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.
Abstract Objective B1a lymphocytes—which constitutively produce most natural antibodies (NAb)—arise from an early wave of progenitors unique to fetal life. Vitamin A regulates early lymphopoiesis. In ...animals, deficiency during this critical period compromises B1 cell populations. The aim of this study was to investigate the effect of maternal supplementation with vitamin A or β-carotene from preconception through lactation on NAb concentrations of offspring. Methods Participants (N = 290) were born to participants of a cluster-randomized, placebo-controlled trial of weekly maternal vitamin A or β-carotene supplementation (7000 μg retinol equivalents) conducted in Sarlahi, Nepal (1994–1997) and assessed at ages 9 to 13 y (2006–2008). Serum retinol was measured by reversed-phase high-performance liquid chromatography at mid-pregnancy and 3 mo of age. Enzyme-linked immunosorbent assay (ELISA) was used to measure children's plasma NAb concentrations at 9 to 13 y. Results Unadjusted geometric mean concentrations were 20.08 U/mL (95% confidence interval CI, 17.82–22.64) in the vitamin A group compared with 17.64 U/mL (95% CI, 15.70–19.81) and 15.96 U/mL (95% CI, 13.43–18.96) in the β-carotene and placebo groups ( P = 0.07), respectively. After adjustment, maternal vitamin A supplementation was associated with a 0.39 SD increase in NAb concentrations ( P = 0.02). The effect was mediated by infant serum retinol in our statistical models. Although girls had 1.4-fold higher NAb concentrations ( P < 0.001), sex did not modify the vitamin A effect. Conclusions In an undernourished population, maternal vitamin A supplementation enhanced NAb concentrations of preadolescent children. We posit that this was due to a greater allotment of B1a precursors during fetal life and a sustained higher count of NAb-secreting B1a cells.
Subclinical micronutrient deficiencies remain a hidden aspect of malnutrition for which comprehensive data are lacking in school-aged children. We assessed the micronutrient status of Nepalese ...children, aged 6 to 8 y, born to mothers who participated in a community-based antenatal micronutrient supplementation trial from 1999 to 2001. Of 3305 participants, plasma indicators were assessed in a random sample of 1000 children. Results revealed deficiencies of vitamins A (retinol <0.70 μ mol/L, 8.5%), D (25-hydroxyvitamin D <50 nmol/L, 17.2%), E (α-tocopherol <9.3 μ mol/L, 17.9%), K (decarboxy prothombin >2 μ g/L, 20%), B-12 (cobalamin <150 pmol/L, 18.1%), B-6 pyridoxal-5′-phosphate (PLP) <20 nmol/L, 43.1%, and β-carotene (41.5% <0.09 μ mol/L), with little folate deficiency (6.2% <13.6 nmol/L). Deficiencies of iron ferritin <15 μ g/L, 10.7%; transferrin receptor (TfR) >8.3 mg/L, 40.1%; TfR:ferritin >500 μ g/μ g, 14.3%, iodine (thyroglobulin >40 μ g/L, 11.4%), and selenium (plasma selenium <0.89 μ mol/L, 59.0%) were observed, whereas copper deficiency was nearly absent (plasma copper <11.8 μ mol/L, 0.7%). Hemoglobin was not assessed. Among all children, 91.7% experienced at least 1 micronutrient deficiency, and 64.7% experienced multiple deficiencies. Inflammation (α-1 acid glycoprotein >1 g/L, C-reactive protein >5 mg/L, or both) was present in 31.6% of children, affecting the prevalence of deficiency as assessed by retinol, β-carotene, PLP, ferritin, TfR, selenium, copper, or having any or multiple deficiencies. For any nutrient, population deficiency prevalence estimates were altered by ≤5.4% by the presence of inflammation, suggesting that the majority of deficiencies exist regardless of inflammation. Multiple micronutrient deficiencies coexist in school-aged children in rural Nepal, meriting more comprehensive strategies for their assessment and prevention.
Optimal breastfeeding practices, reflected by early initiation and feeding of colostrum, avoidance of prelacteal feeds, and continued exclusivity or predominance of breastfeeding, are critical for ...assuring proper infant nutrition, growth and development.
We used data from a nationally representative survey in 21 district sites across the Mountains, Hills and Terai (southern plains) of Nepal in 2013. Determinants of early initiation of breastfeeding, feeding of colostrum, prelacteal feeding and predominant breastfeeding were explored in 1015 infants < 12 months of age. Prelacteal feeds were defined as food/drink other than breast milk given to newborns in first 3 days. Predominant breastfeeding was defined as a child < 6 months of age is mainly breastfed, not fed solid/semi-solid foods, infant formula or non-human milk, in the past 7 days. Adjusted prevalence ratios (APR) and 95% confidence intervals (CI) were estimated, using log Poisson regression models with robust variance for clustering.
The prevalence of breastfeeding within an hour of birth, colostrum feeding, prelacteal feeding and predominant breastfeeding was 41.8, 83.5, 32.7 and 57.2% respectively. Compared to infants not fed prelacteal feeds, infants given prelacteal feeds were 51% less likely to be breastfed within the first hour of birth (APR 0.49; 95% CI 0.36, 0.66) and 55% less likely to be predominantly breastfed (APR 0.45; 95% CI 0.32, 0.62). Infants reported to have received colostrum were more likely to have begun breastfeeding within an hour of birth (APR 1.26; 95% CI 1.04, 1.54) compared to those who did not receive colostrum. Infants born to mothers ≥ 20 years of age were less likely than adolescent mothers to initiate breastfeeding within 1 hour of birth. Infants in the Terai were 10% less likely to have received colostrum (APR 0.90; 95% CI 0.83, 0.97) and 2.72 times more likely to have received prelacteal feeds (APR 2.72; 95% CI 1.67, 4.45) than those in the Mountains.
Most infants in Nepal receive colostrum but less than half initiate breastfeeding within an hour of birth and one-third are fed prelacteal feeds, which may negatively affect breastfeeding and health throughout early infancy.
To understand which anthropometric diagnostic criteria best discriminate higher from lower risk of death in children and explore programme implications.
A multiple cohort individual data ...meta-analysis of mortality risk (within 6 months of measurement) by anthropometric case definitions. Sensitivity, specificity, informedness and inclusivity in predicting mortality, face validity and compatibility with current standards and practice were assessed and operational consequences were modelled.
Community-based cohort studies in twelve low-income countries between 1977 and 2013 in settings where treatment of wasting was not widespread.
Children aged 6 to 59 months.
Of the twelve anthropometric case definitions examined, four (weight-for-age
-score (WAZ) <-2), (mid-upper arm circumference (MUAC) <125 mm), (MUAC < 115 mm or WAZ < -3) and (WAZ < -3) had the highest informedness in predicting mortality. A combined case definition (MUAC < 115 mm or WAZ < -3) was better at predicting deaths associated with weight-for-height
-score <-3 and concurrent wasting and stunting (WaSt) than the single WAZ < -3 case definition. After the assessment of all criteria, the combined case definition performed best. The simulated workload for programmes admitting based on MUAC < 115 mm or WAZ < -3, when adjusted with a proxy for required intensity and/or duration of treatment, was 1·87 times larger than programmes admitting on MUAC < 115 mm alone.
A combined case definition detects nearly all deaths associated with severe anthropometric deficits suggesting that therapeutic feeding programmes may achieve higher impact (prevent mortality and improve coverage) by using it. There remain operational questions to examine further before wide-scale adoption can be recommended.
Low birth weight predicts risk of infant death. However, several birth measurements may be equally predictive, for which cutoffs and associated risks are less explored.
We assessed and optimized ...population cutoffs of birth length, weight, and midupper arm circumference (MUAC), head circumference (HC), and chest circumference (CC) for predicting neonatal (≤28 d) and infant (≤365 d) mortality in northwest Bangladesh.
Among 28,026 singletons born in an antenatal micronutrient supplement trial, 21,174 received anthropometry ≤72 h after birth, among whom 583 died in infancy. Optimization for predicting mortality for each measurement was guided by the Youden Index (sensitivity + specificity – 1). Relative risk ratios (RRRs) and positive predictive values (PPVs) were calculated across cutoff ranges for individual and any pair of measurements.
Optimal cutoffs, harmonized to 100-g or 0.5-cm readings, for neonatal and infant mortality were 44.5 cm for length, 2200 g for weight, 9.0 cm for MUAC, 31.0 cm for HC, and 28.5 cm for CC, below which all predicted mortality. However, a CC <28.5 cm, alone and combined with HC <31.0 cm, yielded the highest RRR 9.68 (95% CI: 7.84, 11.94) and 15.74 (95% CI: 12.54, 19.75), respectively and PPV (11.3% and 10.7%) for neonatal mortality and highest RRR 6.02 (95% CI: 5.15, 7.02) and 9.19 (95% CI: 7.72, 10.95) and PPV (16.3% and 14.5%) for infant mortality. Pairs of measurements revealed a higher RRR for neonatal and infant mortality than individual measurements of any one pair, although the ranges of PPV remained comparable.
In Bangladesh, multiple birth measurements alone or in combination, particularly chest circumference, predict neonatal and infant mortality.
Provitamin A carotenoid-biofortified maize is a conventionally bred staple crop designed to help prevent vitamin A deficiency. Lactating women are a potential target group, because regularly eating ...biofortified maize may increase vitamin A in breast milk-a critical source of vitamin A for breastfeeding infants.
We assessed whether daily consumption of biofortified orange maize would increase the retinol concentration in the breast milk of Zambian women.
Lactating women (n = 149) were randomly assigned to receive orange maize delivering 600 μg retinol equivalents (REs)/d as carotenoid plus placebo (OM), low-carotenoid white maize plus 600 μg REs/d as retinyl palmitate (VA), or white maize plus placebo (WM). Boiled maize (287 g dry weight/d) was served as 2 meals/d, 6 d/wk for 3 wk. We measured initial and final breast milk plasma retinol and β-carotene concentrations, and plasma inflammatory protein concentrations.
Groups were comparable at enrollment, with an overall geometric mean milk retinol concentration of 0.95 μmol/L (95% CI: 0.86, 1.05 μmol/L); 56% of samples had milk retinol <1.05 μmol/L. Median capsule and maize intake was 97% and 258 g dry weight/d, respectively. Final milk β-carotene did not vary across groups (P = 0.76). Geometric mean (95% CI) milk retinol concentration tended to be higher in the OM 1.15 μmol/L (0.96, 1.39 μmol/L) and VA 1.17 μmol/L (0.99, 1.38 μmol/L) groups than in the WM group 0.91 μmol/L (0.72, 1.14 μmol/L); P = 0.13, and the proportion of women with milk retinol <1.05 μmol/L was 52.1%, 42.9%, and 36.7% in the WM, OM, and VA groups, respectively (P-trend = 0.16).
Daily biofortified maize consumption did not increase mean milk retinol concentration in lactating Zambian women; however, there was a plausible downward trend in the risk of low milk retinol across intervention groups. This trial was registered at clinicaltrials.gov as NCT01922713.
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.
Perception-based Likert scale are commonly used to assess household food insecurity. The aim of this study was to evaluate the psychometric properties and external construct validity of the 9-item ...Food Access Survey Tool (FAST) in a population-based randomized controlled trial.
Participating women (n = 11,992) were asked to recall the frequencies of nine food insecurity experiences over the past 6 months on a 5-point Likert scale. The Rasch partial credit model was used to study the item category severity and differential item functioning (DIF) by literacy status, respondents' age, land ownership and household sizes. Principal component analysis (PCA), non-parametric methods, and cumulative ordinal logistic regression models were applied to examine the Rasch model assumptions, namely unidimensionality, monotonicity and measurement invariance (non-DIF).
All items demonstrated good model fit with acceptable values of fit statistics (infit). PCA as well as other indices (Cronbach's alpha = 0.85, scalability coefficient = 0.48) indicated that all items fit in a single statistical dimension. The ordered responses of nine items displayed monotonic increasing item category severity as expected theoretically. All nine items were flagged with statistically significant DIF between key demographic-and socioeconomic subgroups (p < 0.001); however, none of the detected DIF was considered practically significant given small effect sizes (variance explained by group membership and interaction term < 1%). The total summed score over the polytomous FAST was inversely associated with household wealth, dietary diversity score and maternal body mass index, demonstrating external construct validity.
The polytomous FAST is internally and externally valid tool to measure household food insecurity in rural Bangladesh. Validation of this type of studies are recommended for similar Likert food insecurity scales.
Prevalence of young adult hearing loss is high in low-resource societies; the reasons for this are likely complex but could involve early childhood undernutrition.
We evaluated preschool childhood ...stunting, wasting, and underweight as risk factors for hearing loss in young adulthood in Sarlahi District, southern Nepal.
Ear health was assessed in 2006–2008 in a cohort of 2193 subjects aged 16–23 y, who as children <60 mo of age participated in a 16-mo placebo-controlled, randomized vitamin A supplementation trial from 1989 to 1991. At each of five 4-mo assessments, field staff measured children's weight, height, and mid-upper arm circumference (MUAC) and recorded validated parental history of ear discharge in the previous 7 d. Children were classified as stunted <–2 z score height-for-age (HAZ), underweight <–2 z score weight-for-age (WAZ), or wasted <–2 z score MUAC-for-age (MUACAZ) or body mass index-for-age (BMIAZ). At follow-up, hearing was tested by audiometry and tympanometry, with hearing loss defined as pure-tone average >30dB in the worse ear (0.5, 1, 2, 4 kHz) and middle-ear dysfunction as abnormal tympanometric peak height (<0.3 or >1.4 mmho) or width (<50 or >110 daPa).
Hearing loss, present in 5.9% (95% CI: 5.01%, 7.00%) of subjects, was associated with early childhood stunting (OR: 1.64; 95% CI: 1.10, 1.45), underweight (OR: 1.70; 95% CI: 1.18, 2.44) and wasting by BMIAZ (OR: 1.88; 95% CI: 1.19, 2.97) and MUACAZ (OR: 2.14; 95% CI: 1.47, 3.12). Abnormal tympanometry, affecting 16.6% (95% CI: 15.06%, 18.18%), was associated with underweight (OR: 1.46; 95% CI: 1.16, 1.84) and wasting by BMIAZ (OR: 1.80; 95% CI: 1.32, 2.46) and MUACAZ (OR: 1.42; 95% CI: 1.10, 1.84), but not stunting (OR: 1.18; 95% CI: 0.93, 1.49) in early childhood. Highest ORs were observed for subjects with both hearing loss and abnormal tympanometry, ranging from 1.87 to 2.24 (all lower 95% CI >1.00).
Early childhood undernutrition is a modifiable risk factor for early adulthood hearing loss.
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