We present the design, methods and population characteristics of a large community trial that assessed the efficacy of a weekly supplement containing vitamin A or beta-carotene, at recommended ...dietary levels, in reducing maternal mortality from early gestation through 12 weeks postpartum. We identify challenges faced and report solutions in implementing an intervention trial under low-resource, rural conditions, including the importance of population choice in promoting generalizability, maintaining rigorous data quality control to reduce inter- and intra- worker variation, and optimizing efficiencies in information and resources flow from and to the field.
This trial was a double-masked, cluster-randomized, dual intervention, placebo-controlled trial in a contiguous rural area of ~435 sq km with a population of ~650,000 in Gaibandha and Rangpur Districts of Northwestern Bangladesh. Approximately 120,000 married women of reproductive age underwent 5-weekly home surveillance, of whom ~60,000 were detected as pregnant, enrolled into the trial and gave birth to ~44,000 live-born infants. Upon enrollment, at ~ 9 weeks' gestation, pregnant women received a weekly oral supplement containing vitamin A (7000 ug retinol equivalents (RE)), beta-carotene (42 mg, or ~7000 ug RE) or a placebo through 12 weeks postpartum, according to prior randomized allocation of their cluster of residence. Systems described include enlistment and 5-weekly home surveillance for pregnancy based on menstrual history and urine testing, weekly supervised supplementation, periodic risk factor interviews, maternal and infant vital outcome monitoring, birth defect surveillance and clinical/biochemical substudies.
The primary outcome was pregnancy-related mortality assessed for 3 months following parturition. Secondary outcomes included fetal loss due to miscarriage or stillbirth, infant mortality under three months of age, maternal obstetric and infectious morbidity, infant infectious morbidity, maternal and infant micronutrient status, fetal and infant growth and prematurity, external birth defects and postnatal infant growth to 3 months of age.
Aspects of study site selection and its "resonance" with national and rural qualities of Bangladesh, the trial's design, methods and allocation group comparability achieved by randomization, field procedures and innovative approaches to solving challenges in trial conduct are described and discussed. This trial is registered with http://Clinicaltrials.gov as protocol NCT00198822.
Although safe motherhood strategies recommend that women seek timely care from health facilities for obstetric complications, few studies have described facility availability of emergency obstetric ...care (EmOC). We sought to describe and compare availability and readiness to provide EmOC among public and private health facilities commonly visited for pregnancy-related complications in two districts of northwest Bangladesh. We also described aspects of financial and geographic access to healthcare and key constraints to EmOC provision.
Using data from a large population-based community trial, we identified and surveyed the 14 health facilities (7 public, 7 private) most frequently visited for obstetric complications and near misses as reported by women. Availability of EmOC was based on provision of medical services, assessed through clinician interviews and record review. Levels of EmOC availability were defined as basic or comprehensive. Readiness for EmOC provision was based on scores in four categories: staffing, equipment, laboratory capacity, and medicines. Readiness scores were calculated using unweighted averages. Costs of C-section procedures and geographic locations of facilities were described. Textual analysis was used to identify key constraints.
The seven surveyed private facilities offered comprehensive EmOC compared to four of the seven public facilities. With 100% representing full readiness, mean EmOC readiness was 81% (range: 63%-91%) among surveyed private facilities compared to 67% (range: 48%-91%) in public facilities (p = 0.040). Surveyed public clinics had low scores on staffing and laboratory capacity (69%; 50%). The mean cost of the C-section procedure in private clinics was $77 (standard deviation: $16) and free in public facilities. The public sub-district facilities were the only facilities located in rural areas, with none providing comprehensive EmOC. Shortages in specialized staff were listed as the main barrier to EmOC provision in public facilities.
Although EmOC availability and readiness was higher among the surveyed seven most commonly visited private clinics, public facilities appeared to be more affordable for C-section and more geographically accessible. Strategies to retain anesthesiologists and surgeons, such as non-financial incentives, are needed to improve EmOC provision in the public sector. Centralized blood banks are recommended to streamline safe blood acquisition for obstetric surgeries.
Vitamin A supplementation (VAS) for children aged 6-59 months occurs regularly in most sub-Saharan African countries. The present study aimed to explore child, household and delivery platform factors ...associated with VAS coverage and identify barriers to compliance in thirteen African countries.
We pooled data (n ~60 000) from forty-four household coverage surveys and used bivariate and multivariable regression analyses to assess the effects of supplementation strategy, rural v. urban residence, child sex, child age, caregiver education and campaign awareness on child VAS status. Setting/Subjects Primary caregivers of children aged 6-59 months in thirteen countries.
Door-to-door distribution resulted in higher VAS coverage than fixed-site plus outreach approaches (91 v. 63 %) and was a significant predictor of supplementation in the adjusted model (OR=19·0; 95 % CI 17·2, 21·1; P<0·001). Having been informed about the campaign was the main predictor of VAS in the door-to-door (OR=6·8; 95 % CI 5·8, 7·9; P<0·001) and fixed-site plus outreach (OR=72·5; 95 % CI 66·6, 78·8; P<0·001) groups.
Door-to-door provision of VAS may achieve higher coverage than fixed-site models in the African context. However, the phase-out of door-to-door polio immunization campaigns in most sub-Saharan African countries threatens the main distribution vehicle for VAS. Our findings suggest well-informed communities are key to attaining higher coverage using fixed-site delivery alternatives.
Growth failure in sub-Saharan Africa leads to a high prevalence of child stunting starting in infancy, and is attributed to dietary inadequacy, poor hygiene, and morbidity.
To evaluate the impact of ...a program in Malawi providing a lipid-based nutrient supplement to infants from 6–23 months of age, accompanied by a social and behavior change communication intervention to optimize caregiver feeding and handwashing practices.
This impact evaluation was a quasi-experimental, longitudinal study with 1 program and 1 comparison district. Infants were enrolled at 6–7 months of age. Anthropometry, child morbidity, and caregiver feeding and handwashing practices were assessed at enrollment and at 6, 12, and 18 month follow-ups (ages 6, 12, 18, and 24 months, respectively). Changes in the length-for-age z-score (LAZ), weight-for-length z-score (WLZ), and midupper arm circumference (MUAC) were compared using mixed-effects models. Program impacts on child stunting (LAZ < −2), wasting (WLZ < −2), morbidity, and feeding and handwashing practices were estimated using difference-in-differences.
We enrolled 367 infants across the program (n = 176) and comparison (n = 191) districts. The combined prevalences of stunting and wasting at enrollment were 42.1% and 1.4%, respectively, and did not differ by district. At enrollment, the prevalence of severe stunting (LAZ < −3) was higher in the program (15.5%) versus comparison (7.6%) district (P = 0.02), with corresponding lower LAZ scores (−1.9 vs. −1.7, respectively; P = 0.12). Growth velocities favored program children, such that LAZ, WLZ, and MUAC measurements increased by +0.12/y (P = 0.06), +0.12/y (P = 0.04), and +0.24 cm/y (P < 0.001), respectively, leading to comparable LAZ distributions across districts by 24 months of age. Program exposure was associated with 19.8 percentage point (pp) and 13.8 pp reductions in the prevalences of malaria (P = 0.001) and fever (P = 0.02), respectively, at the 18-month follow-up. Improvements of 20 pp (P < 0.01) in minimum dietary diversity and minimum acceptable diet were seen in the program versus comparison district at 18 months of follow-up.
The program improved child growth patterns, with benefits to health and diet apparent after 18 months of exposure. This trial was registered at clinicaltrials.gov as NCT02985359.
▪
Household food insecurity (HFI) can lead to a poor diet and malnutrition. Yet, little is known about the extent to which maternal diet covaries with food insecurity during pregnancy and lactation.
...Longitudinal associations between HFI and maternal dietary diversity from early pregnancy to 3 mo postpartum were examined in rural Bangladesh.
We repeatedly assessed dietary intake by using a 7-d food-frequency questionnaire in the first and third trimesters of pregnancy and at 3 mo postpartum among 14,600 women enrolled into an antenatal micronutrient supplementation trial. Maternal dietary diversity score (DDS) was constructed as the sum of 10 food groups reportedly consumed at each assessment. Households were classified at 6 mo postpartum as being food secure or having mild, moderate, or severe HFI on the basis of a 9-item standard scale. Generalized estimating equations were used to estimate the longitudinal relation between HFI status and DDS and the likelihood of individual food-group consumption, adjusting for confounders at the maternal and household levels.
The DDS decreased with progressively worse HFI, an association best explained by a derived household wealth index. Compared with women from food-secure households, women of mild, moderate, and severe HFI were less likely, in a dose-response fashion, to have consumed dairy products adjusted ORs (95% CIs): 0.73 (0.69, 0.78), 0.62 (0.58, 0.66), and 0.52 (0.48, 0.55), respectively, eggs 0.81 (0.76, 0.85), 0.73 (0.68, 0.77), and 0.61 (0.57, 0.65), meat 0.83 (0.79, 0.88), 0.73 (0.69, 0.78), and 0.60 (0.56, 0.64), fish 0.87 (0.80, 0.94), 0.76 (0.70, 0.83), and 0.59 (0.54, 0.65), legumes and nuts 0.88 (0.83, 0.93), 0.81 (0.76, 0.87), and 0.79 (0.74, 0.85), and yellow and orange fruit and vegetables 0.85 (0.80, 0.91), 0.78 (0.73, 0.84), and 0.72 (0.67, 0.78). Neither intakes of dark-green leafy vegetables nor of vegetable oil were associated with HFI status.
Antenatal and postnatal maternal dietary diversity, especially intakes of animal-source foods, fruit, and vegetables, declined with worsening food insecurity in rural Bangladesh.
Maternal vitamin A deficiency is a public health concern in the developing world. Its prevention may improve maternal and infant survival.
To assess efficacy of maternal vitamin A or beta carotene ...supplementation in reducing pregnancy-related and infant mortality.
Cluster randomized, double-masked, placebo-controlled trial among pregnant women 13 to 45 years of age and their live-born infants to 12 weeks (84 days) postpartum in rural northern Bangladesh between 2001 and 2007. Interventions Five hundred ninety-six community clusters (study sectors) were randomized for pregnant women to receive weekly, from the first trimester through 12 weeks postpartum, 7000 μg of retinol equivalents as retinyl palmitate, 42 mg of all-trans beta carotene, or placebo. Married women (n = 125,257) underwent 5-week surveillance for pregnancy, ascertained by a history of amenorrhea and confirmed by urine test. Blood samples were obtained from participants in 32 sectors (5%) for biochemical studies.
All-cause mortality of women related to pregnancy, stillbirth, and infant mortality to 12 weeks (84 days) following pregnancy outcome.
Groups were comparable across risk factors. For the mortality outcomes, neither of the supplement group outcomes was significantly different from the placebo group outcomes. The numbers of deaths and all-cause, pregnancy-related mortality rates (per 100,000 pregnancies) were 41 and 206 (95% confidence interval CI, 140-273) in the placebo group, 47 and 237 (95% CI, 166-309) in the vitamin A group, and 50 and 250 (95% CI, 177-323) in the beta carotene group. Relative risks for mortality in the vitamin A and beta carotene groups were 1.15 (95% CI, 0.75-1.76) and 1.21 (95% CI, 0.81-1.81), respectively. In the placebo, vitamin A, and beta carotene groups the rates of stillbirth and infant mortality were 47.9 (95% CI, 44.3-51.5), 45.6 (95% CI, 42.1-49.2), and 51.8 (95% CI, 48.0-55.6) per 1000 births and 68.1 (95% CI, 63.7-72.5), 65.0 (95% CI, 60.7-69.4), and 69.8 (95% CI, 65.4-72.3) per 1000 live births, respectively. Vitamin A compared with either placebo or beta carotene supplementation increased plasma retinol concentrations by end of study (1.46 95% CI, 1.42-1.50 μmol/L vs 1.13 95% CI, 1.09-1.17 μmol/L and 1.18 95% CI, 1.14-1.22 μmol/L, respectively; P < .001) and reduced, but did not eliminate, gestational night blindness (7.1% for vitamin A vs 9.2% for placebo and 8.9% for beta carotene P < .001 for both).
Use of weekly vitamin A or beta carotene in pregnant women in Bangladesh, compared with placebo, did not reduce all-cause maternal, fetal, or infant mortality.
clinicaltrials.gov Identifier: NCT00198822.
Vitamin A deficiency remains a nutritional concern in sub-Saharan Africa. Conventionally bred maize hybrids with high provitamin A carotenoid concentrations may have the potential to improve vitamin ...A status in maize-consuming populations.
We evaluated the efficacy of regular provitamin A carotenoid-biofortified "orange" maizemeal (∼15 μg β-carotene/g) consumption in improving vitamin A status and reducing vitamin A deficiency in children.
This was a cluster-randomized controlled trial in the rural farming district of Mkushi, Zambia. All 4- to 8-y-old children in an ∼400-km(2) area were identified and grouped by proximity into clusters of ∼15-25 children. We randomly assigned clusters to 1) orange maizemeal (n = 25), 2) white maizemeal (n = 25), or 3) a parallel, nonintervention group (n = 14). Children in intervention clusters (n = 1024) received 200 g maizemeal for 6 d/wk over 6 mo; the maizemeal was prepared according to standardized recipes and served in cluster-level kitchens. Staff recorded attendance and leftovers. We collected venous blood before and after the intervention to measure serum retinol, β-carotene, C-reactive protein, and α1-acid glycoprotein.
Intervention groups were comparable at baseline, and vitamin A status was better than anticipated (12.1% deficient on the basis of serum retinol <0.7 μmol/L). Although attendance at meals did not differ (85%), median daily maize intake was higher in white (154 g/d) than in orange (142 g/d) maizemeal clusters. At follow-up, mean serum β-carotene was 0.14 μmol/L (95% CI: 0.09, 0.20 μmol/L) higher in orange maizemeal clusters (P < 0.001), but mean serum retinol (1.00 ± 0.33 μmol/L overall) and deficiency prevalence (17.1% overall) did not differ between arms.
In this marginally nourished population, regular biofortified maizemeal consumption increased serum β-carotene concentrations but did not improve serum retinol. This trial was registered at clinicaltrials.gov as NCT01695148.
To evaluate the impact of a peer facilitator (PF) approach for improving mothers' knowledge and practices relating to maternal and child nutrition.
A quasi-experimental design nested within a ...large-scale integrated nutrition programme, Suaahara, in Nepal. Suaahara interventions were implemented in all study sites, but peer facilitators were used in only half of the study sites.
Rural, disadvantaged villages in three districts of Nepal: Bhojpur, Bajhang and Rupandehi.
Mothers of children aged 6-23·9 months (n 1890).
Differences over time between comparison (C) and intervention (I) groups show that the PF approach had a significant positive impact on several indicators of mothers' knowledge and practices relating to maternal and child nutrition: (i) knowing that fruits and vegetables are good for children 6-23·9 months (C: -0·7, I: 10·6; P=0·03); (ii) child dietary diversity (C: 0·02, I: 0·04; P=0·02); (iii) child minimum dietary diversity (≥4 of 7 food groups; (C: 6·9, I: 16·0; P=0·02); (iv) maternal dietary diversity (C: 0·1, I: 0·4; P=0·01); and (v) maternal minimum dietary diversity (≥4 food groups; C: 3·6, I: 14·0; P=0·03). Additionally, exposure to a PF three or more times in the past 6 months was positively associated with a small improvement in maternal (β=0·06, P=0·04) and child (β=0·06, P=0·02) dietary diversity scores. Improvements were not observed in maternal health-seeking behaviours such as number of antenatal care visits.
Peer mobilization is a potential approach for improving health- and nutrition-related knowledge and behaviours among women in hard-to-reach communities of Nepal.
Background: Tocopherols were discovered for their role in animal reproduction, but little is known about the contribution of deficiencies of vitamin E to human pregnancy loss. Objective: We sought to ...determine whether higher first-trimester concentrations of α-tocopherol and γ-tocopherol were associated with reduced odds of miscarriage (pregnancy losses <24 wk of gestation) in women in rural Bangladesh. Design: A case-cohort study in 1605 pregnant Bangladeshi women median (IQR) gestational age: 10 wk (8–13 wk) who participated in a placebo-controlled vitamin A– or β-carotene–supplementation trial was done to assess ORs of miscarriage in women with low α-tocopherol (<12.0 μmol/L) and γ-tocopherol (<0.81 μmol/L; upper tertile cutoff of the γ-tocopherol distribution in women who did not miscarry). Results: In all women, plasma α- and γ-tocopherol concentrations were low median (IQR): 10.04 μmol/L (8.07–12.35 μmol/L) and 0.66 μmol/L (0.50–0.95 μmol/L), respectively. In a logistic regression analysis that was adjusted for cholesterol and the other tocopherol, low α-tocopherol was associated with an OR of 1.83 (95% CI: 1.04, 3.20), whereas a low γ-tocopherol concentration was associated with an OR of 0.62 (95% CI: 0.41, 0.93) for miscarriage. Subgroup analyses revealed that opposing ORs were evident only in women with BMI (in kg/m ²) ≥18.5 and serum ferritin concentration ≤150 μg/L, although low BMI and elevated ferritin conferred stronger risk of miscarriage. Conclusions: In pregnant women in rural Bangladesh, low plasma α-tocopherol was associated with increased risk of miscarriage, and low γ-tocopherol was associated with decreased risk of miscarriage. Maternal vitamin E status in the first trimester may influence risk of early pregnancy loss. The JiVitA-1 study, from which data for this report were derived, was registered at clinicaltrials.gov as NCT00198822.
We assessed the effect of supplementing newborns with 50000 IU of vitamin A on all-cause infant mortality through 24 weeks of age.
This was a community-based, double-masked, cluster-randomized, ...placebo-controlled trial conducted in 19 unions in rural northwest Bangladesh. The study was nested into and balanced across treatment arms of an ongoing placebo-controlled, weekly maternal vitamin A or beta-carotene supplementation trial. Study-defined sectors (N = 596) were evenly randomized for newborns of participating mothers to receive a single, oral supplement of vitamin A (50000 IU) or placebo as droplets of oil squeezed from a gelatinous capsule. Mothers provided informed consent for newborn participation at approximately 28 weeks' gestation. After birth, typically at home (where >90% of births occurred), infants were supplemented and their vital status was followed through 24 weeks of age. The main outcome measure was mortality through 24 weeks of age.
We obtained maternal consent to dose 17116 live-born infants (99.8% of all eligible) among whom 15937 (93.1%) were visited to be supplemented <30 days after birth and for whom vital status at 24 weeks of age was known. Dosed infants (n = 15902 99.8%) received their study supplement at a median age of 7 hours. Relative to control subjects, the risk of death in vitamin A-supplemented infants was 0.85, reflecting a 15% reduction in all-cause mortality. Protective relative risks were indistinguishable by infant gender, gestational age, birth weight, age at dosing, maternal age, parity, or across the 3 treatment arms of the maternal supplementation trial.
Newborn vitamin A dosing improved infant survival through the first 6 months of life in Bangladesh. These results corroborate previous findings from studies in Indonesia and India and provide additional evidence that vitamin A supplementation shortly after birth can reduce infant mortality in South Asia.
PDF
