Cah Nbs 17ohp Interpretation

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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.
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# 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.

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## 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]].

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## 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.

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## 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.

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## 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.

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## 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).

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## 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.).

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## 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.

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## 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.