The impact of community health worker-led home delivery of antiretroviral therapy on virological suppression: a non-inferiority cluster-randomized health systems trial in Dar es Salaam, Tanzania.

BACKGROUND: Home delivery of antiretroviral therapy (ART) by community health workers (CHWs) may improve ART retention by reducing the time burden and out-of-pocket expenditures to regularly attend an ART clinic. In addition, ART home delivery may shorten waiting times and improve quality of care for those in facility-based care by decongesting ART clinics. This trial aims to determine whether ART home delivery for patients who are clinically stable on ART combined with facility-based care for those who are not stable on ART is non-inferior to the standard of care (facility-based care for all ART patients) in achieving and maintaining virological suppression. METHODS: This is a non-inferiority cluster-randomized trial set in Dar es Salaam, Tanzania. A cluster is one of 48 healthcare facilities with its surrounding catchment area. 24 clusters were randomized to ART home delivery and 24 to the standard of care. The intervention consists of home visits by CHWs to provide counseling and deliver ART to patients who are stable on ART, while the control is the standard of care (facility-based ART and CHW home visits without ART home delivery). In addition, half of the healthcare facilities in each study arm were randomized to standard counseling during home visits (covering family planning, prevention of HIV transmission, and ART adherence), and half to standard plus nutrition counseling (covering food production and dietary advice). The non-inferiority design applies to the endpoints of the ART home delivery trial; the primary endpoint is the proportion of ART patients at a healthcare facility who are virally suppressed at the end of the study period. The margin of non-inferiority for this primary endpoint was set at nine percentage points. DISCUSSION: As the number of ART patients in sub-Saharan Africa is expected to rise, this trial provides causal evidence on the effectiveness of a home-based care model that could decongest ART clinics and reduce patients' healthcare expenditures. More broadly, this trial will inform the increasing policy interest in task-shifting of chronic disease care from facility- to community-based healthcare workers. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02711293 . Registration date: 16 March 2016.

Active Tuberculosis in HIV-Exposed Tanzanian Children up to 2 years of Age: Early-Life Nutrition, Multivitamin Supplementation and Other Potential Risk Factors.

BACKGROUND: Over half a million children worldwide develop active tuberculosis (TB) each year. Early-life nutritional exposures have rarely been examined in relation to pediatric TB among HIV-exposed children. We therefore investigated independent associations of early-life nutritional exposures with active TB among HIV-exposed children up to 2 years of age. METHODS: Participants were children from a randomized controlled multivitamin supplementation trial conducted in Dar es Salaam, Tanzania, from August 2004 to May 2008, who received daily multivitamin supplements or placebo for 24 months. RESULTS: Lower mean corpuscular volumes [relative risks (RR): 0.48, 95% confidence interval (CI): 0.27, 0.87] and higher birth weights (RR: 0.61, 95% CI: 0.37, 0.99) were protective against active TB, whereas multivitamin supplementation was not associated with TB risk (RR: 0.87, 95% CI: 0.65, 1.16). CONCLUSIONS: Knowledge of nutrition-related risk and protective factors for TB in HIV-exposed children could enhance preventive and case-finding activities in this population, contributing to efforts to reduce the global TB burden.

The Effect of Low Dose Iron and Zinc Intake on Child Micronutrient Status and Development during the First 1000 Days of Life: A Systematic Review and Meta-Analysis.

Adequate supply of micronutrients during the first 1000 days is essential for normal development and healthy life. We aimed to investigate if interventions administering dietary doses up to the recommended nutrient intake (RNI) of iron and zinc within the window from conception to age 2 years have the potential to influence nutritional status and development of children. To address this objective, a systematic review and meta-analysis of randomized and quasi-randomized fortification, biofortification, and supplementation trials in women (pregnant and lactating) and children (6-23 months) delivering iron or zinc in doses up to the recommended nutrient intake (RNI) levels was conducted. Supplying iron or zinc during pregnancy had no effects on birth outcomes. There were limited or no data on the effects of iron/zinc during pregnancy and lactation on child iron/zinc status, growth, morbidity, and psychomotor and mental development. Delivering up to 15 mg iron/day during infancy increased mean hemoglobin by 4 g/L (p < 0.001) and mean serum ferritin concentration by 17.6 µg/L (p < 0.001) and reduced the risk for anemia by 41% (p < 0.001), iron deficiency by 78% (ID; p < 0.001) and iron deficiency anemia by 80% (IDA; p < 0.001), but had no effect on growth or psychomotor development. Providing up to 10 mg of additional zinc during infancy increased plasma zinc concentration by 2.03 µmol/L (p < 0.001) and reduced the risk of zinc deficiency by 47% (p < 0.001). Further, we observed positive effects on child weight for age z-score (WAZ) (p < 0.05), weight for height z-score (WHZ) (p < 0.05), but not on height for age z-score (HAZ) or the risk for stunting, wasting, and underweight. There are no studies covering the full 1000 days window and the effects of iron and zinc delivered during pregnancy and lactation on child outcomes are ambiguous, but low dose daily iron and zinc use during 6-23 months of age has a positive effect on child iron and zinc status.

The Proportion of Anemia Associated with Iron Deficiency in Low, Medium, and High Human Development Index Countries: A Systematic Analysis of National Surveys.

Iron deficiency is commonly assumed to cause half of all cases of anemias, with hereditary blood disorders and infections such as hookworm and malaria being the other major causes. In countries ranked as low, medium, and high by the Human Development Index, we conducted a systematic review of nationally representative surveys that reported the prevalence of iron deficiency, iron deficiency anemia, and anemia among pre-school children and non-pregnant women of reproductive age. Using random effects meta-analyses techniques, data from 23 countries for pre-school children and non-pregnant women of reproductive age was pooled, and the proportion of anemia attributable to iron deficiency was estimated by region, inflammation exposure, anemia prevalence, and urban/rural setting. For pre-school children and non-pregnant women of reproductive age, the proportion of anemia associated with iron deficiency was 25.0% (95% CI: 18.0, 32.0) and 37.0% (95% CI: 28.0, 46.0), respectively. The proportion of anemia associated with iron deficiency was lower in countries where anemia prevalence was >40%, especially in rural populations (14% for pre-school children; 16% for non-pregnant women of reproductive age), and in countries with very high inflammation exposure (20% for pre-school children; 25% for non-pregnant women of reproductive age). Despite large heterogeneity, our analyses suggest that the proportion of anemia associated with iron deficiency is lower than the previously assumed 50% in countries with low, medium, or high Human Development Index ranking. Anemia-reduction strategies and programs should be based on an analysis of country-specific data, as iron deficiency may not always be the key determinant of anemia.

Supplementation with multivitamins and vitamin A and incidence of malaria among HIV-infected Tanzanian women.

INTRODUCTION: HIV and malaria infections occur in the same individuals, particularly in sub-Saharan Africa. We examined whether daily multivitamin supplementation (vitamins B complex, C, and E) or vitamin A supplementation altered malaria incidence in HIV-infected women of reproductive age. METHODS: HIV-infected pregnant Tanzanian women recruited into the study were randomly assigned to daily multivitamins (B complex, C, and E), vitamin A alone, both multivitamins and vitamin A, or placebo. Women received malaria prophylaxis during pregnancy and were followed monthly during the prenatal and postpartum periods. Malaria was defined in 2 ways: presumptive diagnosis based on a physician's or nurse's clinical judgment, which in many cases led to laboratory investigations, and periodic examination of blood smears for malaria parasites. RESULTS: Multivitamin supplementation compared with no multivitamins significantly lowered women's risk of presumptively diagnosed clinical malaria (relative risk: 0.78, 95% confidence interval: 0.67 to 0.92), although multivitamins increased their risk of any malaria parasitemia (relative risk: 1.24, 95% confidence interval: 1.02 to 1.50). Vitamin A supplementation did not change malaria incidence during the study. CONCLUSIONS: Multivitamin supplements have been previously shown to reduce HIV disease progression among HIV-infected women, and consistent with that, these supplements protected against development of symptomatic malaria. The clinical significance of increased risk of malaria parasitemia among supplemented women deserves further research, however. Preventive measures for malaria are warranted as part of an integrated approach to the care of HIV-infected individuals exposed to malaria.

[Factors associated with neonatal death in high-risk infants: a multicenter study in High-Risk Neonatal Units in Northeast Brazil]. / Fatores associados ao óbito neonatal de recém-nascidos de alto risco: estudo multicêntrico em Unidades Neonatais de Alto Risco no Nordeste brasileiro.

This study aimed to identify factors associated with in-hospital mortality in High-Risk Neonatal Units (NICU) belonging to the North-Northeast Perinatal Health Network in Northeast Brazil. The explanatory variables were individual maternal characteristics, prenatal care, childbirth and neonatal care, and infant characteristics. This was a longitudinal, multicenter hospital-based study. The study population consisted of 3,623 live born infants admitted to 34 NICUs. After adjusting for the three hierarchical levels in the model for determination of death in the NICU up to the 27 th day of life, the following showed statistically significant association: type of delivery - cesarean section (OR = 0.72; 95%CI: 0.56-0.95), non-use of prenatal steroids (OR =1.51; 95%CI: 1.01-2.25), preeclampsia (OR = 0.73; 95%CI: 0.56-0.95), oligohydramnios (OR = 1.57; 95%CI: 1, 17-2.10), birth weight < 2500g (OR = 1.40; 95%CI: 1.03-1.90), 5-minute Apgar score < 7 (OR = 2.63; 95%CI: 2.21-3.14), endotracheal intubation (OR = 1.95; 95%CI: 1.31-2.91), and non-use of surfactant (OR = 0.54; 95%CI: 0.43-0.69). Death during NICU care is determined by conditions of the pregnancy, childbirth, and the newborn.

Anaemia, prenatal iron use, and risk of adverse pregnancy outcomes: systematic review and meta-analysis.

OBJECTIVES: To summarise evidence on the associations of maternal anaemia and prenatal iron use with maternal haematological and adverse pregnancy outcomes; and to evaluate potential exposure-response relations of dose of iron, duration of use, and haemoglobin concentration in prenatal period with pregnancy outcomes. DESIGN: Systematic review and meta-analysis DATA SOURCES: Searches of PubMed and Embase for studies published up to May 2012 and references of review articles. STUDY SELECTION CRITERIA: Randomised trials of prenatal iron use and prospective cohort studies of prenatal anaemia; cross sectional and case-control studies were excluded. RESULTS: 48 randomised trials (17 793 women) and 44 cohort studies (1 851 682 women) were included. Iron use increased maternal mean haemoglobin concentration by 4.59 (95% confidence interval 3.72 to 5.46) g/L compared with controls and significantly reduced the risk of anaemia (relative risk 0.50, 0.42 to 0.59), iron deficiency (0.59, 0.46 to 0.79), iron deficiency anaemia (0.40, 0.26 to 0.60), and low birth weight (0.81, 0.71 to 0.93). The effect of iron on preterm birth was not significant (relative risk 0.84, 0.68 to 1.03). Analysis of cohort studies showed a significantly higher risk of low birth weight (adjusted odds ratio 1.29, 1.09 to 1.53) and preterm birth (1.21, 1.13 to 1.30) with anaemia in the first or second trimester. Exposure-response analysis indicated that for every 10 mg increase in iron dose/day, up to 66 mg/day, the relative risk of maternal anaemia was 0.88 (0.84 to 0.92) (P for linear trend<0.001). Birth weight increased by 15.1 (6.0 to 24.2) g (P for linear trend=0.005) and risk of low birth weight decreased by 3% (relative risk 0.97, 0.95 to 0.98) for every 10 mg increase in dose/day (P for linear trend<0.001). Duration of use was not significantly associated with the outcomes after adjustment for dose. Furthermore, for each 1 g/L increase in mean haemoglobin, birth weight increased by 14.0 (6.8 to 21.8) g (P for linear trend=0.002); however, mean haemoglobin was not associated with the risk of low birth weight and preterm birth. No evidence of a significant effect on duration of gestation, small for gestational age births, and birth length was noted. CONCLUSIONS: Daily prenatal use of iron substantially improved birth weight in a linear dose-response fashion, probably leading to a reduction in risk of low birth weight. An improvement in prenatal mean haemoglobin concentration linearly increased birth weight.

The effect of multiple anthropometric deficits on child mortality: meta-analysis of individual data in 10 prospective studies from developing countries.

BACKGROUND: Child stunting, wasting, and underweight have been individually associated with increased mortality. However, there has not been an analysis of the mortality risk associated with multiple anthropometric deficits. OBJECTIVE: The objective was to quantify the association between combinations of stunting, wasting, and underweight and mortality among children <5 y of age. DESIGN: We analyzed data from 10 cohort studies or randomized trials in low- and middle-income countries in Africa, Asia, and Latin America with 53,767 participants and 1306 deaths. Height-for-age, weight-for-height, and weight-for-age were calculated by using the 2006 WHO growth standards, and children were classified into 7 mutually exclusive combinations: no deficits; stunted only; wasted only; underweight only; stunted and underweight but not wasted; wasted and underweight but not stunted; and stunted, wasted, and underweight (deficit defined as < -2 z scores). We calculated study-specific mortality HRs using Cox proportional hazards models and used a random-effects model to pool HRs across studies. RESULTS: The risk of all-cause mortality was elevated among children with 1, 2, and 3 anthropometric deficits. In comparison with children with no deficits, the mortality HRs were 3.4 (95% CI: 2.6, 4.3) among children who were stunted and underweight but not wasted; 4.7 (95% CI: 3.1, 7.1) in those who were wasted and underweight but not stunted; and 12.3 (95% CI: 7.7, 19.6) in those who were stunted, wasted, and underweight. CONCLUSION: Children with multiple deficits are at a heightened risk of mortality and may benefit most from nutrition and other child survival interventions.

Associations of suboptimal growth with all-cause and cause-specific mortality in children under five years: a pooled analysis of ten prospective studies.

BACKGROUND: Child undernutrition affects millions of children globally. We investigated associations between suboptimal growth and mortality by pooling large studies. METHODS: Pooled analysis involving children 1 week to 59 months old in 10 prospective studies in Africa, Asia and South America. Utilizing most recent measurements, we calculated weight-for-age, height/length-for-age and weight-for-height/length Z scores, applying 2006 WHO Standards and the 1977 NCHS/WHO Reference. We estimated all-cause and cause-specific mortality hazard ratios (HR) using proportional hazards models comparing children with mild (-2≤Z<-1), moderate (-3≤Z<-2), or severe (Z<-3) anthropometric deficits with the reference category (Z≥-1). RESULTS: 53 809 children were eligible for this re-analysis and contributed a total of 55 359 person-years, during which 1315 deaths were observed. All degrees of underweight, stunting and wasting were associated with significantly higher mortality. The strength of association increased monotonically as Z scores decreased. Pooled mortality HR was 1.52 (95% Confidence Interval 1.28, 1.81) for mild underweight; 2.63 (2.20, 3.14) for moderate underweight; and 9.40 (8.02, 11.03) for severe underweight. Wasting was a stronger determinant of mortality than stunting or underweight. Mortality HR for severe wasting was 11.63 (9.84, 13.76) compared with 5.48 (4.62, 6.50) for severe stunting. Using older NCHS standards resulted in larger HRs compared with WHO standards. In cause-specific analyses, all degrees of anthropometric deficits increased the hazards of dying from respiratory tract infections and diarrheal diseases. The study had insufficient power to precisely estimate effects of undernutrition on malaria mortality. CONCLUSIONS: All degrees of anthropometric deficits are associated with increased risk of under-five mortality using the 2006 WHO Standards. Even mild deficits substantially increase mortality, especially from infectious diseases.

Fatores associados ao obito neonatal de recem-nascidos de alto risco: estudo multicentrico em Unidades Neonatais de Alto Risco no Nordeste brasileiro / Factors associated with neonatal death in high-risk infants: a multicenter study in High-Risk Neonatal Units in Northeast Brazil / Los factores asociados a la muerte neonatal de alto riesgo de recien nacidos: estudio multicentrico en Unidades Neonatales de Alto Riesgo en el noreste de Brasil

Este estudo pretendeu determinar os fatores associados à mortalidade intra-hospitalar, utilizando como variáveis explicativas as características individuais da mãe, da assistência ao pré-natal, parto e período neonatal e dos recém-nascidos internados em Unidades Neonatais de Alto Risco (UTIN) integrantes da Rede Norte-Nordeste de Saúde Perinatal no Nordeste do Brasil. Foi realizado estudo longitudinal, multicêntrico de base hospitalar. A população do estudo compreendeu 3.623 nascidos vivos internados em 34 UTIN. Após o ajuste para os três níveis hierárquicos do modelo de determinação do óbito em UTIN até o 27 o dia de vida, associaram-se: tipo de parto – cesariana (OR = 0,72; IC95%: 0,56-0,95); não uso de corticoide antenatal (OR = 1,51; IC95%: 1,01-2,25); pré-eclâmpsia (OR = 0,73; IC95%: 0,56-0,95); oligodramnia (OR = 1,57; IC95%: 1,17-2,10); peso ao nascer < 2.500g (OR = 1,40; IC95%: 1,03-1,90); escore de Apgar 5 o minuto < 7 (OR = 2,63; IC95%: 2,21-3,14); uso de tubo endotraqueal (OR = 1,95; IC95%: 1,31-2,91); não uso de surfactante (OR = 0,54; IC95%: 0,43-0,69). O óbito em UTIN é determinado pelas condições assistenciais à gestação, parto e recém-nato.

This study aimed to identify factors associated with in-hospital mortality in High-Risk Neonatal Units (NICU) belonging to the North-Northeast Perinatal Health Network in Northeast Brazil. The explanatory variables were individual maternal characteristics, prenatal care, childbirth and neonatal care, and infant characteristics. This was a longitudinal, multicenter hospital-based study. The study population consisted of 3,623 live born infants admitted to 34 NICUs. After adjusting for the three hierarchical levels in the model for determination of death in the NICU up to the 27 th day of life, the following showed statistically significant association: type of delivery – cesarean section (OR = 0.72; 95%CI: 0.56-0.95), non-use of prenatal steroids (OR =1.51; 95%CI: 1.01-2.25), preeclampsia (OR = 0.73; 95%CI: 0.56-0.95), oligohydramnios (OR = 1.57; 95%CI: 1, 17-2.10), birth weight < 2500g (OR = 1.40; 95%CI: 1.03-1.90), 5-minute Apgar score < 7 (OR = 2.63; 95%CI: 2.21-3.14), endotracheal intubation (OR = 1.95; 95%CI: 1.31-2.91), and non-use of surfactant (OR = 0.54; 95%CI: 0.43-0.69). Death during NICU care is determined by conditions of the pregnancy, childbirth, and the newborn.

Este estudio tuvo como objetivo determinar los factores asociados a la mortalidad hospitalaria, utilizando como variables explicativas las características individuales de la madre, la atención prenatal, el parto y los bebés recién nacidos internados en Unidades Neonatales de Alto Riesgo (UCIN), miembros de la red norte-noreste de salud perinatal en el noreste de Brasil. Fue realizado estudio longitudinal, multicéntrico basado en el hospital. La población de estudio incluyó 3.623 nacidos vivos admitidos en 34 UCIN. Después de ajustar los tres niveles jerárquicos para la determinación del modelo de muerte en la UCI neonatal hasta los 27 días de vida, se les asociaba un tipo de parto: cesárea (OR = 0,72; IC95%: 0,56-0,95); uso de corticosteroides prenatales (OR = 1,51; IC95%: 1,01-2,25); preeclampsia (OR = 0,73; IC95%: 0,56-0,95); oligohidramnios (OR = 1,57; IC95%: 1,17-2,10); peso al nacer < 2.500g (OR = 1.40; IC95%: 1,03-1,90); Apgar 5 minutos < 7 (OR = 2,63; IC95%: 2.21-3.14); intubación endotraqueal (OR = 1,95; IC95%: 1,31-2,91); uso de surfactante (OR = 0,54; IC95%: 0,43-0,69). La muerte durante el cuidado en una UCIN está determinada por las condiciones durante el embarazo, el parto y el recién nacido.