Anemia and Iron Supplementation in Relation to Viral Load and Mortality among 70,442 People Living with Human Immunodeficiency Virus in Tanzania.

BACKGROUND: Anemia may be associated with poor clinical outcomes among people living with human immunodeficiency virus (HIV) (PLHIV) despite highly active antiretroviral therapy (HAART). There are concerns that iron supplementation may be unsafe to prevent and treat anemia among PLHIV. OBJECTIVE: The objective of the study was to evaluate the associations of anemia and iron supplementation with mortality and viral load among PLHIV in Tanzania. METHODS: We analyzed data from a cohort of 70,442 nonpregnant adult PLHIV in Tanzania conducted between 2015 and 2019. Regression models evaluated the relationships between anemia severity and iron supplement use with mortality and unsuppressed HIV-1 viral load among all participants and stratified by whether participants were initiating or continuing HAART. RESULTS: Anemia was associated with an increased risk of mortality and unsuppressed viral load for participants who initiated or continued HAART. Iron supplement use was associated with reduced mortality risk but also had a greater risk of an unsuppressed viral load among participants continuing HAART. There was no association of iron supplement use with mortality, and unsuppressed viral load among PLHIV that were initiating HAART. There was a stronger negative association between iron supplement use and the risk of having an unsuppressed viral load among participants with stage III/IV disease compared with stage I/II disease. CONCLUSIONS: Anemia is associated with increased risk of mortality and unsuppressed viral load, but the benefits and safety of iron supplements appear to differ for those initiating compared with continuing ART as well as by HIV disease severity.

Prevalence of and risk factors for iron deficiency among pregnant women with moderate or severe anaemia in Nigeria: a cross-sectional study.

BACKGROUND: Anaemia during pregnancy causes adverse outcomes to the woman and the foetus, including anaemic heart failure, prematurity, and intrauterine growth restriction. Iron deficiency anaemia (IDA) is the leading cause of anaemia and oral iron supplementation during pregnancy is widely recommended. However, little focus is directed to dietary intake. This study estimates the contribution of IDA among pregnant women and examines its risk factors (including dietary) in those with moderate or severe IDA in Lagos and Kano states, Nigeria. METHODS: In this cross-sectional study, 11,582 women were screened for anaemia at 20-32 weeks gestation. The 872 who had moderate or severe anaemia (haemoglobin concentration < 10 g/dL) were included in this study. Iron deficiency was defined as serum ferritin level < 30 ng/mL. We described the sociodemographic and obstetric characteristics of the sample and their self-report of consumption of common food items. We conducted bivariate and multivariable logistic regression analysis to identify risk factors associated with IDA. RESULTS: Iron deficiency was observed among 41% (95%CI: 38 - 45) of women with moderate or severe anaemia and the prevalence increased with gestational age. The odds for IDA reduces from aOR: 0.36 (95%CI: 0.13 - 0.98) among pregnant women who consume green leafy vegetables every 2-3 weeks, to 0.26 (95%CI: 0.09 - 0.73) among daily consumers, compared to those who do not eat it. Daily consumption of edible kaolin clay was associated with increased odds of having IDA compared to non-consumption, aOR 9.13 (95%CI: 3.27 - 25.48). Consumption of soybeans three to four times a week was associated with higher odds of IDA compared to non-consumption, aOR: 1.78 (95%CI: 1.12 - 2.82). CONCLUSION: About 4 in 10 women with moderate or severe anaemia during pregnancy had IDA. Our study provides evidence for the protective effect of green leafy vegetables against IDA while self-reported consumption of edible kaolin clay and soybeans appeared to increase the odds of having IDA during pregnancy. Health education on diet during pregnancy needs to be strengthened since this could potentially increase awareness and change behaviours that could reduce IDA among pregnant women with moderate or severe anaemia in Nigeria and other countries.

The Management of Opioid-Induced Constipation in Cancer and Advanced Illness: A Meta-Analysis.

CONTEXT: Constipation is a common problem among patients with cancer. By some accounts, about 60% of cancer patients experience constipation. There is limited empirical evidence of the clinical effectiveness of pharmacologic agents in opioid-induced constipation in advanced diseases. OBJECTIVES: We sought to quantitatively summarize the therapeutic effectiveness of the pharmacologic means of managing opioid-induced constipation. METHODS: Randomized control trials (RCTs) identified from medical literature databases that reported quantitative measures of the effect of pharmacotherapeutic agents to treat opioid induced constipation in patients with cancers and other advanced illnesses were included in this study. A conventional random effects meta-analysis was conducted including >3 trials with the same exposure and outcome assessed, and a network-meta-analysis was conducted for all placebo-controlled trials. RESULTS: Eighteen studies that examined the effect of various pharmacotherapeutic agents were included. The medications were Methylnatrexone (N = 5), Naldemedine (N = 5), other conventional agents (N = 4) and herbal medicines (N = 4). In conventional meta-analysis, methylnaltrexone increased the proportion achieving rescue-free laxation by 2.68 fold (95% CI: 1.34, 5.37; P = 0.0054) within 4 hours of the administration compared to placebo. In network meta-analysis, the pooled RR of the pharmacotherapeutic agents on rescue-free bowel movements as 2.26 (95% CI: 1.52, 3.36) for methylnaltrexone, 1.58 (95% CI: 0.94, 2.66) for naldemedine, and 0.74 (95% CI: 0.45, 1.23) for polyethylene glycol, compared to placebo. CONCLUSION: Methylnatrexone and Naldemedine have currently shown promise in randomized trials concerning opioid-induced constipation in cancer and advanced illness. It is imperative that future research ascertain not just the relative therapeutic efficacy but also the cost-benefit analyses of these newer regimens with more commonly used and accessible laxatives.

Effect of intake of probiotics and probiotic fermented foods on clinical outcomes among people living with HIV: A systematic review and meta-analysis.

OBJECTIVE: The objective of the study was to determine the effect of probiotics and of probiotic-fermented foods on CD4 T-cell count, viral load, anaemia and body mass index (BMI) among people living with HIV (PLHIV). METHODS: In this article, we systematically reviewed the evidence on the influence of probiotic supplementation on CD4 lymphocyte count, viral load and anaemia among PLHIV on highly active antiretroviral therapy (HAART) and those who were HAART-naive. Medical literature databases identified randomised trials and pre-post studies of probiotic supplementation and HIV-related outcomes, and random effects meta-analysis was conducted. RESULTS: The preponderance of the evidence suggests that probiotic supplementation only improved CD4 lymphocyte count modestly, with quantitatively greater impact among individuals who were HAART-naive compared to HAART-experienced individuals. Probiotic supplementation improved CD4 lymphocyte count by 53 cells/mm3 (95% CI: 22 to 85) from 18 studies. Probiotic supplementation however reduced haemoglobin concentration by -2.1 g/L (95% CI: -4.0 to -0.2). Although viral load remain unchanged in HAART-experienced participants following probiotic supplementation, HAART-naïve participants saw a decrease in viral load. There were too few studies on the impact of probiotic supplementation on viral load (N = 1). CONCLUSION: Probiotic supplementation resulted in a modest increase in CD4 lymphocyte count among HAART-naive individuals with no significant change observed among HAART-experienced ones. Viral load and haemoglobin concentration also remained unchanged following probiotic supplementation. Further rigorous and well-powered studies may evaluate the effect of probiotic supplementation on important clinical outcomes among PLHIV on HAART.

Nutrition counselling and clinical outcomes in HIV: A systematic review and meta-analysis.

BACKGROUND: People living with the HIV (PLHIV) are at an increased risk of various diseases due to a weakened immune system, particularly if they are naïve or poorly adherent to antiretroviral therapy (ART). Nutrients play a critical role in improving immune health, especially among this population. We systematically reviewed the evidence concerning the impact of nutritional counselling on the occurrence of important clinical outcomes among PLHIV. METHODS: Medical literature databases (PubMed, EMBASE and Web of Science) were searched from inception to October 2022 for relevant published studies (n = 12) of nutritional counselling and HIV-related outcomes in adults on ART. Random-effects meta-analyses were conducted when the exposure-outcome relationships were similar in three or more studies. RESULTS: Although the methodologies of nutritional intervention varied across all studies, overall, the evidence from the meta-analysis indicates a nsignificant positive association between nutrition counselling and improvements in CD4 cell count, body mass index and low-density lipoprotein concentration. However, the existing literature does not provide enough evidence to establish a significant impact of nutrition counselling on other immune, anthropometric, and metabolic outcomes including viral load, weight, and lean mass due to the differences in the study designs. CONCLUSION: Well-powered randomized controlled trials are needed that explore the effect of evidence-based, individualized nutrition counselling on HIV-related clinical outcomes.

Dietary Iron Intake and HIV-Related Outcomes Among Adults Initiating Antiretroviral Therapy in Tanzania.

OBJECTIVE: Anemia is highly prevalent among people living with HIV (PLWHIV) and is often due to iron deficiency. This study evaluated the relationship of dietary iron intake levels and sources with mortality and clinical outcomes among adults initiating HAART. DESIGN: We conducted a secondary analysis of a multivitamin supplementation trial among 2293 PLWHIV initiating HAART in Dar es Salaam, Tanzania. METHODS: Dietary iron intake was assessed with a food frequency questionnaire at HAART initiation, and participants followed until death or censoring. Total, animal-, and plant-sourced iron were categorized into quartiles. Intake of food groups was categorized into 0-1, 2-3, and ≥4 servings/wk. Cox proportional hazards models estimated hazard ratios for mortality and incident clinical outcomes. RESULTS: There were 175 deaths (8%). Red meat intake was associated with a lower risk of all-cause mortality (HR: 0.54; 95% CI: 0.35 to 0.83), AIDS-related mortality (HR: 0.49; 95% CI: 0.28 to 0.85), and severe anemia (HR: 0.57; 95% CI: 0.35 to 0.91), when intake ≥4 servings/wk, compared with 0-1 servings/wk. Legume intake was a lower risk of associated with all-cause mortality (HR: 0.49; 95% CI: 0.31 to 0.77) and AIDS-related mortality (HR: 0.37; 95% CI: 0.23 to 0.61), when intake ≥4 servings/wk, compared with 0-1 servings/wk. Although total dietary iron and overall plant-sourced iron intake were not associated with the risk of mortality or HIV-related outcomes, the highest quartile of animal-sourced iron intake was associated with a lower risk of all-cause mortality (HR: 0.56; 95% CI: 0.35 to 0.90) and a lower risk of AIDS-related mortality (HR: 0.50; 95% CI: 0.30 to 0.90), compared with the lowest quartile. CONCLUSION: Intake of iron-rich food groups may be associated with a lower risk of mortality and critical HIV-related outcomes among adults initiating HAART. TRIAL REGISTRATION: The parent trial was registered at Clinicaltrials.gov . Identifier: NCT00383669.

The effect of iron supplementation on maternal iron deficiency anemia does not differ by baseline anemia type among Tanzanian pregnant women without severe iron deficiency anemia.

PURPOSE: Whether anemia type modifies the risk of pregnancy and newborn outcomes and the effectiveness of iron supplementation is unclear. We examined the association of iron deficiency anemia (IDA) and non-iron deficiency anemia (NIDA) on the risks of these outcomes and the extent to which anemia type modifies the impact of prenatal iron supplementation. METHODS: This was a secondary analysis of a placebo-controlled trial of iron supplementation among 1450 HIV-negative women in Tanzania. Eligibility criteria included gestational age < 27 weeks, hemoglobin > 85 g/L, and ferritin > 12 µg/L. Individuals were categorized as non-anemia, IDA or NIDA using hemoglobin, ferritin and CRP. Analyses were conducted using regression models and likelihood ratio tests. RESULTS: Compared to the non-anemia group, delivery hemoglobin was lower by 15 g/L (95% CI 10.9, 19.3) in the baseline IDA group, and 7.3 g/L (95% CI 3.1, 11.5) in the baseline NIDA group. The RRs of anemia severity, iron deficiency, placental malaria, stillbirths, perinatal mortality, birthweight, and preterm birth were not different among women in the baseline NIDA group (vs. non-anemia) compared to the baseline IDA group (vs. non-anemia). The difference in the mean delivery hemoglobin for iron supplementation and placebo arms was 8 g/L (95% CI 6, 11) in the non-anemia group, 7 g/L (95% CI 2, 13) in the NIDA group, and 16 g/L (95% CI 10, 22) in the IDA group. CONCLUSION: Iron supplementation is effective even among pregnant women with NIDA. TRIAL REGISTRATION: NCT01119612 (May 7, 2010).

Iron status among HIV-infected adults during the first year of antiretroviral therapy in Tanzania.

BACKGROUND: The influence of inflammation on iron status among people living with HIV (PLWHIV) has not been well explored. We evaluated the trajectory of iron status among PLWHIV during the first year of highly active antiretroviral therapy (HAART), compared alternative approaches for inflammation correction, and assessed the associations of iron status with HIV-1 viral load and anthropometric outcomes. METHODS: We conducted a secondary analysis of data from a randomized trial among 400 adults initiating HAART in Tanzania. Ferritin and C-reactive protein (CRP) were measured at baseline, 1, 6 or 12 months. Ferritin was considered in four ways: unadjusted, and adjusted for inflammation using higher cut-off (HC), Thurnham-corrected (TC) and regression-corrected (RC) approaches. For unadjusted, TC and RC ferritin, iron deficiency (ID) was defined using ferritin < 15 µg/L and elevated iron status was defined using ferritin > 150 µg/L among females and > 200 µg/L among males. For HC ferritin, elevated iron status was defined based on serum ferritin > 500 µg/L, while ID was defined using ferritin < 70 µg/L in the presence of inflammation and < 15 µg/L in the absence of inflammation. Regression models evaluated the trajectory of ferritin concentration across categories of baseline characteristics, and assessed the association of iron status with viral and anthropometric outcomes. RESULTS: The prevalence of iron deficiency at HAART initiation was 9% for unadjusted, 17% for HC, 12% for TC and 22% for RC ferritin. The prevalence of elevated iron status was 42% for unadjusted, 18% for HC, 31% for TC, and 15% for RC ferritin. The prevalence of iron deficiency for all three methods increased during the first year of HAART, while the prevalence of elevated iron status decreased. Baseline elevated iron status defined using HC ferritin was associated with a greater risk of HIV-1 viral load > 1000 copies/mL [relative risk (RR) = 4.29, 95% CI: 1.38-13.3] and incidence of being underweight [body mass index (BMI) < 18.5 kg/m2 , hazard ratio (HR) = 3.65, 95% confidence interval (CI): 1.38-9.67]. Neither baseline-elevated iron status defined using TC or RC ferritin nor baseline iron deficiency defined using any of the three methods was associated with HIV-1 viral load or anthropometric outcomes. CONCLUSIONS: Whether and how inflammation correction is done influences findings of studies of iron status among PLWHIV.

Public Health Surveillance for Adverse Events Following COVID-19 Vaccination in Africa.

Local, national, and international health agencies have advocated multi-pronged public health strategies to limit infections and prevent deaths. The availability of safe and effective vaccines is critical in the control of a pandemic. Several adverse events have been reported globally following reception of different vaccines, with limited or no data from Africa. This cross-sectional epidemiological study investigated adverse events following COVID-19 vaccination in Africans from April-June, 2021 using a structured online questionnaire. Out of 1200 participants recruited, a total of 80.8% (n = 969) respondents from 35 countries, including 22 African countries and 13 countries where Africans live in the diaspora, reported adverse events. Over half of the vaccinees were male (53.0%) and frontline healthcare workers (55.7%), respectively. A total of 15.6% (n = 151) reported previous exposure to SARS-CoV-2, while about one-fourth, 24.8% (n = 240), reported different underlying health conditions prior to vaccination. Fatal cases were 5.1% (n = 49), while other significant heterogenous events were reported in three categories: very common, common, and uncommon, with the latter including enlarged lymph nodes 2.4% (n = 23), menstrual disorder 0.5% (n = 5), and increased libido 0.2% (n = 2). The study provided useful data for concerned authorities and institutions to prepare plans that will address issues related to COVID-19 vaccines.

Calcium Intake and Iron Status in Human Studies: A Systematic Review and Dose-Response Meta-Analysis of Randomized Trials and Crossover Studies.

BACKGROUND: The interaction between dietary (and supplementary) divalent ions has been a long-standing issue in human nutrition research. Developing an optimal calcium and iron supplementation recommendation requires detailed knowledge of the potential trade-offs between: 1) the clinical effects of concurrent intake on iron absorption and hematological indices; and 2) the potentially negative effects of separated ingestion on adherence to iron and/or calcium supplements. Human clinical studies have examined the effects of calcium intake on iron status, but there are no meta-analyses or recent reviews summarizing the findings. OBJECTIVES: To synthesize peer-reviewed, human, randomized, and cross-over studies on effects of calcium consumption on iron indices without age, gender, or any other restrictions. METHODS: Weighted mean differences for total, heme, and nonheme iron absorption (%) and serum ferritin (µg/L) were obtained from pooled analysis of the highest daily calcium intake compared to the lowest daily calcium intake. RESULTS: The negative effect of calcium intake was statistically significant in short-term iron absorption studies, but the effect magnitude was low [weighted mean difference (WMD) = -5.57%; 95% CI: -7.09 to -4.04]. The effect of calcium on the iron status was mixed. The inverse dose-response association of calcium intake with the serum ferritin concentration was significant (P value = 0.0004). There was, however, no reduction in the hemoglobin concentration (WMD = 1.22g/L;  95% CI:  0.37-2.07). CONCLUSIONS: The existing body of studies is insufficient to make recommendations with high confidence due to heterogeneity in designs, limitations of ferritin as an iron biomarker, and a lack of intake studies in pregnant women. Prescribing separation of prenatal calcium and iron supplements in free-living individuals is unlikely to affect the anemia burden. There is a need for effectiveness trials comparing the effects of prescribing separated intake to concurrent intake, with functional endpoints as primary outcomes and adherence to each supplement as intermediate outcomes.

Effect of micronutrient supplements on influenza and other respiratory tract infections among adults: a systematic review and meta-analysis.

Acute respiratory tract infections (ARIs) are a leading cause of ill-health and death globally. Individual or multiple micronutrients have been shown to modulate immune function and affect the risk and severity of a number of infectious diseases. We systematically reviewed the evidence on the impact of micronutrient supplements to reduce the occurrence of ARIs and shorten the duration of ARI symptoms among adults. Random effects meta-analyses were conducted to estimate the pooled effects of vitamin D, vitamin C, zinc and multiple micronutrient supplementation (MMS) on the occurrence of ARIs and the duration of ARI symptoms. Vitamin D supplementation reduced the risk of ARI (risk ratio (RR)=0.97; 95% CI 0.94 to 1.00; p=0.028) and shortened the duration of symptoms (per cent difference: -6% (95% CI -9% to -2%; p=0.003)). The RR of vitamin D to prevent ARI was farther from the null when diagnosis was based on clinical diagnosis or laboratory testing, compared with self-report and when the loading dose was <60 000 IU. Vitamin C supplementation reduced the risk of ARIs (RR=0.96; 95% CI 0.93 to 0.99; p=0.01) and shortened the duration of symptoms (per cent difference: -9% (95% CI -16% to -2%; p=0.014)). The effect of vitamin C on preventing ARI was stronger among men and in middle-income countries, compared with women and high-income countries, respectively. Zinc supplementation did not reduce the risk of ARIs but shortened the duration of symptoms substantially (per cent difference: -47% (95% CI -73% to -21%; p=0.0004)). Our synthesis of global evidence from randomised controlled trials indicates that micronutrient supplements including zinc, vitamins C and D, and multiple micronutrient supplements may be modestly effective in preventing ARIs and improving their clinical course. Further research is warranted to better understand the effectiveness that individual or multiple micronutrients have on SARS-CoV-2 infection and treatment outcomes.

Spatio-temporal trends in anaemia among pregnant women, adolescents and preschool children in sub-Saharan Africa.

OBJECTIVE: We investigated the spatiotemporal trends in the burden of maternal, adolescent and child anaemia in sub-Saharan Africa (SSA) and evaluated some individual and household predictors of anaemia. DESIGN: Average Hb concentrations and anaemia prevalence were estimated, plotted over time and mapped by country and sub-region. Multilevel linear regression models were used to evaluate individual and household predictors of Hb concentration. PARTICIPANTS: Data from Demographic and Health Surveys (DHS) spanning 2000-2018 were merged into data sets for 37 623 pregnant women, 89 815 older adolescent girls and 401 438 preschool children. SETTING: The merged DHS represent nationally representative samples from thirty-three countries. RESULTS: Prevalence of anaemia remains high in SSA, affecting 60, 36 and 44 % of children, adolescents and pregnant women, respectively. Anaemia prevalence among children did not materially improve from 2000 to 2018. Anaemia prevalence among older adolescent girls and pregnant women did not also improve, but this masks a period of improvement followed by depreciation in population anaemia status. Pregnant adolescents had 12·5 g/l (95 % CI: 11·3, 13·6) lower Hb concentration compared with non-pregnant adolescents and 1·7 g/l (95 % CI: 0·7, 2·6) lower Hb concentration compared with pregnant women > 40 years, respectively. Stunting and wasting were associated with 1·3-3·3 g/l lower Hb concentration among children. Other significant predictors of Hb concentration were educational attainment, wealth quintiles, source of drinking water, number of children < 5 years in the household and possession of bed-nets. CONCLUSION: Anaemia in SSA has not improved remarkably since year 2000 and remains excessive among children.

Factors associated with sub-microscopic placental malaria and its association with adverse pregnancy outcomes among HIV-negative women in Dar es Salaam, Tanzania: a cohort study.

BACKGROUND: Malaria infection during pregnancy has negative health consequences for both mothers and offspring. Sub-microscopic malaria infection during pregnancy is common in most African countries. We sought to identify factors associated with sub-microscopic placental malaria, and its association with adverse pregnancy outcomes among HIV-negative pregnant women in Dar es Salaam, Tanzania. METHODS: We recruited a cohort of pregnant women during their first trimester and assessed for the occurrence of placental malaria and pregnancy outcomes. The follow-up was done monthly from recruitment until delivery. Histopathology placental malaria positive results were defined as the presence of malaria pigment or parasitized erythrocytes on the slide (histology-positive (HP)), and the sub-microscopic placental infection was defined as positive Plasmodium falciparum DNA by polymerase chain reaction (DNA PCR) amplification in a negative histopathology test. Adverse pregnancy outcomes investigated included low birth weight (birth weight below 2.5 kg), prematurity (live birth below 37 weeks), and small-for-gestational-age (SGA) (live born with a birth weight below 10th percentile for gestational age and sex). Weighted baseline category logit, log-binomial, and log-Poisson models were used to assess factors associated with placental malaria, and its association with adverse pregnancy outcomes. RESULTS: Among 1115 women who had histopathology and DNA PCR performed, 93 (8%) had HP placental infection, and 136 (12%) had the sub-microscopic placental infection. The risk of sub-microscopic placental malaria was greater in women who did not use mosquito prevention methods such as bed nets, fumigation, or mosquito coils (odds ratio (OR) = 1.75; 95% confidence interval (CI): 1.05-2.92; P = 0.03) and in women who were anemic (OR = 1.59; 95% CI: 1.20-2.11; P = 0.001). Women who were underweight had reduced odds of sub-microscopic placental malaria infection (OR = 0.33; 95% CI: 0.17-0.62; P = 0.001). Women who were overweight/obese had 1.48 times higher the odds of HP placental malaria compared to normal weight (OR = 1.48; 95% CI: 1.03-2.11; P = 0.03). HP placental malaria infection was associated with an increased risk of SGA births (RR = 1.30, 95% CI: 0.98-1.72, P = 0.07). In contrast, the sub-microscopic infection was associated with a reduced risk of SGA births (RR = 0.61, 95% CI: 0.43-0.88, P = 0.01). Placental malaria was not associated with low birth weight or prematurity. CONCLUSION: Malaria prevention methods and maternal nutrition status during early pregnancy were important predictors of sub-microscopic placental malaria. More research is needed to understand sub-microscopic placental malaria and the possible mechanisms mediating the association between placental malaria and SGA.

Vitamin A and Zinc Supplementation Among Pregnant Women to Prevent Placental Malaria: A Randomized, Double-Blind, Placebo-Controlled Trial in Tanzania.

AbstractVitamin A and zinc are important for immune function and may improve host defense against malaria and reduce the risk of adverse pregnancy outcomes. Our objective was to determine whether daily oral supplementation with either or both nutrients starting in the first trimester reduces the risk of placental malaria and adverse pregnancy outcomes. We undertook a randomized, double-blind placebo-controlled trial with a factorial design among 2,500 human immunodeficiency virus-negative primigravid or secundigravid pregnant women in their first trimester of pregnancy in Dar es Salaam, Tanzania. We randomly allocated equal numbers of participants to 2,500 IU of vitamin A, 25 mg of zinc, both 2,500 IU of vitamin A and 25 mg of zinc, or a placebo until delivery. A total of 625 participants were allocated to each treatment group. Our primary outcome, placental malaria infection (past or current), was assessed in all randomized participants for whom placental samples were obtained at delivery (N = 1,404), which represents 56% of total participants and 62% of all pregnancies lasting 28 weeks or longer (N = 2,266). Birth outcomes were obtained for 2,434 of the 2,500 randomized participants. Secondary outcomes included small for gestational age (SGA) births and prematurity. All analyses were intent to treat. Those who received zinc had a lower risk of histopathology-positive placental malaria compared with those who did not receive zinc (risk ratio = 0.64, 95% confidence interval = 0.44, 0.91), but neither nutrient had an effect on polymerase chain reaction-positive malaria, SGA, or prematurity. No safety concerns were identified. We recommend additional studies in other geographic locations to confirm these findings.

Iron Supplementation in Iron-Replete and Nonanemic Pregnant Women in Tanzania: A Randomized Clinical Trial.

IMPORTANCE: Anemia is common in pregnancy and increases the risk of adverse outcomes. Iron deficiency is a leading cause of anemia in sub-Saharan Africa, and iron supplementation is the standard of care during pregnancy; however, recent trials among children have raised concerns regarding the safety of iron supplementation in malaria-endemic regions. There is limited evidence on the safety of iron supplementation during pregnancy in these areas. OBJECTIVE: To evaluate the safety and efficacy of iron supplementation during pregnancy in a malaria-endemic region. DESIGN, SETTING, AND PARTICIPANTS: We conducted a randomized, double-blind, placebo-controlled clinical trial among pregnant women presenting for antenatal care in Dar es Salaam, Tanzania, from September 28, 2010, through October 4, 2012. Iron-replete, nonanemic women were eligible if they were uninfected with human immunodeficiency virus, primigravidae or secundigravidae, and at or before 27 weeks of gestation. Screening of 21,316 women continued until the target enrollment of 1500 was reached. Analyses followed the intent-to-treat principle and included all randomized participants. INTERVENTIONS: Participants were randomized to receive 60 mg of iron or placebo, returning every 4 weeks for standard prenatal care, including malaria screening, prophylaxis with the combination of sulfadoxine and pyrimethamine, and treatment, as needed. MAIN OUTCOMES AND MEASURES: The primary outcomes were placental malaria, maternal hemoglobin level at delivery, and birth weight. RESULTS: Among 1500 study participants (750 randomized for each group), 731 in iron group and 738 in placebo group had known birth outcomes and 493 in iron group and 510 in placebo group had placental samples included in the analysis. Maternal characteristics were similar at baseline in the iron and placebo groups, and 1354 (91.7%) used malaria control measures. The risk of placental malaria was not increased by maternal iron supplementation (relative risk [RR], 1.03; 95% CI, 0.65-1.65), and iron supplementation did not significantly affect birth weight (3155 vs 3137 g, P = .89). Compared with placebo, iron supplementation significantly improved the mean increase from baseline to delivery for hemoglobin (0.1 vs -0.7 g/dL, P < .001) and serum ferritin (41.3 vs 11.3 µg/L, P < .001). Iron supplementation significantly decreased the risk of anemia at delivery by 40% (RR, 0.60; 95% CI, 0.51-0.71) but not severe anemia (RR, 0.68; 95% CI, 0.41-1.14). Iron supplementation significantly reduced the risk of maternal iron deficiency at delivery by 52% (RR, 0.48; 95% CI, 0.32-0.70) and the risk of iron deficiency anemia by 66% (RR, 0.34; 95% CI, 0.19-0.62). CONCLUSIONS AND RELEVANCE: Prenatal iron supplementation among iron-replete, nonanemic women was not associated with an increased risk of placental malaria or other adverse events in the context of good malaria control. Participants receiving supplementation had improved hematologic and iron status at delivery compared with the placebo group. These findings provide support for continued administration of iron during pregnancy in malaria-endemic regions. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01119612.

Physical activity and risk of gastric cancer: a meta-analysis of observational studies.

BACKGROUND: Studies evaluating the relationship of physical activity and stomach cancer risk have yielded inconsistent and largely inconclusive results. We therefore conducted a systematic review and meta-analysis of observational studies that assessed the relationship between physical activity and risk of gastric cancer. METHODS: Following a standard protocol, we searched medical literature databases (PubMed, EMBASE, CINAHL, PsycINFO and Google Scholar) from inception to July 2012, and conducted a random effects meta-analysis. RESULTS: Seven prospective cohorts and four case-control studies of physical activity and gastric cancer risk, with 1,535,006 people and 7944 cases of gastric cancer were included. We found a modest protective association between sufficient physical activity and gastric cancer risk (relative risk: 0.81 (95% CI 0.69 to 0.96); I(2)=68.5%) in the prospective studies and (relative risk: 0.78 (95% CI 0.66 to 0.91); I(2)=0%) in case-control studies. The association appeared weaker in smokers than in non-smokers (p heterogeneity=0.035). The association may also be weaker for gastric cardia cancer relative to the distal non-cardia subtypes. Physical activity type (recreational or occupational), intake of alcohol, total energy intake, consumption of fruits and vegetables and infection with Helicobacter pylori had no influence on the association. The effect measure from cohort studies (relative risk: 0.82 (95% CI 0.70 to 0.97); I(2)=61.7%) and case-control studies (relative risk: 0.83 (95% CI 0.66 to 1.04); I(2)=49.8%) did not differ materially at higher physical activity levels. CONCLUSIONS: We conclude that a regular physical activity may be protective against stomach cancer risk.