Higher Dietary Intake of Animal Protein Foods in Pregnancy Is Associated with Lower Risk of Adverse Birth Outcomes.

BACKGROUND: The prevalence of adverse birth outcomes is highest in resource-limited settings such as sub-Saharan Africa. Maternal consumption of diets with adequate nutrients during pregnancy may protect against these adverse outcomes. OBJECTIVES: The objective was to determine the association between maternal dietary consumption of animal source foods (ASFs) and the risk of adverse birth outcomes among HIV-negative pregnant women in Tanzania. METHODS: Using dietary intake data from 7564 HIV-negative pregnant women, we used Poisson regression with the empirical variance (generalized estimating equation) to estimate the RR of adverse birth outcomes-preterm birth, very preterm birth, small for gestational age (SGA), low birth weight (LBW), stillbirth, and neonatal death-for higher and lower frequency of ASF intake. RESULTS: Median daily dietary intake of animal protein was 17 g (IQR: 1-48 g). Higher frequency of ASF protein intake was associated with lower risk of neonatal death (quartile 4 compared with quartile 1; RR: 0.59; 95% CI: 0.38, 0.90; P-trend = 0.01). Higher fish intake was associated with lower risk of very preterm birth (high tertile compared with low; RR: 0.76; 95% CI: 0.58, 0.99; P-trend = 0.02). Any meat intake was protective of preterm birth (RR: 0.73; 95% CI: 0.65, 0.82; P < 0.001), very preterm birth (P < 0.001), LBW (P < 0.001), and neonatal death (P = 0.01) but was associated with increased risk of SGA (RR:1.19; 95% CI: 1.01, 1.36; P = 0.04). Any egg intake was protective of very preterm birth (RR: 0.50; 95% CI: 0.31, 0.83; P = 0.01) as compared with no egg intake. Finally, any dairy intake was associated with lower risk of preterm birth (RR: 0.82; 95% CI: 0.68, 0.98; P = 0.03) and very preterm birth (RR: 0.53; 95% CI: 0.34, 0.84; P = 0.01). CONCLUSIONS: Higher frequency of dietary intake of ASF is associated with lower risk of adverse birth outcomes in urban Tanzania. Promoting prenatal dietary intake of ASF may improve birth outcomes in this region and similar resource-limited settings.

Effects of prenatal and postnatal maternal multiple micronutrient supplementation on child growth and morbidity in Tanzania: a double-blind, randomized-controlled trial.

BACKGROUND: Maternal micronutrient status is critical for child growth and nutrition. It is unclear whether maternal multiple micronutrient supplementation (MMS) during pregnancy and lactation improves child growth and prevents child morbidity. METHODS: This study aimed to determine the effects of prenatal and postnatal maternal MMS on child growth and morbidity. In this double-blind, randomized-controlled trial, 8428 HIV-negative pregnant women were enrolled from Dar es Salaam, Tanzania, between 2001 and 2004. From pregnancy (12-27 weeks of gestation) through to 6 weeks postpartum, participants were randomized to receive daily oral MMS or placebo. All women received daily iron and folic acid during pregnancy. From 6 weeks postpartum through to 18 months postpartum, 3100 women were re-randomized to MMS or placebo. Child-growth measures, haemoglobin concentrations and infectious morbidities were assessed longitudinally from birth to ≤18 months. RESULTS: Prenatal MMS led to modest increases in weight-for-age z-scores (mean difference: 0.050; 95% confidence interval: 0.002, 0.099; p = 0.04) and length-for-age z-score (mean difference: 0.062; 95% confidence interval: 0.013, 0.111; p = 0.01) during the first 6 months of life but not thereafter. Prenatal or postnatal MMS did not have benefits for other child outcomes. CONCLUSIONS: Whereas maternal MMS is a proven strategy to prevent adverse birth outcomes, other approaches may also need to be considered to curb the high burdens of child morbidity and growth faltering.

Impaired Hematological Status Increases the Risk of Mortality among HIV-Infected Adults Initiating Antiretroviral Therapy in Tanzania.

BACKGROUND: Hematological status may predict HIV disease progression and mortality among adults initiating highly active antiretroviral therapy (HAART). OBJECTIVES: We aimed to examine the relation of anemia and iron status at HAART initiation with survival and morbidity outcomes. METHODS: We conducted a case-cohort study of 570 HIV-infected adults initiating HAART who were enrolled in a trial of multivitamins in Tanzania. Hemoglobin, serum ferritin, and hepcidin concentrations were assessed at HAART initiation and participants were followed up monthly. We adjusted serum ferritin for inflammation using a regression correction method to characterize hematological status. Cox proportional hazards models were used to estimate HRs for mortality and incident clinical outcomes. RESULTS: We found an 83% prevalence of anemia, 15% prevalence of iron deficiency anemia, and 66% prevalence of anemia of chronic diseases (ACD). The prevalence of elevated iron was 33% and 19% had iron deficiency (ID). After multivariate adjustment, severe anemia (HR: 2.57; 95% CI: 1.49, 4.45) and ACD (HR: 4.71; 95% CI: 2.91, 7.62) were associated with increased risk of mortality as compared with nonanemic participants. In addition, both ID (HR: 2.65; 95% CI: 1.08, 7.78) and elevated iron (HR: 2.83; 95% CI: 2.10, 3.82) were associated with increased risk of mortality as compared with normal iron concentrations. Severe anemia and elevated iron concentrations were associated with incident wasting and >10% weight loss (P values <0.05). CONCLUSIONS: Anemia and both ID and elevated iron were associated with increased mortality among HIV-infected adults initiating HAART. Safety and efficacy studies including anemia etiology, timing of HAART initiation, and dose of iron supplementation among HIV patients appear warranted.This trial was registered at clinicaltrials.gov as NCT00383669.

Maternal dietary diversity and dietary quality scores in relation to adverse birth outcomes in Tanzanian women.

BACKGROUND: Preterm birth (PTB), small for gestational age (SGA), and low birth weight (LBW) are risk factors for morbidity and mortality among infants. High-quality maternal diets during pregnancy may protect against these adverse birth outcomes. OBJECTIVES: The aim of this study was to prospectively examine the association of maternal dietary diversity and quality during pregnancy with birth outcomes among women in Dar es Salaam, Tanzania. METHODS: We analyzed data from 7553 HIV-negative pregnant women enrolled in a multivitamin trial at 12-27 weeks of gestation. Dietary intake was assessed using 24-h dietary recalls. Dietary diversity scores (DDS; range: 0-10) were computed as the number of food groups consumed by women, using FAO's Minimum Dietary Diversity for Women index. The Prime Diet Quality Score (PDQS; range: 0-42) assessed maternal diet quality based on consumption of 21 healthy and unhealthy food groups. Log binomial regression methods were used to assess associations of DDS and PDQS with PTB, SGA, LBW, and fetal loss. RESULTS: In the previous 24 h, 99.9% of all women had consumed cereal and staples, 57.9% meats, 4.7% eggs, and 0.5% nuts and seeds. Median DDS was 3.0 (IQR: 2.5-3.5). For the PDQS, all women consumed ≥4 servings/wk of green leafy vegetables and refined grains. Higher DDS was associated with lower risk of SGA (RR highest compared with lowest quintile: 0.74; 95% CI: 0.62, 0.89). Higher PDQS was associated with lower risk of PTB (RR highest compared with lowest quintile: 0.55; 95% CI: 0.46, 0.66), LBW (RR: 0.53; 95% CI: 0.40, 0.70), and fetal loss (RR: 0.53; 95% CI, 0.34, 0.82). CONCLUSIONS: PDQS was inversely associated with PTB, LBW, and fetal loss, and DDS was inversely associated with SGA. These findings suggest that in addition to dietary diversity, diet quality should be considered as important in understanding dietary risk factors for poor birth outcomes.This trial was registered at clinicaltrials.gov as NCT00197548.

Vitamin B12 is Low in Milk of Early Postpartum Women in Urban Tanzania, and was not Significantly Increased by High dose Supplementation.

The effect of maternal multivitamin supplementation on breast milk vitamin B12 concentrations has not been examined in Tanzania, where the prevalence of maternal plasma B12 insufficiency is 25.6%. Multivitamins (containing 50 µg vitamin B12) or placebo were provided during pregnancy and in the postpartum period. Breast milk samples were collected at or around six weeks postpartum from 491 participants in a trial of multivitamins (NCT00197548). Linear and logistic regression models were used to examine the effect of supplements on vitamin B12 concentration in milk and its associations with other variables including potential confounders. Median vitamin B12 concentration in breast milk was 206 pmol/L and 70% of women had levels indicating inadequacy (<310 pmol/L). Multivitamin supplements did not significantly reduce the odds of inadequate vitamin B12 in breast milk, suggesting suboptimal absorption. A single unit increase in maternal hemoglobin at six weeks was associated with 18% lower odds of inadequate vitamin B12 in breast milk. Participants with higher BMI at baseline had double the odds of having inadequate vitamin B12 than the reference group (<22 kg/m2). Trials to determine the optimal dose, route, and duration of supplementation to improve maternal B12 status in Sub-Saharan Africa are of utmost importance.

Breast milk vitamin B12 concentration and incidence of diarrhea and respiratory infections among infants in urban Tanzania: a prospective cohort study.

OBJECTIVE: A recent trial of vitamin B12 supplementation among Indian children 6-30 months found no effect on the incidence of diarrhea and respiratory infections. These results differ with studies in adults that showed improvement of the immune response following treatment with vitamin B12. We sought to determine how the adequacy of vitamin B12 concentrations in breast milk could act as immune modulator and protect against the incidence of diarrhea and respiratory infections of children up to 18 months in urban Tanzania. RESULTS: A prospective cohort study was undertaken to determine the association of breast milk vitamin B12 concentration with the incidence of acute respiratory infection and diarrhea among infants in urban Tanzania. A random sample of 491 women enrolled in a trial of multivitamins provided milk for B12 analysis at or around 6 weeks postpartum. Of 491 women, 345 had breast milk vitamin B12 inadequacy (< 310 pmol/L). Using generalized estimating equations, we found no overall association of milk vitamin B12 concentration with incident diarrhea and acute respiratory infections in infants. Studies measuring longitudinal changes of breast milk B12 concentration over time are needed to clarify the role of breast milk vitamin B12 in childhood infections.

Hemoglobin and hepcidin have good validity and utility for diagnosing iron deficiency anemia among pregnant women.

BACKGROUND/OBJECTIVES: Screening and diagnosis of iron deficiency anemia (IDA) is cumbersome as it may require testing for hemoglobin, ferritin, and an inflammatory biomarker. The aim of this study was to compare the diagnostic capacity of hematologic biomarkers to detect IDA among pregnant women in Tanzania. SUBJECTS/METHODS: We pooled data from an iron supplementation trial of 1500 iron-replete pregnant woman and a prospective cohort of 600 iron-deficient pregnant women. Receiver operating characteristic curves (ROC) for hematologic biomarkers were used to assess the sensitivity, specificity, and area under the curve (AUC) for iron deficiency (ID) and iron deficiency anemia (IDA), crude, or corrected for inflammation. Regression models assessed the relationship of baseline biomarker categories (gestational age <27 weeks) and IDA at delivery. RESULTS: Hemoglobin had the largest AUC for crude ID (0.96), while hepcidin had the largest AUC for corrected ID (0.80). The optimal hepcidin cutoff for the diagnosis of corrected IDA based on maximal sensitivity and specificity was ≤1.6 µg/L. An hepcidin cutoff of <4.3 µg/L had a sensitivity of 95% for regression-corrected ID. Among iron-replete women who did not receive iron, the association of baseline hemoglobin >110 g/L with IDA at delivery (RR = 0.73; 95% CI: 0.47, 1.13) was attenuated. Baseline hepcidin >1.6 µg/L was associated with reduced risk of anemia at delivery by 49% (95% CI: 27%, 45%). CONCLUSIONS: Ascertaining hemoglobin and hepcidin levels may improve the targeting of iron supplementation programs in resource-limited countries, though hepcidin's high costs may limit its use.

Prenatal Zinc and Vitamin A Reduce the Benefit of Iron on Maternal Hematologic and Micronutrient Status at Delivery in Tanzania.

BACKGROUND: Zinc and vitamin A supplementation have both been shown to affect iron status, hemoglobin (Hb) concentration, and anemia in animal and human studies. However, evidence on their combined use in pregnancy, in the context of iron-folic acid (IFA) supplementation, remains limited. OBJECTIVE: This study determined the effects of prenatal zinc, vitamin A, and iron supplementation on maternal hematologic and micronutrient status at delivery in Tanzania. METHODS: We analyzed 2 large randomized controlled trials, using generalized estimating equations, and examined the effect of daily zinc (25 mg) and vitamin A (2500 IU) supplementation starting in the first trimester of pregnancy compared with placebo (n = 2500), and separately evaluated the safety and efficacy of daily iron (60 mg) supplementation among iron-replete pregnant women (n = 1500). Blood samples from baseline and delivery were tested for Hb, serum ferritin, soluble transferrin receptor, plasma zinc, and zinc protoporphyrin. RESULTS: Zinc and vitamin A supplementation were associated with lower Hb concentrations at delivery of  -0.26 g/dL (95% CI: -0.50, -0.02 g/dL) and -0.25 g/dL (95% CI: -0.49, -0.01 g/dL), respectively. Vitamin A increased mean ferritin concentrations at delivery (14.3 µg/L, 95% CI: 1.84, 29.11 µg/L), but was associated with increased risk of severe anemia (RR: 1.41; 95% CI: 1.06, 1.88). Among women who were iron replete at baseline, iron supplementation reduced the risk of iron depletion at delivery by 47% (RR: 0.53; 95% CI: 0.43, 0.65). There was no effect of zinc or iron supplements on plasma zinc concentrations. CONCLUSIONS: Our findings support existing WHO guidelines on prenatal iron, vitamin A, and zinc supplementation among pregnant women. In this setting, scaling uptake of prenatal iron supplements is warranted, but prenatal zinc and vitamin A supplementation did not benefit maternal hematologic status at delivery. In settings where vitamin A deficiency is endemic, the efficacy and safety of the WHO recommended prenatal vitamin A supplementation require further evaluation.

Factors associated with plasma n-3 and n-6 polyunsaturated fatty acid levels in Tanzanian infants.

BACKGROUND/OBJECTIVES: To identify factors associated with plasma polyunsaturated fatty acid (PUFA) levels among 3-month-old Tanzanian infants. SUBJECTS/METHODS: Infants (n = 238) and mothers (n = 193) randomly selected from participants in the neonatal vitamin A supplementation randomized controlled trial. A cross-sectional study of maternal-infant pairs at 3 months postpartum. RESULTS: All infant total, n-3, n-6, and individual PUFA levels were correlated with maternal levels. Infant plasma n-3 PUFA levels were higher when maternal n-3 PUFA levels were higher (mean difference in infant % fatty acid per unit increase in maternal levels ± standard error: 0.79 ± 0.08; P < 0.01). Infant plasma docosahexaenoic acid (DHA) levels were positively associated with maternal DHA levels (0.77 ± 0.09; P < 0.01) but were lower for twin births (-0.55 ± 0.27; P = 0.03). Greater birth weight in kilograms (1.00 ± 0.43; P = 0.02) and higher maternal n-6 PUFA levels (0.20 ± 0.07; P < 0.01) were positively associated with higher infant n-6 PUFA levels, whereas maternal mono-unsaturated fatty acid (MUFA) levels (-0.26 ± 0.08; P < 0.01), maternal mid upper arm circumference (MUAC) (-0.22 ± 0.11; P = 0.04), and male sex (-0.99 ± 0.45; P = 0.03) were associated with lower infant plasma n-6 PUFA levels. Infant plasma arachidonic acid (AA) levels were positively associated with maternal plasma AA levels (0.38 ± 0.09; P < 0.01), but inversely associated with twin births (-1.37 ± 0.67; P = 0.04). CONCLUSIONS: Greater birth weight and higher maternal plasma PUFA levels at 3 months postpartum were significantly associated with higher infant plasma PUFA levels at 3 months age. Twin births, male sex, and higher maternal MUFA levels were associated with lower infant plasma PUFA levels. Nutrition counseling for optimal intake of PUFA-rich foods, to lactating mothers in resource-limited settings may be beneficial for improved infant health.

Anemia, Iron Deficiency, and Iron Supplementation in Relation to Mortality among HIV-Infected Patients Receiving Highly Active Antiretroviral Therapy in Tanzania.

Anemia in HIV-infected patients improves with highly active antiretroviral therapy (HAART); however, it may still be associated with mortality among patients receiving treatment. We examined the associations of anemia severity and iron deficiency anemia (IDA) at HAART initiation and during monthly prospective follow-up with mortality among 40,657 adult HIV-infected patients receiving HAART in Dar es Salaam, Tanzania. Proportional hazards models were used to examine the associations of anemia severity and IDA at HAART initiation and during follow-up with mortality. A total of 6,261 deaths were reported. Anemia severity at HAART initiation and during follow-up was associated with an increasing risk of mortality (trend tests P < 0.001). There was significantly higher mortality risk associated with IDA at HAART initiation and during follow-up versus no anemia or iron deficiency (both P < 0.001). These associations differed significantly by gender, body mass index, and iron supplement use (all interaction test P < 0.001). The magnitude of association was stronger among men. Mortality risk with severe anemia was 13 times greater versus no anemia among obese patients, whereas it was only two times greater among underweight patients. Higher mortality risk was observed among iron supplement users, irrespective of anemia severity. Anemia and IDA were significantly associated with a higher mortality risk in patients receiving HAART. Iron supplementation indicated an increased mortality risk, and its role in HIV infections should be examined in future studies. Given the low cost of assessing anemia, it can be used frequently to identify high-risk patients in resource-limited settings.

Effectiveness of a multivitamin supplementation program among HIV-infected adults in Tanzania.

OBJECTIVE: The objective of this study was to assess the effectiveness of a routine multivitamin supplementation program for adults living with HIV in Tanzania. DESIGN: We conducted a retrospective cohort study of 67 707 adults enrolled in the Dar es Salaam HIV care and treatment program during 2004-2012. METHODS: The Dar es Salaam HIV care and treatment program intended to provide all adult patients with multivitamin supplements (vitamins B-complex, C, and E) free of charge; however, intermittent stockouts and other implementation issues did not afford universal coverage. We use Cox proportional hazard models to assess the time-varying association of multivitamin supplementation with mortality and clinical outcomes. RESULTS: The study cohort contributed 41 540 and 129 315 person-years of follow-up time to the antiretroviral therapy (ART)-naive and ART-experienced analyses, respectively. Among 48 207 ART-naive adults, provision of multivitamins reduced the risk of mortality [adjusted hazard ratio (aHR): 0.69; 95% confidence interval (CI): 0.59-0.81], incident tuberculosis (TB) (aHR: 0.83; 0.76-0.91), and meeting ART eligibility criteria (aHR: 0.78; 95% CI: 0.73-0.83) after adjustment for time-varying confounding. Among 46 977 ART-experienced patients, multivitamins reduced mortality (hazard ratio: 0.86; 95% CI: 0.80-0.92), incident TB (aHR: 0.78; 95% CI: 0.73-0.84), and immunologic failure (aHR: 0.70; 95% CI: 0.67-0.73). The survival benefits associated with provision multivitamins appeared to be greatest during the first year of ART and declined over time (P value <0.001). CONCLUSION: Multivitamin supplementation appears to be a simple, effective, safe, and scalable program to improve survival, reduce incidence of TB, and improve treatment outcomes for adult HIV patients in Tanzania.

Dietary iron and calcium intakes during pregnancy are associated with lower risk of prematurity, stillbirth and neonatal mortality among women in Tanzania.

OBJECTIVE: Prematurity, stillbirth and other adverse birth outcomes remain major concerns in resource-limited settings. Poor dietary intake of micronutrients during pregnancy has been associated with increased risk of adverse outcomes. We determined the relationships between dietary Fe and Ca intakes during pregnancy and risks of adverse birth outcomes among HIV-negative women. DESIGN: Women's diet was assessed through repeated 24 h diet recalls in pregnancy. Mean intakes of total Fe, Fe from animal sources and Ca during pregnancy were examined in relation to adverse birth outcomes and neonatal mortality. Women were prescribed daily Fe supplements as per standard perinatal care. SETTING: Dar es Salaam, Tanzania. SUBJECTS: A cohort of 7634 pregnant women. RESULTS: Median (interquartile range) daily dietary intake of total Fe, animal Fe and Ca was 11·9 (9·3-14·7), 0·5 (0-1·1) and 383·9 (187·4-741·2) mg, respectively. Total Fe intake was significantly associated with reduced risk of stillbirth (trend over quartiles, P=0·010). Animal Fe intake was significantly associated with reduced risk of preterm birth and extreme preterm birth. Animal Fe intake was inversely related to neonatal mortality risk; compared with women in the lowest intake quartile, those in the top quartile were 0·51 times as likely to have neonatal death (95 % CI 0·33, 0·77). Higher Ca intake was associated with reduced risk of preterm birth (relative risk; 95 % CI: 0·76; 0·65, 0·88) and extreme preterm birth (0·63; 0·47, 0·86). Women in the highest Ca intake quartile had reduced risk of neonatal mortality (0·59; 0·37, 0·92). CONCLUSIONS: Daily dietary Fe and Ca intakes among pregnant women are very low. Improvement of women's diet quality during gestation is likely to improve the risks of adverse birth outcomes.

Multivitamin and iron supplementation to prevent periconceptional anemia in rural tanzanian women: a randomized, controlled trial.

OBJECTIVE: Women's nutritional status during conception and early pregnancy can influence maternal and infant outcomes. This study examined the efficacy of pre-pregnancy supplementation with iron and multivitamins to reduce the prevalence of anemia during the periconceptional period among rural Tanzanian women and adolescent girls. DESIGN: A double-blind, randomized controlled trial was conducted in which participants were individually randomized to receive daily oral supplements of folic acid alone, folic acid and iron, or folic acid, iron, and vitamins A, B-complex, C, and E at approximately single recommended dietary allowance (RDA) doses for six months. SETTING: Rural Rufiji District, Tanzania. SUBJECTS: Non-pregnant women and adolescent girls aged 15-29 years (n = 802). RESULTS: The study arms were comparable in demographic and socioeconomic characteristics, food security, nutritional status, pregnancy history, and compliance with the regimen (p>0.05). In total, 561 participants (70%) completed the study and were included in the intention-to-treat analysis. Hemoglobin levels were not different across treatments (median: 11.1 g/dL, Q1-Q3: 10.0-12.4 g/dL, p = 0.65). However, compared with the folic acid arm (28%), there was a significant reduction in the risk of hypochromic microcytic anemia in the folic acid and iron arm (17%, RR: 0.61, 95% CI: 0.42-0.90, p = 0.01) and the folic acid, iron, and multivitamin arm (19%, RR: 0.66, 95% CI: 0.45-0.96, p = 0.03). Inverse probability of treatment weighting (IPTW) to adjust for potential selection bias due to loss to follow-up did not materially change these results. The effect of the regimens was not modified by frequency of household meat consumption, baseline underweight status, parity, breastfeeding status, or level of compliance (in all cases, p for interaction>0.2). CONCLUSIONS: Daily oral supplementation with iron and folic acid among women and adolescents prior to pregnancy reduces risk of anemia. The potential benefits of supplementation on the risk of periconceptional anemia and adverse pregnancy outcomes warrant investigation in larger studies. TRIAL REGISTRATION: ClinicalTrials.gov NCT01183572.

Dietary patterns, nutrient intake, and sociodemographic characteristics in HIV-infected Tanzanian pregnant women.

Routinely collected dietary intakes were available for 925 HIV-infected pregnant women participating in a longitudinal clinical trial of vitamin supplementation in Dar es Salaam, Tanzania. Information on sociodemographic and economic characteristics was recorded. Dietary macronutrient intakes were computed and analyzed using the Tanzania Food Composition Tables. Women's age, parity, education level, and economic independence were positively related to diet intake. Women younger than 25 years were at highest risk of inadequate food and nutrient intake. By World Health Organization recommendations, almost two-thirds of the participants were energy deficient, and nearly half were protein deficient.

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.

Sex differences in the effects of maternal vitamin supplements on mortality and morbidity among children born to HIV-infected women in Tanzania.

We examined whether there are sex differences in the effect of vitamin supplements on birth outcomes, mortality and morbidity by 2 years of age among children born to HIV-infected women in Tanzania. A randomised placebo-controlled trial was conducted among 959 mother-infant pairs. HIV-infected pregnant women were randomly assigned to receive a daily oral dose of one of four regimens: multivitamins (vitamins B-complex, C and E), vitamin A plus beta-carotene, multivitamins including vitamin A plus beta-carotene or placebo. Supplements were administered during pregnancy and continued after delivery. The beneficial effect of multivitamins on decreasing the risk of low birth weight was stronger among girls (relative risks (RR) = 0.39, 95 % CI 0.22, 0.67) than among boys (RR = 0.81, 95 % CI 0.44, 1.49; P for interaction = 0.08). Maternal multivitamin supplements resulted in 32 % reduction in mortality among girls (RR = 0.68, 95 % CI 0.47, 0.97), whereas no effect was found among boys (RR = 1.20, 95 % CI 0.80, 1.78; P for interaction = 0.04). Multivitamins had beneficial effects on the overall risks of diarrhoea that did not differ by sex. Vitamin A plus beta-carotene alone increased the risk of HIV transmission, but had no effects on mortality, and we found no sex differences in these effects. Sex differential effects of multivitamins on mortality may be due to sex-related differences in the immunological or genetic factors. More research is warranted to examine the effect of vitamins by sex and better understand biological mechanisms mediating such effects.

Vitamin D status of HIV-infected women and its association with HIV disease progression, anemia, and mortality.

BACKGROUND: Vitamin D has a potential role in slowing HIV disease progression and preventing mortality based on its extensive involvement in the immune system; however, this relationship has not been examined in large studies or in resource-limited settings. METHODOLOGY/PRINCIPAL FINDINGS: Vitamin D levels were assessed in 884 HIV-infected pregnant women at enrollment in a trial of multivitamin supplementation (not including vitamin D) in Tanzania. Women were followed up for a median of 69.5 months, and information on hemoglobin levels, HIV disease progression, and mortality was recorded. Proportional hazard models and generalized estimating equations were used to assess the relationship of these outcomes with vitamin D status. CONCLUSIONS/SIGNIFICANCE: Low vitamin D status (serum 25-hydroxyvitamin D<32 ng/mL) was significantly associated with progression to WHO HIV disease stage III or greater in multivariate models (incidence rate ratio [RR]: 1.25; 95% confidence intervals [CI]: 1.05, 1.50). No significant relationship was observed between vitamin D status and T-cell counts during follow-up. Women with low vitamin D status had 46% higher risk of developing severe anemia during follow-up, compared to women with adequate vitamin D levels (RR: 1.46; 95% CI: 1.09, 1.96). Women in the highest vitamin D quintile had a 42% lower risk of all-cause mortality, compared to the lowest quintile (RR: 0.58; 95% CI: 0.40, 0.84). Vitamin D status had a protective association with HIV disease progression, all-cause mortality, and development of anemia during follow-up in HIV-infected women. If confirmed in randomized trials, vitamin D supplementation could represent a simple and inexpensive method to prolonging the time to initiation of antiretroviral therapy in HIV-infected patients, particularly in resource-limited settings.

Perinatal outcomes, including mother-to-child transmission of HIV, and child mortality and their association with maternal vitamin D status in Tanzania.

BACKGROUND: Vitamin D is a strong immunomodulator and may protect against adverse pregnancy outcomes, mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV), and child mortality. METHODS: A total of 884 HIV-infected pregnant women who were participating in a vitamin supplementation trial in Tanzania were monitored to assess pregnancy outcomes and child mortality. The association of these outcomes with maternal vitamin D status at enrollment was examined in an observational analysis. RESULTS: No association was observed between maternal vitamin D status and adverse pregnancy outcomes, including low birth weight and preterm birth. In multivariate models, a low maternal vitamin D level (<32 ng/mL) was associated with a 50% higher risk (95% confidence interval [CI], 2%-120%) of MTCT of HIV at 6 weeks, a 2-fold higher risk of MTCT of HIV through breast-feeding among children who were HIV uninfected at 6 weeks (95% CI, 1.08-3.82), and a 46% higher overall risk of HIV infection (95% CI, 11%-91%). Children born to women with a low vitamin D level had a 61% higher risk of dying during follow-up (95% CI, 25%-107%). CONCLUSIONS: If found to be efficacious in randomized trials, vitamin D supplementation could prove to be an inexpensive method of reducing the burden of HIV infection and death among children, particularly in resource-limited settings.

Effect of selenium supplements on hemoglobin concentration and morbidity among HIV-1-infected Tanzanian women.

Selenium deficiency may increase risks of anemia and morbidity among people with human immunodeficiency virus infection. We therefore investigated the effect of selenium supplements (200 microg of selenomethionine) on these end points among 915 pregnant Tanzanian women. Hemoglobin concentration was measured at baseline (at 12-27 weeks of gestation) and at 6 weeks and 6 months postpartum, and morbidity data were collected during monthly visits to the clinic. Selenium supplements had no effect on hemoglobin concentrations during follow-up (mean difference, 0.05 g/dL; 95% confidence interval, -0.07 to 0.16 g/dL) but reduced diarrheal morbidity risk by 40% (relative risk, 0.60; 95% confidence interval, 0.42-0.84). There was no effect on the other morbidity end points.

Effect of vitamin A and zinc supplementation on gastrointestinal parasitic infections among Mexican children.

OBJECTIVE: Gastrointestinal parasites continue to be an important cause of morbidity and stunting among children in developing countries. We evaluated the effect of vitamin A and zinc supplementation on infections by Giardia lamblia, Ascaris lumbricoides, and Entamoeba histolytica. METHODS: A randomized, double-blind, placebo-controlled trial was conducted among 707 children who were 6 to 15 months of age and from periurban areas of Mexico City, Mexico, between January 2000 and May 2002. Children, who were assigned to receive either vitamin A every 2 months, a daily zinc supplement, a combined vitamin A and zinc supplement, or a placebo, were followed for 1 year. The primary end points were the 12-month rates and durations of infection for the 3 parasites and rates of parasite-associated diarrheal disease as determined in stools collected once a month and after diarrheal episodes. RESULTS: G. lamblia infections were reduced and A. lumbricoides infections increased among children in the combined vitamin A and zinc group or the zinc alone group, respectively. Durations of Giardia infections were reduced among children in all 3 treatment arms, whereas Ascaris infections were reduced in the vitamin A and zinc group. In contrast, E. histolytica infection durations were longer among zinc-supplemented children. Finally, E. histolytica- and A. lumbricoides-associated diarrheal episodes were reduced among children who received zinc alone or a combined vitamin A and zinc supplement, respectively. CONCLUSIONS: We found that vitamin A and zinc supplementation was associated with distinct parasite-specific health outcomes. Vitamin A plus zinc reduces G. lamblia incidence, whereas zinc supplementation increases A. lumbricoides incidence but decreases E. histolytica-associated diarrhea.