Person:

Sudfeld, Christopher

Background: HIV-infected adults initiating antiretroviral therapy (ART) in sub-Saharan Africa continue to experience high rates of morbidity and mortality during the initial months of treatment. Observational studies in high-income and resource-limited settings indicate that HIV-infected adults with low vitamin D levels may be at increased risk of mortality, HIV disease progression, and incidence of pulmonary tuberculosis (TB). As a result, vitamin D3 supplementation may improve survival and treatment outcomes for HIV-infected adults initiating ART. Methods/Design The Trial of Vitamins-4 (ToV4) is an individually randomized, double-blind, placebo-controlled trial of vitamin D3 (cholecalciferol) supplementation conducted among 4000 HIV-infected adults with low vitamin D levels [25-hydroxyvitamin D (25(OH)D) <30 ng/mL] initiating ART in Dar es Salaam, Tanzania. The two primary aims of the trial are to determine the effect of a vitamin D3 supplementation regimen on incidence of (1) mortality and (2) pulmonary TB as compared to a matching placebo regimen. The primary safety outcome of the study is incident hypercalcemia. The investigational vitamin D3 regimen consists of oral supplements containing 50,000 IU vitamin D3 taken under direct observation at randomization and once a week for 3 weeks (four doses) followed by daily oral supplements containing 2000 IU vitamin D3 taken at home from the fourth week until trial discharge at 1 year post ART initiation. Trial participants are followed up at weekly clinic visits during the first month of ART and at monthly clinic visits thereafter until trial discharge at 1 year post ART initiation. Secondary aims of the trial are to examine the effect of the vitamin D3 regimen on CD4 T cell reconstitution, incidence of non-TB comorbidities, body mass index (BMI), depression and anxiety, physical activity, bone health, and immunologic biomarkers. Discussion The ToV4 will provide causal evidence on the effect of vitamin D3 supplementation on incidence of pulmonary TB and mortality among HIV-infected Tanzanian adults initiating ART. The trial will also give insight to whether vitamin D3 supplementation trials for the prevention of pulmonary TB should be pursued in HIV-uninfected populations. Trial registration ClinicalTrials.gov, NCT01798680. Registered on 21 February 2013. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-1819-5) contains supplementary material, which is available to authorized users.

Background: Few studies have differentiated risk factors for term-small for gestational age (SGA), preterm-appropriate for gestational age (AGA), and preterm-SGA, despite evidence of varying risk of child mortality and poor developmental outcomes. Methods: We analyzed birth outcome data from singleton infants, who were enrolled in a large randomized, double-blind, placebo-controlled trial of neonatal vitamin A supplementation conducted in Tanzania. SGA was defined as birth weight <10th percentile for gestation age and sex using INTERGROWTH standards and preterm birth as delivery at <37 complete weeks of gestation. Risk factors for term-SGA, preterm-AGA, and preterm-SGA were examined independently using log-binomial regression. Results: Among 19,269 singleton Tanzanian newborns included in this analysis, 68.3 % were term-AGA, 15.8 % term-SGA, 15.5 % preterm-AGA, and 0.3 % preterm-SGA. In multivariate analyses, significant risk factors for term-SGA included maternal age <20 years, starting antenatal care (ANC) in the 3rd trimester, short maternal stature, being firstborn, and male sex (all p < 0.05). Independent risk factors for preterm-AGA were maternal age <25 years, short maternal stature, firstborns, and decreased wealth (all p < 0.05). In addition, receiving ANC services in the 1st trimester significantly reduced the risk of preterm-AGA (p = 0.01). Significant risk factors for preterm-SGA included maternal age >30 years, being firstborn, and short maternal stature which appeared to carry a particularly strong risk (all p < 0.05). Conclusion: Over 30 % of newborns in this large urban and rural cohort of Tanzanian newborns were born preterm and/or SGA. Interventions to promote early attendance to ANC services, reduce unintended young pregnancies, increased maternal height, and reduce poverty may significantly decrease the burden of SGA and preterm birth in sub-Saharan Africa. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR) – ACTRN12610000636055, registered on 3rd August 2010.

Infant mortality accounts for the majority of child deaths in Tanzania, and malnutrition is an important underlying cause. The objectives of this cross-sectional study were to describe the micronutrient status of infants in Tanzania and assess predictors of infant micronutrient deficiency. We analyzed serum vitamin D, vitamin B12, folate, and ferritin levels from 446 infants at two weeks of age, 408 infants at three months of age, and 427 mothers three months post-partum. We used log-Poisson regression to estimate relative risk of being deficient in vitamin D and vitamin B12 for infants in each age group. The prevalence of vitamin D and vitamin B12 deficiency decreased from 60% and 30% at two weeks to 9% and 13% at three months respectively. Yet, the prevalence of insufficiency at three months was 49% for vitamin D and 17% for vitamin B12. Predictors of infant vitamin D deficiency were low birthweight, urban residence, maternal education, and maternal vitamin D status. Maternal vitamin B12 status was the main predictor for infant vitamin B12 deficiency. The majority of infants had sufficient levels of folate or ferritin. Further research is necessary to examine the potential benefits of improving infants’ nutritional status through vitamin D and B12 supplements.

Objective: This study explored the risk factors for infant hospitalization in urban and peri-urban/rural Tanzania.

Methods: We conducted a prospective cohort study examining predictors of hospitalization during the first year of life among infants enrolled at birth in a large randomized controlled trial of neonatal vitamin A supplementation conducted in urban Dar es Salaam (n = 11 895) and peri-urban/rural Morogoro region (n = 20 104) in Tanzania. Demographic, socioeconomic, environmental and birth outcome predictors of hospitalization were assessed using proportional hazard models.

Results: The rate of hospitalization was highest during the neonatal period in both Dar es Salaam (102/10 000 neonatal-months) and Morogoro region (78/10 000 neonatal-months). Hospitalization declined with increased age and was lowest for infants 6–12 months of age in both Dar es Salaam (11/10 000 infant-months) and Morogoro region (16/10 000 infant-months). In both Dar es Salaam and Morogoro region, older maternal age, male sex, low birth weight and being small for gestational age were significant predictors of higher risk of hospitalization (p < 0.05). Increased wealth and having a flush toilet were significantly associated with an increased risk of hospitalization in Morogoro region only (p < 0.05).

Conclusions: This study determined high rates of neonatal hospitalization in Tanzania. Interventions to increase birth size may decrease risk of hospitalization. Equity in access to hospitals for poor rural families in Tanzania requires attention.