ModifiedColorado Rocky Mountain Health PlansPolicy 2026T0607M

Inhaled Nitric Oxide (iNO) Therapy — Neonatal/Infant Coverage Criteria

Medical policy governing the use of inhaled nitric oxide therapy for UnitedHealthcare Commercial and Individual Exchange benefit plans, focused on neonatal/infant indications and evidence summaries.

Policy Summary

PayerColorado Rocky Mountain Health Plans

PolicyInhaled Nitric Oxide (iNO) Therapy — Neonatal/Infant Coverage Criteria

Policy CodePolicy 2026T0607M

Change TypeModified — clarified indications and exclusions

Effective DateJan 1, 2026

Next Review DateN/A

Key ActionObtain prior authorization with documentation of gestational age (≥34 weeks), diagnosis of hypoxic respiratory failure or echocardiographic PPHN, absence of CDH, and failure of conventional treatments.

SourceLink

POLICY UPDATE CHANGES

Policy explicitly states iNO is proven and medically necessary for term or near-term infants (≥34 weeks) with hypoxic respiratory failure or echocardiographic evidence of PPHN when CDH is absent and conventional treatments have failed.

Notes that iNO is unproven and not medically necessary for newborns with congenital diaphragmatic hernia and for preterm newborns <34 weeks gestation.

States that iNO treatment for individuals outside of infancy is experimental or investigational due to lack of FDA-approved indications.

Template Update

≥34gestational age threshold

20 ppminitial concentration

94799unlisted service code

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Not supportedstance for preterm <34w

MetHb / possible long-term riskssafety concerns

Coverage Criteria for Inhaled Nitric Oxide (iNO)

Coverage for Term/Near-term Infants (Initial therapy)

Covered when ALL of the following are met

Term/Near-term infants with hypoxic respiratory failure or PPHN: Infant born at least 34 weeks gestation with hypoxic respiratory failure or echocardiographic evidence of persistent pulmonary hypertension of the newborn (PPHN)gestational age >= 34 weeks

Absence of congenital diaphragmatic hernia: No congenital diaphragmatic hernia (CDH)

Infants with CDH are excluded due to different response

Failure of conventional treatments (e.g., mechanical ventilation)

iNO may be used as bridge therapy postoperatively for pulmonary hypertension during acute recovery

Population-specific coverage criteria

Coverage considerations based on clinical population and evidence:

Term/Near-term neonates with hypoxic respiratory failure and pulmonary hypertension: iNO is indicated and has demonstrated benefit for improving oxygenation and reducing need for ECMO in term and near-term (>34 weeks) neonates with clinical or echocardiographic evidence of pulmonary hypertension

Supported by FDA INOmax indication and guideline guidance

Preterm infants (<34 weeks): Routine, early rescue, or later rescue use of iNO does not consistently improve survival or decrease bronchopulmonary dysplasia (BPD); evidence does not support routine prophylactic use in preterm infants

Multiple RCTs, systematic reviews and guideline assessments report no consistent benefit and potential harms (e.g., increased severe IVH)

Preterm subgroup — African American infants: Individual participant meta-analysis (Askie et al., 2018) found reduced composite death or BPD in African American preterm infants in selected trials, but this is post hoc and hypothesis-generating rather than conclusive

Consider only in exceptional/high-risk cases with supporting documentation

Congenital diaphragmatic hernia (CDH):

Inhaled nitric oxide (iNO) is explicitly not proven and not medically necessary for newborns with congenital diaphragmatic hernia (CDH) and for preterm newborns who are less than 34 weeks gestation. The policy states that, outside the defined term/near‑term indication, iNO use in these populations lacks sufficient evidence of efficacy and therefore may be denied.

iNO treatment for individuals outside the Infancy age group is considered experimental or investigational because there are no FDA‑approved indications for such use. The FDA‑cleared product INOmax is indicated for term and near‑term neonates (>34 weeks) with hypoxic respiratory failure and pulmonary hypertension; uses beyond infancy lack regulatory approval and supportive evidence.

Routine use of iNO in preterm infants (<34 weeks gestation) for prevention of bronchopulmonary dysplasia (BPD) or as standard respiratory support is not recommended. Systematic reviews and guideline statements, including Cochrane analyses and NICE guidance, do not show consistent benefit and advise against routine prophylactic use in preterm babies unless other specific indications (e.g., pulmonary hypoplasia or pulmonary hypertension) exist.

This policy is intended to assist in interpreting standard benefit plans but must be used in conjunction with the member‑specific benefit plan document and any applicable federal or state mandates. Where there is a conflict between this Medical Policy and the member‑specific benefit plan, the member‑specific plan governs; always verify benefits before initiating iNO therapy.

Use of iNO for preterm infants born at less than 34 weeks gestation is considered not medically necessary because high‑quality evidence and systematic reviews fail to demonstrate clear clinical benefit and identify potential harms (for example, increased risk of severe intraventricular hemorrhage and necrotizing enterocolitis). Clinical decision‑making should reflect this unfavorable benefit–harm balance.

Evidence does not support early routine, early rescue, or later rescue strategies of iNO in preterm infants (<34 weeks). Multiple randomized trials and systematic reviews show no consistent improvement in survival, reduction in BPD, or improved neurodevelopmental outcomes with these approaches, and therefore such uses are not supported as routine therapy.

Coding and Related Parameters

Referenced CPT CodesCPT

94799

Unlisted pulmonary service or procedure

Initial iNO concentration cited as effective

Initial iNO concentration20 ppm

Population studiedTerm and near-term infants with hypoxic respiratory failure

Outcome notedImproved oxygenation in trials at 20 ppm

PaO2/Oxygenation index thresholds for iNO in PPHN

PaO2 threshold on 100% O2PaO2 < 100 mm Hg

Oxygenation index thresholdOxygenation index > 25

Context

Provider Requirements, Prior Authorization, and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization is required for inhaled nitric oxide (iNO) when billed under CPT 94799 (unlisted respiratory procedure) for FDA‑indicated neonatal use (INOmax) and for other indications where the member’s benefit plan requires prior authorization. Submit clinical documentation that supports the FDA‑indicated criteria where applicable.

Prior authorization required for services billed under CPT 94799
Include member identifiers, dates of service, and facility

Note

Policy Interpretation and Member‑Plan Verification

This policy is intended to help interpret standard benefit plans; however, the member-specific benefit plan document governs coverage decisions. Verify the member’s plan, applicable state or federal mandates, and any Medicare guidance (NCD/LCD) prior to rendering or billing services. In case of conflict, the member-specific benefit document prevails.

Check member-specific benefit plan and applicable mandates before initiating iNO

Background and Rationale

Inhaled nitric oxide (iNO) is a selective pulmonary vasodilator that dilates pulmonary vessels, lowers pulmonary vascular resistance, and is used in neonates to improve oxygenation and reduce the need for extracorporeal membrane oxygenation (ECMO) in cases of hypoxic respiratory failure and persistent pulmonary hypertension of the newborn (PPHN). Its use requires appropriate monitoring because it can increase methemoglobin and has been associated with potential long‑term harms in some studies.

Definitions and Product Information

Infancy — Definition

DefinitionThe period from birth through the first year of life.

ReferenceBarfield 2016 (as cited in policy)

Scope implicationPolicy statements referring to 'infancy' apply to patients up to 12 months old

INOmax — FDA-cleared inhaled nitric oxide product

ProductINOmax (nitric oxide gas)

FDA indicationTreatment of term and near-term (>34 weeks) neonates with hypoxic respiratory failure associated with clinical or echocardiographic evidence of pulmonary hypertension.

Policy Summary

PayerColorado Rocky Mountain Health Plans

PolicyInhaled Nitric Oxide (iNO) Therapy — Neonatal/Infant Coverage Criteria

Policy CodePolicy 2026T0607M

Change TypeModified — clarified indications and exclusions

Effective DateJan 1, 2026

Next Review DateN/A

SourceLink

On This Page

Systematic reviews and trials do not show clear benefit of iNO for CDH on death or need for ECMO; routine use is not recommended and may be harmful in infants with left ventricular systolic dysfunction

Consider only with documented echocardiography showing pulmonary hypertension and preserved LV systolic function and a documented oxygenation response

Postoperative pulmonary hypertension in infants/children with congenital heart disease (CHD): Evidence is inconclusive; clinical guidance supports use of iNO and/or inhaled prostacyclin as initial therapy for postoperative pulmonary hypertensive crises — iNO may be considered as bridge therapy with documentation of conventional therapy trial and clinical response

Decisions should be individualized and documented

Indication for iNO in mechanically ventilated term and near-term newborns with PPHN to improve oxygenation and reduce need for ECMO

Medicare Advantage: follow NCD/LCD or MAO determinations when applicable

Denial Risk

Off‑Label Use in Preterm Infants — Denial Risk

iNO (e.g., INOmax) is not FDA‑approved for preterm infants (≤ 34 weeks gestation). Requests for iNO for preterm newborns (<34 weeks) or for congenital diaphragmatic hernia (CDH) are at high risk for denial unless compelling, documented medical rationale and member benefits expressly allow off‑label coverage.

iNO not approved for preterm infants (≤ 34 weeks); use in this population is off‑label and may be non‑covered
Requests for CDH are likely to be denied

Note

Member‑Specific Benefit Verification Required

Coverage decisions must reference and be consistent with the member‑specific benefit plan. Prior authorization and claim payment are determined by that plan’s terms, which may differ from this Medical Policy. Always verify eligibility, benefits, and any plan limits or exclusions before treatment.

Member‑specific benefit governs coverage decisions
Verify eligibility and benefit limits prior to treatment

Documentation Required

Required Documentation Elements

Document clinical justification thoroughly. Required elements include: gestational age at birth (to confirm ≥34 weeks when claiming FDA‑indicated neonatal use), primary diagnosis (e.g., hypoxic respiratory failure, PPHN), absence of CDH if claiming coverage, prior conventional therapies tried and their outcomes (e.g., mechanical ventilation), echocardiographic findings if applicable, and details of the delivery/administration system (device, settings, and monitoring).

Document gestational age to confirm ≥34 weeks when applicable
Document diagnosis, echocardiography findings, and absence of CDH
Document prior conventional treatments tried (e.g., mechanical ventilation) and rationale for iNO
Include device/delivery system and monitoring information

Step Therapy

Step Therapy / Sequencing

iNO coverage follows a stepwise approach. For FDA‑indicated neonatal use, iNO is covered for term and near‑term infants (≥34 weeks) with hypoxic respiratory failure/PPHN after failure of conventional treatments. In postoperative pediatric pulmonary hypertension, iNO may be covered as bridge therapy during the acute recovery phase per practice guidelines.

iNO covered after failure of conventional treatments (e.g., mechanical ventilation) for eligible neonates
Postoperative PH: iNO may be used as bridge therapy during acute recovery

INOmax is not approved for use in preterm infants (≤ 34 weeks).

PPHN — Definition and context

DefinitionPersistent pulmonary hypertension of the newborn (PPHN) — a condition in which pulmonary vascular resistance remains high causing hypoxemia.

Clinical contextPPHN in mechanically ventilated term and near-term newborns may be treated with iNO to improve oxygenation and reduce need for ECMO when oxygenation thresholds are met.

Guidance sourceEuropean Paediatric Pulmonary Vascular Disease Network (EPPVDN) consensus statement

Inhaled nitric oxide (iNO) — definition and mechanism

DefinitionInhaled nitric oxide (iNO): a selective pulmonary vasodilator administered as a gas to lower pulmonary vascular resistance and improve oxygenation in neonates with hypoxic respiratory failure and pulmonary hypertension.

MechanismDelivered via a regulated nitric oxide delivery system to selectively dilate pulmonary vessels, reducing pulmonary artery pressure and improving ventilation-perfusion matching.

Safety noteiNO increases methemoglobin and has been associated in some studies with potential long-term harms; use is limited by age and indication per guidance and FDA labeling.