Two Randomized Trials of Low-Dose Calcium Supplementation in Pregnancy.

BACKGROUND: The World Health Organization recommends 1500 to 2000 mg of calcium daily as supplementation, divided into three doses, for pregnant persons in populations with low dietary calcium intake in order to reduce the risk of preeclampsia. The complexity of the dosing scheme, however, has led to implementation barriers. METHODS: We conducted two independent randomized trials of calcium supplementation, in India and Tanzania, to assess the noninferiority of a 500-mg daily dose to a 1500-mg daily dose of calcium supplementation. In each trial, the two primary outcomes were preeclampsia and preterm birth, and the noninferiority margins for the relative risks were 1.54 and 1.16, respectively. RESULTS: A total of 11,000 nulliparous pregnant women were included in each trial. The cumulative incidence of preeclampsia was 3.0% in the 500-mg group and 3.6% in the 1500-mg group in the India trial (relative risk, 0.84; 95% confidence interval [CI], 0.68 to 1.03) and 3.0% and 2.7%, respectively, in the Tanzania trial (relative risk, 1.10; 95% CI, 0.88 to 1.36) - findings consistent with the noninferiority of the lower dose in both trials. The percentage of live births that were preterm was 11.4% in the 500-mg group and 12.8% in the 1500-mg group in the India trial (relative risk, 0.89; 95% CI, 0.80 to 0.98), which was within the noninferiority margin of 1.16; in the Tanzania trial, the respective percentages were 10.4% and 9.7% (relative risk, 1.07; 95% CI, 0.95 to 1.21), which exceeded the noninferiority margin. CONCLUSIONS: In these two trials, low-dose calcium supplementation was noninferior to high-dose calcium supplementation with respect to the risk of preeclampsia. It was noninferior with respect to the risk of preterm live birth in the trial in India but not in the trial in Tanzania. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT03350516; Clinical Trials Registry-India number, CTRI/2018/02/012119; and Tanzania Medicines and Medical Devices Authority Trials Registry number, TFDA0018/CTR/0010/5).

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.

Associations Between Social Support and Symptoms of Antenatal Depression with Infant Growth and Development Among Mothers Living with HIV in Tanzania.

Children born to mothers living with HIV may experience greater risk of poor growth and development outcomes than their HIV-unexposed peers. Few studies have examined the relationship between maternal depression and social support with infant growth and development in the context of HIV. We conducted a prospective cohort study of 2,298 pregnant women living with HIV in Dar es Salaam, Tanzania, assessing antenatal depression (Hopkins Symptoms Checklist-25) and social support (Duke-UNC Functional Social Support Questionnaire) at 12-27 weeks of gestation. At one-year age, infant anthropometry and caregiver-reported infant development were assessed. Generalized estimating equations were used to assess mean differences (MD) and relative risks (RR) for growth and developmental outcomes. Symptoms consistent with maternal antenatal depression had 67% prevalence and were associated with infant wasting (RR 2.61; 95% confidence interval (CI) 1.03-6.65; z = 2.02; p = 0.04), but no other growth or developmental outcomes. Greater maternal social support was not associated with infant growth outcomes. Greater affective support was associated with better cognitive (MD 0.18; CI 0.01-0.35; z = 2.14; p = 0.03) and motor (MD 0.16; CI 0.01-0.31; z = 2.04; p = 0.04) development scores. Greater instrumental support was associated with better cognitive (MD 0.26; CI 0.10-0.42; z = 3.15; p < 0.01), motor (MD 0.17; CI 0.02-0.33; z = 2.22; p = 0.03), and overall (MD 0.19; CI 0.03-0.35; z = 2.35; p = 0.02) development scores. Depressive symptoms were associated with greater risk of wasting, while social support was associated with better infant development scores. Strategies to improve mental health and social support for mothers living with HIV during the antenatal period may benefit infant growth and development.

Timing of Antiretroviral Therapy: Initiation and Birth Outcomes Among Pregnant Women With Human Immunodeficiency Virus in Tanzania

BACKGROUND: Combination antiretroviral therapy (cART) initiation during pregnancy reduces the risk of perinatal human immunodeficiency virus (HIV) transmission; however, studies have suggested that there may be unintended adverse consequences on birth outcomes for selected cART regimens. METHODS: We analyzed adverse birth outcomes among a prospective cohort of 1307 pregnant women with HIV in Dar es Salaam who initiated cART during the first or second trimester of a singleton pregnancy. Our primary analysis compared birth outcomes by gestational age at cART initiation among these women initiating cART in pregnancy. RESULTS: Among women who initiated cART in pregnancy, there was no relationship of gestational age at cART initiation with the risk of fetal death or stillbirth. However, women who initiated cART before 20 weeks of gestation compared with after 20 weeks had increased risk of preterm birth (risk ratio [RR], 1.30; 95% confidence interval [CI], 1.03-1.67) but decreased risk of small-for-gestational age birth (RR, 0.71; 95% CI, .55-.93). CONCLUSIONS: With increasing use of cART preconception and early in pregnancy, clinicians should be aware of the benefits and potential risks of cART regimens to optimize birth outcomes.

Vitamin D3 supplementation during pregnancy and lactation for women living with HIV in Tanzania: A randomized controlled trial.

BACKGROUND: Observational studies suggest that vitamin D deficiency among people living with HIV is associated with a greater risk of disease progression and death. Low levels of vitamin D in pregnancy are also associated with poor fetal and infant growth. Therefore, vitamin D supplementation may improve clinical outcomes for pregnant women living with HIV and improve fetal and postnatal growth for their infants. METHODS AND FINDINGS: We conducted a randomized, triple-blind, placebo-controlled trial of vitamin D3 supplementation among pregnant and lactating women living with HIV in Dar es Salaam, Tanzania (ClinicalTrials.gov NCT02305927). Participants were randomized with 1:1 allocation stratified by study clinic to receive either daily 3,000 IU vitamin D3 supplements or matching placebo supplements from the second trimester of pregnancy (12-27 weeks) until 1 year postpartum. The primary outcomes were (i) maternal HIV progression or death, (ii) small-for-gestational-age (SGA) live births (<10th percentile), and (iii) infant stunting at 1 year of age (length-for-age z-score < -2). We also examined the effect of vitamin D3 supplementation on secondary maternal and infant health outcomes, maternal and infant serum 25-hydroxyvitamin D (25[OH]D) concentrations, and maternal hypercalcemia. An intent-to-treat analysis was used as the primary analytic approach. We enrolled 2,300 pregnant women between June 15, 2015, and April 17, 2018, and follow-up of mothers and infants was completed on October 20, 2019. There were 1,148 pregnant women randomly assigned to the vitamin D3 group, and 1,152 to the placebo group. The proportion of mothers lost to follow-up at 1 year postpartum was 6.6% in the vitamin D3 group (83 of 1,148) and 6.6% in the placebo group (76 of 1,152). The proportion of children lost to follow-up at 1 year of age was 5.5% in the vitamin D3 group (59 of 1,074 live births) and 5.2% in the placebo group (57 of 1,093 live births). There was no difference in the risk of maternal HIV progression or death, with 166 events during 1,461 person-years of follow-up in the vitamin D3 group and 141 events during 1,469 person-years of follow-up in the placebo group (hazard ratio 1.21, 95% CI 0.97 to 1.52, p = 0.09). There was no difference in the risk of SGA birth between the vitamin D3 (229 SGA births among 1,070 live births) and placebo groups (236 SGA births among 1,091 live births) (relative risk 1.03, 95% CI 0.87 to 1.22, p = 0.70). There was also no difference in the risk of infant stunting at 1 year of age between the vitamin D3 (407 events among 867 infants) and placebo groups (413 events among 873 infants) (relative risk 1.00, 95% CI 0.92 to 1.10, p = 0.95). In terms of adverse events, no cases of maternal hypercalcemia were identified. One hypersensitivity reaction to the trial supplements occurred for a pregnant woman in the placebo group. A limitation of our study is that our findings may not be generalizable to HIV-negative pregnant women or contexts where severe vitamin D deficiency is prevalent. CONCLUSIONS: The trial findings do not support routine vitamin D supplementation for pregnant and lactating women living with HIV in Tanzania. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02305927.

Cholecalciferol Supplementation Does Not Affect the Risk of HIV Progression, Viral Suppression, Comorbidities, Weight Loss, and Depression among Tanzanian Adults Initiating Antiretroviral Therapy: Secondary Outcomes of a Randomized Trial.

BACKGROUND: Observational studies suggest that blood concentrations of 25-hydroxyvitamin D [25(OH)D] are associated with morbidity, viral suppression, and mortality among adults living with HIV. OBJECTIVES: We evaluated the effect of cholecalciferol (vitamin D3) supplementation on the risk of HIV disease progression, HIV-1 viral suppression, comorbidities, weight change, and depression among HIV-infected individuals that were initiating antiretroviral therapy (ART) in Dar es Salaam, Tanzania. METHODS: We conducted a randomized, double-blind, placebo-controlled trial of vitamin D3 supplementation among 4000 HIV-infected adult men and nonpregnant women initiating ART with insufficient serum 25(OH)D concentrations (<30 ng/mL). Participants were randomly assigned to receive either weekly 50,000-IU doses for 4 wk followed by daily 2000 IU vitamin D3 until 1 y or a matching placebo regimen given in weekly followed by daily doses until 1 y. Participants were followed up at weekly visits for the first month followed by monthly visits thereafter. We conducted intent-to-treat analyses to assess the effect of vitamin D3 supplementation on the secondary trial outcomes of HIV progression or death, viral suppression, comorbidities, change in BMI, >10% weight loss, incident wasting, and depression. RESULTS: During follow-up, 345 participants (17.2%) in the vitamin D3 group and 371 participants (18.6%) in the placebo group experienced HIV disease progression or death and there was no difference in risk between groups (RR: 0.91; 95% CI: 0.79, 1.06). Vitamin D3 supplementation did not affect the risk of an unsuppressed HIV-1 viral load (>1000 copies/mL) after 6 mo (RR: 1.10; 95% CI: 0.87, 1.41) and there was also no effect on change in BMI, risk of >10% weight loss, wasting, comorbidities, and depression (P values >0.05). CONCLUSIONS: Vitamin D supplementation did not affect the risk of HIV progression, viral suppression, common morbidities, weight-related indicators, or depression among adults initiating ART in Tanzania.This trial was registered at clinicaltrials.gov as NCT01798680.

Depression and Viral Suppression Among Adults Living with HIV in Tanzania.

Limited information is available on the association between depression and viral suppression among people living with HIV (PLH) in sub-Saharan Africa. We conducted a prospective cohort study of 3996 adults initiating antiretroviral therapy (ART) in Dar es Salaam, Tanzania. Log-binomial models were used to assess the association between depression and the risk of an unsuppressed viral load (> 400 copies/mL) after 6 months of ART. Women who had depression at both initiation and after 6 months of treatment had 1.94 times (95% CI 1.22, 3.09; z = 2.78, p < 0.01) the risk of an unsuppressed viral load after 6 months of treatment as compared to women who did not have depression at either time point. Men with the top tertile of depressive symptoms after 6 months of treatment had 1.58 times the risk of an unsuppressed viral load (95% CI 1.04, 2.38; z = 2.15, p = 0.03) as compared to the lowest tertile. Research should be pursued on interventions to prevent and address depression among adults initiating ART to potentially support achievement of viral suppression.

A qualitative inquiry of access to and quality of primary healthcare in seven communities in East and West Africa (SevenCEWA): perspectives of stakeholders, healthcare providers and users.

BACKGROUND: Universal health coverage is one of the Sustainable Development Goal targets known to improve population health and reduce financial burden. There is little qualitative data on access to and quality of primary healthcare in East and West Africa. The aim of this study was to describe the viewpoints of healthcare users, healthcare providers and other stakeholders on health-seeking behaviour, access to and quality of healthcare in seven communities in East and West Africa. METHODS: A qualitative study was conducted in four communities in Nigeria and one community each in Kenya, Uganda and Tanzania in 2018. Purposive sampling was used to recruit: 155 respondents (mostly healthcare users) for 24 focus group discussions, 25 healthcare users, healthcare providers and stakeholders for in-depth interviews and 11 healthcare providers and stakeholders for key informant interviews. The conceptual framework in this study combined elements of the Health Belief Model, Health Care Utilisation Model, four 'As' of access to care, and pathway model to better understand the a priori themes on access to and quality of primary healthcare as well as health-seeking behaviours of the study respondents. A content analysis of the data was done using MAXQDA 2018 qualitative software to identify these a priori themes and emerging themes. RESULTS: Access to primary healthcare in the seven communities was limited, especially use of health insurance. Quality of care was perceived to be unacceptable in public facilities whereas cost of care was unaffordable in private facilities. Health providers and users as well as stakeholders highlighted shortage of equipment, frequent drug stock-outs and long waiting times as major issues, but had varying opinions on satisfaction with care. Use of herbal medicines and other traditional treatments delayed or deterred seeking modern healthcare in the Nigerian sites. CONCLUSIONS: There was a substantial gap in primary healthcare coverage and quality in the selected communities in rural and urban East and West Africa. Alternative models of healthcare delivery that address social and health inequities, through affordable health insurance, can be used to fill this gap and facilitate achieving universal health coverage.

Hypertension prevalence, awareness, treatment, and control and predicted 10-year CVD risk: a cross-sectional study of seven communities in East and West Africa (SevenCEWA).

BACKGROUND: Few studies have characterized the epidemiology and management of hypertension across several communities with comparable methodologies in sub-Saharan Africa. We assessed prevalence, awareness, treatment, and control of hypertension and predicted 10-year cardiovascular disease risk across seven sites in East and West Africa. METHODS: Between June and August 2018, we conducted household surveys among adults aged 18 years and above in 7 communities in Kenya, Nigeria, Tanzania, and Uganda. Following a standardized protocol, we collected data on socio-demographics, health insurance, and healthcare utilization; and measured blood pressure using digital blood pressure monitors. We estimated the 10-year cardiovascular disease (CVD) risk using a country-specific risk score and fitted hierarchical models to identify determinants of hypertension prevalence, awareness, and treatment. RESULTS: We analyzed data of 3549 participants. The mean age was 39·7 years (SD 15·4), 60·5% of whom were women, 9·6% had ever smoked cigarettes, and 32·7% were overweight/obese. A quarter of the participants (25·4%) had hypertension, more than a half of whom (57·2%) were aware that they had diagnosed hypertension. Among those diagnosed, 50·5% were taking medication, and among those taking medication 47·3% had controlled blood pressure. After adjusting for other determinants, older age was associated with increased hypertension prevalence, awareness, and treatment whereas primary education was associated with lower hypertension prevalence. Health insurance was associated with lower hypertension prevalence and higher chances of treatment. Median predicted 10-yr CVD risk across sites was 4·9% (Interquartile range (IQR), 2·4%, 10·3%) and 13·2% had predicted 10-year CVD risk of 20% or greater while 7·1% had predicted 10-year CVD risk of > 30%. CONCLUSION: In seven communities in east and west Africa, a quarter of participants had hypertension, about 40% were unaware, half of those aware were treated, and half of those treated had controlled blood pressure. The 10-year predicted CVD risk was low across sites. Access to health insurance is needed to improve awareness, treatment, and control of hypertension in sub-Saharan Africa.

Public knowledge of risk factors and warning signs for cardiovascular disease among young and middle-aged adults in rural Tanzania.

BACKGROUND: Improving cardiovascular health requires public knowledge and reduction of modifiable cardiovascular disease (CVD) risk factors. This study assessed knowledge of risk factors and warning signs for CVDs among young and middle-aged adults in Morogoro, Tanzania. METHODS: We conducted a community-based survey as part of cluster randomized controlled study of community health workers (CHWs) intervention for reduction of blood pressure among young and middle-aged adults in rural Morogoro. Information on socio-demographic characteristics, knowledge of risk factors and warning signs for CVDs was collected using an interviewer administered questionaire. Knowledge was assessed using open-ended questions followed by closed-ended questions. Descriptive statistics were used to describe knowledge of risk factors and warning signs. Logistic regression analysis was used to investigate factors associated with adequate knowledge of risk factors and warning signs for CVDs. RESULTS: Two-thirds (65.7%) of the participants had heard about CVDs. The main sources of information were mainly relatives/ neighbors (64.8%) and radio (53.0%). Only 28.3% of the participants reported health care providers as source of information about CVDs. More than half of the participants (52.4%) did not mention even one risk factor spontaneously while 55.2% were unable to mention any warning sign. When asked to select from a list, 6.9% were unable to correctly identify any risk factor whereas 11.8% could not correctly identify even a single warning sign. Quarter of participants (25.4%) had good knowledge score of risk factors, 17.5% had good knowledge score of warning signs and 16.3% had overall good knowledge of both risk factors and warning signs. Residing in Ulanga, having higher education level, having ever checked blood pressure and being overweight/obese predicted adequacy of knowledge score for both risk factors and warning signs. CONCLUSION: Knowledge of risk factors and warning signs in this rural population of young and middle-aged adults was generally low. Health care providers were less likely to provide health education regarding risk factors and warning signs for CVDs. Health promotion interventions to increase population knowledge of risk factors and warning signs should be implemented for successful reduction of CVDs in Tanzania.

Determinants of delayed or incomplete diphtheria-tetanus-pertussis vaccination in parallel urban and rural birth cohorts of 30,956 infants in Tanzania.

BACKGROUND: Delayed vaccination increases the time infants are at risk for acquiring vaccine-preventable diseases. Factors associated with incomplete vaccination are relatively well characterized in resource-limited settings; however, few studies have assessed immunization timeliness. METHODS: We conducted a prospective cohort study examining Diphtheria-Tetanus-Pertussis (DTP) vaccination timing among newborns enrolled in a Neonatal Vitamin A supplementation trial (NEOVITA) conducted in urban Dar es Salaam (n = 11,189) and rural Morogoro Region (n = 19,767), Tanzania. We used log-binomial models to assess the relationship of demographic, socioeconomic, healthcare access, and birth characteristics with late or incomplete DTP1 and DTP3 immunization. RESULTS: The proportion of infants with either delayed or incomplete vaccination was similar in Dar es Salaam (DTP1 11.5% and DTP3 16.0%) and Morogoro (DTP1 9.2% and DTP3 17.3%); however, the determinants of delayed or incomplete vaccination as well as their magnitude of association differed by setting. Both maternal and paternal education were more strongly associated with vaccination status in rural Morogoro region as compared to Dar es Salaam (p-values for heterogeneity < 0.05). Infants in Morogoro who had fathers and mothers with no education had 36% (95% CI: 22-52%) and 22% (95% CI: 10-34%) increased risk of delayed or incomplete DTP3 vaccination as compared to those with primary school education, respectively. In Dar es Salaam, mothers who attended their first antenatal care (ANC) visit in the 3rd trimester had 1.55 (95% CI: 1.36-1.78) times the risk of delayed or not received vaccination as compared to those with a 2nd trimester booking, while there was no relationship in Morogoro. In rural Morogoro, infants born at home had 17% (95% CI: 8-27%) increased risk for delayed or no receipt of DTP3 vaccination. In both settings, younger maternal age and poorer households were at increased risk for delayed or incomplete vaccination. CONCLUSION: We found some risk factors for delayed and incomplete vaccination were shared between urban and rural Tanzania; however, we found several context-specific risk factors as well as determinants that differed in their magnitude of risk between contexts. Immunization programs should be tailored to address context-specific barriers and enablers to improve timely and complete vaccination.

Elevated blood pressure among primary school children in Dar es salaam, Tanzania: prevalence and risk factors.

BACKGROUND: Whilst the burden of non-communicable diseases is increasing in developing countries, little data is available on blood pressure among Tanzanian children. This study aimed at determining the blood pressure profiles and risk factors associated with elevated blood pressure among primary school children in Dar es Salaam, Tanzania. METHODS: We conducted a cross sectional survey among 446 children aged 6-17 years from 9 randomly selected primary schools in Dar es Salaam. We measured blood pressure using a standardized digital blood pressure measuring machine (Omron Digital HEM-907, Tokyo, Japan). We used an average of the three blood pressure readings for analysis. Elevated blood pressure was defined as average systolic or diastolic blood pressure ≥ 90th percentile for age, gender and height. RESULTS: The proportion of children with elevated blood pressure was 15.2% (pre-hypertension 4.4% and hypertension 10.8%). No significant gender differences were observed in the prevalence of elevated BP. Increasing age and overweight/obese children were significantly associated with elevated BP (p = 0.0029 and p < 0.0001) respectively. Similar associations were observed for age and overweight/obesity with hypertension. (p = 0.0506 and p < 0.0001) respectively. In multivariate analysis, age above 10 years (adjusted RR = 3.63, 95% CI = 1.03-7.82) was significantly and independently associated with elevated BP in this population of school age children. CONCLUSIONS: We observed a higher proportion of elevated BP in this population of school age children. Older age and overweight/obesity were associated with elevated BP. Assessment of BP and BMI should be incorporated in school health program in Tanzania to identify those at risk so that appropriate interventions can be instituted before development of associated complications.

Development and validation of an early childhood development scale for use in low-resourced settings.

BACKGROUND: Low-cost, cross-culturally comparable measures of the motor, cognitive, and socioemotional skills of children under 3 years remain scarce. In the present paper, we aim to develop a new caregiver-reported early childhood development (ECD) scale designed to be implemented as part of household surveys in low-resourced settings. METHODS: We evaluate the acceptability, test-retest reliability, internal consistency, and discriminant validity of the new ECD items, subscales, and full scale in a sample of 2481 18- to 36-month-old children from peri-urban and rural Tanzania. We also compare total and subscale scores with performance on the Bayley Scales of Infant Development (BSID-III) in a subsample of 1036 children. Qualitative interviews from 10 mothers and 10 field workers are used to inform quantitative data. RESULTS: Adequate levels of acceptability and internal consistency were found for the new scale and its motor, cognitive, and socioemotional subscales. Correlations between the new scale and the BSID-III were high (r > .50) for the motor and cognitive subscales, but low (r < .20) for the socioemotional subscale. The new scale discriminated between children's skills based on age, stunting status, caregiver-reported disability, and adult stimulation. Test-retest reliability scores were variable among a subset of items tested. CONCLUSIONS: Results of this study provide empirical support from a low-income country setting for the acceptability, reliability, and validity of a new caregiver-reported ECD scale. Additional research is needed to test these and other caregiver reported items in children in the full 0 to 3 year range across multiple cultural and linguistic settings.

Effect of neonatal vitamin A supplementation on mortality in infants in Tanzania (Neovita): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Supplementation of vitamin A in children aged 6-59 months improves child survival and is implemented as global policy. Studies of the efficacy of supplementation of infants in the neonatal period have inconsistent results. We aimed to assess the efficacy of oral supplementation with vitamin A given to infants in the first 3 days of life to reduce mortality between supplementation and 180 days (6 months). METHODS: We did an individually randomised, double-blind, placebo-controlled trial of infants born in the Morogoro and Dar es Salaam regions of Tanzania. Women were identified during antenatal clinic visits or in the labour wards of public health facilities in Dar es Salaam. In Kilombero, Ulanga, and Kilosa districts, women were seen at home as part of the health and demographic surveillance system. Newborn infants were eligible for randomisation if they were able to feed orally and if the family intended to stay in the study area for at least 6 months. We randomly assigned infants to receive one dose of 50,000 IU of vitamin A or placebo in the first 3 days after birth. Infants were randomly assigned in blocks of 20, and investigators, participants' families, and data analysis teams were masked to treatment assignment. We assessed infants on day 1 and day 3 after dosing, as well as at 1, 3, 6, and 12 months after birth. The primary endpoint was mortality at 6 months, assessed by field interviews. The primary analysis included only children who were not lost to follow-up. This trial is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR), number ACTRN12610000636055. FINDINGS: Between Aug 26, 2010, and March 3, 2013, 31,999 newborn babies were randomly assigned to receive vitamin A (n=15,995) or placebo (n=16,004; 15,428 and 15,464 included in analysis of mortality at 6 months, respectively). We did not find any evidence for a beneficial effect of vitamin A supplementation on mortality in infants at 6 months (26 deaths per 1000 livebirths in vitamin A vs 24 deaths per 1000 livebirths in placebo group; risk ratio 1·10, 95% CI 0·95-1·26; p=0·193). There was no evidence of a differential effect for vitamin A supplementation on mortality by sex; risk ratio for mortality at 6 months for boys was 1·08 (0·90-1·29) and for girls was 1·12 (0·91-1·39). There was also no evidence of adverse effects of supplementation within 3 days of dosing. INTERPRETATION: Neonatal vitamin A supplementation did not result in any immediate adverse events, but had no beneficial effect on survival in infants in Tanzania. These results strengthen the evidence against a global policy recommendation for neonatal vitamin A supplementation. FUNDING: Bill & Melinda Gates Foundation to WHO.

Risk factors for small-for-gestational-age and preterm births among 19,269 Tanzanian newborns.

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 3(rd) 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 1(st) 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 3(rd) August 2010.

Malnutrition and Its Determinants Are Associated with Suboptimal Cognitive, Communication, and Motor Development in Tanzanian Children.

BACKGROUND: A large volume of literature has shown negative associations between stunting and child development; however, there is limited evidence for associations with milder forms of linear growth faltering and determinants of malnutrition in developing countries. OBJECTIVE: The objective of this study was to assess the association between anthropometric growth indicators across their distribution and determinants of malnutrition with development of Tanzanian children. METHODS: We used the Bayley Scales of Infant Development III to assess a cohort of 1036 Tanzanian children between 18 and 36 mo of age who were previously enrolled in a neonatal vitamin A trial. Linear regression models were used to assess standardized mean differences in child development for anthropometry z scores, along with pregnancy, delivery, and early childhood factors. RESULTS: Height-for-age z score (HAZ) was linearly associated with cognitive, communication, and motor development z scores across the observed range in this population (all P values for linear relation < 0.05). Each unit increase in HAZ was associated with +0.09 (95% CI: 0.05, 0.13), +0.10 (95% CI: 0.07, 0.14), and +0.13 (95% CI: 0.09, 0.16) higher cognitive, communication, and motor development z scores, respectively. The relation of weight-for-height z score (WHZ) was nonlinear with only wasted children (WHZ <-2) experiencing deficits (P values for nonlinear relation < 0.05). Wasted children had -0.63 (95% CI: -0.97, -0.29), -0.32 (95% CI: -0.64, 0.01), and -0.54 (95% CI: -0.86, -0.23) z score deficits in cognitive, communication, and motor development z scores, respectively, relative to nonwasted children. Maternal stature and flush toilet use were associated with higher cognitive and motor z scores, whereas being born small for gestational age (SGA) was associated with a -0.16 (95% CI: -0.30, -0.01) z score deficit in cognition. CONCLUSIONS: Mild to severe chronic malnutrition was associated with increasing developmental deficits in Tanzanian children, whereas only wasted children exhibited developmental delays during acute malnutrition. Interventions to reduce SGA, improve sanitation, and increase maternal stature may have positive effects on child development. This trial was registered with the Australian New Zealand Clinical Trials Registry as ACTRN12610000636055.

Predictors of Hospitalization During the First Year of Life among 31999 Tanzanian Infants.

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.

First-line antiretroviral therapy and changes in lipid levels over 3 years among HIV-infected adults in Tanzania.

BACKGROUND: With the rapid rollout of antiretroviral therapy (ART) in sub-Saharan Africa (SSA), there has been an increasing concern about cardiovascular risks related to ART. However, data from human immunodeficiency virus (HIV)-infected populations from this region are very limited. METHODS: Among 6385 HIV-infected adults in Dar es Salaam, Tanzania, we investigated the nonfasting lipid changes over 3 years following ART initiation and their associations with different first-line ART agents that are commonly used in SSA. RESULTS: In the first 6 months of ART, the prevalence of dyslipidemia decreased from 69% to 54%, with triglyceride (TG) decreasing from 127 mg/dL to 113 mg/dL and high-density lipoprotein (HDL) cholesterol increasing from 39 mg/dL to 52 mg/dL. After 6 months, TG returned to its baseline level and increased to 139 mg/dL at 3 years; total cholesterol and low-density lipoprotein cholesterol continued to increase whereas HDL cholesterol leveled off. The prevalence of dyslipidemia increased to 73% after a 3-year follow-up. In multivariate analyses, patients on zidovudine-containing regimens had a greater reduction in TG levels at 6 months (-16.0 vs -6.3 mg/dL), and a lower increase at 3 years compared to patients on stavudine-containing regimens (2.1 vs 11.7 mg/dL, P < .001); patients on nevirapine-based regimens had a higher increase in HDL cholesterol levels at 3 years compared to those on efavirenz-based regimens (13.6 vs 9.5 mg/dL, P = .01). CONCLUSIONS: Our findings support the latest World Health Organization guidelines on the substitution of stavudine in first-line ART in resource-limited settings, and provide further evidence for selection of lipid-friendly ART for patients in SSA.

Consumption and acceptability of whole grain staples for lowering markers of diabetes risk among overweight and obese Tanzanian adults.

BACKGROUND: Dietary changes characterized by a reduction in carbohydrate quality are occurring in developing countries and may be associated with a higher prevalence of obesity and chronic diseases such as type 2 diabetes mellitus. We assessed the preferences and acceptability of unrefined whole grain carbohydrate staples (i.e., brown rice, unrefined maize and unrefined sorghum ugali) as substitutes for commonly consumed refined carbohydrates in Tanzania. METHODS: A questionnaire was used to collect sociodemographic information and dietary habits, and pre-and post-tasting questionnaires were administered for test foods. A 10-point LIKERT scale was used to rate attributes of the three test foods. RESULTS: White rice and refined maize ugali were the most commonly consumed carbohydrate staples in this population; 98% and 91%, respectively. Occasional consumption of unrefined maize and sorghum ugali was reported by 32% and 23% of the participants, respectively. All of the test foods were highly rated for smell, taste, color, appearance and texture. Taste was rated highest for unrefined maize ugali. Almost all of the participants were willing to participate in a future dietary intervention involving regular consumption of these unrefined carbohydrates for at least six months duration. CONCLUSIONS: These findings suggest that whole grain carbohydrates are highly acceptable, and that there is a promising potential for their use in future dietary intervention studies in Tanzania.