Cah Nbs 17ohp Interpretation

CAH Newborn Screening (17-OHP) Interpreter

Source: Balsamo A et al., Front Pediatr 2020;8:593315 — Newborn Screening section; Dabas A et al., Indian Pediatrics 2020;57:159–164; ICMR Task Force NBS report 2018.

Scope: any baby with a dried-blood-spot (DBS) 17-OHP result from a newborn screening program. This skill covers interpretation and action — not the screening logistics themselves.

STEP 1 — Know what NBS for CAH actually catches

NBS using DBS 17-OHP detects classic CYP21A2 deficiency (21-OHD) — the form responsible for ≥ 90% of CAH.

What the screen will MISS or mishandle:

Take-home: a negative NBS does not rule out non-21-OHD CAH in a sick or ambiguous newborn. Use [[cah-newborn-subtype-differentiator]].

STEP 2 — Use gestational-age and birth-weight adjusted cut-offs

The single most common cause of NBS false positives is using a one-size-fits-all cut-off. Stressed, preterm, low-birth-weight, and sick newborns physiologically have higher 17-OHP.

Each screening centre should publish its own cut-offs. Typical tiered framework (adapt to local lab):

*Values are indicative — use your local laboratory's GA- and BW-stratified cut-offs. Conversion: 1 ng/mL ≈ 3 nmol/L.

Timing of sample: ideal between 48–72 h of life (after the physiological 17-OHP fall). Samples taken < 24 h are unreliable.

STEP 3 — Triage the result

A. Clearly negative (below GA-stratified cut-off)

• No further CAH workup unless clinical suspicion (ambiguous genitalia, SW, hypoglycaemia, hyperpigmentation, family history).
• Remember: rule-out is only for 21-OHD.

B. Borderline (intermediate band)

• Repeat DBS 17-OHP at 1–2 weeks of life.
• If second sample still borderline → run second-tier LC-MS/MS on the same blood spot or send a serum sample (see Step 4).
• Examine the baby — genitalia, hydration, electrolytes, BP.

C. Clearly positive (above upper threshold)

• Treat as a confirmed screen-positive immediately — do not wait for repeat.
• Same day:
  1. Clinical exam (genitalia, hydration, hyperpigmentation, glucose).
  2. Serum 17-OHP, electrolytes (Na, K), glucose, ACTH, cortisol, renin, aldosterone, androstenedione, testosterone.
  3. Karyotype if genitalia ambiguous.
  4. Pelvic / adrenal ultrasound (look for adrenal hyperplasia, uterus in 46,XX virilised).
  5. Counsel family — pending confirmation.
• If clinically unwell (SW, hypoglycaemia, shock) → manage as [[cah-adrenal-crisis-protocol]] and start hydrocortisone empirically after drawing baseline samples.

STEP 4 — Use second-tier LC-MS/MS to cut the false-positive rate

A second-tier mass-spec panel on the original DBS punch dramatically improves the positive predictive value of NBS.

Typical panel:

• 17-OHP (re-quantified)
• 21-deoxycortisol (21-DOF) — the most specific marker for 21-OHD
• Androstenedione (Δ4A)
• Cortisol (F)
• Ratios: (17-OHP + Δ4A) / F; 21-DOF / F

An elevated 21-DOF and a high (17-OHP + Δ4A)/F ratio strongly confirm CYP21A2-D and reduce false positives from stress, prematurity, and HSD3B2-D.

This is feasible in most national NBS labs in 2026; if not available locally, send serum 17-OHP at 24 h after a screen-positive alongside the rest of the work-up in Step 3.

STEP 5 — Immediate clinical action plan for a positive screen

Don't wait for confirmation if the baby is sick. Treat first, refine the diagnosis after.

1. Examine — genitalia (Prader stage), hydration, BP, hyperpigmentation, glucose.
2. Sample — electrolytes, glucose, serum 17-OHP, cortisol, ACTH, renin, aldosterone, androstenedione, testosterone, karyotype.
3. Stabilise — IV fluids, glucose; if any feature of crisis → IV hydrocortisone per [[cah-adrenal-crisis-protocol]].
4. Start treatment when confirmed (or empirically if sick) — see [[cah-infant-hydrocortisone-dosing]] and [[cah-fludrocortisone-salt-supplementation]].
5. Family counselling — diagnosis, lifelong replacement, sick-day rules, future pregnancy implications (autosomal recessive — 25% recurrence; offer genetic counselling).
6. Issue the disease card (see [[cah-adrenal-crisis-protocol]] Step 2).

STEP 6 — Avoid these common errors

• Anchoring on a single cut-off across all GA/BW strata → false positives in preterms, false negatives in healthy terms.
• Sampling before 24 h of life → physiological elevation.
• Assuming NBS rules out all CAH — it does not (see Step 1).
• Discharging a screen-positive baby without exam and electrolytes — SW crisis can emerge in the 2nd week.
• Starting hydrocortisone before drawing diagnostic samples unless the baby is in crisis.
• Failing to repeat in a borderline preterm with persistent stress (still in NICU, sepsis, etc.).

Quick reference

• NBS = 17-OHP on DBS at 48–72 h.
• Detects CYP21A2-D; misses other forms.
• Use GA-/BW-stratified cut-offs.
• Borderline → repeat in 1–2 weeks + 2nd-tier LC-MS/MS.
• Positive → same-day clinical exam, electrolytes, serum panel, pelvic/adrenal US, karyotype if ambiguous.
• Sick baby + positive screen → treat as crisis first, refine diagnosis after samples are drawn.
• 21-DOF on LC-MS/MS is the most specific confirmatory marker.

Related skills

• [[cah-newborn-subtype-differentiator]] — when the screen result and phenotype don't fit 21-OHD.
• [[cah-adrenal-crisis-protocol]] — for the sick screen-positive newborn.
• [[cah-infant-hydrocortisone-dosing]] — start maintenance therapy once confirmed.