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).

Antenatal depression and adverse birth outcomes among pregnant women living with HIV in Dar es Salaam, Tanzania.

BACKGROUND: Women who experience antenatal depression may be at increased risk of adverse birth outcomes. Few studies have examined this association among women living with HIV (WHIV). METHODS: We conducted a prospective cohort study of 2298 pregnant WHIV on antiretroviral therapy (ART) in Dar es Salaam, Tanzania, who were participants in a randomized trial of vitamin D3 supplementation. Depressive symptoms were assessed at 12-27 weeks gestation using the Hopkins Symptoms Checklist (HSCL-25). Generalized estimating equations to account for twins were used to assess the relative risks of adverse birth outcomes. RESULTS: Approximately 67 % of the women in our study population reported symptoms consistent with depression. We observed a 4.0 % prevalence of stillbirth and a 25.1 % prevalence of preterm birth. We found that low social support, higher education, and more recent initiation of ART were associated with a greater risk of antenatal depression. There was no association of antenatal depression with risk of fetal loss, stillbirth, low birth weight, birth weight, preterm birth, gestational age at delivery, or small-for-gestational age. LIMITATIONS: Depression was self-reported and only collected at one timepoint in pregnancy. Our findings may not be generalizable to all WHIV. CONCLUSIONS: Our findings illustrate the high risk of both depression and adverse birth outcomes among WHIV and underscore the need for interventions to improve their mental health and the health of their infants; however, the relationship between depression and birth outcomes remains unclear. Further research on this topic is merited, particularly examining the chronicity and timing of depression in pregnancy.

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.

Assessing environmental enteric dysfunction via multiplex assay and its relation to growth and development among HIV-exposed uninfected Tanzanian infants.

BACKGROUND: Environmental enteric dysfunction (EED) may contribute to poor growth and development in young children. While validated EED biomarkers are currently lacking, multiplex assays are able to capture multiple domains of the condition. The purpose of this exploratory study was to examine the relationship between biomarkers of EED and subsequent growth and development among Tanzanian HIV-exposed uninfected (HEU) infants. METHODOLOGY: We enrolled 467 infants of mothers living with HIV who had participated in a trial of vitamin D3 supplementation during pregnancy. Infant serum samples collected at 6 weeks (n = 365) and 6 months (n = 266) were analyzed for anti-flagellin and anti-lipopolysaccharide (LPS) IgA and IgG via ELISA as well as the 11-plex Micronutrient and EED Assessment Tool (MEEDAT), which incorporates two biomarkers of EED [intestinal fatty acid-binding protein (I-FABP) and soluble CD14 (sCD14)]. Outcomes were 12-month growth [length-for-age z-score (LAZ), weight-for-length z-score (WLZ), and weight-for-age z-score (WAZ)] and development [Caregiver Reported Early Development Instruments (CREDI) z-scores] and were assessed using linear regression. FINDINGS: In primary analyses, higher quartiles of 6-month anti-LPS IgG concentrations were significantly associated with lower LAZ at 12 months (ptrend = 0.040). In secondary analyses, higher log2-transformed 6-week anti-flagellin IgA and 6-month anti-LPS IgA concentrations were significantly associated with lower LAZ at 12 months. No associations were observed between I-FABP or sCD14 and infant growth. However, higher log2-transformed 6-week sCD14 concentrations were significantly associated with lower overall CREDI z-scores, while higher log2-transformed 6-month I-FABP concentrations were significantly associated with higher overall CREDI z-scores. CONCLUSIONS: Unlike anti-flagellin and anti-LPS Igs, MEEDAT's biomarkers of EED (I-FABP and sCD14) were not associated with subsequent linear growth among HEU infants in Tanzania. The relationship between EED and infant development warrants further study.

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.

Association of Exposure to Intimate Partner Violence With Maternal Depressive Symptoms and Early Childhood Socioemotional Development Among Mothers and Children in Rural Tanzania.

Importance: Approximately 1 in 4 women experience intimate partner violence (IPV) or nonpartner sexual violence during their lifetime. Mothers exposed to IPV are more likely to experience depressive symptoms and to discipline their children harshly, which may affect their children's socioemotional development; however, there is limited evidence on these outcomes. Objective: To examine the association between IPV, maternal depressive symptoms, harsh child discipline, and child stimulation with child socioemotional development. Design, Setting, and Participants: This study used cross-sectional follow-up data collected from February 19 to October 10, 2014, from a birth cohort of children aged 18 to 36 months who were enrolled in a randomized, double-blind, placebo-controlled trial of neonatal vitamin A supplementation in the Morogoro region of Tanzania. Data analysis occurred between September 10, 2019, and January 20, 2020. Exposures: Lifetime experience of IPV was assessed using an abbreviated module of the Tanzania Demographic and Health Survey, maternal depressive symptoms were assessed with the Patient Health Questionnaire, and data on harsh child discipline and maternal stimulation of their children were collected using modules of the United Nations Children's Fund Multiple Indicator Cluster Survey. Main Outcomes and Measures: Child socioemotional development was measured by the Caregiver-Reported Early Childhood Development Instruments. Results: A total of 981 mother-child dyads were included in the analytic sample; 388 children (39.6%) were between ages 18 and 24 (mean [SD] age, 27.06 [6.08]) months, and 515 (52.5%) were male children. A negative association was observed between maternal report of physical IPV only (mean difference, -0.022; 95% CI, -0.045 to -0.006) and physical and sexual IPV (mean difference, -0.045; 95% CI, -0.077 to -0.013) with child socioemotional scores, but neither was statistically significant after including depressive symptoms in the model, which is consistent with mediation. Furthermore, a negative association was observed between maternal mild to severe depressive symptoms and child socioemotional development, including adjustment for IPV (mean difference, -0.073; 95% CI, -0.103 to -0.043). Harsh disciplinary practices and stimulation were not associated with child socioemotional development after adjusting for IPV, maternal depressive symptoms, and other factors. Conclusions and Relevance: The findings of this study suggest that maternal depressive symptoms may explain the negative association between IPV and child socioemotional development.

Biomarkers of environmental enteric dysfunction and adverse birth outcomes: An observational study among pregnant women living with HIV in Tanzania.

BACKGROUND: Environmental enteric dysfunction (EED) may contribute to adverse birth outcomes in low-resource settings. We examined the associations of EED biomarkers with birth outcomes in pregnant women living with human immunodeficiency virus in Dar es Salaam, Tanzania. METHODS: We performed a cohort study of 706 HIV-infected pregnant women. Maternal serum samples collected at 32 weeks gestation were analyzed for markers of EED (anti-flagellin and anti-LPS immunoglobulins, intestinal fatty acid-binding protein [I-FABP] and soluble CD14), systemic inflammation (C-reactive protein and α1-acid glycoprotein [AGP]), and growth hormone resistance (insulin-like growth factor 1 [IGF-1] and fibroblast growth factor 21 [FGF21]. Associations of biomarkers categorized into quartiles with birth outcomes (birthweight, gestational duration, birthweight-for-gestational age, and stillbirth) were assessed using linear and log-binomial regression models adjusted for multiple sociodemographic and clinical variables. FINDINGS: Maternal EED biomarkers were not significantly associated with birthweight, gestation duration, or birthweight-for-gestational age. However, higher quintiles of I-FABP concentrations were associated with greater risk of stillbirth (ptrend=0·02). Higher AGP was associated with lower birthweight and was associated with increased risk of small-for-gestational age births. Higher IGF-1 was associated with higher birthweight and birthweight-for-gestational age while higher FGF21 was associated with shorter gestation and higher risk of preterm birth. INTERPRETATION: Maternal biomarkers of EED, systemic inflammation, and growth hormones were differentially associated with birth outcomes. Biomarkers of EED may be useful to identify pregnant women at risk of adverse birth outcomes, but further research is needed to confirm these findings and elucidate biological mechanisms. FUNDING: National Institutes of Health.

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.

Non-specific effects of BCG and DTP vaccination on infant mortality: An analysis of birth cohorts in Ghana and Tanzania.

BACKGROUND: Vaccines may induce non-specific effects on survival and health outcomes, in addition to protection against targeted pathogens or disease. Observational evidence suggests that infant Baccillus Calmette-Guérin (BCG) vaccination may provide non-specific survival benefits, while diphtheria-tetanus-pertussis (DTP) vaccination may increase the risk of mortality. Non-specific vaccine effects have been hypothesized to modify the effect of neonatal vitamin A supplementation (NVAS) on mortality. METHODS: 22,955 newborns in Ghana and 31,999 newborns in Tanzania were enrolled in two parallel, randomized, double-blind, placebo-controlled trials of neonatal vitamin A supplementation from 2010 to 2014 and followed until 1-year of age. Cox proportional hazard models were used to estimate associations of BCG and DTP vaccination with infant survival. RESULTS: BCG vaccination was associated with a decreased risk of infant mortality after controlling for confounders in both countries (Ghana adjusted hazard ratio (aHR): 0.51, 95% CI: 0.38-0.68; Tanzania aHR: 0.08, 95% CI: 0.07-0.10). Receiving a DTP vaccination was associated with a decreased risk of death (Ghana aHR: 0.39, 95% CI: 0.26-0.59; Tanzania aHR: 0.19, 95% CI: 0.16-0.22). There was no evidence of interaction between BCG or DTP vaccination status and infant sex or NVAS. CONCLUSION: We demonstrated that BCG and DTP vaccination were associated with decreased risk of infant mortality in Ghana and Tanzania with no evidence of interaction between DTP or BCG vaccination, NVAS, and infant sex. Our study supports global recommendations on BCG and DTP vaccination and programmatic efforts to ensure all children have access to timely vaccination. CLINICAL TRIALS REGISTRATION: Ghana (Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12610000582055) and Tanzania (ANZCTR: ACTRN12610000636055).

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.

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.

School readiness among children born to women living with HIV in Dar es Salaam, Tanzania: a cohort study protocol.

INTRODUCTION: Children who are born to women living with HIV are at a greater risk of suboptimal neurodevelopment; however, evidence from sub-Saharan Africa is limited and functional developmental outcomes are rarely assessed in this vulnerable population. The School Readiness among HIV-Exposed Children (SRHEC) cohort study aims to assess the school readiness of preschool aged children born to women living with HIV and to identify the biological, environmental and social factors that contribute to school readiness in this population. METHODS AND ANALYSIS: The SRHEC cohort is an observational follow-up study of children born to HIV-infected pregnant women who were previously enrolled in a maternal vitamin D supplementation randomised, placebo-controlled trial in Dar es Salaam, Tanzania. This parent trial enrolled 2300 pregnant women and followed mothers and infants up to 1-year postpartum. Mother/caregiver and child pairs will be eligible for the SRHEC follow-up study if the child is between 3 and 6.5 years of age at assessment, and the mother/caregiver provides informed consent. The International Development and Early Learning Assessment tool will be used to assess children's school readiness, including their early literacy, early numeracy, motor, socialemotional, and executive function skills. Data on maternal and child health and nutritional status (eg, anthropometry, blood pressure and diet) will be collected using standardised instruments and survey-based questionnaires. Data on maternal/caregiver depression and anxiety, maternal exposure to intimate partner violence, and HIV-related stigma will also be collected. Generalised linear and logistic regressions will be used to assess the relationship between child school readiness and biological, social, environmental factors. ETHICS AND DISSEMINATION: This study received ethical clearance from the Tanzanian National Institute of Medical Research, the Muhimbili University of Health and Allied Sciences, and the Harvard T.H. Chan School of Public Health. We will disseminate our results in the form of scientific conference presentations and peer-reviewed publications.

Non-inferiority of low-dose compared to standard high-dose calcium supplementation in pregnancy: study protocol for two randomized, parallel group, non-inferiority trials in India and Tanzania.

BACKGROUND: Hypertensive disorders of pregnancy are important causes of maternal morbidity and mortality, as well as preterm birth, the leading cause of death for children under 5 years globally. The World Health Organization currently recommends that pregnant women receive high-dose calcium supplementation (1500-2000 mg elemental calcium) for prevention of preeclampsia in populations with low dietary calcium intake. Trials of low-dose calcium supplementation (< 1000 mg elemental calcium/day) during pregnancy have also shown similar reductions in the risk of preeclampsia; however, no trials to date have directly compared low-dose to the standard high-dose calcium supplementation. Our objective is to assess the non-inferiority of low-dose as compared to standard high-dose calcium supplementation in pregnancy. METHODS/DESIGN: We will conduct two independent trials in Bangalore, India (n = 11,000 pregnancies), and Dar es Salaam, Tanzania (n = 11,000 pregnancies). The trial designs are individually randomized, parallel group, quadruple-blind, non-inferiority trials of low-dose calcium supplementation (500 mg elemental calcium/day) as compared to standard high-dose calcium supplementation (1500 mg elemental calcium/day) among nulliparous pregnant women. Pregnant women will be enrolled in the trial before 20 weeks of gestation and will receive the randomized calcium regimen from randomization until the time of delivery. The co-primary outcomes are (i) preeclampsia and (ii) preterm birth; we will test non-inferiority of the primary outcomes for low-dose as compared to the standard high-dose supplementation regimen in each trial. The trials' secondary outcomes include gestational hypertension, severe features of preeclampsia, pregnancy-related death, third trimester severe anemia, fetal death, stillbirth, low birthweight, small-for-gestational age birth, and infant death. DISCUSSION: The trials will provide causal evidence on the non-inferiority of low-dose as compared to the standard high-dose supplementation in India and Tanzania. A single tablet, low-dose calcium supplementation regimen may improve individual-level adherence, reduce programmatic costs, and ultimately expand implementation of routine calcium supplementation in pregnancy in populations with low dietary calcium intake. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03350516 ; registered on 22 November 2018. Clinical Trials Registry-India identifier: CTRI/2018/02/012119 ; registered on 23 February 2018. Tanzania Medicines and Medical Devices Authority Trials Registry identifier: TFDA0018/CTR/0010/5 ; registered on 20 December 2018.

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.

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.

Willingness and ability to pay for healthcare insurance: A cross-sectional study of Seven Communities in East and West Africa (SevenCEWA).

Willingness and ability to pay for insurance that would cover primary healthcare services has not been evaluated consistently in different African communities. We conducted a cross-sectional community health survey and examined willingness and ability to pay in 3676 adults in seven communities in four countries: Nigeria, Tanzania, Uganda and Kenya. We used an open-ended contingency valuation method to estimate willingness to pay and examined ability to pay indirectly by calculating the ratio of healthcare expenditure to total household income. Slightly more than three quarters (78.8%) of participants were willing to pay for a health insurance scheme, and just a little above half (54.7%) were willing to pay for all household members. Across sites, median amount willing to pay was $2 per person per month. A little above half (57.6%) of households in Nigeria were able to pay the premium. The main predictors of likelihood of being unwilling to pay for the health insurance scheme were increasing age [aOR 0.99 (95% CI 0.98, 1.00)], being female [0.68 (0.51, 0.92], single [0.32 (0.21, 0.49)], unemployment [0.54 (0.34, 0.85)], being enrolled in another health insurance scheme [0.45 (0.28, 0.74)] and spending more on healthcare [1.00 (0.99, 1.00)]. But being widow [2.31 (1.30, 4.10)] and those with primary and secondary education [2.23 (1.54, 3.22)] had increased likelihood of being willing to pay for health insurance scheme. Retired respondents [adjusted mean difference $-3.79 (-7.56, -0.02)], those with primary or secondary education [$-3.05 (-5.42, -0.68)] and those with high healthcare expenditure [$0.02 (0.00, 0.04)] predicted amount willing to pay for health insurance scheme. The willingness to pay for health insurance scheme is high among the seven communities studied in East and West Africa with socio-demography, economic and healthcare cost as main predictive factors.

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.

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.

Prevalence, Awareness, Treatment, and Control of Hypertension among Young and Middle-Aged Adults: Results from a Community-Based Survey in Rural Tanzania.

BACKGROUND: Hypertension, which is the single most important risk factor for CVDs, is increasing at an alarming rate in most developing countries. This study estimated the prevalence, awareness, treatment, and control of hypertension among young and middle-aged adults in rural Morogoro, Tanzania. Furthermore, it explored factors associated with both prevalence and awareness of hypertension. METHODS: A cross-sectional survey was conducted as part of the cluster randomized controlled study of community health workers (CHWs) interventions for reduction of blood pressure in a randomly selected sample of young and middle-aged population in rural Morogoro. Sociodemographics, lifestyle-related factors, history of diagnosis, and treatment for hypertension were collected using a questionnaire adopted from the STEPS survey tool. Blood pressure, height, and weight were measured at home following standard procedures. Descriptive statistics were used to estimate prevalence, awareness, treatment, and control of hypertension. Multiple logistic regression models were used to assess determinants of hypertension and awareness. RESULT: The prevalence of hypertension was 29.3% (95% CI: 27.7-31.0). Among individuals with hypertension, only 34.3% were aware of their hypertension status. Only around one-third (35.4%) of those who were aware of their hypertension status were currently on antihypertensive medication. Hypertension control was attained in only 29.9% among those on medications. Older age (p < 0.001), use of raw table salt (p < 0.001), and being overweight/obese (p < 0.001) were associated with hypertension. Predictors of awareness of hypertension status were older age, being a female, higher socioeconomic status, use of raw table salt, a history of diabetes, and overweight/obesity (all p < 0.001). Alcohol drinking was associated with low awareness for hypertension status (p < 0.001). CONCLUSION: There is high prevalence of hypertension with low rates of awareness, treatment, and control among young and middle-aged adults in rural Tanzania. Community-level health promotion and screening campaigns for hypertension and other CVD risk factors should be intensified.