Risk factors of anaemia and iron deficiency in Somali children and women: Findings from the 2019 Somalia Micronutrient Survey.

There are limited data on the prevalence of anaemia and iron deficiency (ID) in Somalia. To address this data gap, Somalia's 2019 micronutrient survey assessed the prevalence of anaemia and ID in children (6-59 months) and non-pregnant women of reproductive age (15-49 years). The survey also collected data on vitamin A deficiency, inflammation, malaria and other potential risk factors for anaemia and ID. Multivariable Poisson regressions models were used to identify the risk factors for anaemia and ID in children and women. Among children, the prevalence of anaemia and ID were 43.4% and 47.2%, respectively. Approximately 36% and 6% of anaemia were attributable to iron and vitamin A deficiencies, respectively, whereas household possession of soap was associated with approximately 11% fewer cases of anaemia. ID in children was associated with vitamin A deficiency and stunting, whereas inflammation was associated with iron sufficiency. Among women, 40.3% were anaemic, and 49.7% were iron deficient. In women, ID and number of births were significantly associated with anaemia in multivariate models, and approximately 42% of anaemia in women was attributable to ID. Increased parity was associated with ID, and incubation and early convalescent inflammation was associated with ID, whereas late convalescent inflammation was associated with iron sufficiency. ID is the main risk factor of anaemia in both women and children and contributed to a substantial portion of the anaemia cases. To tackle both anaemia and ID in Somalia, food assistance and micronutrient-specific programmes (e.g. micronutrient powders and iron supplements) should be enhanced.

Children's Oxygen Administration Strategies And Nutrition Trial (COAST-Nutrition): a protocol for a phase II randomised controlled trial.

Background: To prevent poor long-term outcomes (deaths and readmissions) the integrated global action plan for pneumonia and diarrhoea recommends under the 'Treat' element of Protect, Prevent and Treat interventions the importance of continued feeding but gives no specific recommendations for nutritional support. Early nutritional support has been practiced in a wide variety of critically ill patients to provide vital cell substrates, antioxidants, vitamins, and minerals essential for normal cell function and decreasing hypermetabolism. We hypothesise that the excess post-discharge mortality associated with pneumonia may relate to the catabolic response and muscle wasting induced by severe infection and inadequacy of the diet to aid recovery. We suggest that providing additional energy-rich, protein, fat and micronutrient ready-to-use therapeutic feeds (RUTF) to help meet additional nutritional requirements may improve outcome. Methods: COAST-Nutrition is an open, multicentre, Phase II randomised controlled trial in children aged 6 months to 12 years hospitalised with suspected severe pneumonia (and hypoxaemia, SpO 2 <92%) to establish whether supplementary feeds with RUTF given in addition to usual diet for 56-days (experimental) improves outcomes at 90-days compared to usual diet alone (control). Primary endpoint is change in mid-upper arm circumference (MUAC) at 90 days and/or as a composite with 90-day mortality. Secondary outcomes include anthropometric status, mortality, readmission at days 28 and 180. The trial will be conducted in four sites in two countries (Uganda and Kenya) enrolling 840 children followed up to 180 days. Ancillary studies include cost-economic analysis, molecular characterisation of bacterial and viral pathogens, evaluation of putative biomarkers of pneumonia, assessment of muscle and fat mass and host genetic studies.   Discussion: This study is the first step in providing an option for nutritional support following severe pneumonia and will help in the design of a large Phase III trial. Registration: ISRCTN10829073 (6 th June 2018) PACTR202106635355751 (2 nd June 2021).

Effects of vitamin D deficiency on neurobehavioural outcomes in children: a systematic review.

Introduction: Vitamin D plays an important role in brain development in experimental studies; however, the effect of vitamin D deficiency on child development remains inadequately characterized. We aimed to estimate the effects of vitamin D deficiency on neurobehavioural outcomes in children up to 18 years of age. Methods: We searched PubMed, EMBASE, PsycINFO, Scopus, Cochrane Library, Web of Science and Open Grey for published studies up to 10th January 2020. We included all studies that assessed the effects of maternal or child vitamin D status or vitamin D supplementation on neurobehavioural outcomes in children. Study findings were synthesized qualitatively as the high level of heterogeneity in study populations and methodologies precluded a quantitative meta-analysis. Results: Our search identified 5,633 studies, of which 31 studies with 31,375 participants from 18 countries were included in the systematic review. Of the studies identified, one was a randomised controlled trial (RCT) of vitamin D supplementation in children, while 30 were observational. The RCT (n=55) reported a beneficial effect of supplementation with lower doses compared to higher doses of vitamin D on motor development. Twelve mother-child studies (n=17,136) and five studies in children (n=1,091) reported an association between low maternal or child 25-hydroxyvitamin D levels and impaired neurobehavioural outcomes in children, while 15 mother-child studies (n=20,778) and eight studies in children (n=7,496) reported no association. Conclusions: Although animal studies point to an effect of vitamin D deficiency on brain development, there are few studies on the effects of vitamin D deficiency on neurobehavioural outcomes in children and their findings are inconsistent. There is a need for well-conducted, adequately powered studies to further determine these effects in children. Registration: PROSPERO ID CRD42018087619; registered on 15 February 2018.

Prevalence of vitamin D deficiency in Africa: a systematic review and meta-analysis.

BACKGROUND: Vitamin D deficiency is associated with non-communicable and infectious diseases, but the vitamin D status of African populations is not well characterised. We aimed to estimate the prevalence of vitamin D deficiency in children and adults living in Africa. METHODS: For this systematic review and meta-analysis, we searched PubMed, Web of Science, Embase, African Journals Online, and African Index Medicus for studies on vitamin D prevalence, published from database inception to Aug 6, 2019, without language restrictions. We included all studies with measured serum 25-hydroxyvitamin D (25[OH]D) concentrations from healthy participants residing in Africa. We excluded case reports and case series, studies that measured 25(OH)D only after a clinical intervention, and studies with only a meeting abstract or unpublished material available. We used a standardised data extraction form to collect information from eligible studies; if the required information was not available in the published report, we requested raw data from the authors. We did a random-effects meta-analysis to obtain the pooled prevalence of vitamin D deficiency in African populations, with use of established cutoffs and mean 25(OH)D concentrations. We stratified meta-analyses by participant age group, geographical region, and residence in rural or urban areas. The study is registered with PROSPERO, number CRD42018112030. FINDINGS: Our search identified 1692 studies, of which 129 studies with 21 474 participants from 23 African countries were included in the systematic review and 119 studies were included in the meta-analyses. The pooled prevalence of low vitamin D status was 18·46% (95% CI 10·66-27·78) with a cutoff of serum 25(OH)D concentration less than 30 nmol/L; 34·22% (26·22-43·68) for a cutoff of less than 50 nmol/L; and 59·54% (51·32-67·50) for a cutoff of less than 75 nmol/L. The overall mean 25(OH)D concentration was 67·78 nmol/L (95% CI 64·50-71·06). There was no evidence of publication bias, although heterogeneity was high (I2 ranged from 98·26% to 99·82%). Mean serum 25(OH)D concentrations were lower in populations living in northern African countries or South Africa compared with sub-Saharan Africa, in urban areas compared with rural areas, in women compared with men, and in newborn babies compared with their mothers. INTERPRETATION: The prevalence of vitamin D deficiency is high in African populations. Public health strategies in Africa should include efforts to prevent, detect, and treat vitamin D deficiency, especially in newborn babies, women, and urban populations. FUNDING: Wellcome Trust and the DELTAS Africa Initiative.

Co-trimoxazole or multivitamin multimineral supplement for post-discharge outcomes after severe anaemia in African children: a randomised controlled trial.

BACKGROUND: Severe anaemia is a leading cause of paediatric admission to hospital in Africa; post-discharge outcomes remain poor, with high 6-month mortality (8%) and re-admission (17%). We aimed to investigate post-discharge interventions that might improve outcomes. METHODS: Within the two-stratum, open-label, multicentre, factorial randomised TRACT trial, children aged 2 months to 12 years with severe anaemia, defined as haemoglobin of less than 6 g/dL, at admission to hospital (three in Uganda, one in Malawi) were randomly assigned, using sequentially numbered envelopes linked to a second non-sequentially numbered set of allocations stratified by centre and severity, to enhanced nutritional supplementation with iron and folate-containing multivitamin multimineral supplements versus iron and folate alone at treatment doses (usual care), and to co-trimoxazole versus no co-trimoxazole. All interventions were administered orally and were given for 3 months after discharge from hospital. Separately reported randomisations investigated transfusion management. The primary outcome was 180-day mortality. All analyses were done in the intention-to-treat population; follow-up was 180 days. This trial is registered with the International Standard Randomised Controlled Trial registry, ISRCTN84086586, and follow-up is complete. FINDINGS: From Sept 17, 2014, to May 15, 2017, 3983 eligible children were randomly assigned to treatment, and followed up for 180 days. 164 (4%) were lost to follow-up. 1901 (95%) of 1997 assigned multivitamin multimineral supplement, 1911 (96%) of 1986 assigned iron and folate, and 1922 (96%) of 1994 assigned co-trimoxazole started treatment. By day 180, 166 (8%) children in the multivitamin multimineral supplement group versus 169 (9%) children in the iron and folate group had died (hazard ratio [HR] 0·97, 95% CI 0·79-1·21; p=0·81) and 172 (9%) who received co-trimoxazole versus 163 (8%) who did not receive co-trimoxazole had died (HR 1·07, 95% CI 0·86-1·32; p=0·56). We found no evidence of interactions between these randomisations or with transfusion randomisations (p>0·2). By day 180, 489 (24%) children in the multivitamin multimineral supplement group versus 509 (26%) children in the iron and folate group (HR 0·95, 95% CI 0·84-1·07; p=0·40), and 500 (25%) children in the co-trimoxazole group versus 498 (25%) children in the no co-trimoxazole group (1·01, 0·89-1·15; p=0·85) had had one or more serious adverse events. Most serious adverse events were re-admissions, occurring in 692 (17%) children (175 [4%] with at least two re-admissions). INTERPRETATION: Neither enhanced supplementation with multivitamin multimineral supplement versus iron and folate treatment or co-trimoxazole prophylaxis improved 6-month survival. High rates of hospital re-admission suggest that novel interventions are urgently required for severe anaemia, given the burden it places on overstretched health services in Africa. FUNDING: Medical Research Council and Department for International Development.

Immediate Transfusion in African Children with Uncomplicated Severe Anemia.

BACKGROUND: The World Health Organization recommends not performing transfusions in African children hospitalized for uncomplicated severe anemia (hemoglobin level of 4 to 6 g per deciliter and no signs of clinical severity). However, high mortality and readmission rates suggest that less restrictive transfusion strategies might improve outcomes. METHODS: In this factorial, open-label, randomized, controlled trial, we assigned Ugandan and Malawian children 2 months to 12 years of age with uncomplicated severe anemia to immediate transfusion with 20 ml or 30 ml of whole-blood equivalent per kilogram of body weight, as determined in a second simultaneous randomization, or no immediate transfusion (control group), in which transfusion with 20 ml of whole-blood equivalent per kilogram was triggered by new signs of clinical severity or a drop in hemoglobin to below 4 g per deciliter. The primary outcome was 28-day mortality. Three other randomizations investigated transfusion volume, postdischarge supplementation with micronutrients, and postdischarge prophylaxis with trimethoprim-sulfamethoxazole. RESULTS: A total of 1565 children (median age, 26 months) underwent randomization, with 778 assigned to the immediate-transfusion group and 787 to the control group; 984 children (62.9%) had malaria. The children were followed for 180 days, and 71 (4.5%) were lost to follow-up. During the primary hospitalization, transfusion was performed in all the children in the immediate-transfusion group and in 386 (49.0%) in the control group (median time to transfusion, 1.3 hours vs. 24.9 hours after randomization). The mean (±SD) total blood volume transfused per child was 314±228 ml in the immediate-transfusion group and 142±224 ml in the control group. Death had occurred by 28 days in 7 children (0.9%) in the immediate-transfusion group and in 13 (1.7%) in the control group (hazard ratio, 0.54; 95% confidence interval [CI], 0.22 to 1.36; P = 0.19) and by 180 days in 35 (4.5%) and 47 (6.0%), respectively (hazard ratio, 0.75; 95% CI, 0.48 to 1.15), without evidence of interaction with other randomizations (P>0.20) or evidence of between-group differences in readmissions, serious adverse events, or hemoglobin recovery at 180 days. The mean length of hospital stay was 0.9 days longer in the control group. CONCLUSIONS: There was no evidence of differences in clinical outcomes over 6 months between the children who received immediate transfusion and those who did not. The triggered-transfusion strategy in the control group resulted in lower blood use; however, the length of hospital stay was longer, and this strategy required clinical and hemoglobin monitoring. (Funded by the Medical Research Council and Department for International Development; TRACT Current Controlled Trials number, ISRCTN84086586.).

Transfusion and Treatment of severe anaemia in African children (TRACT): a study protocol for a randomised controlled trial.

BACKGROUND: In sub-Saharan Africa, where infectious diseases and nutritional deficiencies are common, severe anaemia is a common cause of paediatric hospital admission, yet the evidence to support current treatment recommendations is limited. To avert overuse of blood products, the World Health Organisation advocates a conservative transfusion policy and recommends iron, folate and anti-helminthics at discharge. Outcomes are unsatisfactory with high rates of in-hospital mortality (9-10%), 6-month mortality and relapse (6%). A definitive trial to establish best transfusion and treatment strategies to prevent both early and delayed mortality and relapse is warranted. METHODS/DESIGN: TRACT is a multicentre randomised controlled trial of 3954 children aged 2 months to 12 years admitted to hospital with severe anaemia (haemoglobin < 6 g/dl). Children will be enrolled over 2 years in 4 centres in Uganda and Malawi and followed for 6 months. The trial will simultaneously evaluate (in a factorial trial with a 3 x 2 x 2 design) 3 ways to reduce short-term and longer-term mortality and morbidity following admission to hospital with severe anaemia in African children. The trial will compare: (i) R1: liberal transfusion (30 ml/kg whole blood) versus conservative transfusion (20 ml/kg) versus no transfusion (control). The control is only for children with uncomplicated severe anaemia (haemoglobin 4-6 g/dl); (ii) R2: post-discharge multi-vitamin multi-mineral supplementation (including folate and iron) versus routine care (folate and iron) for 3 months; (iii) R3: post-discharge cotrimoxazole prophylaxis for 3 months versus no prophylaxis. All randomisations are open. Enrolment to the trial started September 2014 and is currently ongoing. Primary outcome is cumulative mortality to 4 weeks for the transfusion strategy comparisons, and to 6 months for the nutritional support/antibiotic prophylaxis comparisons. Secondary outcomes include mortality, morbidity (haematological correction, nutritional and infectious), safety and cost-effectiveness. DISCUSSION: If confirmed by the trial, a cheap and widely available 'bundle' of effective interventions, directed at immediate and downstream consequences of severe anaemia, could lead to substantial reductions in mortality in a substantial number of African children hospitalised with severe anaemia every year, if widely implemented. TRIAL REGISTRATION: Current Controlled Trials ISRCTN84086586 , Approved 11 February 2013.

Malaria and Age Variably but Critically Control Hepcidin Throughout Childhood in Kenya.

Both iron deficiency (ID) and malaria are common among African children. Studies show that the iron-regulatory hormone hepcidin is induced by malaria, but few studies have investigated this relationship longitudinally. We measured hepcidin concentrations, markers of iron status, and antibodies to malaria antigens during two cross-sectional surveys within a cohort of 324 Kenyan children ≤ 8 years old who were under intensive surveillance for malaria and other febrile illnesses. Hepcidin concentrations were the highest in the youngest, and female infants, declined rapidly in infancy and more gradually thereafter. Asymptomatic malaria and malaria antibody titres were positively associated with hepcidin concentrations. Recent episodes of febrile malaria were associated with high hepcidin concentrations that fell over time. Hepcidin concentrations were not associated with the subsequent risk of either malaria or other febrile illnesses. Given that iron absorption is impaired by hepcidin, our data suggest that asymptomatic and febrile malaria contribute to the high burden of ID seen in African children. Further, the effectiveness of iron supplementation may be sub-optimal in the presence of asymptomatic malaria. Thus, strategies to prevent and eliminate malaria may have the added benefit of addressing an important cause of ID for African children.

Routine paediatric sickle cell disease (SCD) outpatient care in a rural Kenyan hospital: utilization and costs.

BACKGROUND: More than 70% of children with sickle cell disease (SCD) are born in sub-Saharan Africa where the prevalence at birth of this disease reaches 2% or higher in some selected areas. There is a dearth of knowledge on comprehensive care received by children with SCD in sub-Saharan Africa and its associated cost. Such knowledge is important for setting prevention and treatment priorities at national and international levels. This study focuses on routine care for children with SCD in an outpatient clinic of the Kilifi District Hospital, located in a rural area on the coast of Kenya. OBJECTIVE: To estimate the per-patient costs for routine SCD outpatient care at a rural Kenyan hospital. METHODS: We collected routine administrative and primary cost data from the SCD outpatient clinic and supporting departments at Kilifi District Hospital, Kenya. Costs were estimated by evaluating inputs - equipment, medication, supplies, building use, utility, and personnel - to reflect the cost of offering this service within an existing healthcare facility. Annual economic costs were similarly calculated based on input costs, prorated lifetime of equipment and appropriate discount rate. Sensitivity analyses evaluated these costs under different pay scales and different discount rate. RESULTS: We estimated that the annual economic cost per patient attending the SCD clinic was USD 138 in 2010 with a range of USD 94 to USD 229. CONCLUSION: This study supplies the first published estimate of the cost of routine outpatient care for children born with SCD in sub-Saharan Africa. Our study provides policy makers with an indication of the potential future costs of maintaining specialist outpatient clinics for children living with SCD in similar contexts.

Mortality in sickle cell anemia in Africa: a prospective cohort study in Tanzania.

BACKGROUND: The World Health Organization has declared Sickle Cell Anemia (SCA) a public health priority. There are 300,000 births/year, over 75% in Africa, with estimates suggesting that 6 million Africans will be living with SCA if average survival reaches half the African norm. Countries such as United States of America and United Kingdom have reduced SCA mortality from 3 to 0.13 per 100 person years of observation (PYO), with interventions such as newborn screening, prevention of infections and comprehensive care, but implementation of interventions in African countries has been hindered by lack of locally appropriate information. The objective of this study was to determine the incidence and factors associated with death from SCA in Dar-es-Salaam. METHODS AND FINDINGS: A hospital-based cohort study was conducted, with prospective surveillance of 1,725 SCA patients recruited from 2004 to 2009, with 209 (12%) lost to follow up, while 86 died. The mortality rate was 1.9 (95%CI 1.5, 2.9) per 100 PYO, highest under 5-years old [7.3 (4.8-11.0)], adjusting for dates of birth and study enrollment. Independent risk factors, at enrollment to the cohort, predicting death were low hemoglobin (<5 g/dL) [3.8 (1.8-8.2); p = 0.001] and high total bilirubin (≥102 µmol/L) [1.7 (1.0-2.9); p = 0.044] as determined by logistic regression. CONCLUSIONS: Mortality in SCA in Africa is high, with the most vulnerable period being under 5-years old. This is most likely an underestimate, as this was a hospital cohort and may not have captured SCA individuals with severe disease who died in early childhood, those with mild disease who are undiagnosed or do not utilize services at health facilities. Prompt and effective treatment for anemia in SCA is recommended as it is likely to improve survival. Further research is required to determine the etiology, pathophysiology and the most appropriate strategies for management of anemia in SCA.