{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T04:40:22Z","timestamp":1781930422519,"version":"3.54.5"},"reference-count":56,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2020,11,4]],"date-time":"2020-11-04T00:00:00Z","timestamp":1604448000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000061","name":"Fogarty International Center","doi-asserted-by":"publisher","award":["D43TW010132"],"award-info":[{"award-number":["D43TW010132"]}],"id":[{"id":"10.13039\/100000061","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Severe anaemia is a common clinical problem among young children in sub-Saharan Africa. However, the effect of severe anaemia on neurodevelopment of these children is not well described. Therefore, we assessed the neurodevelopmental performance of preschool children diagnosed with severe anaemia in Northern Uganda.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>We conducted a prospective cohort study among children &lt; 5 years of age 14 days post discharge after an episode of severe anaemia (Hb &lt; 5.0 g\/dl; n = 171; mean Hb = 3.9g\/dl) at Lira Regional Referral Hospital, Uganda. Neurodevelopmental outcomes (cognitive, language and motor) were assessed using Bayley Scales of Infant and Toddler Development, 3<jats:sup>rd<\/jats:sup> edition (Bayley-III). Age-adjusted z-scores for each domain were calculated using scores from healthy community control children (n = 88) recruited from the same environment for each age category. Multiple linear regression was used to compare z-scores in the cognitive, language and motor scales between the two groups after adjusting for weight-for-age z-score, socioeconomic status, mother\u2019s education, and father\u2019s employment on all the scales.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>The prevalence of neurodevelopmental impairment was 2.3% (95% CI: 0.8\u20136.1) for cognition, 1.7% (95%: 0.6\u20135.3) for language and 3.5% (95% CI: 1.6\u20137.6) for motor scales and 4.6% (95% CI: 2.3\u20139.1) for deficits in \u22651 area of neurodevelopment. Significant differences were observed between the two groups with the SA group performing worse on cognition [adjusted mean score, (Standard error, SE), <jats:italic>P-<\/jats:italic>value] [-0.20, (0.01) vs. 0.00, (0.01), <jats:italic>P<\/jats:italic> = 0.02]; language [-0.25, (0.01) vs. 0.00, (0.01), <jats:italic>P<\/jats:italic>&lt; 0.001]; and motor [-0.17, (0.01) vs. 0.00, (0.01), <jats:italic>P<\/jats:italic> = 0.05] scales.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>In children &lt; 5 years of age, severe anaemia was associated with neurocognitive (cognition, language and motor) deficits in the immediate period post treatment. Further research is needed to identify risk factors and determine the long-term effects of poor neurodevelopment in young children with severe anaemia.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0240694","type":"journal-article","created":{"date-parts":[[2020,11,4]],"date-time":"2020-11-04T18:45:15Z","timestamp":1604515515000},"page":"e0240694","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Neurodevelopmental performance among pre-schoolers treated for severe anaemia at Lira Regional Referral Hospital, Uganda"],"prefix":"10.1371","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0060-0842","authenticated-orcid":true,"given":"Andrew S.","family":"Ssemata","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert O.","family":"Opoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Ssenkusu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noeline","family":"Nakasujja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandy C.","family":"John","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Bangirana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2020,11,4]]},"reference":[{"issue":"5","key":"pone.0240694.ref001","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1182\/blood-2013-06-508325","article-title":"A systematic analysis of global anemia burden from 1990 to 2010","volume":"123","author":"NJ Kassebaum","year":"2014","journal-title":"Blood"},{"issue":"8","key":"pone.0240694.ref002","doi-asserted-by":"crossref","first-page":"e2903","DOI":"10.1371\/journal.pone.0002903","article-title":"Long term outcome of severe anaemia in Malawian children","volume":"3","author":"KS Phiri","year":"2008","journal-title":"PloS one"},{"issue":"4","key":"pone.0240694.ref003","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1017\/S1368980008002401","article-title":"Worldwide prevalence of anaemia, WHO vitamin and mineral nutrition information system, 1993\u20132005","volume":"12","author":"E McLean","year":"2009","journal-title":"Public health nutrition"},{"issue":"1","key":"pone.0240694.ref004","doi-asserted-by":"crossref","first-page":"e16","DOI":"10.1016\/S2214-109X(13)70001-9","article-title":"Global, regional, and national trends in haemoglobin concentration and prevalence of total and severe anaemia in children and pregnant and non-pregnant women for 1995\u20132011: a systematic analysis of population-representative data","volume":"1","author":"GA Stevens","year":"2013","journal-title":"The Lancet Global Health"},{"issue":"1","key":"pone.0240694.ref005","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s12878-017-0081-0","article-title":"Prevalence of Anaemia and associated risk factors among children in North-Western Uganda: a cross sectional study","volume":"17","author":"ID Legason","year":"2017","journal-title":"BMC hematology"},{"issue":"6","key":"pone.0240694.ref006","doi-asserted-by":"crossref","first-page":"e1000438","DOI":"10.1371\/journal.pmed.1000438","article-title":"Mapping the risk of anaemia in preschool-age children: the contribution of malnutrition, malaria, and helminth infections in West Africa","volume":"8","author":"RJS Magalhaes","year":"2011","journal-title":"PLoS medicine"},{"issue":"1","key":"pone.0240694.ref007","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1186\/s12936-016-1266-x","article-title":"Malaria illness mediated by anaemia lessens cognitive development in younger Ugandan children","volume":"15","author":"MJ Boivin","year":"2016","journal-title":"Malaria journal"},{"issue":"5","key":"pone.0240694.ref008","doi-asserted-by":"crossref","first-page":"614","DOI":"10.4269\/ajtmh.2001.65.614","article-title":"Factors contributing to anemia after uncomplicated falciparum malaria","volume":"65","author":"RN Price","year":"2001","journal-title":"The American journal of tropical medicine and hygiene"},{"issue":"1","key":"pone.0240694.ref009","doi-asserted-by":"crossref","first-page":"e0209476","DOI":"10.1371\/journal.pone.0209476","article-title":"Community perceptions of paediatric severe anaemia in Uganda","volume":"14","author":"A Dhabangi","year":"2019","journal-title":"PloS one"},{"issue":"1","key":"pone.0240694.ref010","doi-asserted-by":"crossref","first-page":"e0210982","DOI":"10.1371\/journal.pone.0210982","article-title":"Adherence to clinical guidelines is associated with reduced inpatient mortality among children with severe anemia in Ugandan hospitals","volume":"14","author":"RO Opoka","year":"2019","journal-title":"PloS one"},{"issue":"1","key":"pone.0240694.ref011","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s12916-014-0246-7","article-title":"Anaemia and blood transfusion in African children presenting to hospital with severe febrile illness","volume":"13","author":"S Kiguli","year":"2015","journal-title":"BMC medicine"},{"issue":"12","key":"pone.0240694.ref012","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1001\/jama.288.12.1499","article-title":"Anemia and blood transfusion in critically ill patients","volume":"288","author":"JL Vincent","year":"2002","journal-title":"Jama"},{"issue":"5","key":"pone.0240694.ref013","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/S0035-9203(97)90025-0","article-title":"Management of severe malarial anaemia in Gambian children","volume":"91","author":"K Bojang","year":"1997","journal-title":"Transactions of the Royal Society of Tropical Medicine and Hygiene"},{"issue":"9081","key":"pone.0240694.ref014","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1016\/S0140-6736(97)04229-3","article-title":"Randomised placebo-controlled trial of iron supplementation and malaria chemoprophylaxis for prevention of severe anaemia and malaria in Tanzanian infants","volume":"350","author":"C Menendez","year":"1997","journal-title":"The Lancet"},{"issue":"7","key":"pone.0240694.ref015","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1111\/j.1365-3156.2010.02542.x","article-title":"Impact of hookworm infection and deworming on anaemia in non\u2010pregnant populations: a systematic review","volume":"15","author":"JL Smith","year":"2010","journal-title":"Tropical medicine & international health"},{"issue":"9267","key":"pone.0240694.ref016","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1016\/S0140-6736(00)04643-2","article-title":"Intermittent treatment for malaria and anaemia control at time of routine vaccinations in Tanzanian infants: a randomised, placebo-controlled trial","volume":"357","author":"D Schellenberg","year":"2001","journal-title":"The Lancet"},{"issue":"9372","key":"pone.0240694.ref017","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1016\/S0140-6736(03)13504-0","article-title":"Effect of intermittent treatment with amodiaquine on anaemia and malarial fevers in infants in Tanzania: a randomised placebo-controlled trial","volume":"361","author":"JJ Massaga","year":"2003","journal-title":"The Lancet"},{"issue":"4","key":"pone.0240694.ref018","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1159\/000443320","article-title":"Severe neonatal anaemia, MRI findings and neurodevelopmental outcome","volume":"109","author":"IA Zonnenberg","year":"2016","journal-title":"Neonatology"},{"issue":"5","key":"pone.0240694.ref019","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1542\/peds.2007-0770","article-title":"Patterns of brain injury in neonates exposed to perinatal sentinel events","volume":"121","author":"A Okereafor","year":"2008","journal-title":"Pediatrics"},{"key":"pone.0240694.ref020","first-page":"317","article-title":"Clinical Neuropsychological Assessment of Children","author":"J Warner-Rogers","year":"2013","journal-title":"Clinical Neuropsychology: A Practical Guide to Assessment and Management for Clinicians"},{"issue":"5","key":"pone.0240694.ref021","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1136\/archdischild-2014-308114","article-title":"Child development assessment tools in low-income and middle-income countries: how can we use them more appropriately?","volume":"100","author":"S Sabanathan","year":"2015","journal-title":"Archives of disease in childhood"},{"issue":"4","key":"pone.0240694.ref022","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1080\/09297049.2018.1497588","article-title":"Building capacity in neurodevelopment assessment of children in sub-Saharan Africa: A quality assurance model to implement standardized neurodevelopment testing","volume":"25","author":"H Ruise\u00f1or-Escudero","year":"2019","journal-title":"Child Neuropsychology"},{"issue":"3","key":"pone.0240694.ref023","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1093\/cid\/ciu293","article-title":"Severe malarial anemia is associated with long-term neurocognitive impairment","volume":"59","author":"P Bangirana","year":"2014","journal-title":"Clinical Infectious Diseases"},{"issue":"4","key":"pone.0240694.ref024","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1097\/00000542-200204000-00014","article-title":"Oxygen reverses deficits of cognitive function and memory and increased heart rate induced by acute severe isovolemic anemia","volume":"96","author":"RB Weiskopf","year":"2002","journal-title":"Anesthesiology: The Journal of the American Society of Anesthesiologists"},{"issue":"6","key":"pone.0240694.ref025","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1097\/00000542-200006000-00023","article-title":"Acute severe isovolemic anemia impairs cognitive function and memory in humans","volume":"92","author":"RB Weiskopf","year":"2000","journal-title":"Anesthesiology: The Journal of the American Society of Anesthesiologists"},{"issue":"1","key":"pone.0240694.ref026","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1111\/j.1467-8624.2009.01380.x","article-title":"How the timing and quality of early experiences influence the development of brain architecture","volume":"81","author":"SE Fox","year":"2010","journal-title":"Child development"},{"issue":"1","key":"pone.0240694.ref027","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1111\/nyas.12314","article-title":"Issues in the timing of integrated early interventions: contributions from nutrition, neuroscience, and psychological research","volume":"1308","author":"TD Wachs","year":"2014","journal-title":"Annals of the New York Academy of Sciences"},{"issue":"1","key":"pone.0240694.ref028","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1186\/s12913-018-3382-5","article-title":"High rate of inappropriate blood transfusions in the management of children with severe anemia in Ugandan hospitals","volume":"18","author":"RO Opoka","year":"2018","journal-title":"BMC health services research"},{"issue":"1","key":"pone.0240694.ref029","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1111\/j.1365-3156.2005.01518.x","article-title":"Severe malaria in children in areas with low, moderate and high transmission intensity in Uganda","volume":"11","author":"R Idro","year":"2006","journal-title":"Tropical Medicine & International Health"},{"issue":"14","key":"pone.0240694.ref030","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.1212\/WNL.0000000000004537","article-title":"Neurologic complications of sickle cell disease in Africa: a systematic review and meta-analysis","volume":"89","author":"JJ Noubiap","year":"2017","journal-title":"Neurology"},{"key":"pone.0240694.ref031","volume-title":"Uganda clinical guidelines","author":"Ministry of Health Uganda","year":"2012"},{"key":"pone.0240694.ref032","doi-asserted-by":"crossref","DOI":"10.1155\/2017\/1631760","article-title":"Use of the bayley scales of infant and toddler development, to assess developmental outcome in infants and young children in an urban setting in South Africa","volume":"2017","author":"DE Ballot","year":"2017","journal-title":"International Scholarly Research Notices"},{"issue":"1","key":"pone.0240694.ref033","doi-asserted-by":"crossref","first-page":"e92","DOI":"10.1542\/peds.2007-3709","article-title":"Cerebral malaria in children is associated with long-term cognitive impairment","volume":"122","author":"CC John","year":"2008","journal-title":"Pediatrics"},{"issue":"11","key":"pone.0240694.ref034","doi-asserted-by":"crossref","first-page":"e7898","DOI":"10.1371\/journal.pone.0007898","article-title":"Socioeconomic predictors of cognition in Ugandan children: implications for community interventions","volume":"4","author":"P Bangirana","year":"2009","journal-title":"PLoS One"},{"issue":"6","key":"pone.0240694.ref035","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1093\/heapol\/czl029","article-title":"Constructing socio-economic status indices: how to use principal components analysis","volume":"21","author":"S Vyas","year":"2006","journal-title":"Health policy and planning"},{"issue":"1","key":"pone.0240694.ref036","first-page":"115","article-title":"Estimating wealth effects without expenditure data\u2014or tears: an application to educational enrollments in states of India","volume":"38","author":"D Filmer","year":"2001","journal-title":"Demography"},{"issue":"4","key":"pone.0240694.ref037","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1093\/ije\/dyg099","article-title":"The World Health Organization global database on child growth and malnutrition: methodology and applications","volume":"32","author":"M De Onis","year":"2003","journal-title":"International journal of epidemiology"},{"key":"pone.0240694.ref038","volume-title":"WHO child growth standards: length\/height for age, weight-for-age, weight-for-length, weight-for-height and body mass index-for-age, methods and development","author":"World Health Organization","year":"2006"},{"key":"pone.0240694.ref039","author":"N Bayley","year":"2006","edition":"3"},{"issue":"2","key":"pone.0240694.ref040","doi-asserted-by":"crossref","first-page":"e12527","DOI":"10.1111\/mcn.12527","article-title":"Nutrition, hygiene, and stimulation education to improve growth, cognitive, language, and motor development among infants in Uganda: A cluster\u2010randomized trial","volume":"14","author":"GK Muhoozi","year":"2018","journal-title":"Maternal & child nutrition"},{"issue":"1","key":"pone.0240694.ref041","doi-asserted-by":"crossref","first-page":"30270","DOI":"10.3402\/fnr.v60.30270","article-title":"Nutritional and developmental status among 6-to 8-month-old children in southwestern Uganda: a cross-sectional study","volume":"60","author":"GK Muhoozi","year":"2016","journal-title":"Food & nutrition research"},{"issue":"8","key":"pone.0240694.ref042","doi-asserted-by":"crossref","first-page":"e458","DOI":"10.1016\/S2214-109X(15)00099-6","article-title":"Effects of a parenting intervention to address maternal psychological wellbeing and child development and growth in rural Uganda: a community-based, cluster-randomised trial","volume":"3","author":"DR Singla","year":"2015","journal-title":"The Lancet Global Health"},{"issue":"2","key":"pone.0240694.ref043","doi-asserted-by":"crossref","first-page":"e360","DOI":"10.1542\/peds.2006-2027","article-title":"Cognitive impairment after cerebral malaria in children: a prospective study","volume":"119","author":"MJ Boivin","year":"2007","journal-title":"Pediatrics"},{"key":"pone.0240694.ref044","first-page":"65","article-title":"A simple sequentially rejective multiple test procedure","author":"S Holm","year":"1979","journal-title":"Scandinavian journal of statistics"},{"issue":"5","key":"pone.0240694.ref045","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1097\/00001503-200410000-00003","article-title":"Anaemia and the brain","volume":"17","author":"GM Hare","year":"2004","journal-title":"Current Opinion in Anesthesiology"},{"issue":"s1","key":"pone.0240694.ref046","article-title":"Long\u2010term brain and behavioral consequences of early iron deficiency","volume":"69","author":"MK Georgieff","year":"2011","journal-title":"Nutrition reviews"},{"key":"pone.0240694.ref047","volume-title":"Seminars in pediatric neurology","author":"B Lozoff","year":"2006"},{"issue":"5","key":"pone.0240694.ref048","doi-asserted-by":"crossref","first-page":"1468S","DOI":"10.1093\/jn\/133.5.1468S","article-title":"Iron Deficiency Alters Brain Development and Functioning, 2","volume":"133","author":"J Beard","year":"2003","journal-title":"The Journal of nutrition"},{"issue":"3","key":"pone.0240694.ref049","first-page":"99","article-title":"Research Article (New England Journal of Medicine) Severe anemia in Malawian children","volume":"28","author":"JC Calis","year":"2016","journal-title":"Malawi Medical Journal"},{"issue":"2","key":"pone.0240694.ref050","doi-asserted-by":"crossref","first-page":"568S","DOI":"10.1093\/jn\/131.2.568S","article-title":"Iron biology in immune function, muscle metabolism and neuronal functioning","volume":"131","author":"JL Beard","year":"2001","journal-title":"The Journal of nutrition"},{"issue":"9809","key":"pone.0240694.ref051","doi-asserted-by":"crossref","first-page":"2123","DOI":"10.1016\/S0140-6736(10)62304-5","article-title":"Anaemia in low-income and middle-income countries","volume":"378","author":"Y Balarajan","year":"2012","journal-title":"The Lancet"},{"key":"pone.0240694.ref052","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/B978-0-12-374177-6.10003-0","volume-title":"Bayley-III clinical use and interpretation","author":"RE Crais","year":"2010"},{"issue":"1","key":"pone.0240694.ref053","first-page":"67","article-title":"Consequences of anemia on language development of children from a public day care center","volume":"27","author":"JN Santos","year":"2009","journal-title":"Revista Paulista de Pediatria"},{"issue":"3","key":"pone.0240694.ref054","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1007\/s00787-006-0567-y","article-title":"Language development at ten months","volume":"16","author":"E Hohm","year":"2007","journal-title":"European child & adolescent psychiatry"},{"issue":"2","key":"pone.0240694.ref055","doi-asserted-by":"crossref","first-page":"25","DOI":"10.4269\/ajtmh.2004.71.25","article-title":"Reducing the burden of anemia in infants and young children in malaria-endemic countries of Africa: from evidence to action","volume":"71","author":"J Crawley","year":"2004","journal-title":"The American journal of tropical medicine and hygiene"},{"issue":"9556","key":"pone.0240694.ref056","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/S0140-6736(07)60076-2","article-title":"Child development: risk factors for adverse outcomes in developing countries","volume":"369","author":"SP Walker","year":"2007","journal-title":"The lancet"}],"updated-by":[{"DOI":"10.1371\/journal.pone.0244913","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2021,1,5]],"date-time":"2021-01-05T00:00:00Z","timestamp":1609804800000}}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0240694","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,11,16]],"date-time":"2020-11-16T19:54:26Z","timestamp":1605556466000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0240694"}},"subtitle":[],"editor":[{"given":"Samson","family":"Gebremedhin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2020,11,4]]},"references-count":56,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2020,11,4]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0240694","relation":{"correction":[{"id-type":"doi","id":"10.1371\/journal.pone.0244913","asserted-by":"object"}]},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,4]]}}}