{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T20:20:22Z","timestamp":1777494022290,"version":"3.51.4"},"reference-count":29,"publisher":"Georg Thieme Verlag KG","issue":"14","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Am J Perinatol"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:p>Objective\u2003While advanced therapies for severe persistent pulmonary hypertension of the newborn (PPHN) such as inhaled nitric oxide (iNO) and extracorporeal membrane oxygenation (ECMO) are standard treatments in high-income countries, these therapies are often unavailable in resource-limited settings such as middle-income countries. However, there are small clinical trials illustrating the efficacy of sildenafil at reducing mortality in PPHN. This analysis sought to determine the cost-utility of enteral sildenafil for the treatment of severe PPHN.<\/jats:p><jats:p>Study Design\u2003A Markov-state transition model was constructed for the two clinical approaches to compare costs, clinical outcomes, and quality of life: (1) \u201cconventional,\u201d (2) \u201csildenafil.\u201d The impact of sildenafil was modeled as a relative risk modifier of the conventional strategy's mortality risk. Transitional probabilities, costs, and utility metrics were extracted from the literature. Sensitivity analyses for each model input as well as 100-patient Monte Carlo simulations were used to test the durability of the model conclusion.<\/jats:p><jats:p>Results\u2003The sildenafil strategy was cost-effective for upper but not lower middle-income countries with an incremental cost-effectiveness ratio of $2,339 per quality-adjusted life year. This conclusion was durable across a wide-range of model assumptions; the sildenafil strategy only failed to meet criteria for cost-effectiveness when sildenafil therapy had a mortality relative risk efficacy of &gt;0.89, if life expectancy in that country is &lt;40 years, or if the lifetime forecasted costs of a survivor's life was quite high.<\/jats:p><jats:p>Conclusion\u2003Enteral sildenafil is a cost-effective intervention for severe PPHN for upper middle-income countries where ECMO and iNO are not available.<\/jats:p><jats:p>Key Points<\/jats:p>","DOI":"10.1055\/s-0040-1713819","type":"journal-article","created":{"date-parts":[[2020,7,2]],"date-time":"2020-07-02T22:39:56Z","timestamp":1593729596000},"page":"1505-1512","source":"Crossref","is-referenced-by-count":8,"title":["Cost-Utility of Sildenafil for Persistent Pulmonary Hypertension of the Newborn"],"prefix":"10.1055","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9299-1926","authenticated-orcid":false,"given":"Patrick D.","family":"Evers","sequence":"additional","affiliation":[{"name":"Division of Pediatric Cardiology, Oregon Health and Sciences University, Portland, Oregon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul J.","family":"Critser","sequence":"additional","affiliation":[{"name":"Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle","family":"Cash","sequence":"additional","affiliation":[{"name":"Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa","family":"Magness","sequence":"additional","affiliation":[{"name":"Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan","family":"Hoelle","sequence":"additional","affiliation":[{"name":"Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Russel","family":"Hirsch","sequence":"additional","affiliation":[{"name":"Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio"},{"name":"Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2020,7,2]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1542\/peds.105.1.14","article-title":"Persistent pulmonary hypertension of the newborn in the era before nitric oxide: practice variation and outcomes","volume":"105","author":"M C Walsh-Sukys","year":"2000","journal-title":"Pediatrics"},{"issue":"09","key":"ref2","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1056\/NEJM199702273360902","article-title":"Inhaled nitric oxide and persistent pulmonary hypertension of the newborn","volume":"336","author":"J D Roberts Jr","year":"1997","journal-title":"N Engl J Med"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.jpeds.2019.06.053","article-title":"Morbidity of persistent pulmonary hypertension of the newborn in the first year of life","volume":"213","author":"M A Steurer","year":"2019","journal-title":"J Pediatr"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1542\/peds.98.4.706","article-title":"Four patterns of response to inhaled nitric oxide for persistent pulmonary hypertension of the newborn","volume":"98","author":"A P Goldman","year":"1996","journal-title":"Pediatrics"},{"issue":"02","key":"ref5","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1542\/peds.114.2.417","article-title":"Cost-effectiveness of inhaled nitric oxide for the management of persistent pulmonary hypertension of the newborn","volume":"114","author":"S A Lorch","year":"2004","journal-title":"Pediatrics"},{"issue":"04","key":"ref6","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1542\/peds.2005-0523","article-title":"Oral sildenafil in infants with persistent pulmonary hypertension of the newborn: a pilot randomized blinded study","volume":"117","author":"H Baquero","year":"2006","journal-title":"Pediatrics"},{"issue":"03","key":"ref7","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1055\/s-0029-1239496","article-title":"The use of sildenafil in persistent pulmonary hypertension of the newborn","volume":"27","author":"A Vargas-Origel","year":"2010","journal-title":"Am J Perinatol"},{"issue":"04","key":"ref8","first-page":"159","article-title":"Oral sildenafil as an alternative treatment in the persistent pulmonary hypertension in newborns","volume":"73","author":"R Torres","year":"2006","journal-title":"Rivista Mexicana Pediatr"},{"issue":"06","key":"ref9","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/j.jpeds.2009.06.012","article-title":"Intravenous sildenafil in the treatment of neonates with persistent pulmonary hypertension","volume":"155","author":"R H Steinhorn","year":"2009","journal-title":"J Pediatr"},{"key":"ref10","first-page":"CD005494","article-title":"Sildenafil for pulmonary hypertension in neonates","volume":"8","author":"L E Kelly","year":"2017","journal-title":"Cochrane Database Syst Rev"},{"issue":"06","key":"ref12","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1542\/peds.107.6.1351","article-title":"Child health status, neurodevelopmental outcome, and parental satisfaction in a randomized, controlled trial of nitric oxide for persistent pulmonary hypertension of the newborn","volume":"107","author":"M Ellington Jr","year":"2001","journal-title":"Pediatrics"},{"issue":"03","key":"ref13","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1067\/mpd.2002.122730","article-title":"Neurodevelopmental and medical outcomes of persistent pulmonary hypertension in term newborns treated with nitric oxide","volume":"140","author":"P H Lipkin","year":"2002","journal-title":"J Pediatr"},{"issue":"05","key":"ref14","doi-asserted-by":"crossref","first-page":"791","DOI":"10.2105\/AJPH.2017.303696","article-title":"Injury mortality in individuals with autism","volume":"107","author":"J Guan","year":"2017","journal-title":"Am J Public Health"},{"issue":"04","key":"ref15","doi-asserted-by":"crossref","first-page":"e1203","DOI":"10.1542\/peds.2006-0127","article-title":"A comparison of health care utilization and costs of children with and without autism spectrum disorders in a large group-model health plan","volume":"118","author":"L A Croen","year":"2006","journal-title":"Pediatrics"},{"issue":"01","key":"ref16","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.jpeds.2009.01.040","article-title":"Improving decision analyses: parent preferences (utility values) for pediatric health outcomes","volume":"155","author":"A E Carroll","year":"2009","journal-title":"J Pediatr"},{"issue":"01","key":"ref17","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.ridd.2005.11.002","article-title":"Cost-impact of young adults with high-functioning autistic spectrum disorder","volume":"28","author":"K J\u00e4rbrink","year":"2007","journal-title":"Res Dev Disabil"},{"issue":"10","key":"ref19","first-page":"989","article-title":"Cost of neonatal intensive care in a tertiary care center","volume":"42","author":"A Narang","year":"2005","journal-title":"Indian Pediatr"},{"issue":"09","key":"ref20","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1007\/s13312-013-0234-6","article-title":"Cost of neonatal intensive care delivered through district level public hospitals in India","volume":"50","author":"S Prinja","year":"2013","journal-title":"Indian Pediatr"},{"key":"ref22","volume-title":"WHO | Public Spending on Health: A Closer Look at Global Trends","author":"K Xu","year":"2018"},{"issue":"02","key":"ref23","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1017\/S0266462320000124","article-title":"Using QALYs versus DALYs to measure cost-effectiveness: How much does it matter?","volume":"36","author":"X Feng","year":"2020","journal-title":"Int J Technol Assess Health Care"},{"issue":"05","key":"ref24","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1016\/j.jtcvs.2004.08.012","article-title":"Cost-utility analysis of salvage cardiac extracorporeal membrane oxygenation in children","volume":"129","author":"W T Mahle","year":"2005","journal-title":"J Thorac Cardiovasc Surg"},{"key":"ref26","first-page":"759","volume-title":"Use and misuse of cost-effectiveness analysis thresholds in low- and middle-income countries: trends in cost-per-DALY studies","author":"A A Leech","year":"2018"},{"issue":"01","key":"ref27","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1093\/heapol\/czw096","article-title":"Understanding and improving the one and three times GDP per capita cost-effectiveness thresholds","volume":"32","author":"L A Robinson","year":"2017","journal-title":"Health Policy Plan"},{"issue":"17","key":"ref28","doi-asserted-by":"crossref","first-page":"1758","DOI":"10.1161\/CIRCULATIONAHA.107.727289","article-title":"Pulmonary vascular disease in the developing world","volume":"118","author":"G Butrous","year":"2008","journal-title":"Circulation"},{"issue":"S 06","key":"ref29","doi-asserted-by":"crossref","first-page":"85S","DOI":"10.1378\/chest.09-2816","article-title":"Worldwide physician education and training in pulmonary hypertension: pulmonary vascular disease: the global perspective","volume":"137","author":"C G Elliott","year":"2010","journal-title":"Chest"},{"issue":"06","key":"ref30","doi-asserted-by":"crossref","first-page":"e334","DOI":"10.1016\/S2214-109X(14)70213-X","article-title":"Cost-effectiveness of surgery and its policy implications for global health: a systematic review and analysis","volume":"2","author":"T E Chao","year":"2014","journal-title":"Lancet Glob Health"},{"issue":"05","key":"ref31","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1097\/QCO.0000000000000096","article-title":"Global burden of childhood diarrhea and interventions","volume":"27","author":"J K Das","year":"2014","journal-title":"Curr Opin Infect Dis"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1016\/S0140-6736(07)61694-8","article-title":"Maternal and child undernutrition: effective action at national level","volume":"371","author":"J Bryce","year":"2008","journal-title":"Lancet"},{"issue":"01","key":"ref33","doi-asserted-by":"crossref","first-page":"51","DOI":"10.5935\/0103-507X.20140008","article-title":"Predictors of extubation failure and reintubation in newborn infants subjected to mechanical ventilation [in Portuguese]","volume":"26","author":"A C Costa","year":"2014","journal-title":"Rev Bras Ter Intensiva"}],"container-title":["American Journal of Perinatology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0040-1713819.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,31]],"date-time":"2022-10-31T21:44:44Z","timestamp":1667252684000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0040-1713819"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,2]]},"references-count":29,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2021,11,22]]},"published-print":{"date-parts":[[2021,12]]}},"URL":"https:\/\/doi.org\/10.1055\/s-0040-1713819","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0735-1631","1098-8785"],"issn-type":[{"value":"0735-1631","type":"print"},{"value":"1098-8785","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,2]]}}}