| name | cah-nbs-17ohp-interpretation |
| description | Interpret a newborn screening (NBS) 17-hydroxyprogesterone (17-OHP) result for congenital adrenal hyperplasia (CAH) — including gestational-age and birth-weight adjusted cut-offs, when to repeat, when to run a second-tier LC-MS/MS multi-steroid profile, which CAH subtypes the screen will and will not detect, and the immediate clinical action plan for a screen-positive baby. Use when a clinician asks "is this 17-OHP positive", "what to do with a high NBS 17-OHP", "screen-positive CAH next steps", "false positive NBS CAH preterm baby", "second tier CAH testing", "does NBS detect 11β-hydroxylase or 17α-hydroxylase deficiency", or any newborn screening 17-OHP interpretation question. Source: Balsamo A, et al. Frontiers in Pediatrics 2020;8:593315 (Newborn Screening section); cross-referenced with ICMR / IAP newborn screening recommendations and Speiser PW et al. Endocrine Society CPG 2018. |
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:
| CAH subtype | Detected by 17-OHP NBS? |
|---|
| Classic 21-OHD (SW, SV) | Yes — high sensitivity if cut-offs are GA-adjusted |
| Non-classic 21-OHD | Often missed — 17-OHP not high enough at birth |
| 11β-OHD (CYP11B1-D) | Sometimes — 17-OHP may be mildly elevated |
| 17α-OHD (CYP17A1-D) | No — 17-OHP is low/normal |
| StAR-D, CYP11A1-D | No — all steroids low |
| 3β-HSD (HSD3B2-D) | May give false positive (cross-reactivity from high Δ5 steroids) |
| POR-D | Mildly elevated 17-OHP — easily missed or misclassified |
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):
| Strata | Recommended action thresholds (DBS 17-OHP, nmol/L)* |
|---|
| Term, > 2500 g, well | Negative < 30; borderline 30–90; positive > 90 |
| Preterm 32–36 wk OR 1500–2500 g | Negative < 60; borderline 60–165; positive > 165 |
| Preterm < 32 wk OR < 1500 g OR ICU/sick | Negative < 120; borderline 120–270; positive > 270 |
*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:
- Clinical exam (genitalia, hydration, hyperpigmentation, glucose).
- Serum 17-OHP, electrolytes (Na, K), glucose, ACTH, cortisol, renin, aldosterone, androstenedione, testosterone.
- Karyotype if genitalia ambiguous.
- Pelvic / adrenal ultrasound (look for adrenal hyperplasia, uterus in 46,XX virilised).
- 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.
- Examine — genitalia (Prader stage), hydration, BP, hyperpigmentation, glucose.
- Sample — electrolytes, glucose, serum 17-OHP, cortisol, ACTH, renin, aldosterone, androstenedione, testosterone, karyotype.
- Stabilise — IV fluids, glucose; if any feature of crisis → IV hydrocortisone per [[cah-adrenal-crisis-protocol]].
- Start treatment when confirmed (or empirically if sick) — see [[cah-infant-hydrocortisone-dosing]] and [[cah-fludrocortisone-salt-supplementation]].
- Family counselling — diagnosis, lifelong replacement, sick-day rules, future pregnancy implications (autosomal recessive — 25% recurrence; offer genetic counselling).
- 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.
