{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T23:06:48Z","timestamp":1791932808871,"version":"4.3.4"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2021,3,11]],"date-time":"2021-03-11T00:00:00Z","timestamp":1615420800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Calvin Bland Endowment"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,7,20]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Hydroxyurea (HU) is used in children with sickle cell disease (SCD) to increase fetal hemoglobin (HF), contributing to a decrease in physical symptoms and potential protection against cerebral microvasculopathy. There has been minimal investigation into the association between HU use and cognition in this population. This study examined the relationship between HU status and cognition in children with SCD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Thirty-seven children with SCD HbSS or HbS\/\u03b20 thalassaemia (sickle cell anemia; SCA) ages 4:0\u201311\u2009years with no history of overt stroke or chronic transfusion completed a neuropsychological test battery. Other medical, laboratory, and demographic data were obtained. Neuropsychological function across 3 domains (verbal, nonverbal, and attention\/executive) was compared for children on HU (n\u2009=\u20099) to those not taking HU (n\u2009=\u200928).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Children on HU performed significantly better than children not taking HU on standardized measures of attention\/executive functioning and nonverbal skills. Performance on verbal measures was similar between groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These results suggest that treatment with HU may not only reduce physical symptoms, but may also provide potential benefit to cognition in children with SCA, particularly in regard to attention\/executive functioning and nonverbal skills. Replication with larger samples and longitudinal studies are warranted.<\/jats:p><\/jats:sec>","DOI":"10.1093\/jpepsy\/jsab015","type":"journal-article","created":{"date-parts":[[2021,2,19]],"date-time":"2021-02-19T20:47:27Z","timestamp":1613767647000},"page":"710-718","source":"Crossref","is-referenced-by-count":8,"title":["Hydroxyurea Use Associated with Nonverbal and Executive Skills in Sickle Cell Anemia"],"prefix":"10.1093","volume":"46","author":[{"given":"Reem A","family":"Tarazi","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Drexel University College of Medicine, Philadelphia, PA"},{"name":"Division of Hematology, St. Christopher\u2019s Hospital for Children, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina E","family":"Patrick","sequence":"additional","affiliation":[{"name":"Department of Neurology, Division of Pediatric Neurology, University of Washington School of Medicine, Seattle Children\u2019s Hospital, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Iampietro","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Psychiatry and Behavioral Sciences, The Children\u2019s Hospital of Philadelphia, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nataly","family":"Apollonsky","sequence":"additional","affiliation":[{"name":"Division of Hematology, St. Christopher\u2019s Hospital for Children, Philadelphia, PA"},{"name":"Department of Pediatrics, Drexel University College of Medicine, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,3,11]]},"reference":[{"key":"2021072018495523500_jsab015-B1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2020\/8181425","article-title":"Laboratory biomarkers, cerebral blood flow velocity, and intellectual function in children with sickle cell disease","volume":"2020","author":"Apollonsky","year":"2020","journal-title":"Advances in Hematology"},{"issue":"6 Pt 1","key":"2021072018495523500_jsab015-B2","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1542\/peds.97.6.864","article-title":"Cognitive functioning and brain magnetic resonance imaging in children with sickle cell disease","volume":"97","author":"Armstrong","year":"1996","journal-title":"Pediatrics"},{"issue":"2","key":"2021072018495523500_jsab015-B3","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1080\/09297040600800956","article-title":"Neurocognitive sequelae of pediatric sickle cell disease: a review of literature","volume":"13","author":"Berkelhammer","year":"2007","journal-title":"Child Neuropsychology"},{"issue":"12","key":"2021072018495523500_jsab015-B4","doi-asserted-by":"crossref","first-page":"932","DOI":"10.7326\/0003-4819-148-12-200806170-00220","article-title":"National Institutes of Health consensus development conference statement: hydroxyurea treatment for sickle cell disease","volume":"148","author":"Brawley","year":"2008","journal-title":"Annals of Internal Medicine"},{"issue":"2","key":"2021072018495523500_jsab015-B5","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/s00277-016-2861-1","article-title":"Cognitive and fine motor deficits in a pediatric sickle cell disease cohort of mixed ethnic origin","volume":"96","author":"Burkhardt","year":"2017","journal-title":"Annals of Hematology"},{"issue":"20","key":"2021072018495523500_jsab015-B38004743","doi-asserted-by":"publisher","first-page":"1317","DOI":"10.1056\/NEJM199505183322001","article-title":"Effect of Hydroxyurea on the Frequency of Painful Crises in Sickle Cell Anemia","volume":"332","author":"Charache","year":"1995","journal-title":"New England Journal of Medicine"},{"key":"2021072018495523500_jsab015-B6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0065-3101(24)00238-X","article-title":"Fetal hemoglobin, sickling, and sickle cell disease","volume":"37","author":"Charache","year":"1990","journal-title":"Advances in Pediatrics"},{"key":"2021072018495523500_jsab015-B7","volume-title":"Conners\u2019 Kiddie Continuous Performance Test (K-CPT)","author":"Conners","year":"2006"},{"key":"2021072018495523500_jsab015-B8","volume-title":"Conners' Continuous Performance Test","author":"Conners","year":"2000","edition":"2nd edn,)"},{"issue":"16","key":"2021072018495523500_jsab015-B9","doi-asserted-by":"crossref","first-page":"3684","DOI":"10.1182\/blood-2011-05-349621","article-title":"Associated risk factors for silent cerebral infarcts in sickle cell anemia: low baseline hemoglobin, sex, and relative high systolic blood pressure","volume":"119","author":"DeBaun","year":"2012","journal-title":"Blood"},{"key":"2021072018495523500_jsab015-B10","volume-title":"Differential Ability Scales","author":"Elliott","year":"2007","edition":"2nd edn"},{"issue":"12","key":"2021072018495523500_jsab015-B11","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1002\/ajh.24906","article-title":"A clinically meaningful fetal hemoglobin threshold for children with sickle cell anemia during hydroxyurea therapy","volume":"92","author":"Estepp","year":"2017","journal-title":"American Journal of Hematology"},{"issue":"11","key":"2021072018495523500_jsab015-B12","doi-asserted-by":"crossref","first-page":"3628","DOI":"10.1182\/blood.V97.11.3628","article-title":"Five years of experience with hydroxyurea in children and young adults with sickle cell disease","volume":"97","author":"Ferster","year":"2001","journal-title":"Blood"},{"issue":"6","key":"2021072018495523500_jsab015-B13","doi-asserted-by":"crossref","first-page":"1960","DOI":"10.1182\/blood.V88.6.1960.bloodjournal8861960","article-title":"Hydroxyurea for treatment of severe sickle cell anemia: a pediatric clinical trial","volume":"88","author":"Ferster","year":"1996","journal-title":"Blood"},{"issue":"22","key":"2021072018495523500_jsab015-B14","doi-asserted-by":"crossref","first-page":"2436","DOI":"10.1182\/blood-2018-09-876318","article-title":"Hydroxyurea reduces cerebral metabolic stress in patients with sickle cell anemia","volume":"133","author":"Fields","year":"2019","journal-title":"Blood"},{"issue":"4","key":"2021072018495523500_jsab015-B15","doi-asserted-by":"crossref","first-page":"S512","DOI":"10.1016\/j.amepre.2009.12.022","article-title":"Population estimates of sickle cell disease in the U.S","volume":"38","author":"Hassell","year":"2010","journal-title":"American Journal of Preventive Medicine"},{"issue":"51","key":"2021072018495523500_jsab015-B16","doi-asserted-by":"crossref","DOI":"10.1097\/MD.0000000000018225","article-title":"The role of hydroxyurea to prevent silent stroke in sickle cell disease: systematic review and meta-analysis","volume":"98","author":"Hasson","year":"2019","journal-title":"Medicine"},{"issue":"4","key":"2021072018495523500_jsab015-B17","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1111\/j.1467-7687.2006.00503.x","article-title":"Physiological correlates of intellectual function in children with sickle cell disease: hypoxaemia, hyperaemia and brain infarction","volume":"9","author":"Hogan","year":"2006","journal-title":"Developmental Science"},{"issue":"4","key":"2021072018495523500_jsab015-B18","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/S0022-3476(96)70121-X","article-title":"Clinical and hematologic effects of hydroxyurea in children with sickle cell anemia","volume":"129","author":"Jayabose","year":"1996","journal-title":"The Journal of Pediatrics"},{"issue":"1","key":"2021072018495523500_jsab015-B19","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.blre.2006.07.001","article-title":"Deconstructing sickle cell disease: reappraisal of the role of hemolysis in the development of subclinical subphenotypes","volume":"21","author":"Kato","year":"2007","journal-title":"Blood Reviews"},{"issue":"7","key":"2021072018495523500_jsab015-B20","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1111\/dmcn.13113","article-title":"Intelligence quotient in paediatric sickle cell disease: a systematic review and meta-analysis","volume":"58","author":"Kawadler","year":"2016","journal-title":"Developmental Medicine & Child Neurology"},{"issue":"2","key":"2021072018495523500_jsab015-B21","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1002\/ajh.23604","article-title":"Parent education and biologic factors influence on cognition in sickle cell anemia","volume":"89","author":"King","year":"2014","journal-title":"American Journal of Hematology"},{"issue":"5","key":"2021072018495523500_jsab015-B22","first-page":"1550","article-title":"Safety of hydroxyurea in children with sickle cell anemia: results of the HUG-KIDS study, a phase I\/II trial. Pediatric Hydroxyurea Group","volume":"94","author":"Kinney","year":"1999","journal-title":"Blood"},{"key":"2021072018495523500_jsab015-B23","volume-title":"NEPSY, second edition (NEPSY-II)","author":"Korkman","year":"2007"},{"issue":"2","key":"2021072018495523500_jsab015-B24","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1542\/peds.112.2.324","article-title":"Transcranial Doppler ultrasonography and neurocognitive functioning in children with sickle cell disease","volume":"112","author":"Kral","year":"2003","journal-title":"Pediatrics"},{"issue":"7","key":"2021072018495523500_jsab015-B25","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1002\/pbc.20819","article-title":"Hydroxyurea therapy lowers TCD velocities in children with sickle cell disease","volume":"47","author":"Kratovil","year":"2006","journal-title":"Pediatric Blood & Cancer"},{"issue":"6","key":"2021072018495523500_jsab015-B26","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1038\/sj.tpj.6500433","article-title":"Fetal hemoglobin in sickle cell anemia: genetic determinants of response to hydroxyurea","volume":"7","author":"Ma","year":"2007","journal-title":"The Pharmacogenomics Journal"},{"issue":"2","key":"2021072018495523500_jsab015-B27","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1080\/02739610902813245","article-title":"Barriers to treatment adherence for pediatric patients with sickle cell disease and their families","volume":"38","author":"Modi","year":"2009","journal-title":"Children's Health Care"},{"issue":"6","key":"2021072018495523500_jsab015-B28","doi-asserted-by":"crossref","DOI":"10.1111\/bjh.16519","article-title":"Association between hydroxycarbamide exposure and neurocognitive function in adolescents with sickle cell disease","volume":"189","author":"Partanen","year":"2020","journal-title":"British Journal of Hematology"},{"issue":"2","key":"2021072018495523500_jsab015-B29","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1172\/JCI111464","article-title":"Hydroxyurea enhances fetal hemoglobin production in sickle cell anemia","volume":"74","author":"Platt","year":"1984","journal-title":"Journal of Clinical Investigation"},{"issue":"8","key":"2021072018495523500_jsab015-B30","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1093\/jpepsy\/jsz031","article-title":"Cognitive function in sickle cell disease across domains, cerebral infarct status, and the lifespan: a meta-analysis","volume":"44","author":"Prussien","year":"2019","journal-title":"Journal of Pediatric Psychology"},{"issue":"2","key":"2021072018495523500_jsab015-B31","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1093\/jpepsy\/jsz100","article-title":"Correlates of cognitive function in sickle cell disease: a meta-analysis","volume":"45","author":"Prussien","year":"2020","journal-title":"Journal of Pediatric Psychology"},{"issue":"2","key":"2021072018495523500_jsab015-B32","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1080\/09297040600584626","article-title":"The association of oral hydroxyurea therapy with improved cognitive function in sickle cell disease","volume":"13","author":"Puffer","year":"2007","journal-title":"Child Neuropsychology"},{"key":"2021072018495523500_jsab015-B33","volume-title":"Stanford Binet Intelligence Scales","author":"Roid","year":"2003","edition":"5th edn"},{"issue":"8","key":"2021072018495523500_jsab015-B34","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1093\/jpepsy\/27.8.739","article-title":"Cognitive functioning in children with sickle cell disease: a meta-analysis","volume":"27","author":"Schatz","year":"2002","journal-title":"Journal of Pediatric Psychology"},{"issue":"5","key":"2021072018495523500_jsab015-B35","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1097\/00004703-200410000-00001","article-title":"Interactions of biomedical and environmental risk factors for cognitive development: a preliminary study of sickle cell disease","volume":"25","author":"Schatz","year":"2004","journal-title":"Journal of Developmental & Behavioral Pediatrics"},{"issue":"6","key":"2021072018495523500_jsab015-B36","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1016\/S0022-3476(96)70335-9","article-title":"Hydroxyurea therapy in children severely affected with sickle cell disease","volume":"128","author":"Scott","year":"1996","journal-title":"The Journal of Pediatrics"},{"key":"2021072018495523500_jsab015-B37","volume-title":"Wide Range Assessment of Memory and Learning","author":"Sheslow","year":"2003","edition":"2nd edn"},{"issue":"3","key":"2021072018495523500_jsab015-B38","first-page":"382","article-title":"Cognitive impairment in children with hemoglobin SS sickle cell disease: relationship to MR imaging findings and hematocrit","volume":"24","author":"Steen","year":"2003","journal-title":"American Journal of Neuroradiology"},{"key":"2021072018495523500_jsab015-B39","volume-title":"HCUP Statistical Brief","author":"Steiner","year":"2006"},{"issue":"6","key":"2021072018495523500_jsab015-B40","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1542\/peds.2008-0441","article-title":"Hydroxyurea for sickle cell disease: a systematic review for efficacy and toxicity in children","volume":"122","author":"Strouse","year":"2008","journal-title":"Pediatrics"},{"issue":"2","key":"2021072018495523500_jsab015-B41","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1080\/09297040600611312","article-title":"Neuropsychological functioning in preschool-age children with sickle cell disease: the role of illness-related and psychosocial factors","volume":"13","author":"Tarazi","year":"2007","journal-title":"Child Neuropsychology"},{"issue":"3","key":"2021072018495523500_jsab015-B42","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/jpepsy\/27.3.235","article-title":"Neurocognitive development of young children with sickle cell disease through three years of age","volume":"27","author":"Thompson","year":"2002","journal-title":"Journal of Pediatric Psychology"},{"issue":"5","key":"2021072018495523500_jsab015-B43","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1002\/pbc.21738","article-title":"A pilot study of hydroxyurea to prevent chronic organ damage in young children with sickle cell anemia","volume":"52","author":"Thornburg","year":"2009","journal-title":"Pediatric Blood & Cancer"},{"issue":"3","key":"2021072018495523500_jsab015-B44","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1067\/mpd.2001.116935","article-title":"Neuropsychologic performance in school-aged children with sickle cell disease: a report from the Cooperative Study of Sickle Cell Disease","volume":"139","author":"Wang","year":"2001","journal-title":"The Journal of Pediatrics"},{"key":"2021072018495523500_jsab015-B45","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1182\/blood.V130.Suppl_1.760.760","article-title":"Effects of hydroxyurea (HU) on neurocognitive performance in children with sickle cell disease: a prospective trial","volume":"130","author":"Wang","year":"2017","journal-title":"Blood"},{"issue":"9778","key":"2021072018495523500_jsab015-B46","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1016\/S0140-6736(11)60355-3","article-title":"Hydroxycarbamide in very young children with sickle cell anemia: a multicentre, randomised, controlled trial (BABY HUG)","volume":"377","author":"Wang","year":"2011","journal-title":"The Lancet"},{"issue":"10091","key":"2021072018495523500_jsab015-B47","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/S0140-6736(17)30193-9","article-title":"Sickle cell disease","volume":"390","author":"Ware","year":"2017","journal-title":"The Lancet"},{"issue":"26","key":"2021072018495523500_jsab015-B48","doi-asserted-by":"crossref","first-page":"3850","DOI":"10.1182\/blood-2014-08-435768","article-title":"Update on the use of hydroxyurea therapy in sickle cell disease","volume":"124","author":"Wong","year":"2014","journal-title":"Blood"},{"issue":"3","key":"2021072018495523500_jsab015-B49","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1080\/09297049.2015.1111318","article-title":"Association of social-environmental factors with cognitive function in children with sickle cell disease","volume":"23","author":"Yarboi","year":"2017","journal-title":"Child Neuropsychology"},{"issue":"6","key":"2021072018495523500_jsab015-B50","doi-asserted-by":"crossref","first-page":"2039","DOI":"10.1182\/blood-2003-07-2475","article-title":"Sustained long-term hematologic efficacy of hydroxyurea at maximum tolerated dose in children with sickle cell disease","volume":"103","author":"Zimmerman","year":"2004","journal-title":"Blood"}],"container-title":["Journal of Pediatric Psychology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jpepsy\/article-pdf\/46\/6\/710\/39199685\/jsab015.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jpepsy\/article-pdf\/46\/6\/710\/39199685\/jsab015.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,24]],"date-time":"2024-08-24T14:08:16Z","timestamp":1724508496000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jpepsy\/article\/46\/6\/710\/6168458"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,11]]},"references-count":51,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,3,11]]},"published-print":{"date-parts":[[2021,7,20]]}},"URL":"https:\/\/doi.org\/10.1093\/jpepsy\/jsab015","relation":{},"ISSN":["0146-8693","1465-735X"],"issn-type":[{"value":"0146-8693","type":"print"},{"value":"1465-735X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,7,1]]},"published":{"date-parts":[[2021,3,11]]}}}