{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T06:24:30Z","timestamp":1791699870477,"version":"4.3.4"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,3,11]],"date-time":"2019-03-11T00:00:00Z","timestamp":1552262400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,3,11]],"date-time":"2019-03-11T00:00:00Z","timestamp":1552262400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000002","name":"U.S. Department of Health &amp; Human Services | National Institutes of Health","doi-asserted-by":"publisher","award":["NHLBI R01 HL116585-01"],"award-info":[{"award-number":["NHLBI R01 HL116585-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Congenital heart disease (CHD) is an independent risk factor for brain injury, including stroke, and poor neurodevelopmental outcomes, and placental abnormalities may represent an additional risk factor for brain injury in neonates. The incidence and scope of placental pathology and relationship to fetal brain abnormalities in pregnancies complicated by fetal CHD has not been explored to our knowledge. In order to determine the prevalence of placental pathology findings and whether placental findings are associated with postnatal brain injury in pregnancies complicated by fetal CHD, we reviewed placental pathology reports for 51 pregnancies complicated by CHD and scored available postnatal, pre-operative brain MRI for brain pathology. Overall, 57% of CHD infants had abnormal placental pathology. Pregnancies complicated by CHD with aortic obstruction (AO) were significantly more likely than those with no obstruction to have abnormal placental pathology (79% vs. 44%). There was a trend toward more severe brain lesions amongst patients with brain lesions and placental abnormality (55% moderate\/severe) compared to those without placental abnormality (11% moderate\/severe). These data suggest that placental abnormalities are common in CHD and may have a compounding effect on brain lesions in this high-risk population.<\/jats:p>","DOI":"10.1038\/s41598-019-40894-y","type":"journal-article","created":{"date-parts":[[2019,3,11]],"date-time":"2019-03-11T07:03:05Z","timestamp":1552287785000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Placental Pathology and Neuroimaging Correlates in Neonates with Congenital Heart Disease"],"prefix":"10.1038","volume":"9","author":[{"given":"Sarah D.","family":"Schlatterer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Murnick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marni","family":"Jacobs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"White","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary T.","family":"Donofrio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Limperopoulos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,3,11]]},"reference":[{"key":"40894_CR1","doi-asserted-by":"publisher","unstructured":"Rychik, J. et al. Characterization of the Placenta in the Newborn with Congenital Heart Disease: Distinctions Based on Type of Cardiac Malformation. Pediatr Cardiol, https:\/\/doi.org\/10.1007\/s00246-018-1876-x (2018).","DOI":"10.1007\/s00246-018-1876-x"},{"key":"40894_CR2","doi-asserted-by":"publisher","first-page":"3271","DOI":"10.3109\/14767058.2015.1121480","volume":"29","author":"A Ruiz","year":"2016","unstructured":"Ruiz, A. et al. Placenta-related complications in women carrying a foetus with congenital heart disease. J Matern Fetal Neonatal Med 29, 3271\u20133275, https:\/\/doi.org\/10.3109\/14767058.2015.1121480 (2016).","journal-title":"J Matern Fetal Neonatal Med"},{"key":"40894_CR3","doi-asserted-by":"publisher","first-page":"1024","DOI":"10.1016\/j.placenta.2015.06.013","volume":"36","author":"N Andescavage","year":"2015","unstructured":"Andescavage, N. et al. 3-D volumetric MRI evaluation of the placenta in fetuses with complex congenital heart disease. Placenta 36, 1024\u20131030, https:\/\/doi.org\/10.1016\/j.placenta.2015.06.013 (2015).","journal-title":"Placenta"},{"key":"40894_CR4","doi-asserted-by":"publisher","first-page":"1036","DOI":"10.1002\/mrm.27100","volume":"80","author":"Z Zun","year":"2018","unstructured":"Zun, Z. & Limperopoulos, C. Placental perfusion imaging using velocity-selective arterial spin labeling. Magn Reson Med 80, 1036\u20131047, https:\/\/doi.org\/10.1002\/mrm.27100 (2018).","journal-title":"Magn Reson Med"},{"key":"40894_CR5","doi-asserted-by":"publisher","first-page":"e89419","DOI":"10.1371\/journal.pone.0089419","volume":"9","author":"AM Roescher","year":"2014","unstructured":"Roescher, A. M., Timmer, A., Erwich, J. J. & Bos, A. F. Placental pathology, perinatal death, neonatal outcome, and neurological development: a systematic review. PLoS One 9, e89419, https:\/\/doi.org\/10.1371\/journal.pone.0089419 (2014).","journal-title":"PLoS One"},{"issue":"849","key":"40894_CR6","doi-asserted-by":"publisher","first-page":"e841","DOI":"10.1016\/j.ajog.2015.09.072","volume":"213","author":"IN Mir","year":"2015","unstructured":"Mir, I. N. et al. Placental pathology is associated with severity of neonatal encephalopathy and adverse developmental outcomes following hypothermia. Am J Obstet Gynecol 213(849), e841\u2013847, https:\/\/doi.org\/10.1016\/j.ajog.2015.09.072 (2015).","journal-title":"Am J Obstet Gynecol"},{"key":"40894_CR7","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/j.pediatrneurol.2016.05.001","volume":"61","author":"HY Lu","year":"2016","unstructured":"Lu, H. Y., Zhang, Q., Wang, Q. X. & Lu, J. Y. Contribution of Histologic Chorioamnionitis and Fetal Inflammatory Response Syndrome to Increased Risk of Brain Injury in Infants With Preterm Premature Rupture of Membranes. Pediatr Neurol 61, 94\u201398 e91, https:\/\/doi.org\/10.1016\/j.pediatrneurol.2016.05.001 (2016).","journal-title":"Pediatr Neurol"},{"key":"40894_CR8","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1067\/mpd.2001.109605","volume":"138","author":"C De Felice","year":"2001","unstructured":"De Felice, C. et al. Early neonatal brain injury in histologic chorioamnionitis. J Pediatr 138, 101\u2013104 (2001).","journal-title":"J Pediatr"},{"key":"40894_CR9","doi-asserted-by":"publisher","first-page":"968","DOI":"10.1016\/j.jpeds.2013.06.010","volume":"163","author":"JC Harteman","year":"2013","unstructured":"Harteman, J. C. et al. Placental pathology in full-term infants with hypoxic-ischemic neonatal encephalopathy and association with magnetic resonance imaging pattern of brain injury. J Pediatr 163, 968\u2013995 e962, https:\/\/doi.org\/10.1016\/j.jpeds.2013.06.010 (2013).","journal-title":"J Pediatr"},{"key":"40894_CR10","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1016\/0002-9378(79)90312-0","volume":"133","author":"PA Grannum","year":"1979","unstructured":"Grannum, P. A., Berkowitz, R. L. & Hobbins, J. C. The ultrasonic changes in the maturing placenta and their relation to fetal pulmonic maturity. Am J Obstet Gynecol 133, 915\u2013922 (1979).","journal-title":"Am J Obstet Gynecol"},{"key":"40894_CR11","doi-asserted-by":"crossref","unstructured":"Andropoulos, D. B. et al. Brain immaturity is associated with brain injury before and after neonatal cardiac surgery with high-flow bypass and cerebral oxygenation monitoring. J Thorac Cardiovasc Surg 139, 543\u2013556, doi:S0022-5223(09)01076-9 (2010).","DOI":"10.1016\/j.jtcvs.2009.08.022"},{"key":"40894_CR12","doi-asserted-by":"publisher","first-page":"606 e601","DOI":"10.1016\/j.ajog.2017.02.005","volume":"216","author":"A Khalil","year":"2017","unstructured":"Khalil, A. et al. Is cerebroplacental ratio a marker of impaired fetal growth velocity and adverse pregnancy outcome? Am J Obstet Gynecol 216, 606 e601\u2013606 e610, https:\/\/doi.org\/10.1016\/j.ajog.2017.02.005 (2017).","journal-title":"Am J Obstet Gynecol"},{"key":"40894_CR13","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.1016\/j.placenta.2015.08.003","volume":"36","author":"HN Jones","year":"2015","unstructured":"Jones, H. N. et al. Hypoplastic left heart syndrome is associated with structural and vascular placental abnormalities and leptin dysregulation. Placenta 36, 1078\u20131086, https:\/\/doi.org\/10.1016\/j.placenta.2015.08.003 (2015).","journal-title":"Placenta"},{"key":"40894_CR14","doi-asserted-by":"publisher","first-page":"459","DOI":"10.2350\/10-01-0774-OA.1","volume":"13","author":"A Saleemuddin","year":"2010","unstructured":"Saleemuddin, A. et al. Obstetric and perinatal complications in placentas with fetal thrombotic vasculopathy. Pediatr Dev Pathol 13, 459\u2013464, https:\/\/doi.org\/10.2350\/10-01-0774-OA.1 (2010).","journal-title":"Pediatr Dev Pathol"},{"key":"40894_CR15","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1093\/eurheartj\/eht389","volume":"35","author":"E Llurba","year":"2014","unstructured":"Llurba, E. et al. Maternal and foetal angiogenic imbalance in congenital heart defects. Eur Heart J 35, 701\u2013707, https:\/\/doi.org\/10.1093\/eurheartj\/eht389 (2014).","journal-title":"Eur Heart J"},{"key":"40894_CR16","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.placenta.2010.10.008","volume":"32","author":"B Almog","year":"2011","unstructured":"Almog, B. et al. Placenta weight percentile curves for singleton and twins deliveries. Placenta 32, 58\u201362, https:\/\/doi.org\/10.1016\/j.placenta.2010.10.008 (2011).","journal-title":"Placenta"},{"key":"40894_CR17","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1159\/000330202","volume":"30","author":"M Itsukaichi","year":"2011","unstructured":"Itsukaichi, M. et al. Changes in fetal circulation associated with congenital heart disease and their effects on fetal growth. Fetal Diagn Ther 30, 219\u2013224, https:\/\/doi.org\/10.1159\/000330202 (2011).","journal-title":"Fetal Diagn Ther"},{"key":"40894_CR18","doi-asserted-by":"publisher","first-page":"1546","DOI":"10.1161\/CIRCULATIONAHA.116.021793","volume":"134","author":"NB Matthiesen","year":"2016","unstructured":"Matthiesen, N. B. et al. Congenital Heart Defects and Indices of Placental and Fetal Growth in a Nationwide Study of 924 422 Liveborn Infants. Circulation 134, 1546\u20131556, https:\/\/doi.org\/10.1161\/CIRCULATIONAHA.116.021793 (2016).","journal-title":"Circulation"},{"key":"40894_CR19","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.3389\/fphys.2018.01045","volume":"9","author":"JA Courtney","year":"2018","unstructured":"Courtney, J. A., Cnota, J. F. & Jones, H. N. The Role of Abnormal Placentation in Congenital Heart Disease; Cause, Correlate, or Consequence? Front Physiol 9, 1045, https:\/\/doi.org\/10.3389\/fphys.2018.01045 (2018).","journal-title":"Front Physiol"},{"key":"40894_CR20","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/j.placenta.2006.03.010","volume":"28","author":"M De Falco","year":"2007","unstructured":"De Falco, M. et al. Expression and distribution of notch protein members in human placenta throughout pregnancy. Placenta 28, 118\u2013126, https:\/\/doi.org\/10.1016\/j.placenta.2006.03.010 (2007).","journal-title":"Placenta"},{"key":"40894_CR21","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1016\/j.devcel.2012.01.014","volume":"22","author":"JL de la Pompa","year":"2012","unstructured":"de la Pompa, J. L. & Epstein, J. A. Coordinating tissue interactions: Notch signaling in cardiac development and disease. Dev Cell 22, 244\u2013254, https:\/\/doi.org\/10.1016\/j.devcel.2012.01.014 (2012).","journal-title":"Dev Cell"},{"key":"40894_CR22","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1242\/dev.128.9.1531","volume":"128","author":"Y Dor","year":"2001","unstructured":"Dor, Y. et al. A novel role for VEGF in endocardial cushion formation and its potential contribution to congenital heart defects. Development 128, 1531\u20131538 (2001).","journal-title":"Development"},{"key":"40894_CR23","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1095\/biolreprod.111.096925","volume":"86","author":"CE Dunk","year":"2012","unstructured":"Dunk, C. E. et al. The molecular role of connexin 43 in human trophoblast cell fusion. Biol Reprod 86, 115, https:\/\/doi.org\/10.1095\/biolreprod.111.096925 (2012).","journal-title":"Biol Reprod"},{"key":"40894_CR24","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.placenta.2016.04.020","volume":"43","author":"KJ Gibbins","year":"2016","unstructured":"Gibbins, K. J. et al. Stillbirth, hypertensive disorders of pregnancy, and placental pathology. Placenta 43, 61\u201368, https:\/\/doi.org\/10.1016\/j.placenta.2016.04.020 (2016).","journal-title":"Placenta"},{"key":"40894_CR25","doi-asserted-by":"publisher","first-page":"e0182874","DOI":"10.1371\/journal.pone.0182874","volume":"12","author":"R Bukowski","year":"2017","unstructured":"Bukowski, R. et al. Altered fetal growth, placental abnormalities, and stillbirth. PLoS One 12, e0182874, https:\/\/doi.org\/10.1371\/journal.pone.0182874 (2017).","journal-title":"PLoS One"},{"key":"40894_CR26","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/j.placenta.2017.01.007","volume":"50","author":"J Zeng","year":"2017","unstructured":"Zeng, J., Marcus, A., Buhtoiarova, T. & Mittal, K. Distribution and potential significance of intravillous and intrafibrinous particulate microcalcification. Placenta 50, 94\u201398, https:\/\/doi.org\/10.1016\/j.placenta.2017.01.007 (2017).","journal-title":"Placenta"},{"key":"40894_CR27","doi-asserted-by":"publisher","first-page":"S79","DOI":"10.4103\/2141-9248.138016","volume":"4","author":"J Nigam","year":"2014","unstructured":"Nigam, J. et al. Histopathological study of placentae in low birth weight babies in India. Ann Med Health Sci Res 4, S79\u201383, https:\/\/doi.org\/10.4103\/2141-9248.138016 (2014).","journal-title":"Ann Med Health Sci Res"},{"key":"40894_CR28","doi-asserted-by":"publisher","first-page":"E1328","DOI":"10.1210\/jc.2015-2553","volume":"100","author":"TI Korevaar","year":"2015","unstructured":"Korevaar, T. I. et al. Placental Angiogenic Factors Are Associated With Maternal Thyroid Function and Modify hCG-Mediated FT4 Stimulation. J Clin Endocrinol Metab 100, E1328\u20131334, https:\/\/doi.org\/10.1210\/jc.2015-2553 (2015).","journal-title":"J Clin Endocrinol Metab"},{"key":"40894_CR29","doi-asserted-by":"publisher","first-page":"155","DOI":"10.5694\/mja12.10811","volume":"197","author":"GM Blue","year":"2012","unstructured":"Blue, G. M., Kirk, E. P., Sholler, G. F., Harvey, R. P. & Winlaw, D. S. Congenital heart disease: current knowledge about causes and inheritance. Med J Aust 197, 155\u2013159 (2012).","journal-title":"Med J Aust"},{"key":"40894_CR30","doi-asserted-by":"publisher","first-page":"244 e241","DOI":"10.1016\/j.ajog.2017.10.225","volume":"218","author":"Y Wang","year":"2018","unstructured":"Wang, Y. et al. Prenatal chromosomal microarray analysis in fetuses with congenital heart disease: a prospective cohort study. Am J Obstet Gynecol 218, 244 e241\u2013244 e217, https:\/\/doi.org\/10.1016\/j.ajog.2017.10.225 (2018).","journal-title":"Am J Obstet Gynecol"},{"key":"40894_CR31","doi-asserted-by":"publisher","first-page":"1436","DOI":"10.1016\/S0006-3223(99)00150-X","volume":"46","author":"EW Chow","year":"1999","unstructured":"Chow, E. W. et al. Qualitative MRI findings in adults with 22q11 deletion syndrome and schizophrenia. Biol Psychiatry 46, 1436\u20131442 (1999).","journal-title":"Biol Psychiatry"},{"key":"40894_CR32","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1097\/CRD.0000000000000170","volume":"26","author":"A Morgenthau","year":"2018","unstructured":"Morgenthau, A. & Frishman, W. H. Genetic Origins of Tetralogy of Fallot. Cardiol Rev 26, 86\u201392, https:\/\/doi.org\/10.1097\/CRD.0000000000000170 (2018).","journal-title":"Cardiol Rev"},{"key":"40894_CR33","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1093\/hmg\/ddt400","volume":"23","author":"S Cioffi","year":"2014","unstructured":"Cioffi, S. et al. Tbx1 regulates brain vascularization. Hum Mol Genet 23, 78\u201389, https:\/\/doi.org\/10.1093\/hmg\/ddt400 (2014).","journal-title":"Hum Mol Genet"},{"key":"40894_CR34","doi-asserted-by":"publisher","first-page":"1659","DOI":"10.1176\/appi.ajp.158.10.1659","volume":"158","author":"JD Pinter","year":"2001","unstructured":"Pinter, J. D., Eliez, S., Schmitt, J. E., Capone, G. T. & Reiss, A. L. Neuroanatomy of Down\u2019s syndrome: a high-resolution MRI study. Am J Psychiatry 158, 1659\u20131665, https:\/\/doi.org\/10.1176\/appi.ajp.158.10.1659 (2001).","journal-title":"Am J Psychiatry"},{"key":"40894_CR35","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.nicl.2017.09.020","volume":"17","author":"J De Asis-Cruz","year":"2018","unstructured":"De Asis-Cruz, J., Donofrio, M. T., Vezina, G. & Limperopoulos, C. Aberrant brain functional connectivity in newborns with congenital heart disease before cardiac surgery. NeuroImage. Clinical 17, 31\u201342, https:\/\/doi.org\/10.1016\/j.nicl.2017.09.020 (2018).","journal-title":"NeuroImage. Clinical"},{"key":"40894_CR36","doi-asserted-by":"publisher","first-page":"1541","DOI":"10.1016\/0002-9378(94)90398-0","volume":"171","author":"F Arias","year":"1994","unstructured":"Arias, F. Accuracy of the middle-cerebral-to-umbilical-artery resistance index ratio in the prediction of neonatal outcome in patients at high risk for fetal and neonatal complications. Am J Obstet Gynecol 171, 1541\u20131545 (1994).","journal-title":"Am J Obstet Gynecol"},{"key":"40894_CR37","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/j.ajog.2015.05.024","volume":"213","author":"GR DeVore","year":"2015","unstructured":"DeVore, G. R. The importance of the cerebroplacental ratio in the evaluation of fetal well-being in SGA and AGA fetuses. Am J Obstet Gynecol 213, 5\u201315, https:\/\/doi.org\/10.1016\/j.ajog.2015.05.024 (2015).","journal-title":"Am J Obstet Gynecol"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-40894-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-40894-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-40894-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T02:23:04Z","timestamp":1671243784000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-40894-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,11]]},"references-count":37,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["40894"],"URL":"https:\/\/doi.org\/10.1038\/s41598-019-40894-y","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,11]]},"assertion":[{"value":"15 November 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 February 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 March 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"4137"}}