{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T15:53:48Z","timestamp":1791388428576,"version":"4.3.3"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T00:00:00Z","timestamp":1764288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>\n                      During pregnancy, prostaglandin E\n                      <jats:sub>2<\/jats:sub>\n                      (PGE\n                      <jats:sub>2<\/jats:sub>\n                      ) is released from the placenta and circulates in relatively high concentrations in the fetus. As PGE\n                      <jats:sub>2<\/jats:sub>\n                      suppresses breathing, PGE\n                      <jats:sub>2<\/jats:sub>\n                      concentrations must decrease after birth, but the timing and mechanisms behind this decrease are unknown. We hypothesised that both umbilical cord clamping and lung aeration contribute to the reduction in PGE\n                      <jats:sub>2<\/jats:sub>\n                      concentrations after birth.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>\n                      Instrumented premature lambs (138\u2013141 days gestation) were randomised to receive either physiological-based cord clamping (PBCC; cord clamping after ventilation onset;\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20095) or immediate cord clamping (ICC; before ventilation onset;\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20096). PGE\n                      <jats:sub>2<\/jats:sub>\n                      concentrations were measured in pulmonary and carotid arterial blood 30\u2005s after ventilation onset, after lung aeration and 30\u2005s after cord clamping. All PGE\n                      <jats:sub>2<\/jats:sub>\n                      data are expressed relative to fetal PGE\n                      <jats:sub>2<\/jats:sub>\n                      concentrations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Relative to fetal concentrations, ventilation onset decreased PGE\n                      <jats:sub>2<\/jats:sub>\n                      concentrations in the carotid (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.036) and pulmonary arteries (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.052) in PBCC lambs, whereas cord clamping had no further additional effect on PGE2 concentrations in these lambs. In ICC lambs, cord clamping decreased PGE\n                      <jats:sub>2<\/jats:sub>\n                      concentrations, relative to fetal concentrations, in both the carotid (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001) and pulmonary arteries (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&amp;lt;\u20090.001). Ventilation onset further decreased PGE\n                      <jats:sub>2<\/jats:sub>\n                      concentrations in both the carotid (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.002) and pulmonary arteries (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.014).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Both umbilical cord clamping and ventilation onset independently decrease PGE\n                      <jats:sub>2<\/jats:sub>\n                      concentrations immediately after birth, which may enhance breathing activity, although the effect of cord clamping is reduced by ventilation onset.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fped.2025.1636459","type":"journal-article","created":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T06:28:11Z","timestamp":1764311291000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Circulating prostaglandin E2 concentrations decrease at birth in premature lambs"],"prefix":"10.3389","volume":"13","author":[{"given":"Timothy J. R.","family":"Panneflek","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janneke","family":"Dekker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly J.","family":"Crossley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cailin","family":"Diedericks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristel L. A. M.","family":"Kuypers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ebony R.","family":"Cannata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paige J.","family":"Riddington","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Femmie E.","family":"Bloem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison M.","family":"Thiel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"van den Akker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graeme R.","family":"Polglase","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arjan B.","family":"te Pas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart B.","family":"Hooper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Indya M.","family":"Davies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"101033","DOI":"10.1016\/j.siny.2019.101033","article-title":"Issues in cardiopulmonary transition at birth","volume":"24","author":"Hooper","year":"2019","journal-title":"Semin Fetal Neonatal Med"},{"key":"B2","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1152\/japplphysiol.01358.2013","article-title":"Ventilation\/perfusion mismatch during lung aeration at birth","volume":"117","author":"Lang","year":"2014","journal-title":"J Appl Physiol (1985)"},{"key":"B3","doi-asserted-by":"publisher","first-page":"2113","DOI":"10.1113\/jphysiol.2012.250084","article-title":"Delaying cord clamping until ventilation onset improves cardiovascular function at birth in preterm lambs","volume":"591","author":"Bhatt","year":"2013","journal-title":"J Physiol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1038\/s41390-019-0468-7","article-title":"Stimulating and maintaining spontaneous breathing during transition of preterm infants","volume":"90","author":"Dekker","year":"2021","journal-title":"Pediatr Res"},{"key":"B5","doi-asserted-by":"publisher","first-page":"110053","DOI":"10.1016\/j.resuscitation.2023.110053","article-title":"The vocal cords are predominantly closed in preterm infants <30 weeks gestation during transition after birth; an observational study","volume":"194","author":"Heesters","year":"2023","journal-title":"Resuscitation"},{"key":"B6","doi-asserted-by":"publisher","first-page":"F112","DOI":"10.1136\/archdischild-2017-312681","article-title":"Laryngeal closure impedes non-invasive ventilation at birth","volume":"103","author":"Crawshaw","year":"2018","journal-title":"Arch Dis Child Fetal Neonatal Ed"},{"key":"B7","first-page":"453","article-title":"Stimulation of breathing movements in fetal sheep by inhibitors of prostaglandin synthesis","volume":"1","author":"Kitterman","year":"1979","journal-title":"J Dev Physiol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"2734","DOI":"10.1152\/jappl.1994.77.6.2734","article-title":"Hypoxic inhibition of breathing in fetal sheep: relationship to brain adenosine concentrations","volume":"77","author":"Koos","year":"1994","journal-title":"J Appl Physiol (1985)"},{"key":"B9","doi-asserted-by":"publisher","first-page":"841229","DOI":"10.3389\/fphys.2022.841229","article-title":"Increased prostaglandin E2 in brainstem respiratory centers is associated with inhibition of breathing movements in fetal sheep exposed to progressive systemic inflammation","volume":"13","author":"Stojanovska","year":"2022","journal-title":"Front Physiol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1113\/jphysiol.1987.sp016372","article-title":"Lesions in the upper lateral pons abolish the hypoxic depression of breathing in unanaesthetized fetal lambs in utero","volume":"382","author":"Gluckman","year":"1987","journal-title":"J Physiol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"9894","DOI":"10.1073\/pnas.0611468104","article-title":"The induced prostaglandin E2 pathway is a key regulator of the respiratory response to infection and hypoxia in neonates","volume":"104","author":"Hofstetter","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B12","doi-asserted-by":"publisher","first-page":"917","DOI":"10.3390\/children8100917","article-title":"Chorioamnionitis, inflammation and neonatal apnea: effects on preterm neonatal brainstem and on peripheral airways: chorioamnionitis and neonatal respiratory functions","volume":"8","author":"Vitaliti","year":"2021","journal-title":"Children (Basel)"},{"key":"B13","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1152\/jappl.1988.64.1.409","article-title":"Prostaglandins and control of breathing in newborn piglets","volume":"64","author":"Long","year":"1988","journal-title":"J Appl Physiol (1985)"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1113\/jphysiol.1987.sp016856","article-title":"The nutritional regulation of plasma prostaglandin E concentrations in the fetus and pregnant ewe during late gestation","volume":"394","author":"Fowden","year":"1987","journal-title":"J Physiol"},{"key":"B15","first-page":"217","article-title":"The effect of indomethacin on breathing movements and cerebral blood flow and metabolism in the fetal sheep","volume":"7","author":"Hohimer","year":"1985","journal-title":"J Dev Physiol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1016\/0090-6980(83)90095-3","article-title":"The metabolism of prostaglandin E2 in perinatal rabbit lungs","volume":"26","author":"Simberg","year":"1983","journal-title":"Prostaglandins"},{"key":"B17","first-page":"R135","article-title":"Eicosanoids in third ventricular cerebrospinal fluid of fetal and newborn sheep","volume":"264","author":"Jones","year":"1993","journal-title":"Am J Physiol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1111\/j.1471-0528.1978.tb10463.x","article-title":"Prostaglandins in the human umbilical circulation at birth","volume":"85","author":"Mitchell","year":"1978","journal-title":"Br J Obstet Gynaecol"},{"key":"B19","first-page":"145","article-title":"Decrease in plasma prostaglandin E2 is not essential for the establishment of continuous breathing at birth in sheep","volume":"12","author":"Lee","year":"1989","journal-title":"J Dev Physiol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1796","DOI":"10.1152\/jappl.1991.70.4.1796","article-title":"Umbilical cord occlusion stimulates breathing independent of blood gases and pH","volume":"70","author":"Adamson","year":"1991","journal-title":"J Appl Physiol (1985)"},{"key":"B21","doi-asserted-by":"publisher","first-page":"2539","DOI":"10.1007\/s00431-024-05508-4","article-title":"The influence of chorioamnionitis on respiratory drive and spontaneous breathing of premature infants at birth: a narrative review","volume":"183","author":"Panneflek","year":"2024","journal-title":"Eur J Pediatr"},{"key":"B22","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1007\/s004180100323","article-title":"Regulation of prostaglandin availability in human fetal lung by differential localisation of prostaglandin H synthase-1 and prostaglandin dehydrogenase","volume":"116","author":"Conner","year":"2001","journal-title":"Histochem Cell Biol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1038\/225600a0","article-title":"Inactivation of prostaglandins by the lungs","volume":"225","author":"Piper","year":"1970","journal-title":"Nature"},{"key":"B24","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1016\/S0022-3476(80)80205-8","article-title":"Circulating prostaglandin E2 concentrations and patent ductus arteriosus in fetal and neonatal lambs","volume":"97","author":"Clyman","year":"1980","journal-title":"J Pediatr"},{"key":"B25","year":"2013"},{"key":"B26","doi-asserted-by":"publisher","first-page":"3617","DOI":"10.1111\/bph.15193","article-title":"The ARRIVE guidelines 2.0: updated guidelines for reporting animal research","volume":"177","author":"Percie du Sert","year":"2020","journal-title":"Br J Pharmacol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1152\/japplphysiol.00496.2023","article-title":"Influence of the chest wall on respiratory function at birth in near-term lambs","volume":"136","author":"Diedericks","year":"2024","journal-title":"J Appl Physiol (1985)"},{"key":"B28","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1016\/0090-6980(78)90033-3","article-title":"Plasma prostaglandin levels during early neonatal life following term and pre-term delivery","volume":"16","author":"Mitchell","year":"1978","journal-title":"Prostaglandins"},{"key":"B29","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/0378-3782(92)90059-P","article-title":"The placenta, PGE2 and parturition","volume":"29","author":"Thorburn","year":"1992","journal-title":"Early Hum Dev"},{"key":"B30","doi-asserted-by":"publisher","first-page":"R703","DOI":"10.1152\/ajpregu.1990.259.4.R703","article-title":"Fetal endocrine responses to prolonged hypoxemia in sheep","volume":"259","author":"Hooper","year":"1990","journal-title":"Am J Physiol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1071\/RD9950527","article-title":"Fetal metabolic responses to hypoxia","volume":"7","author":"Hooper","year":"1995","journal-title":"Reprod Fertil Dev"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1568","DOI":"10.1016\/0002-9378(92)91635-N","article-title":"Role of prostaglandins in the metabolic responses of the fetus to hypoxia","volume":"166","author":"Hooper","year":"1992","journal-title":"Am J Obstet Gynecol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1111\/j.1440-1681.2012.05742.x","article-title":"Effects of intrauterine infection or inflammation on fetal lung development","volume":"39","author":"Westover","year":"2012","journal-title":"Clin Exp Pharmacol Physiol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1053\/plac.1999.0452","article-title":"Transfer and metabolism of prostaglandin E(2)in the dual perfused human placenta","volume":"21","author":"Greystoke","year":"2000","journal-title":"Placenta"},{"key":"B35","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1530\/jrf.0.0590525","article-title":"Prostaglandin synthesis and metabolism in the human uterus and midtrimester fetal tissues","volume":"59","author":"Falkay","year":"1980","journal-title":"J Reprod Fertil"},{"key":"B36","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1016\/0028-2243(79)90067-4","article-title":"Fetal and maternal metabolism of prostaglandin F2 alpha in the Guinea pig","volume":"9","author":"Keirse","year":"1979","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"4695","DOI":"10.1113\/jphysiol.2009.174870","article-title":"Dynamic changes in the direction of blood flow through the ductus arteriosus at birth","volume":"587","author":"Crossley","year":"2009","journal-title":"J Physiol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"F539","DOI":"10.1136\/archdischild-2017-314005","article-title":"Haemodynamic effects of umbilical cord milking in premature sheep during the neonatal transition","volume":"103","author":"Blank","year":"2018","journal-title":"Arch Dis Child Fetal Neonatal Ed"},{"key":"B39","doi-asserted-by":"publisher","first-page":"2223","DOI":"10.1016\/S0140-6736(23)02469-8","article-title":"Short, medium, and long deferral of umbilical cord clamping compared with umbilical cord milking and immediate clamping at preterm birth: a systematic review and network meta-analysis with individual participant data","volume":"402","author":"Seidler","year":"2023","journal-title":"Lancet"},{"key":"B40","doi-asserted-by":"publisher","first-page":"101146","DOI":"10.1016\/j.lanepe.2024.101146","article-title":"Physiological versus time based cord clamping in very preterm infants (ABC3): a parallel-group, multicentre, randomised, controlled superiority trial","volume":"48","author":"Knol","year":"2025","journal-title":"Lancet Reg Health Eur"},{"key":"B41","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1038\/pr.2012.119","article-title":"mPGES-1 and prostaglandin E2: vital role in inflammation, hypoxic response, and survival","volume":"72","author":"Siljehav","year":"2012","journal-title":"Pediatr Res"},{"key":"B42","doi-asserted-by":"publisher","first-page":"1207","DOI":"10.1016\/j.jpeds.2015.08.053","article-title":"Prostaglandin E2 mediates cardiorespiratory disturbances during infection in neonates","volume":"167","author":"Siljehav","year":"2015","journal-title":"J Pediatr"},{"key":"B43","article-title":"Embryology, fetal circulation","volume-title":"StatPearls","author":"Marty","year":"2024"},{"key":"B44","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1016\/j.clp.2016.04.001","article-title":"Fetal physiology and the transition to extrauterine life","volume":"43","author":"Morton","year":"2016","journal-title":"Clin Perinatol"},{"key":"B45","doi-asserted-by":"publisher","first-page":"114285","DOI":"10.1016\/j.jpeds.2024.114285","article-title":"Assessment of blood prostaglandin E(2) metabolite levels among infants born preterm with patent ductus arteriosus: a prospective study","volume":"276","author":"Nagafuji","year":"2025","journal-title":"J Pediatr"},{"key":"B46","doi-asserted-by":"publisher","first-page":"734","DOI":"10.1016\/S0022-3476(77)81025-1","article-title":"Plasma prostaglandin E concentrations from birth through childhood","volume":"91","author":"Siegler","year":"1977","journal-title":"J Pediatr"}],"container-title":["Frontiers in Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2025.1636459\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T06:28:13Z","timestamp":1764311293000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2025.1636459\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,28]]},"references-count":46,"alternative-id":["10.3389\/fped.2025.1636459"],"URL":"https:\/\/doi.org\/10.3389\/fped.2025.1636459","relation":{},"ISSN":["2296-2360"],"issn-type":[{"value":"2296-2360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,28]]},"article-number":"1636459"}}