Inhaled Nitric Oxide in Pre-term Infants Form

MEDICAL COVERAGE POLICY SERVICE: Inhaled Nitric Oxide in Preterm Infants Policy Number: 217 Effective Date: 06/01/2025 Last Review: 05/12/2025 Next Review: 05/12/2026 Page 1 of 4 Important note: Unless otherwise indicated, medical policies will apply to all lines of business. Medical necessity as defined by this policy does not ensure the benefit is covered. This medical policy does not replace existing federal or state rules and regulations for the applicable service or supply. In the absence of a controlling federal or state coverage mandate, benefits are ultimately determined by the terms of the applicable benefit plan documents. See the member plan specific benefit plan document for a complete description of plan benefits, exclusions, limitations, and conditions of coverage. In the event of a discrepancy, the plan document always supersedes the information in this policy. SERVICE: Inhaled Nitric Oxide Use in Preterm Infants PRIOR AUTHORIZATION: Not required. This service is subject to retrospective review. POLICY: Please review the plan’s EOC (Evidence of Coverage) or Summary Plan Description (SPD) for details. Note: Unless otherwise indicated (see below), this policy will apply to all lines of business. For Medicare plans, please refer to appropriate Medicare NCD (National Coverage Determination) or LCD (Local Coverage Determination). If there are no applicable NCD or LCD criteria, use the criteria set forth below. For Medicaid plans, please confirm coverage as outlined in the Texas Medicaid Provider Procedures Manual | TMHP (TMPPM). If there are no applicable criteria to guide medical necessity decision making in the TMPPM, use the criteria set forth below. BSWHP may consider inhaled nitric oxide (iNO) medically necessary when the following are met:

1. Hypoxic respiratory failure in a newborn ≥ 34 weeks gestation, AND
2. Diagnosis of pulmonary hypertension, AND
3. Absence of unrepaired congenital diaphragmatic hernia Use of iNO therapy for more than 4 days is subject to medical necessity review. All other indications for iNO are unproven or investigational, including, but not limited to, preterm infants with pulmonary disease. BACKGROUND: Nitric oxide is a colorless, odorless gas. iNO is a selective pulmonary vasodilator whose mechanism of action involves guanylyl cyclase activation leading to production of cyclic guanosine monophosphate and subsequent smooth muscle relaxation. There are several physiologic effects that make iNO an appealing therapy for infants with pulmonary hypertension: iNO can decrease pulmonary vascular resistance, improve ventilation-perfusion inequalities, and reduce right-to-left intra-cardiac shunting of blood through the foramen ovale and ductus arteriosus, all of which can contribute to improved arterial oxygenation and hemodynamic stability.

MEDICAL COVERAGE POLICY SERVICE: Inhaled Nitric Oxide in Preterm Infants Policy Number: 217 Effective Date: 06/01/2025 Last Review: 05/12/2025 Next Review: 05/12/2026 Page 2 of 4 INOmax®, a commercially available inhaled nitric oxide product, is indicated to improve oxygenation and reduce the need for extracorporeal membrane oxygenation in near-term (>34 weeks gestation) and term infants with hypoxic respiratory failure with clinical or echocardiographic evidence of pulmonary hypertension. .
Persistent pulmonary hypertension (PPHN) may occur as a primary developmental defect or as a condition secondary to morbidities such as respiratory distress syndrome (i.e., hyaline membrane disease), meconium aspiration syndrome, pneumonia, sepsis, congenital diaphragmatic hernia, cardiac malformations and pulmonary hypoplasia. Per the AAP, iNO therapy should be given using the indications, dosing, administration, and monitoring guidelines outlined on the product label (http://www.fda.gov). Administration of iNO for indications other than those approved by the FDA or in other neonatal populations, including compassionate use, remains experimental.
. MANDATES: None CODES: Important note: Due to the wide range of applicable diagnosis codes and potential changes to codes, an inclusive list may not be presented, but the following codes may apply. Inclusion of a code in this section does not guarantee that it will be reimbursed, and patient must meet the criteria set forth in the policy language. CPT Codes 94799 – Under Pulmonary Diagnostic Testing and Therapies CPT Not Covered ICD-10 codes I27.0 - Primary pulmonary hypertension I27.2 - Secondary pulmonary hypertension P07.37 - P07.39 - Preterm newborn 34-36 complete weeks P28.5 - Respiratory failure of newborn P29.30 - Pulmonary hypertension of newborn P29.38 - Other persistent fetal circulation ICD10 Not covered P27.x - Chronic respiratory disease originating in the perinatal period POLICY HISTORY: Status Date Action New 09/24/2015 New policy Reviewed 09/29/2016 No changes in coverage Reviewed 09/19/2017 No changes

MEDICAL COVERAGE POLICY SERVICE: Inhaled Nitric Oxide in Preterm Infants Policy Number: 217 Effective Date: 06/01/2025 Last Review: 05/12/2025 Next Review: 05/12/2026 Page 3 of 4 Reviewed 08/14/2018 No changes Reviewed 10/31/2019 No changes Reviewed 11/19/2020 No changes Reviewed 12/23/2021 Updated language. No change in coverage Reviewed 12/29/2022 No changes Reviewed 12/29/2023 No policy changes. Added CPT Code 94799 and reformatted existing criteria. Other formatting changes and added hyperlinks to TMPPM, beginning and ending note sections updated to align with CMS requirements and business entity changes. Reviewed 08/12/2024 No changes Reviewed 05/12/2025 Updated Background Section Updated 08/11/2025 Removed “Medicare NCD or LCD specific InterQual criteria may be used when available.” REFERENCES: The following scientific references were utilized in the formulation of this medical policy. BSWHP will continue to review clinical evidence related to this policy and may modify it at a later date based upon the evolution of the published clinical evidence. Should additional scientific studies become available and they are not included in the list, please forward the reference(s) to BSWHP so the information can be reviewed by the Medical Coverage Policy Committee (MCPC) and the Quality Improvement Committee (QIC) to determine if a modification of the policy is in order.

1. American Academy of Pediatrics. Committee on Fetus and Newborn. Use of Inhaled Nitric Oxide. Recommendations. Pediatrics Vol 106, No.2, August 2000. Available at: pediatrics.aappublications.org/content/pediatrics/106/2/344.full. accessed 9/11/2017.
2. American Academy of Pediatrics. Committee on Fetus and Newborn. Use of inhaled nitric oxide in preterm infants. Pediatrics 2014:133:1 165-170.
3. American Association for Respiratory Care (AARC). Evidence-based clinical practice guideline: inhaled nitric oxide for neonates with acute hypoxic respiratory failure. 2010. Accessed 9/8/17. Available at URL address: http://www.rcjournal.com/cpgs/index.cfm
4. Cole FS, Alleyne C, Barks JD, et al. NIH Consensus Development Conference statement: inhaled nitric-oxide therapy for premature infants. Pediatrics. 2011;127(2):363–369
5. Kinsella JP, Cutter GR, Steinhorn RH, Nelin LD, Walsh WF, Finer NN, Abman SH. Noninvasive inhaled nitric oxide does not prevent bronchopulmonary dysplasia in premature newborns. J Pediatr. 2014 Dec;165(6):1104-1108.
6. Kinsella JP, Steinhorn RH, Krishnan US, Feinstein JA, Adatia I, Austin ED, Rosenzweig EB, Everett AD, Fineman JR, Hanna BD, Hopper RK, Humpl T, Ivy DD, Keller RL, Mullen MP, Raj JU, Wessel DL, Abman SH. Recommendations for the Use of Inhaled Nitric Oxide Therapy in Premature Newborns with Severe Pulmonary Hypertension.. J Pediatr. 2016 Mar;170:312-4. doi: 10.1016/j.jpeds.2015.11.050. Epub 2015 Dec 15. PMID: 26703869
7. Jiang Q, Gao X, Liu C, Chen D, Lin X, Xia S, Zhuang D, Yang C, Zhu W, Liu L, Chen C, Sun B. Early inhaled nitric oxide in preterm infants <34 weeks with evolving bronchopulmonary dysplasia. J Perinatol. 2016 Jul 21. doi: 10.1038/jp.2016.112. PMID: 27442155
8. American Academy of Pediatrics. Maduekwe E, DeCristofaro JD., Neoreviews, March 2017, Volume 18/Issue 3 section on Inhaled Nitric Oxide. Available at

MEDICAL COVERAGE POLICY SERVICE: Inhaled Nitric Oxide in Preterm Infants Policy Number: 217 Effective Date: 06/01/2025 Last Review: 05/12/2025 Next Review: 05/12/2026 Page 4 of 4 http://neoreviews.aappublications.org/content/18/3/e173?utm_source=TrendMD&utm_medium=TrendMD&utm
campaign=NeoRevTrendMD_0. Accessed 9/11/2017.

9. Carey WA, Weaver AL, Mara KC, Clark RH. Inhaled Nitric Oxide in Extremely Premature Neonates with Respiratory Distress Syndrome. Pediatrics March 2018, 141 (3) e20173108; DOI: https://doi.org/10.1542/peds.2017-3108
10. Lakshminrusimha S, Kinsella JP, Abman SH, et al. Just Say No to iNO in Preterms—Really? J Pediatr 2020 Mar;218:243-
11. doi: 10.1016/j.jpeds.2019.10.063. Epub 2019 Dec 4. PMID: 31810629
12. Barrington KJ, Finer N, Pennaforte T. Inhaled nitric oxide for respiratory failure in preterm infants. Cochrane Database Syst Rev. 2017;1:CD000509
13. Hayes Review, annual review March 17, 2021
14. Hayes Review, December 14, 2021 Note: Health Maintenance Organization (HMO) products are offered through Scott and White Health Plan dba Baylor Scott & White Health Plan, and Scott & White Care Plans dba Baylor Scott & White Care Plan. Insured PPO and EPO products are offered through Baylor Scott & White Insurance Company. Scott and White Health Plan dba Baylor Scott & White Health Plan serves as a third-party administrator for self-funded employer-sponsored plans. Baylor Scott & White Care Plan and Baylor Scott & White Insurance Company are wholly owned subsidiaries of Scott and White Health Plan. These companies are referred to collectively in this document as Baylor Scott & White Health Plan.
    RightCare STAR Medicaid is offered through Scott and White Health Plan in the Central Texas Medicaid Rural Service Area (MRSA); FirstCare STAR is offered through SHA LLC dba FirstCare Health Plans (FirstCare) in the Lubbock and West MRSAs; and FirstCare CHIP is offered through FirstCare in the Lubbock Service Area.