{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T23:15:27Z","timestamp":1793834127881,"version":"4.6.1"},"reference-count":51,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2024,3,5]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Neonates with congenital heart disease are at risk for impaired brain development in utero, predisposing children to postnatal brain injury and adverse long\u2010term neurodevelopmental outcomes. Given the vital role of the placenta in fetal growth, we assessed the incidence of placental pathology in fetal congenital heart disease and explored its association with total and regional brain volumes, gyrification, and brain injury after birth.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Placentas from 96 term singleton pregnancies with severe fetal congenital heart disease were prospectively analyzed for macroscopic and microscopic pathology. We applied a placental pathology severity score to relate placental abnormalities to neurological outcome. Postnatal, presurgical magnetic resonance imaging was used to analyze brain volumes, gyrification, and brain injuries. Placental analyses revealed the following abnormalities: maternal vascular malperfusion lesions in 46%, nucleated red blood cells in 37%, chronic inflammatory lesions in 35%, delayed maturation in 30%, and placental weight below the 10th percentile in 28%. Severity of placental pathology was negatively correlated with cortical gray matter, deep gray matter, brainstem, cerebellar, and total brain volumes (\n                      <jats:italic>r<\/jats:italic>\n                      =\u22120.25 to \u22120.31, all\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.05). When correcting for postmenstrual age at magnetic resonance imaging in linear regression, this association remained significant for cortical gray matter, cerebellar, and total brain volume (adjusted\n                      <jats:italic>R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      =0.25\u20130.47, all\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Placental pathology occurs frequently in neonates with severe congenital heart disease and may contribute to impaired brain development, indicated by the association between placental pathology severity and reductions in postnatal cortical, cerebellar, and total brain volumes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.123.033189","type":"journal-article","created":{"date-parts":[[2024,2,29]],"date-time":"2024-02-29T05:18:13Z","timestamp":1709183893000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":44,"title":["Placental Pathology Contributes to Impaired Volumetric Brain Development in Neonates With Congenital Heart Disease"],"prefix":"10.1161","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9665-0291","authenticated-orcid":false,"given":"Maaike","family":"Nijman","sequence":"first","affiliation":[{"name":"Department of Neonatology Wilhelmina Children\u2019s Hospital, University Medical Center Utrecht Utrecht the Netherlands"},{"name":"Department of Pediatric Cardiology Wilhelmina Children\u2019s Hospital, University Medical Center Utrecht Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4537-5645","authenticated-orcid":false,"given":"Lotte E.","family":"van der Meeren","sequence":"additional","affiliation":[{"name":"Department of Pathology Erasmus Medical Center Rotterdam Rotterdam the Netherlands"},{"name":"Department of Pathology Leiden University Medical Center Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7279-4589","authenticated-orcid":false,"given":"Peter G. J.","family":"Nikkels","sequence":"additional","affiliation":[{"name":"Department of Pathology University Medical Center Utrecht Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond","family":"Stegeman","sequence":"additional","affiliation":[{"name":"Department of Neonatology Wilhelmina Children\u2019s Hospital, University Medical Center Utrecht Utrecht the Netherlands"},{"name":"Department of Pediatric Cardiology Wilhelmina Children\u2019s Hospital, University Medical Center Utrecht Utrecht the Netherlands"},{"name":"Department of Pediatrics Beatrix Children\u2019s Hospital, University Medical Center Groningen Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8009-8869","authenticated-orcid":false,"given":"Johannes M. P. J.","family":"Breur","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiology Wilhelmina Children\u2019s Hospital, University Medical Center Utrecht Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolaas J. G.","family":"Jansen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Beatrix Children\u2019s Hospital, University Medical Center Groningen Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5755-5774","authenticated-orcid":false,"given":"Henriette","family":"ter Heide","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiology Wilhelmina Children\u2019s Hospital, University Medical Center Utrecht Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2516-7822","authenticated-orcid":false,"given":"Trinette J.","family":"Steenhuis","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiology Wilhelmina Children\u2019s Hospital, University Medical Center Utrecht Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roel","family":"de Heus","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology University Medical Center Utrecht Utrecht the Netherlands"},{"name":"Department of Obstetrics and Gynecology St. Antonius Hospital Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7372-4291","authenticated-orcid":false,"given":"Mireille N.","family":"Bekker","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology University Medical Center Utrecht Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4221-2779","authenticated-orcid":false,"given":"Nathalie H. P.","family":"Claessens","sequence":"additional","affiliation":[{"name":"Department of Neonatology Wilhelmina Children\u2019s Hospital, University Medical Center Utrecht Utrecht the Netherlands"},{"name":"Department of Pediatrics Wilhelmina Children\u2019s Hospital, University Medical Center Utrecht Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5491-9168","authenticated-orcid":false,"given":"Manon J. N. L.","family":"Benders","sequence":"additional","affiliation":[{"name":"Department of Neonatology Wilhelmina Children\u2019s Hospital, University Medical Center Utrecht Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joppe","family":"Nijman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Alderliesten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rian","family":"Bosch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roelie M.","family":"W\u00f6sten\u2010van Asperen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martijn G.","family":"Slieker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabrielle G.","family":"van Iperen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heynric B.","family":"Grotenhuis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"van Loon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Koomen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bram","family":"van Wijk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul H.","family":"Schoof","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Talacua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique M. J.","family":"van Schooneveld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maaike C. A.","family":"Sprong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique C.","family":"Haak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maartje C.","family":"Snoep","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2012-3435"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-64029-1.00016-3"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.122.039492"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2020.110957"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.114.013051"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A6021"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.21037\/tp-20-224"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.865568"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.121.056305"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/uog.14798"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.122.025516"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2004.06.038"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.01045"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/apm.12833"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2015.12505"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2015.08.003"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.116.021793"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00246-018-1876-x"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-40894-y"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2022.05.038"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00246-022-03018-4"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2022.08.013"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41390-021-01521-7"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(02)01886-7"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1080\/15513819609168713"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2015-0225-CC"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2013.06.010"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13063-022-06098-y"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A7328"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2018.01.054"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2015.10.047"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2006.01.015"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2018.06.018"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1136\/fn.84.3.F211"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-97214-5_24"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2014.11.021"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.2350\/06-01-0015.1"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1111\/apm.12849"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhw306"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1111\/dmcn.15024"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcab046"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-47328-9"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.24603"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.531543"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0095-5108(18)30159-3"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2013.02.002"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsgi.2005.01.029"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamapediatrics.2019.5316"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2015.09.072"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2016.05.001"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1067\/mpd.2001.109605"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.123.033189","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T08:27:35Z","timestamp":1715588855000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.123.033189"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,5]]},"references-count":51,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,3,5]]}},"alternative-id":["10.1161\/JAHA.123.033189"],"URL":"https:\/\/doi.org\/10.1161\/jaha.123.033189","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,5]]},"assertion":[{"value":"2023-10-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-01","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e033189"}}