Is Congenital Adrenal Hyperplasia (CAH) missed at Newborn Screening (NBS)?

From the Guidelines

Congenital adrenal hyperplasia (CAH) can be missed at newborn screening due to various factors, including premature birth, mild forms of the disease, and technical issues with sample collection or laboratory processing 1. When considering the diagnosis of CAH, it is essential to prioritize the most recent and highest quality studies. Although the provided studies do not directly address the issue of CAH being missed at newborn screening, they highlight the importance of accurate and comprehensive screening programs.

Key Factors Contributing to Missed Diagnosis

• Premature infants may have lower baseline hormone levels, making it harder to detect abnormalities
• Milder forms of CAH, such as non-classical CAH, may not show significantly elevated hormone levels in the immediate newborn period
• Technical issues with sample collection, storage, or laboratory processing can lead to missed cases
• Not all forms of CAH are included in standard screening panels, with rarer enzyme deficiencies sometimes being overlooked

Recommendations for Improvement

• Follow-up testing is recommended for infants with ambiguous genitalia, salt-wasting symptoms, or family history of CAH, even with normal screening results
• Comprehensive screening programs that include second-tier testing methods like liquid chromatography-tandem mass spectrometry can reduce false negatives and improve diagnostic accuracy for this potentially life-threatening condition It is crucial to note that the studies provided, such as the one from 2017 1, focus on the diagnosis and treatment of tyrosinemia type I, which, although relevant to newborn screening, does not directly address CAH. However, the principles of comprehensive screening and the importance of accurate diagnostic markers can be applied to CAH as well.

Prioritizing Morbidity, Mortality, and Quality of Life

In the context of CAH, prioritizing morbidity, mortality, and quality of life outcomes is essential. Early detection and treatment of CAH can significantly improve outcomes, reducing the risk of life-threatening complications and improving the quality of life for affected individuals. Therefore, it is recommended to prioritize comprehensive screening programs and follow-up testing to ensure accurate diagnosis and timely treatment of CAH.

From the Research

Congenital Adrenal Hyperplasia Diagnosis

• Congenital adrenal hyperplasia (CAH) can be missed at newborn screening, with nearly one-fifth of patients with classic CAH being missed on the newborn screen 2.
• A study found that 12 out of 64 patients with classic CAH were missed on the newborn screen, with a mean age at diagnosis of 21.7 months 2.
• The study also found that there were no specific features that distinguished patients who were missed on the newborn screen from those who were detected at birth 2.

Newborn Screening for CAH

• Newborn screening for CAH is crucial in reducing morbidity and mortality, especially in salt-wasting cases 3.
• The screening test should be performed soon after birth, and the results should be available quickly to prevent salt-wasting crises 3.
• However, some newborns with simple virilizing CAH may be missed on initial screening using current testing protocols 3.

Treatment and Management of CAH

• Hydrocortisone is the preferred treatment for classic CAH in growing children, but recommendations regarding dosage and administration are inconsistent 4.
• A study found that a high proportion of children are treated with hydrocortisone doses higher than recommended 4.
• The study also found that fludrocortisone is administered in a significant proportion of patients with CAH, with a median daily dosage of 88.8 µg 4.

Challenges and Limitations

• There is a need to set a screening cut-off to avoid false-positive rates and oversaturation of the follow-up system 3.
• Current glucocorticoid treatment regimens cannot optimally replicate normal physiological cortisol levels, and over-treatment or under-treatment is often reported 5.
• Further research is needed to determine the most effective form of glucocorticoid replacement therapy in CAH for children and adults 5.