{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T04:54:37Z","timestamp":1777006477841,"version":"3.51.4"},"reference-count":38,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T00:00:00Z","timestamp":1775952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Background\/Objectives: Abnormalities in the partial pressure of carbon dioxide (PCO2) can occur during respiratory support and may contribute to adverse neonatal outcomes. This study aimed to assess the incidence of early hypocapnia and hypercapnia in mechanically ventilated preterm infants and their major associated outcomes. Methods: A single-center retrospective cohort study (2017\u20132024) was conducted in preterm infants &lt; 32 weeks\u2019 gestation who required &gt; 24 h of invasive ventilation within the first 3 days of life. Perinatal\u2013neonatal data were retrieved from the medical database. Admission blood gas values (arterial and capillary\u2013venous) and the maximum and minimum PCO2 in the first 72 h were evaluated. Normocapnia was defined as PCO2 35\u201345 mmHg, hypocapnia as &lt; 35 mmHg, and hypercapnia as &gt; 45 mmHg. Primary outcomes were the incidence of PCO2 abnormalities; secondary outcomes included death or severe brain injury (SBI), SBI alone, and bronchopulmonary dysplasia (BPD) among survivors. Logistic regression identified independent predictors of the secondary outcomes. Results: Among the 134 infants evaluated, most experienced both hypercapnia and hypocapnia. Hypercapnia occurred in 81.3% of infants, and hypocapnia in 93.2%. Death or SBI was observed in 51.5%, and SBI alone in 42.5%. Gestational age &lt; 28 weeks, air-leak syndromes, and pulmonary hemorrhage were independent predictors of death or SBI. Among survivors, hypercapnia and gestational age &lt; 28 weeks independently predicted BPD. Infants with adverse outcomes had higher maximum PCO2 values and greater PCO2 variability, although these were not independent predictors of SBI or death. Conclusions: PCO2 instability is highly prevalent in ventilated preterm infants, underscoring the need for individualized ventilation strategies. Extreme prematurity emerged as the primary risk factor for adverse outcomes, while hypercapnia was independently associated with BPD.<\/jats:p>","DOI":"10.3390\/jpm16040212","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T07:29:29Z","timestamp":1776065369000},"page":"212","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Early Postnatal Hypocapnia and Hypercapnia in Ventilated Preterm Infants: Incidence and Associations with Adverse Outcomes"],"prefix":"10.3390","volume":"16","author":[{"given":"Ilias","family":"Chatziioannidis","sequence":"first","affiliation":[{"name":"1st Department of Neonatology and Neonatal Intensive Care, Faculty of Medicine, School of Health Sciences, Ippokrateion General Hospital, Aristotle University of Thessaloniki, Kostantinoupoleos 49 Str., 54642 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9961-9537","authenticated-orcid":false,"given":"Angeliki","family":"Kontou","sequence":"additional","affiliation":[{"name":"1st Department of Neonatology and Neonatal Intensive Care, Faculty of Medicine, School of Health Sciences, Ippokrateion General Hospital, Aristotle University of Thessaloniki, Kostantinoupoleos 49 Str., 54642 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleni","family":"Agakidou","sequence":"additional","affiliation":[{"name":"1st Department of Neonatology and Neonatal Intensive Care, Faculty of Medicine, School of Health Sciences, Ippokrateion General Hospital, Aristotle University of Thessaloniki, Kostantinoupoleos 49 Str., 54642 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6770-0542","authenticated-orcid":false,"given":"Theodora","family":"Stathopoulou","sequence":"additional","affiliation":[{"name":"1st Department of Neonatology and Neonatal Intensive Care, Faculty of Medicine, School of Health Sciences, Ippokrateion General Hospital, Aristotle University of Thessaloniki, Kostantinoupoleos 49 Str., 54642 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kostantia","family":"Tsoni","sequence":"additional","affiliation":[{"name":"1st Department of Neonatology and Neonatal Intensive Care, Faculty of Medicine, School of Health Sciences, Ippokrateion General Hospital, Aristotle University of Thessaloniki, Kostantinoupoleos 49 Str., 54642 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christos","family":"Paschaloudis","sequence":"additional","affiliation":[{"name":"1st Department of Neonatology and Neonatal Intensive Care, Faculty of Medicine, School of Health Sciences, Ippokrateion General Hospital, Aristotle University of Thessaloniki, Kostantinoupoleos 49 Str., 54642 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Chotas","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Memorial Hospital of Carbondale, Southern Illinois Healthcare, Carbondale, IL 62901, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6806-6343","authenticated-orcid":false,"given":"Kosmas","family":"Sarafidis","sequence":"additional","affiliation":[{"name":"1st Department of Neonatology and Neonatal Intensive Care, Faculty of Medicine, School of Health Sciences, Ippokrateion General Hospital, Aristotle University of Thessaloniki, Kostantinoupoleos 49 Str., 54642 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1159\/000527641","article-title":"Patterns of Respiratory Support by Gestational Age in Very Preterm Infants","volume":"120","author":"Norman","year":"2023","journal-title":"Neonatology"},{"key":"ref_2","first-page":"CD014895","article-title":"Non-invasive respiratory support in preterm infants as primary mode: A network meta-analysis","volume":"7","author":"Mukerji","year":"2025","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Sarafidis, K., Chotas, W., Agakidou, E., Karagianni, P., and Drossou, V. (2021). The Intertemporal Role of Respiratory Support in Improving Neonatal Outcomes: A Narrative Review. Children, 8.","DOI":"10.3390\/children8100883"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1038\/s41390-021-01473-y","article-title":"Carbon dioxide levels in neonates: What are safe parameters?","volume":"91","author":"Wong","year":"2022","journal-title":"Pediatr. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"F323","DOI":"10.1136\/archdischild-2012-302649","article-title":"Incidence of hypo- and hyper-capnia in a cross-sectional European cohort of ventilated newborn infants","volume":"98","author":"Rimensberger","year":"2013","journal-title":"Arch. Dis. Child. Fetal Neonatal Ed."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"362","DOI":"10.22141\/2224-0551.19.6.2024.1740","article-title":"Is hyperventilation a common iatrogenic problem in the neonatal intensive care unit?","volume":"19","year":"2024","journal-title":"Childs Health"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.siny.2008.08.005","article-title":"Permissive hypercapnia to decrease lung injury in ventilated preterm neonates","volume":"14","author":"Thome","year":"2009","journal-title":"Semin. Fetal Neonatal Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"943","DOI":"10.4187\/respcare.05801","article-title":"Incidence of Hypocapnia, Hypercapnia, and Acidosis and the Associated Risk of Adverse Events in Preterm Neonates","volume":"63","author":"Brown","year":"2018","journal-title":"Respir. Care"},{"key":"ref_9","first-page":"279","article-title":"Hypercapnia during the first 3 days of life is associated with severe intraventricular hemorrhage in very low birth weight infants","volume":"26","author":"Kaiser","year":"2006","journal-title":"J. Perinatol. Off. J. Calif. Perinat. Assoc."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1542\/peds.2006-2434","article-title":"Both extremes of arterial carbon dioxide pressure and the magnitude of fluctuations in arterial carbon dioxide pressure are associated with severe intraventricular hemorrhage in preterm infants","volume":"119","author":"Fabres","year":"2007","journal-title":"Pediatrics"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1046\/j.1440-1754.2002.00041.x","article-title":"Hypocarbia in the ventilated preterm infant and its effect on intraventricular haemorrhage and bronchopulmonary dysplasia","volume":"38","author":"Erickson","year":"2002","journal-title":"J. Paediatr. Child Health"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2603","DOI":"10.1002\/ppul.26108","article-title":"Efficacy and safety of permissive hypercapnia in preterm infants: A systematic review","volume":"57","author":"Ozawa","year":"2022","journal-title":"Pediatr. Pulmonol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e71165","DOI":"10.1002\/ppul.71165","article-title":"Late Permissive Hypercapnia for Mechanically Ventilated Preterm Infants: A Randomized Trial","volume":"60","author":"Travers","year":"2025","journal-title":"Pediatr. Pulmonol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1055\/s-0034-1543950","article-title":"Severe Intraventricular Hemorrhage in Extremely Premature Infants: Are high Carbon Dioxide Pressure or Fluctuations the Culprit?","volume":"32","author":"Altaany","year":"2015","journal-title":"Am. J. Perinatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"F151","DOI":"10.1136\/fn.84.3.F151","article-title":"Ultrasound diagnosis and neurodevelopmental outcome of localised and extensive cystic periventricular leucomalacia","volume":"84","author":"Pierrat","year":"2001","journal-title":"Arch. Dis. Child. Fetal Neonatal Ed."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/S0022-3476(78)80282-0","article-title":"Incidence and evolution of subependymal and intraventricular hemorrhage: A study of infants with birth weights less than 1500 gm","volume":"92","author":"Papile","year":"1978","journal-title":"J. Pediatr."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1164\/ajrccm.163.7.2011060","article-title":"Bronchopulmonary dysplasia","volume":"163","author":"Jobe","year":"2001","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1007\/s10354-016-0506-6","article-title":"Episodes of hypo- and hypercapnia in a cohort of mechanically ventilated VLBW infants: The role of adequate staffing","volume":"167","author":"Poryo","year":"2017","journal-title":"Wien. Med. Wochenschr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.pediatrneurol.2020.04.016","article-title":"Neuroprotection Care Bundle Implementation to Decrease Acute Brain Injury in Preterm Infants","volume":"110","author":"Murthy","year":"2020","journal-title":"Pediatr. Neurol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1159\/000485828","article-title":"Influence of PCO2 Control on Clinical and Neurodevelopmental Outcomes of Extremely Low Birth Weight Infants","volume":"113","author":"Thome","year":"2018","journal-title":"Neonatology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1136\/adc.2005.086371","article-title":"Minimising neonatal brain injury: How research in the past five years has changed my clinical practice","volume":"92","author":"Levene","year":"2007","journal-title":"Arch. Dis. Child."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1007\/s12519-008-0035-5","article-title":"Hypercapnia and hypocapnia in neonates","volume":"4","author":"Zhou","year":"2008","journal-title":"World J. Pediatr."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Fritz, K., Sanidas, G., Cardenas, R., Ghaemmaghami, J., Byrd, C., Simonti, G., Valenzuela, A., Valencia, I., Delivoria-Papadopoulos, M., and Gallo, V. (2024). Hypercapnia Causes Injury of the Cerebral Cortex and Cognitive Deficits in Newborn Piglets. eNeuro, 11.","DOI":"10.1523\/ENEURO.0268-23.2023"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Sweet, D.G., Carnielli, V.P., Greisen, G., Hallman, M., Klebermass-Schrehof, K., Lavizzari, A., Ozek, E., Pas, A.T., Roehr, C.C., and Saugstad, O.D. (2026). European Consensus Guidelines on the Management of Respiratory Distress Syndrome\u20142025. Neonatology, 1\u201326.","DOI":"10.1159\/000551062"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1016\/S2213-2600(15)00204-0","article-title":"Permissive hypercapnia in extremely low birthweight infants (PHELBI): A randomised controlled multicentre trial","volume":"3","author":"Thome","year":"2015","journal-title":"Lancet Respir. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.jpeds.2016.04.083","article-title":"Neonatal Outcomes of Very Low Birth Weight and Very Preterm Neonates: An International Comparison","volume":"177","author":"Shah","year":"2016","journal-title":"J. Pediatr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1159\/000537801","article-title":"Temporal Trends in Severe Brain Injury and Associated Outcomes in Very Preterm Infants","volume":"121","author":"Razak","year":"2024","journal-title":"Neonatology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/j.pedneo.2022.12.016","article-title":"Trends in neonatal mortality and morbidity in very-low-birth-weight (VLBW) infants over a decade: Singapore national cohort study","volume":"64","author":"Lee","year":"2023","journal-title":"Pediatr. Neonatol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"S17","DOI":"10.1007\/s10995-011-0863-0","article-title":"Association of bronchopulmonary dysplasia and hypercarbia in ventilated infants with birth weights of 500\u20131499 g","volume":"15","author":"Subramanian","year":"2011","journal-title":"Matern. Child. Health J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2248","DOI":"10.1111\/apa.16947","article-title":"On carbon dioxide and bronchopulmonary dysplasia","volume":"112","author":"Dassios","year":"2023","journal-title":"Acta Paediatr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1038\/s41390-025-03934-0","article-title":"High-frequency oscillatory ventilation with volume guarantee in infants: A systematic review","volume":"98","author":"Liu","year":"2025","journal-title":"Pediatr. Res."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Solberg, M.T., Bj\u00f8rk, I.T., and Hansen, T.W.R. (2013). Adherence to oxygenation and ventilation targets in mechanically ventilated premature and sick newborns: A retrospective study. BMC Pediatr., 13.","DOI":"10.1186\/1471-2431-13-126"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1055\/s-0029-1243309","article-title":"Blood carbon dioxide levels and adverse outcome in neonatal hypoxic-ischemic encephalopathy","volume":"27","author":"Nadeem","year":"2010","journal-title":"Am. J. Perinatol."},{"key":"ref_34","unstructured":"Canadian Paediatric Society (2025, November 11). Neuroprotection from Acute Brain Injury in Preterm Infants. Available online: https:\/\/cps.ca\/en\/documents\/position\/neuroprotection."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1159\/000528914","article-title":"European Consensus Guidelines on the Management of Respiratory Distress Syndrome: 2022 Update","volume":"120","author":"Sweet","year":"2023","journal-title":"Neonatology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1159\/000499361","article-title":"European Consensus Guidelines on the Management of Respiratory Distress Syndrome\u20142019 Update","volume":"115","author":"Sweet","year":"2019","journal-title":"Neonatology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1136\/archdischild-2018-316692","article-title":"Neonatal care bundles are associated with a reduction in the incidence of intraventricular haemorrhage in preterm infants: A multicentre cohort study","volume":"105","author":"Brouwer","year":"2020","journal-title":"Arch. Dis. Child. Fetal Neonatal Ed."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e003325","DOI":"10.1136\/bmjoq-2025-003325","article-title":"Quality improvement project to reduce intraventricular haemorrhage in very preterm infants failed due to increased life-sustaining intensive care at low gestational age","volume":"14","author":"Erni","year":"2025","journal-title":"BMJ Open Qual."}],"container-title":["Journal of Personalized Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4426\/16\/4\/212\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T04:16:40Z","timestamp":1777004200000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4426\/16\/4\/212"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,12]]},"references-count":38,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["jpm16040212"],"URL":"https:\/\/doi.org\/10.3390\/jpm16040212","relation":{},"ISSN":["2075-4426"],"issn-type":[{"value":"2075-4426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,12]]}}}