Increased Serum Total and Free 25-Hydroxyvitamin D with Daily Intake of Cholecalciferol-Fortified Skim Milk: A Randomized Controlled Trial in Colombian Adolescents.

BACKGROUND: The efficacy of cholecalciferol (vitamin D3) food fortification in low- and middle-income countries near the Equator is unknown. OBJECTIVES: We examined the effects of providing cholecalciferol-fortified skim milk to adolescents and their mothers on serum total 25(OH)D, free 25(OH)D, and vitamin D-binding protein (DBP) concentrations in a randomized controlled trial. METHODS: We randomly assigned 80 Colombian families each with a child aged 12-14.5 y and their mother 1 L of skim milk daily, either fortified with 2400 IU (60 µg) cholecalciferol or unfortified, for 6 wk. We prescribed 500 mL of milk daily to adolescents; mothers consumed the remainder ad libitum. We estimated intent-to-treat effects as the between-arm difference in the change in serum total and free 25(OH)D and DBP concentrations from baseline to the end of follow-up. Secondary analyses included stratification by baseline characteristics and per-protocol comparisons. RESULTS: Among adolescents, fortification effects (95% CI) on serum total 25(OH)D, free 25(OH)D, and DBP concentrations were 5.4 nmol/L (2.1, 8.8 nmol/L), 0.6 pmol/L (-0.2, 1.4 pmol/L), and -416 nmol/L (-944, 112 nmol/L), respectively. Effects on total 25(OH)D were stronger in adolescents with lower DBP concentrations, darker skin, less sunlight exposure, and higher compliance than in their respective counterparts. Fortification increased free 25(OH)D concentrations in high compliers. Among mothers, the effects (95% CI) on total 25(OH)D and DBP concentrations were 4.0 nmol/L (0.6, 7.5 nmol/L) and -128 nmol/L (-637, 381 nmol/L), respectively. There were no adverse events. CONCLUSIONS: Provision of cholecalciferol-fortified skim milk increases serum total 25(OH)D concentrations in Colombian adolescents and adult women.

Vitamin D status in infancy and cardiometabolic health in adolescence.

BACKGROUND: Vitamin D deficiency is associated with obesity-related conditions, but the role of early life vitamin D status on the development of obesity is poorly understood. OBJECTIVES: We assessed whether serum 25-hydroxyvitamin D [25(OH)D] at age 1 y was related to metabolic health through adolescence. METHODS: We quantified serum 25(OH)D in samples obtained at age 1 y from 306 participants in a cohort study in Santiago, Chile. Anthropometry was performed at ages 5, 10, and 16/17 y. At 16/17 y, we determined body composition using DXA and quantified metabolic parameters in a blood sample. We examined the associations of infancy 25(OH)D with BMI-for-age z-score (BMIZ) at ages 5, 10, and 16/17 y; with percentage fat and percentage lean body mass at age 16/17 y; and with a metabolic syndrome (MetS) score and its components at age 16/17 y. RESULTS: Infancy 25(OH)D was inversely associated with BMIZ in childhood. Every 25-nmol/L difference in 25(OH)D was related to an adjusted 0.11 units lower BMIZ at age 5 y (95% CI: -0.20, -0.03; P = 0.01) and a 0.09 unit lower BMIZ change from ages 1 to 5 y (95% CI: -0.17, -0.01; P = 0.02). Also, every 25-nmol/L 25(OH)D in infancy was associated with an adjusted 1.3 points lower percentage body fat mass (95% CI: -2.2, -0.4; P = 0.005) and an adjusted 0.03 units lower MetS score (95% CI: -0.05, -0.01; P = 0.01) at age 16/17 y, through inverse associations with waist circumference and the HOMA-IR. CONCLUSIONS: Serum 25(OH)D at age 1 y is inversely associated with childhood BMIZ, percentage body fat at age 16/17 y, and a MetS score at age 16/17 y. Intervention studies are warranted to examine the effects of vitamin D supplementation in early life on long-term cardiometabolic outcomes.

Sociodemographic, Anthropometric, and Dietary Predictors of Polyunsaturated Fatty Acids in Adipose Tissue Among Mesoamerican Children and Their Parents.

BACKGROUND: Polyunsaturated fatty acid (PUFA) intake is low throughout Latin America. Improving PUFA status could be an effective intervention against chronic disease, but information on sociodemographic and dietary patterning of PUFA status in the region is limited. OBJECTIVE: To characterize sociodemographic, anthropometric, and dietary predictors of PUFA status biomarkers in adipose tissue among children and their parents from Mesoamerica. METHODS: This was a cross-sectional study of 220 children aged 7 to 12 years and 471 parents from capital cities of Guatemala, El Salvador, the Dominican Republic, Honduras, Nicaragua, Panama, Costa Rica, and Belize, as well as Tuxtla Gutiérrez in Mexico. The PUFA from gluteal adipose tissue was quantified using gas chromatography. Participants reported sociodemographic information and the type of vegetable oil used for cooking. We estimated percent mean differences in linoleic acid (LA), total long-chain n-6 PUFA (n-6 LCPUFA), α-linolenic acid (ALA), and total long-chain n-3 PUFA (n-3 LCPUFA) between levels of predictors using multivariable-adjusted linear regression models. RESULTS: Country was the strongest predictor of any PUFA, whereas body mass index was positively associated with n-6 LCPUFA in children and adults. Cooking primarily with soybean oil was positively associated with LA in children and adults and ALA in adults. Cooking with canola oil was positively related to n-6 LCPUFA in adults and n-3 LCPUFA in children and adults. Cooking with palm oil was associated with low adipose tissue levels of all n-6 and n-3 PUFA. CONCLUSIONS: Adipose tissue PUFA status in Mesoamerica is associated with country of origin and the type of oil used for cooking.

Early treatment versus expectative management of patent ductus arteriosus in preterm infants: a multicentre, randomised, non-inferiority trial in Europe (BeNeDuctus trial).

BACKGROUND: Much controversy exists about the optimal management of a patent ductus arteriosus (PDA) in preterm infants, especially in those born at a gestational age (GA) less than 28 weeks. No causal relationship has been proven between a (haemodynamically significant) PDA and neonatal complications related to pulmonary hyperperfusion and/or systemic hypoperfusion. Although studies show conflicting results, a common understanding is that medical or surgical treatment of a PDA does not seem to reduce the risk of major neonatal morbidities and mortality. As the PDA might have closed spontaneously, treated children are potentially exposed to iatrogenic adverse effects. A conservative approach is gaining interest worldwide, although convincing evidence to support its use is lacking. METHODS: This multicentre, randomised, non-inferiority trial is conducted in neonatal intensive care units. The study population consists of preterm infants (GA < 28 weeks) with an echocardiographic-confirmed PDA with a transductal diameter > 1.5 mm. Early treatment (between 24 and 72 h postnatal age) with the cyclooxygenase inhibitor (COXi) ibuprofen (IBU) is compared with an expectative management (no intervention intended to close a PDA). The primary outcome is the composite of mortality, and/or necrotising enterocolitis (NEC) Bell stage ≥ IIa, and/or bronchopulmonary dysplasia (BPD) defined as the need for supplemental oxygen, all at a postmenstrual age (PMA) of 36 weeks. Secondary outcome parameters are short term sequelae of cardiovascular failure, comorbidity and adverse events assessed during hospitalization and long-term neurodevelopmental outcome assessed at a corrected age of 2 years. Consequences regarding health economics are evaluated by cost effectiveness analysis and budget impact analysis. DISCUSSION: As a conservative approach is gaining interest, we investigate whether in preterm infants, born at a GA less than 28 weeks, with a PDA an expectative management is non-inferior to early treatment with IBU regarding to the composite outcome of mortality and/or NEC and/or BPD at a PMA of 36 weeks. TRIAL REGISTRATION: This trial is registered with the Dutch Trial Register NTR5479 (registered on 19 October 2015), the registry sponsored by the United States National Library of Medicine Clinicaltrials.gov NCT02884219 (registered May 2016) and the European Clinical Trials Database EudraCT 2017-001376-28 .

Probiotic supplementation in preterm infants does not affect the risk of retinopathy of prematurity: a meta-analysis of randomized controlled trials.

Retinopathy of prematurity (ROP) is a vascular disorder of the developing retina in preterm infants and is a leading cause of childhood blindness. Perinatal infection plays a pathogenic role in ROP. Probiotic supplementation reduces the risk of late onset sepsis (LOS) in preterm infants but it remains to be determined whether this reduction translates into a reduction of other complications. We conducted a systematic review and meta-analysis to evaluate the possible role of probiotics in altering the risk of ROP. Eleven randomized controlled trials (4250 infants; probiotics: 2121) were included in the meta-analysis that showed a significantly decreased rate of LOS with a risk ratio (RR) of 0.807 and a 95% confidence interval (CI) of 0.705 to 0.924 (P = 0.010; fixed effects model) but could not demonstrate a significant effect of probiotics on any stage ROP (RR 1.053, 95% CI 0.903 to 1.228, P = 0.508, 4 studies), or severe ROP (RR 0.841, 95% CI 0.666 to 1.063, P = 0.148, 9 studies). Meta-regression did not show any significant association between the RR for LOS and the RR for severe ROP. In conclusion, our results suggest that infection prevention by probiotics does not affect the risk of developing ROP in preterm infants.

Cooking with soyabean oil increases whole-blood α-linolenic acid in school-aged children: results from a randomized trial.

OBJECTIVE: Supply of essential n-3 PUFA is limited worldwide. While fish-oil supplementation effectively improves n-3 PUFA status, it may not be a sustainable intervention. The use of α-linolenic acid (ALA)-rich cooking oils in the household may be a suitable alternative but its effect on PUFA status is unclear. We aimed to compare the effect of providing families with soyabean oil, an ALA-rich cooking oil, v. sunflower oil on whole-blood PUFA levels of children aged 11-18 years. DESIGN: In a randomized, masked, parallel trial, we assigned families to receive a one-month supply of either soyabean or sunflower oil. Fatty acid concentrations were quantified in whole-blood samples obtained from the children before and at the end of the intervention. Changes in fatty acids were compared between treatment arms with use of linear regression for repeated measures. SUBJECTS: Sixty low- and middle-income families. SETTING: Bogotá, Colombia. RESULTS: Soyabean oil significantly increased ALA concentrations by 0.05 percentage points of total serum fatty acids whereas sunflower oil decreased them by 0.12 percentage points (soyabean v. sunflower oil effect=0.17; 95% CI 0.11, 0.24). Concentrations of both n-3 and n-6 very-long-chain PUFA, including docosapentaenoic acid, DHA, dihomo-γ-linolenic acid and arachidonic acid, increased significantly in both intervention arms. Levels of oleic acid and palmitic acid decreased, irrespective of oil assignment. Total energy or energy intake from saturated fat did not change. CONCLUSIONS: Replacing cooking oils at the household level is an effective intervention to improve essential PUFA status of children.

Trans-fatty acids in cooking oils in Bogota, Colombia: changes in the food supply from 2008 to 2013.

OBJECTIVE: Long-chain n-3 fatty acid intake in Colombia is low because fish consumption is limited. Vegetable oils with high n-3 fatty acid content are recommended, but their concentrations of trans fats were high in previous studies. Thus, regular monitoring of the fatty acid composition of vegetable oils is required. Our objective was to quantify the fatty acid composition in commercially available oils in Bogota, Colombia and determine if composition changed from 2008 to 2013. DESIGN: Cross-sectional study. We obtained samples of all commercially available oils reported in a survey of low- and middle-income families with a child participating in the Bogota School Children Cohort. SETTING: Bogota, Colombia. SUBJECTS: Not applicable. RESULTS: Sunflower oil had the highest trans-fatty acid content (2.18%). Canola oil had the lowest proportion of trans-fatty acids (0.40%) and the highest n-3 fatty acid content (9.37%). In terms of percentage reduction from 2008 to 2013 in 18:1 and 18:2 trans-fatty acids, canola oil had 89% and 65% reduction, mixed oils had 44% and 48% reduction, and sunflower oil had 25% and 51 % reduction, respectively. Soyabean oil became widely available in 2013. CONCLUSIONS: The content of trans-fatty acids decreased in all oils from 2008 to 2013, suggesting a voluntary reduction by industry. We believe that regular monitoring of the fatty acid composition of oils is warranted.

The development of a diet quality score for preschool children and its validation and determinants in the Generation R Study.

BACKGROUND: Although many studies have examined health effects of infant feeding, studies on diet quality shortly after the weaning and lactation period are scarce. OBJECTIVES: Our aims were to develop and evaluate a diet score that measures overall diet quality in preschool children and to examine the sociodemographic and lifestyle determinants of this score. METHODS: On the basis of national and international dietary guidelines for young children, we developed a diet score containing 10 components: intake of vegetables; fruit; bread and cereals; rice, pasta, potatoes, and legumes; dairy; meat and eggs; fish; oils and fats; candy and snacks; and sugar-sweetened beverages. The total score ranged from 0 to 10 on a continuous scale and was standardized to an energy intake of 1200 kcal/d with the residual method. The score was evaluated in 3629 children participating in the Generation R Study, a population-based prospective cohort study. Food consumption was assessed with a food-frequency questionnaire (FFQ) at a median age of 13 mo. RESULTS: The mean ± SD diet score was 4.1 ± 1.3. The food-based diet score was positively associated with intakes of many nutrients, including n-3 (ω-3) fatty acids [FAs; 0.25 SD increase (95% CI: 0.22, 0.27) per 1 point increase in the diet score], dietary fiber [0.32 (95% CI: 0.30, 0.34)], and calcium [0.13 (95% CI: 0.11, 0.16)], and was inversely associated with intakes of sugars [-0.28 (95% CI: -0.31, -0.26)] and saturated fat [-0.03 (95% CI: -0.05, -0.01)]. A higher diet score was associated with several health-conscious behaviors, such as maternal folic acid supplement use during pregnancy, no smoking during pregnancy, and children watching less television. CONCLUSION: We developed a novel food-based diet score for preschool children that could be applied in future studies to compare diet quality in early childhood and to investigate associations between diet in early childhood and growth, health, and development.

Vitamin A deficiency is associated with gastrointestinal and respiratory morbidity in school-age children.

Infection is an important cause of morbidity throughout childhood. Poor micronutrient status is a risk factor for infection-related morbidity in young children, but it is not clear whether these associations persist during school-age years. We examined the relation between blood concentrations of micronutrient status biomarkers and risk of gastrointestinal and respiratory morbidity in a prospective study of 2774 children aged 5-12 y from public schools in Bogotá, Colombia. Retinol, zinc, ferritin, mean corpuscular volume, hemoglobin, erythrocyte folate, and vitamin B-12 concentrations were measured in blood at enrollment into the cohort. Children were followed for 1 academic year for incidence of morbidity, including diarrhea with vomiting, cough with fever, earache or ear discharge with fever, and doctor visits. Compared with adequate vitamin A status (≥30.0 µg/dL), vitamin A deficiency (<10.0 µg/dL) was associated with increased risk of diarrhea with vomiting [unadjusted incidence rate ratio (IRR): 2.17; 95% CI: 0.95, 4.96; P-trend = 0.03] and cough with fever (unadjusted IRR: 2.36; 95% CI: 1.30, 4.31; P-trend = 0.05). After adjustment for several sociodemographic characteristics and hemoglobin concentrations, every 10 µg/dL plasma retinol was associated with 18% fewer days of diarrhea with vomiting (P < 0.001), 10% fewer days of cough with fever (P < 0.001), and 6% fewer doctor visits (P = 0.01). Every 1 g/dL of hemoglobin was related to 17% fewer days with ear infection symptoms (P < 0.001) and 5% fewer doctor visits (P = 0.009) after controlling for sociodemographic factors and retinol concentrations. Zinc, ferritin, mean corpuscular volume, erythrocyte folate, and vitamin B-12 status were not associated with morbidity or doctor visits. Vitamin A and hemoglobin concentrations were inversely related to rates of morbidity in school-age children. Whether vitamin A supplementation reduces the risk or severity of infection in children over 5 y of age needs to be determined.

Vitamin D status and TB treatment outcomes in adult patients in Tanzania: a cohort study.

OBJECTIVES: Vitamin D is an immunomodulator and can alter response to tuberculosis (TB) treatment, though randomised trials have been inconclusive to date. We present one of the first comprehensive analysis of the associations between vitamin D status and TB treatment, T-cell counts and nutritional outcomes by HIV status. DESIGN: Cohort study. SETTING: Outpatient clinics in Tanzania. PARTICIPANTS: 25-hydroxyvitamin D levels were assessed in a cohort of 677 patients with TB (344 HIV infected) initiating anti-TB treatment at enrolment in a multivitamin supplementation (excluding vitamin D) trial (Clinicaltrials.gov identifier: NCT00197704). PRIMARY AND SECONDARY OUTCOME MEASURES: Information on treatment outcomes such as failure and relapse, HIV disease progression, T-cell counts and anthropometry was collected routinely, with a median follow-up of 52 and 30 months for HIV-uninfected and HIV-infected patients, respectively. Cox and binomial regression, and generalised estimating equations were used to assess the association of vitamin D status with these outcomes. RESULTS: Mean 25-hydroxyvitamin D concentrations at enrolment were 69.8 (±21.5) nmol/L (27.9 (±8.6) ng/mL). Vitamin D insufficiency (<75 nmol/L) was associated with a 66% higher risk of relapse (95% CI 4% to 164%; 133% higher risk in HIV-uninfected patients). Each unit higher 25-hydroxyvitamin D levels at baseline were associated with a decrease of 3 (p=0.004) CD8 and 3 (p=0.01) CD3 T-cells/µL during follow-up in patients with HIV infection. Vitamin D insufficiency was also associated with a greater decrease of body mass index (BMI; -0.21 kg/m(2); 95% CI -0.39 to -0.02), during the first 8 months of follow-up. No association was observed for vitamin D status with mortality or HIV disease progression. CONCLUSIONS: Adequate vitamin D status is associated with a lower risk of relapse and with improved nutritional indicators such as BMI in patients with TB, with or without HIV infection. Further research is needed to determine the optimal dose of vitamin D and effectiveness of daily vitamin D supplementation among patients with TB.

Choline intake during pregnancy and child cognition at age 7 years.

Animal models indicate that exposure to choline in utero improves visual memory through cholinergic transmission and/or epigenetic mechanisms. Among 895 mothers in Project Viva (eastern Massachusetts, 1999-2002 to 2008-2011), we estimated the associations between intakes of choline, vitamin B12, betaine, and folate during the first and second trimesters of pregnancy and offspring visual memory (measured by the Wide Range Assessment of Memory and Learning, Second Edition (WRAML2), Design and Picture Memory subtests) and intelligence (measured using the Kaufman Brief Intelligence Test, Second Edition (KBIT-2)) at age 7 years. Mean second-trimester intakes were 328 (standard deviation (SD), 63) mg/day for choline, 10.5 (SD, 5.1) µg/day for vitamin B12, 240 (SD, 104) mg/day for betaine, and 1,268 (SD, 381) µg/day for folate. Mean age 7 test scores were 17.2 (SD, 4.4) points on the WRAML 2 Design and Picture Memory subtests, 114.3 (SD, 13.9) points on the verbal KBIT-2, and 107.8 (SD, 16.5) points on the nonverbal KBIT-2. In a model adjusting for maternal characteristics, the other nutrients, and child's age and sex, the top quartile of second-trimester choline intake was associated with a child WRAML2 score 1.4 points higher (95% confidence interval: 0.5, 2.4) than the bottom quartile (P-trend = 0.003). Results for first-trimester intake were in the same direction but weaker. Intake of the other nutrients was not associated with the cognitive tests administered. Higher gestational choline intake was associated with modestly better child visual memory at age 7 years.

Vitamin D deficiency associated with increased incidence of gastrointestinal and ear infections in school-age children.

BACKGROUND: Vitamin D deficiency (VDD) is highly prevalent among children worldwide. The effects of VDD include alterations of the immune response and increased risk of infection but little evidence exists in school-age children. We investigated the association of vitamin D status with morbidity in a prospective study of school-age children from Bogotá, Colombia. METHODS: We measured plasma 25-hydroxyvitamin D (25(OH)D) concentrations in a random sample of 475 children (mean ± standard deviation age: 8.9 ± 1.6 years) and followed them for an academic year. Caregivers were asked to record daily information on the incidence of morbidity episodes using pictorial diaries. Baseline vitamin D status was classified according to 25(OH)D concentrations as deficient (<50 nmol/L), insufficient (≥50 and <75 nmol/L) or sufficient (≥75 nmol/L). We used Poisson regression to estimate incidence rate ratios and 95% confidence intervals for days with diarrhea, vomiting, diarrhea with vomiting, cough with fever and earache or discharge with fever, comparing vitamin D-deficient with vitamin D-sufficient children. Estimates were adjusted for child's age, sex and household socioeconomic status. RESULTS: The prevalence of VDD was 10%; an additional 47% of children were vitamin D-insufficient. VDD was associated with increased rates of diarrhea with vomiting (adjusted incidence rate ratio: 2.05; 95% confidence interval: 1.19, 3.53) and earache/discharge with fever (adjusted incidence rate ratio: 2.36; 95% confidence interval: 1.26, 4.44). VDD was not significantly related to cough with fever. CONCLUSIONS: These results suggest that VDD is related to increased incidence of gastrointestinal and ear infections in school-age children. The effect of correcting VDD on reducing risk of these infections needs to be tested in supplementation trials.

Iron deficiency and anemia predict mortality in patients with tuberculosis.

Many studies have documented a high prevalence of anemia among tuberculosis (TB) patients and anemia at TB diagnosis has been associated with an increased risk of death. However, little is known about the factors contributing to the development of TB-associated anemia and their importance in TB disease progression. Data from a randomized clinical trial of micronutrient supplementation in patients with pulmonary TB in Tanzania were analyzed. Repeated measures of anemia with iron deficiency, anemia without iron deficiency, and iron deficiency without anemia were assessed as risk factors for treatment failure, TB recurrence, and mortality. The prevalence of anemia (hemoglobin < 110 g/L) at baseline was 64%, more than one-half of which was related to iron deficiency (mean corpuscular volume , 80 fL). We found no evidence of an association between anemia (with or without iron deficiency) or iron deficiency without anemia at baseline and the risk of treatment failure at 1 mo after initiation. Anemia without iron deficiency was associated with an independent, 4-fold increased risk of TB recurrence [adjusted RR = 4.10 (95% CI = 1.88, 8.91); P < 0.001]. Iron deficiency and anemia (with and without iron deficiency) were associated with a 2- to nearly 3-fold independent increase in the risk of death [adjusted RR for iron deficiency without anemia = 2.89 (95% CI = 1.53, 5.47); P = 0.001; anemia without iron deficiency = 2.72 (95% CI = 1.50, 4.93); P = 0.001; iron deficiency anemia = 2.13 (95% CI = 1.10, 4.11); P = 0.02]. Efforts to identify and address the conditions contributing to TB-associated anemia, including iron deficiency, could play an important role in reducing morbidity and mortality in areas heavily affected by TB.

Vitamin D status and its association with morbidity including wasting and opportunistic illnesses in HIV-infected women in Tanzania.

Vitamin D has a potential role in preventing HIV-related complications, based on its extensive involvement in immune and metabolic function, including preventing osteoporosis and premature cardiovascular disease. However, this association has not been examined in large studies or in resource-limited settings. Vitamin D levels were assessed in 884 HIV-infected pregnant women at enrollment in a trial of multivitamin supplementation (excluding vitamin D) in Tanzania. Information on HIV related complications was recorded during follow-up (median, 70 months). Proportional hazards models and generalized estimating equations were used to assess the relationship of vitamin D status with these outcomes. Women with low vitamin D status (serum 25-hydroxyvitamin D<32 ng/mL) had 43% higher risk of reaching a body mass index (BMI) less than 18 kg/m(2) during the first 2 years of follow-up, compared to women with adequate vitamin D levels (hazard ratio [HR]: 1.43; 95% confidence intervals: [1.03-1.99]). The relationship between continuous vitamin D levels and risk of BMI less than 18 kg/m(2) during follow-up was inverse and linear (p=0.03). Women with low vitamin D levels had significantly higher incidence of acute upper respiratory infections (HR: 1.27 [1.04-1.54]) and thrush (HR: 2.74 [1.29-5.83]) diagnosed during the first 2 years of follow-up. Low vitamin D status was a significant risk factor for wasting and HIV-related complications such as thrush during follow-up in this prospective cohort in Tanzania. If these protective associations are confirmed in randomized trials, vitamin D supplementation could represent a simple and inexpensive method to improve health and quality of life of HIV-infected patients, particularly in resource-limited settings.

Effect of vitamin supplements on HIV shedding in breast milk.

BACKGROUND: Supplementation in lactating HIV-1-infected women with preformed vitamin A and ß-carotene (VA/BC) increases the risk of mother-to-child transmission of HIV through breastfeeding. Identifying a biological mechanism to explain this unexpected finding would lend support to a causal effect. OBJECTIVE: The aim of the study was to evaluate the effect of VA/BC or multivitamin (B complex, vitamin C, and vitamin E) supplementation of HIV-infected women on HIV shedding in breast milk during the first 2 y postpartum. DESIGN: We quantified viral (cell-free) and proviral (cell-associated) HIV loads in breast-milk samples collected ≤15 d after delivery and every 3 mo thereafter from 594 Tanzanian HIV-1-infected women who participated in a randomized trial. Women received 1 of the following 4 daily oral regimens in a 2 × 2 factorial fashion during pregnancy and throughout the first 2 y postpartum: multivitamin, VA/BC, multivitamin including VA/BC, or placebo. RESULTS: The proportion of breast-milk samples with detectable viral load was significantly higher in women who received VA/BC (51.3%) than in women who were not assigned to VA/BC (44.8%; P = 0.02). The effect was apparent ≥6 mo postpartum (relative risk: 1.34; 95% CI: 1.04, 1.73). No associations with proviral load were observed. The multivitamin had no effects. In observational analyses, ß-carotene but not retinol breast-milk concentrations were significantly associated with an increased viral load in milk. CONCLUSIONS: VA/BC supplementation in lactating women increases the HIV load in breast milk. This finding contributes to explaining the adverse effect of VA/BC on mother-to-child transmission. ß-Carotene appears to have an effect on breast-milk viral load, independent of preformed vitamin A. This trial was registered at clinicaltrials.gov as NCT00197756.

Vitamin supplementation increases risk of subclinical mastitis in HIV-infected women.

Subclinical mastitis is common in HIV-infected women and is a risk factor for mother-to-child transmission of HIV. The purpose of this study was to examine the effect of vitamin supplementation [vitamin A + ß-carotene, multivitamins (B complex, C, and E), or multivitamins, including vitamin A + ß-carotene] on the risk of subclinical mastitis during the first 2 y postpartum among HIV-infected women. The study was a randomized, placebo-controlled, clinical trial including 674 HIV-infected, antiretroviral naïve Tanzanian women who were recruited during pregnancy and followed-up after delivery. Breast milk samples were obtained approximately every 3 mo. Any subclinical mastitis was defined as a ratio of the sodium to potassium (Na:K) breast milk concentrations > 0.6 and further classified as either moderate (Na:K ≥ 0.6 and ≤ 1) or severe (Na:K > 1.0). Fifty-eight percent of women had at least 1 episode of any subclinical mastitis. Women assigned to multivitamins (B complex, C, and E) had a 33% greater risk of any subclinical mastitis (P = 0.005) and a 75% greater risk of severe subclinical mastitis (P = 0.0006) than women who received the placebo. Vitamin A + ß-carotene also increased the risk of severe subclinical mastitis by 45% (P = 0.03). Among women with CD4+ T-cell counts ≥ 350 cells/µL, multivitamin intake resulted in a 49% increased risk of any subclinical mastitis (P = 0.006); by contrast, there were no treatment effects among women with CD4+ T-cell counts < 350 cells/µL (P- interaction for treatment × CD4+ T-cell count = 0.10). Supplementation of HIV-infected women with vitamins increased the risk of subclinical mastitis.

Zinc supplementation in children is not associated with decreases in hemoglobin concentrations.

Zinc supplementation has proven beneficial in the treatment of acute child diarrhea and appears to enhance linear growth. There is a theoretical risk of anemia in zinc-supplemented children due to inhibited iron transport via decreased copper absorption. Although many zinc supplementation trials have included hematological measures, the potential effect of zinc on these outcomes has not been quantitatively evaluated in a comprehensive review. We performed a systematic review of randomized trials that examined the effect of zinc supplementation on hemoglobin concentrations in apparently healthy children ages 0-15 y and conducted a random effects meta-analysis of weighted mean differences (WMD) of change in hemoglobin concentrations before and after supplementation. Twenty-one randomized, controlled trials representing 3869 participants were included in the meta-analysis. The duration of treatment ranged from 4 to 15 mo; doses were typically 10-20 mg/d. Zinc supplementation did not affect changes in hemoglobin concentrations (pooled WMD: 0.8 g/L; 95% CI: -0.6, 2.2; P = 0.27). There was no evidence for effect modification by age, zinc dosage, duration of treatment, type of control, baseline hemoglobin status, geographical or healthcare setting, or quality of the studies. These results suggest that zinc supplementation at doses typically used in randomized trials is a safe intervention with regards to hemoglobin concentrations. Some benefits might exist among children with severe anemia or zinc deficiency, which warrant further evaluation.