{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T04:21:39Z","timestamp":1772252499116,"version":"3.50.1"},"reference-count":43,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,10,13]],"date-time":"2020-10-13T00:00:00Z","timestamp":1602547200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["RO3 HD096510"],"award-info":[{"award-number":["RO3 HD096510"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["RO1 HD072929"],"award-info":[{"award-number":["RO1 HD072929"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Oxygen is a pulmonary vasodilator and plays an important role in mediating circulatory transition from fetal to postnatal period. Oxygen tension (PO2) in the alveolus (PAO2) and pulmonary artery (PaO2) are the main factors that influence hypoxic pulmonary vasoconstriction (HPV). Inability to achieve adequate pulmonary vasodilation at birth leads to persistent pulmonary hypertension of the newborn (PPHN). Supplemental oxygen therapy is the mainstay of PPHN management. However, optimal monitoring and targeting of oxygenation to achieve low pulmonary vascular resistance (PVR) and optimizing oxygen delivery to vital organs remains unknown. Noninvasive pulse oximetry measures peripheral saturations (SpO2) and a target range of 91\u201395% are recommended during acute PPHN management. However, for a given SpO2, there is wide variability in arterial PaO2, especially with variations in hemoglobin type (HbF or HbA due to transfusions), pH and body temperature. This review evaluates the role of alveolar, preductal, postductal, mixed venous PO2, and SpO2 in the management of PPHN. Translational and clinical studies suggest maintaining a PaO2 of 50\u201380 mmHg decreases PVR and augments pulmonary vasodilator management. Nevertheless, there are no randomized clinical trials evaluating outcomes in PPHN targeting SpO2 or PO2. Also, most critically ill patients have umbilical arterial catheters and postductal PaO2 may not be an accurate assessment of oxygen delivery to vital organs or factors influencing HPV. The mixed venous oxygen tension from umbilical venous catheter blood gas may assess pulmonary arterial PO2 and potentially predict HPV. It is crucial to conduct randomized controlled studies with different PO2\/SpO2 target ranges for the management of PPHN and compare outcomes.<\/jats:p>","DOI":"10.3390\/children7100180","type":"journal-article","created":{"date-parts":[[2020,10,13]],"date-time":"2020-10-13T08:55:53Z","timestamp":1602579353000},"page":"180","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["How Do We Monitor Oxygenation during the Management of PPHN? Alveolar, Arterial, Mixed Venous Oxygen Tension or Peripheral Saturation?"],"prefix":"10.3390","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8727-3017","authenticated-orcid":false,"given":"Praveen","family":"Chandrasekharan","sequence":"first","affiliation":[{"name":"Division of Neonatology, Department of Pediatrics, University at Buffalo, Buffalo, NY 14260, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9703-9857","authenticated-orcid":false,"given":"Munmun","family":"Rawat","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Pediatrics, University at Buffalo, Buffalo, NY 14260, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6098-2155","authenticated-orcid":false,"given":"Satyan","family":"Lakshminrusimha","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Pediatrics, University of California Davis, Davis, CA 95616, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.1161\/CIR.0000000000000329","article-title":"Pediatric Pulmonary Hypertension: Guidelines From the American Heart Association and American Thoracic Society","volume":"132","author":"Abman","year":"2015","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1136\/adc.66.1_Spec_No.6","article-title":"Doppler assessment of pulmonary artery pressure and extrapulmonary shunting in the acute phase of hyaline membrane disease","volume":"66","author":"Evans","year":"1991","journal-title":"Arch. Dis. Child."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1542\/peds.60.4.444","article-title":"Respiratory distress syndrome: Echocardiographic assessment of cardiovascular function and pulmonary vascular resistance","volume":"60","author":"Halliday","year":"1977","journal-title":"Pediatrics"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1136\/adc.67.4_Spec_No.366","article-title":"Pulmonary and systemic arterial pressure in hyaline membrane disease","volume":"67","author":"Skinner","year":"1992","journal-title":"Arch. Dis. Child."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1542\/peds.90.6.899","article-title":"Persistent pulmonary hypertension in premature neonates with severe respiratory distress syndrome","volume":"90","author":"Walther","year":"1992","journal-title":"Pediatrics"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1097\/MOP.0b013e328360a3f6","article-title":"Pulmonary vascular disease in bronchopulmonary dysplasia: Pulmonary hypertension and beyond","volume":"25","author":"Mourani","year":"2013","journal-title":"Curr. Opin. Pediatr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/j.clp.2015.08.010","article-title":"Pulmonary Hypertension and Vascular Abnormalities in Bronchopulmonary Dysplasia","volume":"42","author":"Mourani","year":"2015","journal-title":"Clin. Perinatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1164\/rccm.200310-1483OC","article-title":"Pulmonary vascular effects of inhaled nitric oxide and oxygen tension in bronchopulmonary dysplasia","volume":"170","author":"Mourani","year":"2004","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_9","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":"Tyson","year":"2000","journal-title":"Pediatrics"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"(2000). Inhaled nitric oxide in term and near-term infants: Neurodevelopmental follow-up of the neonatal inhaled nitric oxide study group (NINOS). J. Pediatr., 136, 611\u2013617.","DOI":"10.1067\/mpd.2000.104826"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.jpeds.2006.11.065","article-title":"Early inhaled nitric oxide therapy for term and near-term newborn infants with hypoxic respiratory failure: Neurodevelopmental follow-up","volume":"150","author":"Konduri","year":"2007","journal-title":"J. Pediatr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1203\/PDR.0b013e3181bab0c7","article-title":"Oxygen concentration and pulmonary hemodynamics in newborn lambs with pulmonary hypertension","volume":"66","author":"Lakshminrusimha","year":"2009","journal-title":"Pediatr. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1146\/annurev.ph.36.030174.001155","article-title":"Fetal and neonatal circulation and respiration","volume":"36","author":"Rudolph","year":"1974","journal-title":"Annu. Rev. Physiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1146\/annurev.me.19.020168.001211","article-title":"The fetal circulation","volume":"19","author":"Rudolph","year":"1968","journal-title":"Annu. Rev. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1172\/JCI105355","article-title":"Response of the pulmonary vasculature to hypoxia and H+ ion concentration changes","volume":"45","author":"Rudolph","year":"1966","journal-title":"J. Clin. Investig."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1002\/uog.9044","article-title":"Left-right difference in fetal liver oxygenation during hypoxia estimated by BOLD MRI in a fetal sheep model","volume":"38","author":"Sorensen","year":"2011","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"101070","DOI":"10.1016\/j.siny.2019.101070","article-title":"Oxygen therapy in preterm infants with pulmonary hypertension","volume":"25","author":"Chandrasekharan","year":"2020","journal-title":"Semin. Fetal Neonatal Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1203\/00006450-199809000-00012","article-title":"Decreased gene expression of endothelial nitric oxide synthase in newborns with persistent pulmonary hypertension","volume":"44","author":"Villanueva","year":"1998","journal-title":"Pediatr. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1161\/01.RES.39.4.536","article-title":"Gestational changes in pulmonary vascular responses in fetal lambs in utero","volume":"39","author":"Lewis","year":"1976","journal-title":"Circ. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1161\/01.CIR.97.3.257","article-title":"Reactivity of the human fetal pulmonary circulation to maternal hyperoxygenation increases during the second half of pregnancy: A randomized study","volume":"97","author":"Rasanen","year":"1998","journal-title":"Circulation"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1203\/00006450-199004000-00010","article-title":"Changes in the pulmonary circulation during birth-related events","volume":"27","author":"Teitel","year":"1990","journal-title":"Pediatr. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/j.clp.2012.06.006","article-title":"The pulmonary circulation in neonatal respiratory failure","volume":"39","author":"Lakshminrusimha","year":"2012","journal-title":"Clin. Perinatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1097\/ALN.0000000000000569","article-title":"Hypoxic pulmonary vasoconstriction: Physiology and anesthetic implications","volume":"122","author":"Lumb","year":"2015","journal-title":"Anesthesiology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1152\/japplphysiol.00733.2004","article-title":"Hypoxic pulmonary vasoconstriction","volume":"98","author":"Moudgil","year":"2005","journal-title":"J. Appl. Physiol. (1985)"},{"key":"ref_25","unstructured":"American Academy of Pediatrics and American Heart Association (2016). Textbook of Neonatal Resuscitation (NRP), American Academy of Pediatrics and American Heart Association. [7th ed.]."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/jp.2014.199","article-title":"Oxygen targeting in preterm infants: A physiological interpretation","volume":"35","author":"Lakshminrusimha","year":"2015","journal-title":"J. Perinatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1542\/peds.2007-0117","article-title":"Pulse oxygen saturation levels and arterial oxygen tension values in newborns receiving oxygen therapy in the neonatal intensive care unit: Is 85% to 93% an acceptable range?","volume":"121","author":"Castillo","year":"2008","journal-title":"Pediatrics"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/S0022-3476(79)80842-2","article-title":"Arterial oxygen tension during active and quiet sleep in the normal neonate","volume":"94","author":"Martin","year":"1979","journal-title":"J. Pediatr."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Bachman, T.E., Iyer, N.P., Newth, C.J.L., Ross, P.A., and Khemani, R.G. (2020). Thresholds for oximetry alarms and target range in the NICU: An observational assessment based on likely oxygen tension and maturity. BMC Pediatr., 20.","DOI":"10.1186\/s12887-020-02225-3"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1152\/japplphysiol.00711.2011","article-title":"Pulmonary hemodynamics and vascular reactivity in asphyxiated term lambs resuscitated with 21 and 100% oxygen","volume":"111","author":"Lakshminrusimha","year":"2011","journal-title":"J. Appl. Physiol. (1985)"},{"key":"ref_31","first-page":"326","article-title":"Influence of alveolar oxygen on pulmonary vasoconstriction in newborn lambs versus sheep","volume":"132","author":"Custer","year":"1985","journal-title":"Am. Rev. Respir. Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1203\/PDR.0b013e3180db29fe","article-title":"Pulmonary hemodynamics in neonatal lambs resuscitated with 21%, 50%, and 100% oxygen","volume":"62","author":"Lakshminrusimha","year":"2007","journal-title":"Pediatr. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.jpeds.2019.10.063","article-title":"Just Say No to iNO in Preterms-Really?","volume":"218","author":"Lakshminrusimha","year":"2020","journal-title":"J. Pediatr."},{"key":"ref_34","first-page":"H1955","article-title":"Ontogeny of NO activity and response to inhaled NO in the developing ovine pulmonary circulation","volume":"267","author":"Kinsella","year":"1994","journal-title":"Am. J. Physiol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Lesneski, A., Hardie, M., Ferrier, W., Lakshminrusimha, S., and Vali, P. (2020). Bidirectional Ductal Shunting and Preductal to Postductal Oxygenation Gradient in Persistent Pulmonary Hypertension of the Newborn. Children, 7.","DOI":"10.3390\/children7090137"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1165\/rcmb.2019-0449OC","article-title":"Optimal Oxygen Targets in Term Lambs with Meconium Aspiration Syndrome and Pulmonary Hypertension","volume":"63","author":"Rawat","year":"2020","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Barrington, K.J. (2000). Umbilical artery catheters in the newborn: Effects of position of the catheter tip. Cochrane Database Syst. Rev., CD000505.","DOI":"10.1002\/14651858.CD000505"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/cc126","article-title":"Venous oxygen measurements in the inferior vena cava in neonates with respiratory failure","volume":"2","author":"Plotz","year":"1998","journal-title":"Crit. Care"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"230","DOI":"10.5152\/balkanmedj.2014.13197","article-title":"Inferior Vena Cava Oxygen Saturation during the First Three Postnatal Days in Preterm Newborns with and without Patent Ductus Arteriosus","volume":"31","author":"Yapakci","year":"2014","journal-title":"Balk. Med. J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1038\/s41390-018-0085-x","article-title":"Effect of various inspired oxygen concentrations on pulmonary and systemic hemodynamics and oxygenation during resuscitation in a transitioning preterm model","volume":"84","author":"Chandrasekharan","year":"2018","journal-title":"Pediatr. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/pr.2015.259","article-title":"Neonatal resuscitation adhering to oxygen saturation guidelines in asphyxiated lambs with meconium aspiration","volume":"79","author":"Rawat","year":"2016","journal-title":"Pediatr. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1183\/20734735.001415","article-title":"Relating oxygen partial pressure, saturation and content: The haemoglobin-oxygen dissociation curve","volume":"11","author":"Collins","year":"2015","journal-title":"Breathe (Sheff)"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1097\/PCC.0000000000001799","article-title":"Monitoring Gas Exchange During Hypothermia for Hypoxic-Ischemic Encephalopathy","volume":"20","author":"Afzal","year":"2019","journal-title":"Pediatr. Crit. Care Med."}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/7\/10\/180\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:20:17Z","timestamp":1760178017000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/7\/10\/180"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,13]]},"references-count":43,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2020,10]]}},"alternative-id":["children7100180"],"URL":"https:\/\/doi.org\/10.3390\/children7100180","relation":{"has-preprint":[{"id-type":"doi","id":"10.20944\/preprints202008.0452.v1","asserted-by":"object"}]},"ISSN":["2227-9067"],"issn-type":[{"value":"2227-9067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,13]]}}}