The global burden of sickle cell disease in children under five years of age: a systematic review and meta-analysis

Sickle cell disease (SCD) is a common haematological disorder, affecting millions of people worldwide. It is most prevalent in malarial endemic areas in the tropics where outcomes are often poor due to resource constraints, resulting in most children dying before reaching adulthood. As increasing pr...

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Published in:	Journal of global health Vol. 8; no. 2; p. 021103
Main Authors:	Wastnedge, Elizabeth, Waters, Donald, Patel, Smruti, Morrison, Kathleen, Goh, Mei Yi, Adeloye, Davies, Rudan, Igor
Format:	Journal Article
Language:	English
Published:	Scotland Edinburgh University Global Health Society 01.12.2018
Subjects:	Age Anemia, Sickle Cell - epidemiology Child, Preschool Children & youth Chromatography Cost of Illness Diagnostic tests Estimates Families & family life Global health Global Health - statistics & numerical data Hemoglobin Humans Infant Infant, Newborn Malaria Medical screening Meta-analysis Morbidity Mortality Mutation Population Research Theme 7: Epidemiology of non-communicable causes of child deaths Sickle cell disease Statistical analysis Studies Systematic review Tropical environments Africa
ISSN:	2047-2978, 2047-2986, 2047-2986
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Abstract	Sickle cell disease (SCD) is a common haematological disorder, affecting millions of people worldwide. It is most prevalent in malarial endemic areas in the tropics where outcomes are often poor due to resource constraints, resulting in most children dying before reaching adulthood. As increasing progress is made towards reducing under 5 mortality from infectious causes, non-communicable diseases (NCDs) including SCD have risen to the forefront of the global health agenda. Despite this, the global mortality burden of SCD remains poorly understood. This study aimed to estimate the incidence and mortality of SCD in children under 5 years of age in order to inform policy and develop sustainable strategies to improve outcomes. We performed a systematic literature search of Medline, EMBASE, Journals@Ovid, and Web of Science for studies on the incidence and mortality of SCD in children under 5, with search dates set from January 1980 and July 2017. We conducted random effects meta-analysis to obtain pooled meta-estimates of birth prevalence and mortality rates globally, and for each World Health Organization (WHO) region. 67 papers were found with relevant data. 52 contained data on incidence and prevalence and 15 contained data on mortality. The overall pooled estimate of mortality from the limited data available was 0.64 per 100 years of child observation (95% CI = 0.28-1.00) with the highest rate seen in Africa 7.3 (95% CI = 4.03-10.57). The global meta-estimate for the birth prevalence of homozygous sickle cell disease was 112 per 100 000 live births (95% CI = 101-123) with a birth prevalence in Africa of 1125 per 100 000 (95% CI = 680.43-1570.54) compared with 43.12 per 100 000 (95% CI = 30.31-55.92) in Europe. There were a number of limitations in the depth and breadth of available data however it is clear that both the highest prevalence and highest mortality of SCD is in Africa. In order to address this burden, there is a need for national comprehensive newborn screening to identify patients, and the development of holistic SCD care programmes to provide therapeutics and education for families and children with SCD. This targeted funding should form part of a broader increased global focus on NCDs in childhood.
AbstractList	BackgroundSickle cell disease (SCD) is a common haematological disorder, affecting millions of people worldwide. It is most prevalent in malarial endemic areas in the tropics where outcomes are often poor due to resource constraints, resulting in most children dying before reaching adulthood. As increasing progress is made towards reducing under 5 mortality from infectious causes, non-communicable diseases (NCDs) including SCD have risen to the forefront of the global health agenda. Despite this, the global mortality burden of SCD remains poorly understood. This study aimed to estimate the incidence and mortality of SCD in children under 5 years of age in order to inform policy and develop sustainable strategies to improve outcomes.MethodologyWe performed a systematic literature search of Medline, EMBASE, Journals@Ovid, and Web of Science for studies on the incidence and mortality of SCD in children under 5, with search dates set from January 1980 and July 2017. We conducted random effects meta-analysis to obtain pooled meta-estimates of birth prevalence and mortality rates globally, and for each World Health Organization (WHO) region.Results67 papers were found with relevant data. 52 contained data on incidence and prevalence and 15 contained data on mortality. The overall pooled estimate of mortality from the limited data available was 0.64 per 100 years of child observation (95% CI = 0.28-1.00) with the highest rate seen in Africa 7.3 (95% CI = 4.03-10.57). The global meta-estimate for the birth prevalence of homozygous sickle cell disease was 112 per 100 000 live births (95% CI = 101-123) with a birth prevalence in Africa of 1125 per 100 000 (95% CI = 680.43-1570.54) compared with 43.12 per 100 000 (95% CI = 30.31-55.92) in Europe.ConclusionThere were a number of limitations in the depth and breadth of available data however it is clear that both the highest prevalence and highest mortality of SCD is in Africa. In order to address this burden, there is a need for national comprehensive newborn screening to identify patients, and the development of holistic SCD care programmes to provide therapeutics and education for families and children with SCD. This targeted funding should form part of a broader increased global focus on NCDs in childhood. Sickle cell disease (SCD) is a common haematological disorder, affecting millions of people worldwide. It is most prevalent in malarial endemic areas in the tropics where outcomes are often poor due to resource constraints, resulting in most children dying before reaching adulthood. As increasing progress is made towards reducing under 5 mortality from infectious causes, non-communicable diseases (NCDs) including SCD have risen to the forefront of the global health agenda. Despite this, the global mortality burden of SCD remains poorly understood. This study aimed to estimate the incidence and mortality of SCD in children under 5 years of age in order to inform policy and develop sustainable strategies to improve outcomes. We performed a systematic literature search of Medline, EMBASE, Journals@Ovid, and Web of Science for studies on the incidence and mortality of SCD in children under 5, with search dates set from January 1980 and July 2017. We conducted random effects meta-analysis to obtain pooled meta-estimates of birth prevalence and mortality rates globally, and for each World Health Organization (WHO) region. 67 papers were found with relevant data. 52 contained data on incidence and prevalence and 15 contained data on mortality. The overall pooled estimate of mortality from the limited data available was 0.64 per 100 years of child observation (95% CI = 0.28-1.00) with the highest rate seen in Africa 7.3 (95% CI = 4.03-10.57). The global meta-estimate for the birth prevalence of homozygous sickle cell disease was 112 per 100 000 live births (95% CI = 101-123) with a birth prevalence in Africa of 1125 per 100 000 (95% CI = 680.43-1570.54) compared with 43.12 per 100 000 (95% CI = 30.31-55.92) in Europe. There were a number of limitations in the depth and breadth of available data however it is clear that both the highest prevalence and highest mortality of SCD is in Africa. In order to address this burden, there is a need for national comprehensive newborn screening to identify patients, and the development of holistic SCD care programmes to provide therapeutics and education for families and children with SCD. This targeted funding should form part of a broader increased global focus on NCDs in childhood. Sickle cell disease (SCD) is a common haematological disorder, affecting millions of people worldwide. It is most prevalent in malarial endemic areas in the tropics where outcomes are often poor due to resource constraints, resulting in most children dying before reaching adulthood. As increasing progress is made towards reducing under 5 mortality from infectious causes, non-communicable diseases (NCDs) including SCD have risen to the forefront of the global health agenda. Despite this, the global mortality burden of SCD remains poorly understood. This study aimed to estimate the incidence and mortality of SCD in children under 5 years of age in order to inform policy and develop sustainable strategies to improve outcomes.BACKGROUNDSickle cell disease (SCD) is a common haematological disorder, affecting millions of people worldwide. It is most prevalent in malarial endemic areas in the tropics where outcomes are often poor due to resource constraints, resulting in most children dying before reaching adulthood. As increasing progress is made towards reducing under 5 mortality from infectious causes, non-communicable diseases (NCDs) including SCD have risen to the forefront of the global health agenda. Despite this, the global mortality burden of SCD remains poorly understood. This study aimed to estimate the incidence and mortality of SCD in children under 5 years of age in order to inform policy and develop sustainable strategies to improve outcomes.We performed a systematic literature search of Medline, EMBASE, Journals@Ovid, and Web of Science for studies on the incidence and mortality of SCD in children under 5, with search dates set from January 1980 and July 2017. We conducted random effects meta-analysis to obtain pooled meta-estimates of birth prevalence and mortality rates globally, and for each World Health Organization (WHO) region.METHODOLOGYWe performed a systematic literature search of Medline, EMBASE, Journals@Ovid, and Web of Science for studies on the incidence and mortality of SCD in children under 5, with search dates set from January 1980 and July 2017. We conducted random effects meta-analysis to obtain pooled meta-estimates of birth prevalence and mortality rates globally, and for each World Health Organization (WHO) region.67 papers were found with relevant data. 52 contained data on incidence and prevalence and 15 contained data on mortality. The overall pooled estimate of mortality from the limited data available was 0.64 per 100 years of child observation (95% CI = 0.28-1.00) with the highest rate seen in Africa 7.3 (95% CI = 4.03-10.57). The global meta-estimate for the birth prevalence of homozygous sickle cell disease was 112 per 100 000 live births (95% CI = 101-123) with a birth prevalence in Africa of 1125 per 100 000 (95% CI = 680.43-1570.54) compared with 43.12 per 100 000 (95% CI = 30.31-55.92) in Europe.RESULTS67 papers were found with relevant data. 52 contained data on incidence and prevalence and 15 contained data on mortality. The overall pooled estimate of mortality from the limited data available was 0.64 per 100 years of child observation (95% CI = 0.28-1.00) with the highest rate seen in Africa 7.3 (95% CI = 4.03-10.57). The global meta-estimate for the birth prevalence of homozygous sickle cell disease was 112 per 100 000 live births (95% CI = 101-123) with a birth prevalence in Africa of 1125 per 100 000 (95% CI = 680.43-1570.54) compared with 43.12 per 100 000 (95% CI = 30.31-55.92) in Europe.There were a number of limitations in the depth and breadth of available data however it is clear that both the highest prevalence and highest mortality of SCD is in Africa. In order to address this burden, there is a need for national comprehensive newborn screening to identify patients, and the development of holistic SCD care programmes to provide therapeutics and education for families and children with SCD. This targeted funding should form part of a broader increased global focus on NCDs in childhood.CONCLUSIONThere were a number of limitations in the depth and breadth of available data however it is clear that both the highest prevalence and highest mortality of SCD is in Africa. In order to address this burden, there is a need for national comprehensive newborn screening to identify patients, and the development of holistic SCD care programmes to provide therapeutics and education for families and children with SCD. This targeted funding should form part of a broader increased global focus on NCDs in childhood.
Author	Goh, Mei Yi Wastnedge, Elizabeth Waters, Donald Rudan, Igor Morrison, Kathleen Adeloye, Davies Patel, Smruti
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References_xml	– volume: 100 start-page: 48 year: 2015 ident: key20181208132233_R3 article-title: Sickle cell disease: a neglected chronic disease of increasing global health importance. publication-title: Arch Dis Child doi: 10.1136/archdischild-2013-303773 – volume: 134 start-page: 493 year: 2011 ident: key20181208132233_R4 article-title: The inherited disorders of haemoglobin: an increasingly neglected global health burden. publication-title: Indian J Med Res – volume: 41 start-page: S398 year: 2011 ident: key20181208132233_R9 article-title: Sickle cell disease in Africa: a neglected cause of early childhood mortality. publication-title: Am J Prev Med doi: 10.1016/j.amepre.2011.09.013 – volume: 101 start-page: 3 year: 2007 ident: key20181208132233_R10 article-title: Sickle cell disease in Africa: burden and research priorities. publication-title: Ann Trop Med Parasitol doi: 10.1179/136485907X154638 – volume: 122 start-page: 933 year: 2008 ident: key20181208132233_R5 article-title: Neonatal screening and clinical care programmes for sickle cell disorders in sub-Saharan Africa: lessons from pilot studies. publication-title: Public Health doi: 10.1016/j.puhe.2007.12.005 – volume: 3 start-page: 18 year: 1989 ident: key20181208132233_R8 article-title: The presentation, management and prevention of crisis in sickle cell disease in Africa. publication-title: Blood Rev doi: 10.1016/0268-960X(89)90022-2 – ident: key20181208132233_R11 – volume: 27 start-page: 195 year: 2005 ident: key20181208132233_R13 article-title: Outcome of holistic care in Nigerian patients with sickle cell anaemia. publication-title: Clin Lab Haematol doi: 10.1111/j.1365-2257.2005.00683.x – volume: 86 start-page: 480 year: 2008 ident: key20181208132233_R14 article-title: Global epidemiology of haemoglobin disorders and derived service indicators. publication-title: Bull World Health Organ doi: 10.2471/BLT.06.036673 – volume: 390 start-page: 311 year: 2017 ident: key20181208132233_R1 article-title: Sickle cell disease. publication-title: Lancet doi: 10.1016/S0140-6736(17)30193-9 – volume: 6 start-page: e1000100 year: 2009 ident: key20181208132233_R7 article-title: The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. publication-title: PLoS Med doi: 10.1371/journal.pmed.1000100 – volume: 13 start-page: 238 year: 2015 ident: key20181208132233_R15 article-title: An accurate and affordable test for the rapid diagnosis of sickle cell disease could revolutionize the outlook for affected children born in resource-limited settings. publication-title: BMC Med doi: 10.1186/s12916-015-0483-4 – volume: 137 start-page: e20160348 year: 2016 ident: key20181208132233_R6 article-title: Time to invest in sickle cell anemia as a global health priority. publication-title: Pediatrics doi: 10.1542/peds.2016-0348 – volume: 102 start-page: 834 year: 2003 ident: key20181208132233_R12 article-title: Effect of a comprehensive clinical care program on disease course in severely ill children with sickle cell anemia in a sub-Saharan African setting. publication-title: Blood doi: 10.1182/blood-2002-05-1453 – volume: 10 start-page: e1001484 year: 2013 ident: key20181208132233_R2 article-title: Global burden of sickle cell anaemia in children under five, 2010–2050: modelling based on demographics, excess mortality, and interventions. publication-title: PLoS Med doi: 10.1371/journal.pmed.1001484
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Snippet	Sickle cell disease (SCD) is a common haematological disorder, affecting millions of people worldwide. It is most prevalent in malarial endemic areas in the... BackgroundSickle cell disease (SCD) is a common haematological disorder, affecting millions of people worldwide. It is most prevalent in malarial endemic areas...
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SubjectTerms	Age Anemia, Sickle Cell - epidemiology Child, Preschool Children & youth Chromatography Cost of Illness Diagnostic tests Estimates Families & family life Global health Global Health - statistics & numerical data Hemoglobin Humans Infant Infant, Newborn Malaria Medical screening Meta-analysis Morbidity Mortality Mutation Population Research Theme 7: Epidemiology of non-communicable causes of child deaths Sickle cell disease Statistical analysis Studies Systematic review Tropical environments
Title	The global burden of sickle cell disease in children under five years of age: a systematic review and meta-analysis
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