CurrentUnitedHealthcarePolicy CS173.K

Inhaled Nitric Oxide Therapy

Defines UnitedHealthcare coverage position for inhaled nitric oxide therapy for neonates and infants, including specific clinical indications (term/near-term infants with hypoxic respiratory failure or PPHN), exclusions (congenital diaphragmatic hernia, preterm <34 weeks), postoperative bridge therapy, and referenced billing code(s). This is Part 1 of 2; extract covers only content present in this part.

Policy Summary

PayerUnitedHealthcare

PolicyInhaled Nitric Oxide Therapy

Policy CodePolicy CS173.K

Change TypeAdministrative; content updates

Effective DateNov 1, 2025

Next Review Date

Key ActionProvider must document gestational age (>=34 weeks) and clinical evidence of hypoxic respiratory failure or echocardiographic evidence of PPHN for coverage determination.

POLICY UPDATE CHANGES

Added reference link to state-specific policy version for Louisiana effective Feb. 1, 2026.

Added language indicating the Medical Policy does not apply to the state of North Carolina; referred to state-specific policy version (11/01/2025).

Updated Description of Services, Clinical Evidence, and References sections to reflect current information and archived previous policy version CS173.J (11/01/2025).

1Primary covered neonatal population (term/near-term ≥34 wks)

1Explicit exclusion (preterm <34 wks)

1Postoperative bridge use (conditional coverage)

State-specific applicability noted (NC excluded; LA link added)

refsReferences updated

Coverage Summary

This policy (Policy Number CS173.K, effective November 1, 2025) defines UnitedHealthcare’s coverage position for Inhaled Nitric Oxide (iNO) therapy for neonates and infants. The coverage stance is mixed: iNO is covered for specific, proven indications in term or near-term infants but is not medically necessary or is conditional in other populations. This document is Part 1 of 2 and includes state-specific applicability notes (the Medical Policy does not apply to North Carolina and a Louisiana state-specific policy link was added on 02/01/2026).

Coverage thresholds and scope-level facts

Gestational age for term/near-term>= 34 weeks

AAP/AHA oxygenation index thresholdOxygenation index > 25

Explicit exclusionpreterm <34 wks; CDH excluded

Postoperative bridge useconditional coverage

Medical Necessity Criteria

Medically Necessary (Proven) Indication — Term or Near-Term Infants

Covered when ALL of the following are met:

ALL of the following

Gestational age: Infant is term or near-term: at least 34 weeks gestation at birth>= 34 weeks
FDA indication and multiple systematic reviews support use in ≥34-week infants (INOmax approval; Wang 2019; Barrington Cochrane).
Diagnosis of hypoxic respiratory failure OR echocardiographic evidence of persistent pulmonary hypertension of the newborn (PPHN)
AHA/ATS recommends iNO for PPHN or hypoxemic respiratory failure with OI >25; evidence shows reduced death or ECMO in term/near-term infants.
Exclusion CDH: Absence of congenital diaphragmatic hernia (CDH)
Studies and systematic reviews indicate lack of benefit and possible harm in CDH; exclude CDH for primary covered indication.

Coding

Reference CPT code for iNO delivery (unlisted pulmonary service)CPT

94799

Unlisted pulmonary service or procedure

Provider Actions & Billing Impact

Documentation Required

Document gestational age and diagnosis

Providers must document the infant's gestational age (>= 34 weeks) and clinical evidence of hypoxic respiratory failure or echocardiographic evidence of persistent pulmonary hypertension of the newborn (PPHN) to support coverage determination for iNO therapy.

Gestational age (>= 34 weeks)
Evidence of hypoxic respiratory failure or echocardiographic evidence of PPHN

Documentation Required

Document failure of conventional therapy

Providers must document prior failure of conventional treatments (for example, mechanical ventilation) before initiating iNO for covered term or near-term infants as this is a required criterion for medical necessity.

Background, Evidence & Definitions

Inhaled nitric oxide (iNO) is a pulmonary vasodilator administered as a gas to improve oxygenation and reduce need for ECMO in selected neonates. Evidence supports benefit in term or near-term infants (≥ 34 weeks gestation) with hypoxic respiratory failure or PPHN, while randomized trials and systematic reviews do not demonstrate clear benefit in preterm infants <34 weeks and indicate possible harms (e.g., severe IVH, NEC). Use in congenital diaphragmatic hernia (CDH) has not shown meaningful benefit and may be harmful. FDA approvals are limited to term and near-term neonates, and the policy describes specific nitric oxide delivery systems and devices (e.g., INOmax delivery system, INOvent, INOmax DS/DSIR, GeNOsyl MV-1000) and required analyzers/monitoring.

Study/Source	Key finding
Wang et al. (2019) meta-analysis	Nine RCTs (n=856) in infants ≥34 wks: iNO reduced combined outcome of death or ECMO (relative risk decrease ~34%); authors recommend NO inhalation for respiratory failure in term/near‑term infants.
Barrington et al. (2017a) Cochrane review	17 RCTs (moderate–high quality evidence): iNO reduces death or ECMO in term/near‑term infants; effective at initial concentration of 20 ppm; no long‑term neurodevelopmental harm identified; CDH analyzed separately.
Multiple systematic reviews / RCTs for preterm infants	Overall evidence fails to show clear benefit of iNO for preterm infants <34 wks; some analyses suggest possible harms (grade 3/4 IVH, increased NEC) and routine use not supported.
Mirza et al. (2025) randomized trial	Single‑center RCT in extremely preterm infants (<29 wks) with early pulmonary hypertension: trial stopped for futility after interim analysis; no reduction in death or BPD (primary outcome similar: 68% vs 62%).
Zheng et al. (2023) meta‑analysis	11 RCTs in preterm infants: iNO associated with lower BPD incidence overall (RR 0.91); benefit greater at 10 ppm vs 5 ppm; iNO group had increased NEC risk overall (RR 1.33) with dose‑dependent findings.
NICE guideline NG124 (2019)	Do not routinely use iNO for preterm babies needing respiratory support for RDS unless other indications (pulmonary hypoplasia or pulmonary hypertension); use in <34 wks is off‑label.
Evidence on congenital diaphragmatic hernia (CDH) — systematic reviews / NINOS trials	Systematic reviews and RCTs show no clear benefit of iNO for CDH on death or ECMO and suggest possible harm despite transient oxygenation improvement; not routinely recommended.
Postoperative pulmonary hypertension / bridge therapy evidence	Evidence inconclusive but practice‑based guidelines support use of iNO as bridge therapy in postoperative pulmonary hypertension in infants; trials limited and results largely inconclusive.
Guideline / Society recommendations (AHA/ATS, EPPVDN)	AHA/ATS: recommend iNO for term/near‑term infants with PPHN or OI>25 to reduce need for ECMO (Class I, LOE A). EPPVDN: iNO indicated for mechanically ventilated term/near‑term newborns with PPHN; in preterm <34 wks may be considered only in select cases (COR IIb, LOE C).
FDA labeling / INOmax clearance	INOmax indicated for treatment of term and near‑term (>34 wks) neonates with hypoxic respiratory failure and pulmonary hypertension; not approved for preterm infants (≤34 wks).

Definitions

InfancyThe period from birth through the first year of life (Barfield 2016).

Term or near-termInfant born at least 34 weeks gestation.

PPHNPersistent pulmonary hypertension of the newborn; characterized by increased pulmonary vascular resistance, right-to-left shunting, and severe hypoxemia.

Revision History

02/01/2026administrative updateLatest

Policy History: Added reference link to Louisiana state-specific policy version effective Feb. 1, 2026 (administrative update).

11/01/2025application/language added

Policy updated to indicate the Medical Policy does not apply to the state of North Carolina; refer to the state-specific policy version (application/language clarification).

11/01/2025content update and archival

Updated Description of Services, Clinical Evidence, and References sections to reflect current information and archived previous policy version CS173.J (content updates and archival).

Policy Summary

PayerUnitedHealthcare

PolicyInhaled Nitric Oxide Therapy

Policy CodePolicy CS173.K

Change TypeAdministrative; content updates

Effective DateNov 1, 2025

Next Review Date

Key ActionProvider must document gestational age (>=34 weeks) and clinical evidence of hypoxic respiratory failure or echocardiographic evidence of PPHN for coverage determination.

On This Page

Conventional therapy failure: Failure of conventional treatments (e.g., mechanical ventilation) prior to iNO initiation

Policy requires failure of conventional treatments before iNO for covered term/near-term infants.

Postoperative Management of Pulmonary Hypertension in Infants

Covered as bridge therapy when ALL of the following are met:

ALL of the following

Postoperative context: Used for postoperative management of pulmonary hypertension associated with heart or lung surgery in infants
Guidelines and practice-based reviews support consideration of iNO for postoperative pulmonary hypertension in infants (AHA/ATS; Cochrane review inconclusive).
Bridge therapy: Used as bridge therapy during the acute recovery phase
Policy states iNO will be covered as bridge therapy during acute recovery despite limited definitive trial evidence.

Not Medically Necessary / Unproven Indications

iNO is unproven and not medically necessary for treating the following:

ANY of the following

Non-term newborns: All newborns other than term or near-term infants meeting the medically necessary criteria (examples listed elsewhere)
Policy explicitly excludes newborns who do not meet the term/near-term ≥34 week criteria.
CDH: Newborns with congenital diaphragmatic hernia (CDH) for primary treatment (benefit not demonstrated; possible harm)
Systematic reviews and RCTs in CDH show no benefit on death/ECMO and suggest possible harm; AARC and other reviews advise against routine use.
Preterm <34wks: Preterm newborns who are less than 34 weeks gestation at birth (routine, rescue, or prophylactic use not supported; possible harms noted)< 34 weeks
Evidence does not support routine use in <34 weeks; possible harms (grade 3/4 IVH, NEC) reported in meta-analyses and guidelines (AAP, NIH).
Outside infancy: Individuals outside the Infancy age group (experimental/investigational due to lack of FDA approved indications)
Policy notes iNO for individuals outside infancy is experimental/investigational and not FDA-approved for those ages.

Conditional / May Be Considered

Situations where evidence is inconclusive and therapy may be considered based on clinical judgment:

ANY of the following

Selected preterm with PH: Selected preterm infants (<34 weeks) with confirmed pulmonary hypertension (EPPVDN: iNO may be considered)< 34 weeks
EPPVDN states iNO may be considered in preterm infants <34 weeks with confirmed PH (COR IIb; LOE C).
Subgroup signals: Subpopulations (e.g., some African American preterm infants) where subgroup analyses suggested benefit — considered hypothesis-generating and not definitive
Meta-analyses found race-based subgroup signals (African American preterm infants) that are post hoc and hypothesis-generating; not conclusive for routine use.

Documented failure of conventional therapies (e.g., mechanical ventilation)

Prior Authorization

Prior authorization may be required per payer processes

Prior authorization may be required by the payer; obtain any required authorization and provide clinical documentation that aligns with the policy coverage criteria when submitting claims.

CPT 94799

Denial Risk

Risk of denial for off-label or excluded uses

Claims for iNO in excluded or off-label scenarios are at risk of denial as not medically necessary per this policy. Affected scenarios include preterm infants <34 weeks gestation, infants with congenital diaphragmatic hernia (CDH), and individuals outside the infancy age group.

Preterm infants <34 weeks
Congenital diaphragmatic hernia (CDH)
Individuals outside infancy
CPT 94799

Billing Rule

Use of unlisted CPT 94799

Report iNO delivery using the unlisted pulmonary service/procedure code (CPT 94799) as referenced; include supporting clinical documentation with the unlisted code per billing guidance to justify medical necessity.

Report unlisted pulmonary service CPT 94799
Include supporting clinical documentation when using unlisted code

Documentation Required

Check federal/state/contractual requirements

Check applicable federal, state, and contractual benefit plan requirements because those terms govern in the event of conflict with this standard policy.

Documentation Required

Use of third-party criteria

UnitedHealthcare may use third-party tools (for example, InterQual) to assist in administering benefits; coverage determinations may reference such external criteria and providers should anticipate that determinations may align with those tools.

Third-party criteria such as InterQual may be used

Documentation Required

State-specific policy applicability

This Medical Policy does not apply to certain states; refer to the state-specific policy version where indicated. The policy was updated to add a Louisiana state-specific policy link effective 2026-02-01 and it does not apply to North Carolina (refer to the NC-specific policy).

North Carolina: refer to state-specific policy
Louisiana: state-specific policy link added effective 2026-02-01