Are CAH Newborn Screening Results Often False Positives?

Yes, false positives are very common with the congenital adrenal hyperplasia (CAH) newborn screening test ^[1][2]. If your baby’s doctor just called to tell you the newborn screen was positive, it is understandable to feel worried. However, a positive newborn screen is simply a signal that more testing is needed, not a final diagnosis ^[1].

While many abnormal screens do not result in a CAH diagnosis, every positive screen requires prompt medical attention.

Immediate Safety Considerations

A baby with severe, salt-wasting CAH may initially look well before their condition rapidly worsens ^[3].

• Follow-up urgency: It is critical to contact the pediatrician or newborn screening program promptly to ask if the baby needs an urgent evaluation today or a routine repeat test.
• When to seek emergency care: Medical guidelines advise going to the emergency room immediately if a baby experiences poor feeding, repeated vomiting, unusual sleepiness or difficulty waking, extreme weakness, fewer wet diapers, rapid weight loss, or appears generally unwell. Do not wait for final screening results if these symptoms appear ^[3].

Why do false positives happen?

The standard first-step newborn screen for CAH measures a hormone called 17-hydroxyprogesterone (17-OHP) ^[1]. In babies with the most common form of CAH (21-hydroxylase deficiency), 17-OHP builds up to high levels ^[1]. This initial test is very sensitive to ensure no cases are missed, but it is not highly specific, meaning it frequently flags babies who do not have CAH ^[4][2].

A baby’s 17-OHP levels can be temporarily elevated for several reasons:

• Premature birth or low birth weight: The adrenal glands in premature and smaller babies are still developing. This immaturity often causes their 17-OHP levels to naturally run higher than in full-term babies ^[1][5].
• Early sample collection: A baby’s 17-OHP levels naturally surge during the first 24 hours of life. If the heel-prick blood sample is collected too soon after birth, the result can exceed the screening cutoff ^[1][6].
• Stress or illness: The physical stress of being a newborn, especially if the baby experiences complications like an infection (sepsis), breathing issues, low blood sugar, or birth asphyxia, can cause the adrenal glands to release more hormones and artificially inflate 17-OHP levels ^[7][8].

What happens next?

Because false positives are common, screening programs use follow-up steps to figure out if the high 17-OHP is due to CAH or another factor. Doctors determine the urgency based on how high the result was and the baby’s overall health:

• Second-tier testing: Some state labs automatically run a more precise test on the original blood spot if the first result is high ^[9][10]. This test, called LC-MS/MS (liquid chromatography-tandem mass spectrometry), looks for a broader profile of hormones. It measures a hormone called 21-deoxycortisol, which tends to remain normal in premature or stressed babies without CAH ^[1][11]. This step can substantially reduce false positives, though it does not replace a doctor’s final evaluation ^[12].
• A repeat newborn screen: If the initial result was borderline, a doctor or the lab may request a second heel-prick sample to see if the 17-OHP levels have dropped ^[9][13]. Screening cutoffs are often adjusted based on a baby’s birth weight and gestational age to improve accuracy ^[5].
• Confirmatory blood tests: For markedly high screens, or if a baby appears unwell, doctors will promptly order a standard blood draw (serum test) ^[9][14]. This checks exact adrenal hormone levels alongside blood salts (electrolytes like sodium and potassium) and glucose, which can quickly identify if a baby is in a dangerous adrenal crisis.