{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:07:46Z","timestamp":1790690866267,"version":"4.1.0"},"reference-count":16,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"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>Background<\/jats:title>\n                    <jats:p>Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disorder unique to pregnancy, associated with elevated maternal bile acid concentrations and adverse perinatal outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This is a prospective cohort study conducted in a level III neonatal unit in Bucharest, Romania. Neonates born to mothers with ICP (serum bile acids \u226510\u2005\u03bcmol\/L within seven days before delivery) will be enrolled alongside gestational age, sex and birthweight-matched controls. Serum samples will be collected at 24\u2005h, 48\u201372\u2005h and on day 7 of life. Quantitative ELISA kits will be used to assess serum biomarkers associated with surfactant dysfunction and lung injury. Perinatal and clinical outcomes will be recorded systematically.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The primary aims are to compare the incidence of respiratory distress syndrome (RDS), the need for surfactant administration and serum biomarker profiles between ICP-exposed and unexposed neonates. Secondary aims include evaluating respiratory support requirements, neonatal morbidity and mortality across groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We expect that neonates exposed to maternal cholestasis will have a higher incidence of RDS, increased surfactant need, and biomarker alterations consistent with pulmonary compromise. This study may improve understanding of bile acid-related lung injury and inform early risk stratification strategies in affected newborns. (NCT06679972).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fped.2026.1640579","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T06:32:17Z","timestamp":1770013937000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Impact of intrahepatic cholestasis of pregnancy on neonatal respiratory outcomes (CHOLE-RESP): protocol for a prospective cohort study"],"prefix":"10.3389","volume":"14","author":[{"given":"Lucia Elena","family":"Niculae","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, \u201cCarol Davila\u201d University of Medicine and Pharmacy","place":["Bucharest, Romania"]},{"name":"Department of Neonatology, \u201cProf. Dr. Panait S\u00e2rbu\u201d Clinical Hospital of Obstetrics and Gynecology","place":["Bucharest, Romania"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandru Stefan","family":"Niculae","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, \u201cCarol Davila\u201d University of Medicine and Pharmacy","place":["Bucharest, Romania"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raluca","family":"Tocariu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, \u201cCarol Davila\u201d University of Medicine and Pharmacy","place":["Bucharest, Romania"]},{"name":"Department of Neonatology, \u201cProf. Dr. Panait S\u00e2rbu\u201d Clinical Hospital of Obstetrics and Gynecology","place":["Bucharest, Romania"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aida","family":"Petca","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, \u201cCarol Davila\u201d University of Medicine and Pharmacy","place":["Bucharest, Romania"]},{"name":"Department of Obstetrics and Gynecology, Elias University Emergency Hospital","place":["Bucharest, Romania"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1186\/s12916-025-03935-0","article-title":"Global and regional incidence of intrahepatic cholestasis of pregnancy: a systematic review and meta-analysis","volume":"23","author":"Jamshidi Kerachi","year":"2025","journal-title":"BMC Med"},{"key":"B2","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1002\/hep.20336","article-title":"Intrahepatic cholestasis of pregnancy: relationships between bile acid levels and fetal complication rates","volume":"40","author":"Glantz","year":"2004","journal-title":"Hepatology"},{"key":"B3","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1016\/S0140-6736(18)31877-4","article-title":"Association of adverse perinatal outcomes of intrahepatic cholestasis of pregnancy with biochemical markers: results of aggregate and individual patient data meta-analyses","volume":"393","author":"Ovadia","year":"2019","journal-title":"Lancet"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1669","DOI":"10.1542\/peds.2005-1801","article-title":"Intrahepatic cholestasis of pregnancy and neonatal respiratory distress syndrome","volume":"117","author":"Zecca","year":"2006","journal-title":"Pediatrics"},{"key":"B5","doi-asserted-by":"publisher","first-page":"e0228213","DOI":"10.1371\/journal.pone.0228213","article-title":"Perinatal outcomes of intrahepatic cholestasis during pregnancy: an 8-year case-control study","volume":"15","author":"Arthuis","year":"2020","journal-title":"PLoS One"},{"key":"B6","doi-asserted-by":"publisher","first-page":"6565","DOI":"10.3390\/jcm12206565","article-title":"Bile acids pneumonia: a respiratory distress syndrome in early-term neonates","volume":"12","author":"Perri","year":"2023","journal-title":"J Clin Med"},{"key":"B7","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.jpeds.2022.04.028","article-title":"Perinatal inflammatory biomarkers and respiratory disease in preterm infants","volume":"246","author":"Collaco","year":"2022","journal-title":"J Pediatr"},{"key":"B8","doi-asserted-by":"publisher","first-page":"200","DOI":"10.7326\/0003-4819-158-3-201302050-00583","article-title":"SPIRIT 2013 statement: defining standard protocol items for clinical trials","volume":"158","author":"Chan","year":"2013","journal-title":"Ann Intern Med"},{"key":"B9","doi-asserted-by":"publisher","first-page":"308274","DOI":"10.1155\/2014\/308274","article-title":"Effect of bile acid on fetal lung in rat model of intrahepatic cholestasis of pregnancy","volume":"2014","author":"Yu","year":"2014","journal-title":"Int J Endocrinol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1542\/peds.114.1.269","article-title":"Bile acid pneumonia: a \u201cnew\u201d form of neonatal respiratory distress syndrome?","volume":"114","author":"Zecca","year":"2004","journal-title":"Pediatrics"},{"key":"B11","doi-asserted-by":"publisher","first-page":"e146","DOI":"10.1542\/peds.2007-1220","article-title":"Bile acid-induced lung injury in newborn infants: a bronchoalveolar lavage fluid study","volume":"121","author":"Zecca","year":"2008","journal-title":"Pediatrics"},{"key":"B12","doi-asserted-by":"publisher","first-page":"L93","DOI":"10.1152\/ajplung.00523.2021","article-title":"Bile acid-induced lung injury: update of reverse translational biology","volume":"323","author":"De Luca","year":"2022","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1038\/s41572-025-00633-2","article-title":"Intrahepatic cholestasis of pregnancy","volume":"11","author":"Dajti","year":"2025","journal-title":"Nat Rev Dis Primers"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2021\/6679322","article-title":"Molecular pathogenesis of intrahepatic cholestasis of pregnancy","volume":"2021","author":"Xiao","year":"2021","journal-title":"Can J Gastroenterol Hepatol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"2066","DOI":"10.3390\/biomedicines13092066","article-title":"Intrahepatic cholestasis of pregnancy: neonatal impact through the Lens of current evidence","volume":"13","author":"Niculae","year":"2025","journal-title":"Biomedicines"},{"key":"B16","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1186\/s12884-024-06730-6","article-title":"Core biomarkers analysis benefit for diagnosis on human intrahepatic cholestasis of pregnancy","volume":"24","author":"Fang","year":"2024","journal-title":"BMC Pregnancy Childbirth"}],"container-title":["Frontiers in Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2026.1640579\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T06:32:18Z","timestamp":1770013938000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2026.1640579\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,2]]},"references-count":16,"alternative-id":["10.3389\/fped.2026.1640579"],"URL":"https:\/\/doi.org\/10.3389\/fped.2026.1640579","relation":{},"ISSN":["2296-2360"],"issn-type":[{"value":"2296-2360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,2]]},"article-number":"1640579"}}