Newborn Screening for Congenital Adrenal Hyperplasia: What Parents Should Know

Congenital Adrenal Hyperplasia (CAH) is a group of inherited disorders affecting the adrenal glands, which produce essential hormones like cortisol, aldosterone, and androgens.

In CAH, an enzyme deficiency disrupts hormone production, leading to imbalances that cause various health issues, from mild to life-threatening.

Early detection of CAH is crucial because, without timely diagnosis, affected infants can experience severe complications like dehydration, salt-wasting, and adrenal crisis, which can lead to serious health outcomes or death. 

Early diagnosis allows for immediate treatment, preventing complications and improving long-term health.

This article informs parents about newborn screening for CAH, explaining the screening process, what results mean, and what to expect if a child is diagnosed. It aims to guide families through the process, ensuring they feel supported and informed.

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What is Newborn Screening?  

Newborn screening is a routine test performed within 24-48 hours after birth to identify specific genetic, metabolic, and endocrine disorders that may not show symptoms immediately but could lead to serious health problems. The primary goal of newborn screening is to detect these disorders early so treatment can begin promptly, preventing complications.

Importance of Newborn Screening

Early detection of disorders through newborn screening allows for immediate medical intervention, which can significantly improve health outcomes and prevent life-threatening complications. Conditions like CAH, if detected early, can be managed with treatment to prevent adrenal crisis, salt-wasting, or other serious issues, giving affected infants the best chance at normal growth and development.

Conditions Included in Newborn Screening 

Newborn screening panels typically include various genetic, metabolic, and endocrine disorders, which may vary slightly by region. These conditions often include phenylketonuria (PKU), hypothyroidism, sickle cell disease, and cystic fibrosis. 

One endocrine disorder screened for is Congenital Adrenal Hyperplasia (CAH), a genetic condition that affects hormone production, specifically cortisol and aldosterone. It can lead to severe health complications if not treated early.

Understanding Congenital Adrenal Hyperplasia (CAH)

Congenital Adrenal Hyperplasia (CAH) is a genetic condition that affects the adrenal glands, which produce hormones like cortisol, aldosterone, and androgens. Cortisol helps manage stress, aldosterone regulates salt and water balance, and androgens influence sexual development. CAH results from gene mutations that control the production of enzymes needed to synthesize these hormones.

Types of CAH

The most common form of CAH is 21-hydroxylase deficiency, accounting for 95% of cases. This deficiency impairs cortisol and aldosterone production, increasing the risk of adrenal crisis due to low cortisol, dehydration, and salt-wasting (loss of sodium) from aldosterone deficiency. These complications can lead to low blood pressure, especially in severe cases. It may present as classic CAH, with severe symptoms early in life, or non-classic CAH, with milder, later-developing symptoms.

Less common forms of CAH include 11β-hydroxylase and 17α-hydroxylase deficiencies, which disrupt hormone production and often cause high blood pressure due to excess mineralocorticoid activity. In these cases, the body's inability to regulate salt and water leads to fluid retention and hypertension.

Other rare forms include:

• 3β-hydroxysteroid dehydrogenase deficiency- affects adrenal and gonadal hormone production, leading to ambiguous genitalia in both sexes and salt-wasting.
• P450 oxidoreductase deficiency- disrupts steroid production, resulting in ambiguous genitalia, skeletal abnormalities, and sexual development issues. 
• StAR gene mutations- lead to steroidogenic acute regulatory protein (StAR) deficiency. This disrupts cholesterol transport into mitochondria, a critical step in steroid synthesis, causing lipoid congenital adrenal hyperplasia, a severe CAH form with near-complete hormone deficiencies, salt-wasting, and life-threatening adrenal insufficiency.

Symptoms and Risks

Symptoms depend on the severity of the enzyme deficiency. In severe cases (classic CAH), newborns may have ambiguous genitalia (in females), dehydration, and low blood pressure from salt-wasting, which can lead to life-threatening adrenal crises if untreated. 

Aldosterone deficiency results in salt loss and low blood pressure. In milder cases (non-classic CAH), it can lead to early puberty, accelerated growth, or fertility problems. Without treatment, CAH can cause recurring adrenal crises and persistently low blood pressure.

How Newborn Screening for CAH Works

Newborn screening for CAH is typically conducted within the first 24 to 48 hours after birth. During this process, a small blood sample is collected through a heel prick and placed on filter paper. The sample is then sent to a laboratory for analysis.

The lab tests the sample for elevated levels of 17-hydroxyprogesterone (17-OHP), the primary marker for CAH. In cases of 21-hydroxylase deficiency, the most common form of CAH, 17-OHP accumulates due to the enzyme deficiency. If high levels of 17-OHP are detected, further diagnostic tests are conducted to confirm the diagnosis.

Timing is critical, as screening within the first 24-48 hours ensures the most accurate hormone measurements, including 17-OHP. Early detection is essential for prompt treatment, helping to prevent serious complications such as adrenal crises, especially in severe cases.

Interpreting Screening Results  

A positive newborn screening result for CAH indicates elevated levels of 17-hydroxyprogesterone (17-OHP), suggesting the possibility of CAH. However, this does not confirm the diagnosis and requires further testing. False positives can occur where elevated 17-OHP levels are detected, but the baby does not have CAH, often due to factors like stress or prematurity. False negatives are rare but possible when the test fails to detect elevated 17-OHP despite the condition being present. Confirmation of the diagnosis requires follow-up testing.

Follow-Up Testing

If CAH is suspected, further tests are conducted to confirm the diagnosis. These may include repeating 17-OHP measurements for more accurate results. Electrolyte tests are also important to detect imbalances caused by aldosterone deficiency, such as low sodium and high potassium levels, which are common in severe forms of CAH. In some cases, genetic testing is performed to identify specific gene mutations responsible for CAH, confirming the diagnosis and determining the type of enzyme deficiency. These follow-up tests are essential for accurate diagnosis and guiding treatment decisions.

What to Expect if Your Baby is Diagnosed with CAH

Receiving a diagnosis of Congenital Adrenal Hyperplasia (CAH) for your baby can be overwhelming, but with early intervention and proper management, the condition can be well-controlled. Here's what to expect:

Immediate Steps

After a CAH diagnosis, your baby will be referred to a pediatric endocrinologist, a specialist in hormone disorders. The endocrinologist will confirm the diagnosis with additional tests, such as hormone levels and electrolyte measurements, and assess the severity. A tailored treatment plan will be developed based on the type of CAH (classic or non-classic). Early diagnosis and treatment are critical to prevent complications like adrenal crises and salt-wasting.

Treatment Options 

The primary treatment for CAH is hormone replacement therapy to replace cortisol and aldosterone. Cortisol replacement, often through hydrocortisone, helps the body manage stress and prevent adrenal crises.  

In salt-wasting CAH, aldosterone replacement, such as fludrocortisone, maintains salt and water balance, sometimes with sodium supplements. Medications may also be used to suppress excess androgen production, which can cause early puberty or ambiguous genitalia, particularly in females. Treatment plans are tailored to your baby’s specific needs and adjusted as they grow.

Monitoring and Ongoing Care 

CAH requires ongoing monitoring to ensure treatment remains effective. Regular blood tests are conducted to monitor hormone and electrolyte levels. Growth and development are closely tracked to ensure your child is progressing normally. Parents receive training to recognize signs of adrenal crisis, such as vomiting or lethargy, and how to respond, especially during illness or stress. In cases of genital abnormalities, surgery may be recommended based on the child's specific needs and the specialist's evaluation. 

Lifelong Management

CAH is a lifelong condition requiring ongoing management. Regular hormone replacement therapy must be adjusted as your child grows. Long-term follow-up with an endocrinologist is needed to monitor hormone levels, growth, and development and to address any puberty or fertility-related issues. Adolescents may face hormonal challenges during puberty, which will be managed by their healthcare team. 

Emotional Support and Counseling  

A CAH diagnosis can be emotionally challenging for families, therefore psychological support and counseling are important to help parents and children cope with the condition. Support groups and mental health professionals can provide guidance and reassurance. Families dealing with CAH often find connecting with other families similarly affected can offer valuable emotional support and practical advice.

Educational and Support Resources 

Educational resources and support are available to help parents understand and manage CAH. Healthcare providers often provide educational materials, and organizations like the CARES Foundations offer information and support for families. These resources help parents navigate treatment options and connect with others facing similar challenges.

Family Planning Considerations 

CAH is a genetic condition inherited in an autosomal recessive pattern, meaning both parents must carry the gene mutation for their child to be affected. Genetic counseling is recommended for families with a child with CAH or those planning more children. A genetic counselor can explain the likelihood of future children inheriting the condition, discuss genetic testing options, and assist with family planning. Prenatal testing for CAH is also available during pregnancy.

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Key Takeaways

• Newborn screening for CAH is essential for early detection and prevention of serious health complications. It involves a simple blood test to measure 17-hydroxyprogesterone (17-OHP). If elevated, further tests confirm the diagnosis. Early detection allows for prompt treatment to manage hormone imbalances and prevent adrenal crises.

• With early detection and proper treatment, children with CAH can lead healthy, fulfilling lives. Hormone replacement therapy and regular monitoring manage the condition, supporting normal growth and development.

• Parents must stay informed and engaged with healthcare providers to ensure the best outcomes. Consistent follow-up and monitoring help ensure treatment remains effective, allowing children with CAH to live healthy, balanced lives.