{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T17:39:41Z","timestamp":1788284381026,"version":"build-2803163510"},"reference-count":34,"publisher":"Georg Thieme Verlag KG","issue":"01","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Am J Perinatol"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>\n            Objective\u2003Prostaglandins (PGs) play a major role in maintaining patency of the ductal arteriosus (DA). Pulmonary 15-hydroxyprostaglandin dehydrogenase (PGDH), which is ecoded by the hydroxyprostaglandin dehydrogenase (HPGD) gene, is the primary enzyme responsible for PG breakdown. Animal studies have shown HPGD-knockout mice have significantly higher prostaglandin E2 levels and no ductal remodeling. Functional variants of the HPGD gene that alter PG breakdown have not been studied in preterm infants with patent ductus arteriosus (PDA).<\/jats:p><jats:p>\n            Study Design\u2003This was an observational cohort study including extreme low birth weight (ELBW) infants classified as having spontaneous, medical, or procedural (transcatheter or surgical ligation) closure of their DA. Urine prostaglandin E metabolite (PGEM) levels were measured in ELBW infants following ibuprofen treatment using competitive ELISA. HPGD genetic variants rs8752, rs2612656, and rs9312555 were analyzed. Kruskal\u2013Wallis, Fisher's exact, chi square, logistic regression, and Wilcoxon signed-rank tests were used; p\u2009&lt;\u20090.05 was considered significant.<\/jats:p><jats:p>\n            Results\u2003Infants in the procedural closure group had a younger gestational age (GA). The incidence of spontaneous closure or medical closure was higher compared to procedural closure in the presence of any minor allele of rs8752 (67 and 27%, respectively; p\u2009=\u20090.01), when adjusted for GA and gender. Haplotype analysis of three variants of HPGD revealed differences when comparing the spontaneous and medical closure group to the procedural group (p\u2009&lt;\u20090.05). Urinary PGEM levels dropped significantly in those ELBW infants who responded to ibuprofen (p\u2009=\u20090.003) in contrast to those who did not respond (p\u2009=\u20090.5).<\/jats:p><jats:p>\n            Conclusion\u2003There was a different genotype distribution for the rs8752 genetic variant of the HPGD gene\u2014as it relates to the mode of treatment for ELBW infants with PDA. We speculate that medical management in the presence of this variant facilitated additional PG breakdown, significantly abrogating the need for procedural closure. Additionally, differences in genotype and haplotype distributions implicate a specific HPGD genetic foundation for DA closure in ELBW infants.<\/jats:p><jats:p>\n            Key Points\n          <\/jats:p>","DOI":"10.1055\/s-0044-1787172","type":"journal-article","created":{"date-parts":[[2024,5,31]],"date-time":"2024-05-31T22:34:27Z","timestamp":1717194867000},"page":"043-051","source":"Crossref","is-referenced-by-count":4,"title":["Genetic Foundation of Prostaglandin Metabolism Influences Patent Ductus Arteriosus Closure in Extremely Low Birth Weight Infants"],"prefix":"10.1055","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-1847-5446","authenticated-orcid":false,"given":"Hannah J.","family":"Sampath","sequence":"additional","affiliation":[{"name":"Division of Newborn Medicine, Regional Neonatal Intensive Care Unit, Maria Fareri Children's Hospital at Westchester Medical Center, Valhalla, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7278-0565","authenticated-orcid":false,"given":"Parvathy","family":"Krishnan","sequence":"additional","affiliation":[{"name":"Division of Newborn Medicine, Regional Neonatal Intensive Care Unit, Maria Fareri Children's Hospital at Westchester Medical Center, Valhalla, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Van","family":"Trinh","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, New York Medical College, Valhalla, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lance A.","family":"Parton","sequence":"additional","affiliation":[{"name":"Division of Newborn Medicine, Regional Neonatal Intensive Care Unit, Maria Fareri Children's Hospital at Westchester Medical Center, Valhalla, New York"},{"name":"Department of Pediatrics, New York Medical College, Valhalla, New York"},{"name":"Department of Pediatrics, Boston Children's Health Physicians, Valhalla, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2024,5,31]]},"reference":[{"issue":"S 01","key":"ref1","doi-asserted-by":"crossref","first-page":"S14","DOI":"10.1038\/sj.jp.7211465","article-title":"Patent ductus arteriosus: pathophysiology and management","volume":"26","author":"E R Hermes-DeSantis","year":"2006","journal-title":"J Perinatol"},{"issue":"02","key":"ref2","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/S0095-5108(18)30293-8","article-title":"Patent ductus arteriosus. Clinical relevance of prostaglandins and prostaglandin inhibitors in PDA pathophysiology and treatment","volume":"22","author":"C Hammerman","year":"1995","journal-title":"Clin Perinatol"},{"issue":"01","key":"ref3","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1111\/chd.12714","article-title":"Molecular and mechanical factors contributing to ductus arteriosus patency and closure","volume":"14","author":"S L Crockett","year":"2019","journal-title":"Congenit Heart Dis"},{"issue":"06","key":"ref4","first-page":"1","article-title":"Molecular mechanisms underlying remodeling of ductus arteriosus: looking beyond the prostaglandin pathway","volume":"22","author":"H W Hsu","year":"2021","journal-title":"Int J Mol Sci"},{"issue":"01","key":"ref5","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1203\/00006450-199901000-00005","article-title":"Permanent anatomic closure of the ductus arteriosus in newborn baboons: the roles of postnatal constriction, hypoxia, and gestation","volume":"45","author":"R I Clyman","year":"1999","journal-title":"Pediatr Res"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.earlhumdev.2018.05.003","article-title":"Closure time of ductus arteriosus after birth based on survival analysis","volume":"121","author":"S Iwashima","year":"2018","journal-title":"Early Hum Dev"},{"issue":"05","key":"ref7","doi-asserted-by":"crossref","first-page":"e20201209","DOI":"10.1542\/peds.2020-1209","article-title":"Patent ductus arteriosus of the preterm infant","volume":"146","author":"S EG Hamrick","year":"2020","journal-title":"Pediatrics"},{"issue":"01","key":"ref8","doi-asserted-by":"crossref","first-page":"e20153730","DOI":"10.1542\/peds.2015-3730","article-title":"Patent ductus arteriosus in preterm infants","volume":"137","author":"W E Benitz","year":"2016","journal-title":"Pediatrics"},{"issue":"01","key":"ref9","doi-asserted-by":"crossref","first-page":"8","DOI":"10.14238\/pi56.1.2016.8-14","article-title":"Prostaglandin E2 and patent ductus arteriosus in premature infants","volume":"56","author":"M Mochammading","year":"2016","journal-title":"Paediatr Indones"},{"issue":"05","key":"ref10","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1161\/ATVBAHA.110.207449","article-title":"Prostaglandins and inflammation","volume":"31","author":"E Ricciotti","year":"2011","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"04","key":"ref11","doi-asserted-by":"crossref","first-page":"H687","DOI":"10.1152\/ajpheart.00294.2023","article-title":"A novel role for PGE2-EP4 in the developmental programming of the mouse ductus arteriosus: consequences for vessel maturation and function","volume":"325","author":"M T Yarboro","year":"2023","journal-title":"Am J Physiol Heart Circ Physiol"},{"issue":"05","key":"ref12","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1111\/ped.12769","article-title":"Prostaglandin E-mediated molecular mechanisms driving remodeling of the ductus arteriosus","volume":"57","author":"U Yokoyama","year":"2015","journal-title":"Pediatr Int"},{"issue":"02","key":"ref13","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/nm0202-91","article-title":"Metabolism of PGE2 by prostaglandin dehydrogenase is essential for remodeling the ductus arteriosus","volume":"8","author":"K G Coggins","year":"2002","journal-title":"Nat Med"},{"issue":"12","key":"ref14","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.1038\/s41372-019-0496-5","article-title":"Duration of significant patent ductus arteriosus and bronchopulmonary dysplasia in extremely preterm infants","volume":"39","author":"H Mirza","year":"2019","journal-title":"J Perinatol"},{"issue":"02","key":"ref15","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1055\/s-0039-1697672","article-title":"Relationship between duration of infant exposure to a moderate-to-large patent ductus arteriosus shunt and the risk of developing bronchopulmonary dysplasia or death before 36 weeks","volume":"37","author":"R I Clyman","year":"2020","journal-title":"Am J Perinatol"},{"issue":"02","key":"ref16","first-page":"184","article-title":"Patent ductus arteriosus, indomethacin and necrotizing enterocolitis in very low birth weight infants: a population-based study","volume":"40","author":"S Dollberg","year":"2005","journal-title":"J Pediatr Gastroenterol Nutr"},{"issue":"01","key":"ref17","doi-asserted-by":"crossref","first-page":"e138","DOI":"10.1542\/peds.2008-2418","article-title":"Failure of ductus arteriosus closure is associated with increased mortality in preterm infants","volume":"123","author":"S Noori","year":"2009","journal-title":"Pediatrics"},{"issue":"02","key":"ref18","doi-asserted-by":"crossref","first-page":"88","DOI":"10.3928\/01913913-20130108-03","article-title":"Patent ductus arteriosus and indomethacin treatment as independent risk factors for plus disease in retinopathy of prematurity","volume":"50","author":"I Tsui","year":"2013","journal-title":"J Pediatr Ophthalmol Strabismus"},{"issue":"03","key":"ref19","doi-asserted-by":"crossref","first-page":"F183","DOI":"10.1136\/fn.75.3.F183","article-title":"Early ductal shunting and intraventricular haemorrhage in ventilated preterm infants","volume":"75","author":"N Evans","year":"1996","journal-title":"Arch Dis Child Fetal Neonatal Ed"},{"issue":"03","key":"ref20","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1111\/j.1651-2227.2001.tb00310.x","article-title":"Patent ductus arteriosus and cystic periventricular leucomalacia in preterm infants","volume":"90","author":"P Pladys","year":"2001","journal-title":"Acta Paediatr"},{"issue":"01","key":"ref21","first-page":"26","article-title":"Correlation between the closure time of patent ductus arteriosus in preterm infants and long-term neurodevelopmental outcome","volume":"11","author":"N Kikuchi","year":"2024","journal-title":"J Cardiovasc Dev Dis"},{"issue":"11","key":"ref22","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1056\/NEJMoa2207418","article-title":"Expectant management or early ibuprofen for patent ductus arteriosus","volume":"388","author":"T Hundscheid","year":"2023","journal-title":"N Engl J Med"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1055\/a-1782-5860","article-title":"Randomized noninferiority trial of expectant management versus early treatment of patent ductus arteriosus in preterm infants","volume":"41","author":"S Potsiurko","year":"2024","journal-title":"Am J Perinatol"},{"issue":"08","key":"ref24","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1001\/jamapediatrics.2020.1447","article-title":"Effect of nonintervention vs oral ibuprofen in patent ductus arteriosus in preterm infants: a randomized clinical trial","volume":"174","author":"S I Sung","year":"2020","journal-title":"JAMA Pediatr"},{"issue":"19","key":"ref25","doi-asserted-by":"crossref","first-page":"4083","DOI":"10.7150\/jca.22025","article-title":"A single nucleotide polymorphism in HPGD gene is associated with prostate cancer risk","volume":"8","author":"X Qi","year":"2017","journal-title":"J Cancer"},{"issue":"07","key":"ref26","doi-asserted-by":"crossref","first-page":"e102093","DOI":"10.1371\/journal.pone.0102093","article-title":"miR-485-5p binding site SNP rs8752 in HPGD gene is associated with breast cancer risk","volume":"9","author":"N He","year":"2014","journal-title":"PLoS ONE"},{"issue":"11","key":"ref27","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1038\/s41419-018-1059-y","article-title":"Down-regulation of HPGD by miR-146b-3p promotes cervical cancer cell proliferation, migration and anchorage-independent growth through activation of STAT3 and AKT pathways","volume":"9","author":"S Yao","year":"2018","journal-title":"Cell Death Dis"},{"issue":"05","key":"ref28","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1111\/j.1365-2125.2008.03118.x","article-title":"An optimized ibuprofen dosing scheme for preterm neonates with patent ductus arteriosus, based on a population pharmacokinetic and pharmacodynamic study","volume":"65","author":"D Hirt","year":"2008","journal-title":"Br J Clin Pharmacol"},{"issue":"04","key":"ref29","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1086\/319501","article-title":"A new statistical method for haplotype reconstruction from population data","volume":"68","author":"M Stephens","year":"2001","journal-title":"Am J Hum Genet"},{"issue":"03","key":"ref30","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1086\/428594","article-title":"Accounting for decay of linkage disequilibrium in haplotype inference and missing-data imputation","volume":"76","author":"M Stephens","year":"2005","journal-title":"Am J Hum Genet"},{"issue":"07","key":"ref31","doi-asserted-by":"crossref","first-page":"e0180811","DOI":"10.1371\/journal.pone.0180811","article-title":"Increased urinary prostaglandin E2 metabolite: a potential therapeutic target of Gitelman syndrome","volume":"12","author":"X Peng","year":"2017","journal-title":"PLoS ONE"},{"issue":"02","key":"ref32","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1542\/peds.2008-1117","article-title":"Genetic contribution to patent ductus arteriosus in the premature newborn","volume":"123","author":"V Bhandari","year":"2009","journal-title":"Pediatrics"},{"issue":"02","key":"ref33","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1093\/carcin\/bgq231","article-title":"Association of hydroxyprostaglandin dehydrogenase 15-(NAD) (HPGD) variants and colorectal cancer risk","volume":"32","author":"B Frank","year":"2011","journal-title":"Carcinogenesis"},{"issue":"03","key":"ref34","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1093\/carcin\/bgp325","article-title":"Polymorphisms in fatty-acid-metabolism-related genes are associated with colorectal cancer risk","volume":"31","author":"B Hoeft","year":"2010","journal-title":"Carcinogenesis"}],"container-title":["American Journal of Perinatology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0044-1787172.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T23:31:35Z","timestamp":1735083095000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0044-1787172"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,31]]},"references-count":34,"journal-issue":{"issue":"01","published-online":{"date-parts":[[2024,12,24]]},"published-print":{"date-parts":[[2025,1]]}},"URL":"https:\/\/doi.org\/10.1055\/s-0044-1787172","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":[[2024,5,31]]}}}