providers should be aware of important clinical considerations:
- Despite inclusion in newborn screening, physicians should be cautioned that a negative newborn screen does not necessarily rule out classic CAH 3
- Any patient with clinical concerns for CAH should receive immediate diagnostic testing regardless of screening results 3, 6
- Early diagnosis through screening helps prevent life-threatening salt-wasting crises and allows for timely treatment to prevent permanent negative effects of androgen overproduction 2, 6
Conclusion
CAH screening is an established component of the recommended uniform screening panel, with particular effectiveness for detecting the most severe salt-wasting form. However, healthcare providers should be aware of its limitations, particularly for moderate forms of the disorder, and maintain clinical vigilance regardless of screening results.