{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T23:48:45Z","timestamp":1790380125726,"version":"4.1.0"},"reference-count":20,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>We conducted a study to determine whether patients born with Trisomy 21 and left-to-right shunts who develop pulmonary vein stenosis (PVS) have a longer exposure to shunt physiology compared to those who do not develop PVS. We included patients seen at Boston Children\u2019s Hospital between 15 August 2006 and 31 August 2017 born with Trisomy 21 and left-to-right shunts who developed PVS within 24 months of age. We conducted a retrospective 3:1 matched case\u2013control study. The primary predictor was length of exposure to shunt as defined as date of birth to the first echocardiogram showing mild or no shunt. Case patients with PVS were more likely to have a longer exposure to shunt than patients in the control group (6 vs. 3 months, p-value 0.002). Additionally, PVS patients were also more likely to have their initial repair \u2265 4 months of age (81% vs. 42%, p-value 0.003) and have a gestational age \u2264 35 weeks (48% vs. 13%, p-value 0.003). Time exposed to shunts may be an important modifiable risk factor for PVS in patients with Trisomy 21.<\/jats:p>","DOI":"10.3390\/children8010019","type":"journal-article","created":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T22:35:48Z","timestamp":1609540548000},"page":"19","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Longer Exposure to Left-to-Right Shunts Is a Risk Factor for Pulmonary Vein Stenosis in Patients with Trisomy 21"],"prefix":"10.3390","volume":"8","author":[{"given":"Connie","family":"Choi","sequence":"first","affiliation":[{"name":"Department of Cardiology, Harvard Medical School, Boston Children\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberlee","family":"Gauvreau","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Harvard Medical School, Boston Children\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Levy","sequence":"additional","affiliation":[{"name":"Division of Newborn Medicine, Department of Pediatrics, Harvard Medical School, Boston Children\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Callahan","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Harvard Medical School, Boston Children\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathy","family":"Jenkins","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Harvard Medical School, Boston Children\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minghui","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Harvard Medical School, Boston Children\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Division of Genetics and Genomics, Department of Pediatrics, Harvard Medical School, Boston Children\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.athoracsur.2017.03.022","article-title":"Primary pulmonary vein stenosis: Outcomes, risk factors and severity score in multicentric study","volume":"104","author":"Kalfa","year":"2017","journal-title":"Ann Thorac. 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Pathol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1002\/ppul.23679","article-title":"Pulmonary vein stenosis of ex-premature infants with pulmonary hypertension and bronchopulmonary dysplasia, epidemiology, and survival from a multicenter cohort","volume":"52","author":"Mahgoub","year":"2017","journal-title":"Pediatric. Pulmonol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e656","DOI":"10.1542\/peds.2008-0075","article-title":"Pulmonary vein stenosis: Prematurity and associated conditions","volume":"122","author":"Drossner","year":"2008","journal-title":"Pediatrics"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"E90","DOI":"10.1111\/chd.12088","article-title":"Pulmonary Vein Stenosis with Down Syndrome: A Rare and Frequently Fatal Cause of Pulmonary Hypertension in Infants and Children","volume":"9","author":"Gowda","year":"2014","journal-title":"Congenit. Heart Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1111\/j.1747-0803.2009.00272.x","article-title":"Host Factor Vulnerability and Development of Progressive Intraluminal Pulmonary Vein Stenosis after Congenital Heart Surgery","volume":"4","author":"Goff","year":"2009","journal-title":"Congenit. Heart Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.jpeds.2007.09.045","article-title":"Prevalence, Neonatal Characteristics, and First-Year Mortality of Down Syndrome: A National Study","volume":"152","author":"Weijerman","year":"2008","journal-title":"J. Pediatrics"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.jtcvs.2007.01.026","article-title":"The presence of Down syndrome is not a risk factor in complete atrioventricular septal defect repair","volume":"134","author":"Lange","year":"2007","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1016\/j.jtcvs.2010.08.093","article-title":"Surgical Management of Complete Atrioventricular Septal Defect: Associations with Surgical Technique, Age, and Trisomy 21","volume":"141","author":"Atz","year":"2011","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.1016\/j.athoracsur.2015.01.063","article-title":"Early Complete Atrioventricular Canal Repair Yields Outcomes Equivalent to Late Repair","volume":"99","author":"Stephens","year":"2015","journal-title":"Ann Thorac. Surg."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1253\/circj.CJ-10-0495","article-title":"Mechanisms of vein graft adaptation to the arterial circulation: Insights into the neotimal algorithm and management strategies","volume":"74","author":"Muto","year":"2010","journal-title":"Circ. 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