Plasma proteome correlates of lipid and lipoprotein: biomarkers of metabolic diversity and inflammation in children of rural Nepal.

Proteins involved in lipoprotein metabolism can modulate cardiovascular health. While often measured to assess adult metabolic diseases, little is known about the proteomes of lipoproteins and their relation to metabolic dysregulation and underlying inflammation in undernourished child populations. The objective of this population study was to globally characterize plasma proteins systemically associated with HDL, LDL, and triglycerides in 500 Nepalese children. Abnormal lipid profiles characterized by elevated plasma triglycerides and low HDL-cholesterol (HDL-C) concentrations were common, especially in children with subclinical inflammation. Among 982 proteins analyzed, the relative abundance of 11, 12, and 52 plasma proteins was correlated with LDL-cholesterol (r = -0.43∼0.70), triglycerides (r = -0.39∼0.53), and HDL-C (r = -0.49∼0.79) concentrations, respectively. These proteins included apolipoproteins and numerous unexpected intracellular and extracellular matrix binding proteins, likely originating in hepatic and peripheral tissues. Relative abundance of two-thirds of the HDL proteome varied with inflammation, with acute phase reactants higher by 4∼40%, and proteins involved in HDL biosynthesis, cholesterol efflux, vitamin transport, angiogenesis, and tissue repair lower by 3∼20%. Untargeted plasma proteomics detects comprehensive sets of both known and novel lipoprotein-associated proteins likely reflecting systemic regulation of lipoprotein metabolism and vascular homeostasis. Inflammation-altered distributions of the HDL proteome may be predisposing undernourished populations to early chronic disease

Maternal vitamin A supplementation increases natural antibody concentrations of preadolescent offspring in rural Nepal

AbstractObjectiveB1a 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.MethodsParticipants (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.ResultsUnadjusted 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.ConclusionsIn 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

Adequacy of Iodine Status and Associations with Gut Health : A Prospective Cohort Study among Infants in 8 Low- and Middle-Income Countries

Peer reviewe

Bioelectrical Impedance among Rural Bangladeshi Women during Pregnancy and in the Postpartum Period

Properties of bioelectrical impedance analysis (BIA) reflect body-composition and may serve as stand-alone indicators of maternal health. Despite these potential roles, BIA properties during pregnancy and lactation in rural South Asian women have not been described previously, although pregnancy and infant health outcomes are often compromised. This paper reports the BIA properties among a large sample of pregnant and postpartum women of rural Bangladesh, aged 12-46 years, participating in a substudy of a community-based, placebo-controlled trial of vitamin A or beta-carotene supplementation. Anthropometry and single frequency (50 kHz) BIA were assessed in 1,435 women during the first trimester (≤12 weeks gestation), in 1,237 women during the third trimester (32-36 weeks gestation), and in 1,141 women at 12-18 weeks postpartum. Resistance and reactance were recorded, and impedance and phase angle were calculated. Data were examined cross-sectionally to maximize sample-size at each timepoint, and the factors relating to BIA properties were explored. Women were typically young, primiparous and lacking formal education (22.2±6.3 years old, 42.2% primiparous, and 39.7% unschooled among the first trimester participants). Weight (kg), resistance (Ω), and reactance (Ω) were 42.1±5.7, 688±77, and 73±12 in the first trimester; 47.7±5.9, 646±77, and 64±12 in the third trimester; and 42.7±5.6, 699±79, and 72±12 postpartum respectively. Resistance declined with age and increased with body mass index. Resistance was higher than that observed in other, non-Asian pregnant populations, likely reflecting considerably smaller body-volume among Bangladeshi women. Resistance and reactance decreased in advanced stage of pregnancy as the rate of gain in weight increased, returning to the first trimester values by the three months postpartum. Normative distributions of BIA properties are presented for rural Bangladeshi women across a reproductive cycle that may be related to pregnancy outcomes and ultimately be used for assessing body-composition in this population

Validation of Two Portable Instruments to Measure Iron Concentration in Groundwater in Rural Bangladesh

Iron is ubiquitous in natural water sources used around the world for drinking and cooking. The health impact of chronic exposure to iron through water, which in groundwater sources can reach well above the World Health Organization's defined aesthetic limit of 0.3 mg/L, is not currently understood. To quantify the impact of consumption of iron in groundwater on nutritional status, it is important to accurately assess naturally-occurring exposure levels among populations. In this study, the validity of iron quantification in water was evaluated using two portable instruments: the HACH DR/890 portable colorimeter (colorimeter) and HACH Iron test-kit, Model IR-18B (test-kit), by comparing field-based iron estimates for 25 tubewells located in northwestern Bangladesh with gold standard atomic absorption spectrophotometry analysis. Results of the study suggest that the HACH test-kit delivers more accurate point-of-use results across a wide range of iron concentrations under challenging field conditions

Iodine status in pregnancy and household salt iodine content in rural Bangladeshm cn_282 1..12

Abstract Adequate maternal iodine intake is essential during pregnancy for the development of the foetus. To assess the extent of iodine insufficiency and its association with household iodized salt in rural Bangladesh, we measured urinary iodine and household salt iodine content among pregnant women in early (Յ16 weeks, n = 1376) and late (Ն32 weeks, n = 1114) pregnancy. Salt (~20 g) and a spot urine sample (~10 mL) were collected from women participating in a randomized, placebo-controlled trial of vitamin A or beta-carotene supplementation in rural northwestern Bangladesh during home visits in early and late pregnancy. Salt iodine was analyzed by iodometric titration, and urinary iodine by the Ohashi method. Almost all salt samples had some detectable iodine, but over 75% contained &lt;15 ppm. Median (interquartile range) urinary iodine concentrations were 66 (34-133) and 55 (28-110) mg L -1 in early and late pregnancy, respectively; urinary iodine &lt;150 mg L -1 was found in~80% of women at both times in pregnancy. Although the risk of iodine insufficiency declined with increasing iodine content of household salt (P for trend &lt;0.05), median urinary iodine did not reach 150 mg L -1 until iodine in household salt was at least 32 ppm and 51 ppm during early and late pregnancy, respectively. Despite a national policy on universal salt iodization, salt iodine content remains insufficient to maintain adequate maternal iodine status throughout pregnancy in rural northern Bangladesh. Alternative measures like direct iodine supplementation during pregnancy could be considered to assure adequate iodine status during this high-risk period of life

Bioelectrical Impedance among Rural Bangladeshi Women during Pregnancy and in the Postpartum Period

Properties of bioelectrical impedance analysis (BIA) reflect body-composition and may serve as stand-alone indicators of maternal health. Despite these potential roles, BIA properties during pregnancy and lactation in rural South Asian women have not been described previously, although pregnancy and infant health outcomes are often compromised. This paper reports the BIA properties among a large sample of pregnant and postpartum women of rural Bangladesh, aged 12-46 years, participating in a substudy of a communitybased, placebo-controlled trial of vitamin A or beta-carotene supplementation. Anthropometry and single frequency (50 kHz) BIA were assessed in 1,435 women during the first trimester ( 6412 weeks gestation), in 1,237 women during the third trimester (32-36 weeks gestation), and in 1,141 women at 12-18 weeks postpartum. Resistance and reactance were recorded, and impedance and phase angle were calculated. Data were examined cross-sectionally to maximize sample-size at each timepoint, and the factors relating to BIA properties were explored. Women were typically young, primiparous and lacking formal education (22.2\ub16.3 years old, 42.2% primiparous, and 39.7% unschooled among the first trimester participants). Weight (kg), resistance (\u3a9), and reactance (\u3a9) were 42.1\ub15.7, 688\ub177, and 73\ub112 in the first trimester; 47.7\ub15.9, 646\ub177, and 64\ub112 in the third trimester; and 42.7\ub15.6, 699\ub179, and 72\ub112 postpartum respectively. Resistance declined with age and increased with body mass index. Resistance was higher than that observed in other, non-Asian pregnant populations, likely reflecting considerably smaller body-volume among Bangladeshi women. Resistance and reactance decreased in advanced stage of pregnancy as the rate of gain in weight increased, returning to the first trimester values by the three months postpartum. Normative distributions of BIA properties are presented for rural Bangladeshi women across a reproductive cycle that may be related to pregnancy outcomes and ultimately be used for assessing body-composition in this population

Growth in Achondroplasia including Stature, Weight, Weight-for-Height and Head Circumference from CLARITY: Achondroplasia Natural History Study-A Multi-center Retrospective Cohort Study of Achondroplasia in the US

BACKGROUND: Achondroplasia is the most common genetic skeletal disorder causing disproportionate short stature/dwarfism. Common additional features include spinal stenosis, midface retrusion, macrocephaly and a generalized spondylometaphyseal dysplasia which manifest as spinal cord compression, sleep disordered breathing, delayed motor skill acquisition and genu varus with musculoskeletal pain. To better understand the interactions and health outcomes of these potential complications, we embarked on a multi-center, natural history study entitled CLARITY (achondroplasia natural history study). One of the CLARITY objectives was to develop growth curves (length/height, weight, head circumference, weight-for-height) and corresponding reference tables of mean and standard deviations at 1 month increments from birth through 18 years for clinical use and research for achondroplasia patients. METHODS: All available retrospective anthropometry data including length/height, weight and head circumference from achondroplasia patients were collected at 4 US skeletal dysplasia centers (Johns Hopkins University, AI DuPont Hospital for Children, McGovern Medical School University of Texas Health, University of Wisconsin School of Medicine and Public Health). Weight-for-age values beyond 3 SD above the mean were excluded from the weight-for-height and weight-for-age curves to create a stricter tool for weight assessment in this population. RESULTS: Over 37,000 length/height, weight and head circumference measures from 1374 patients with achondroplasia from birth through 75 years of age were compiled in a REDCap database. Stature and weight data from birth through 18 years of age and head circumference from birth through 5 years of age were utilized to construct new length/height-for-age, weight-for-age, head circumference-for-age and weight-for-height curves. CONCLUSION: Achondroplasia-specific growth curves are essential for clinical care of growing infants and children with this condition. In an effort to provide prescriptive, rather than purely descriptive, references for weight in this population, extreme weight values were omitted from the weight-for-age and weight-for-height curves. This well-phenotyped cohort may be studied with other global achondroplasia populations (e.g. Europe, Argentina, Australia, Japan) to gain further insight into environmental or ethnic influences on growth

Intestinal permeability and inflammation mediate the association between nutrient density of complementary foods and biochemical measures of micronutrient status in young children: results from the MAL-ED study

Background: Environmental enteric dysfunction (EED) is thought to increase the risk of micronutrient deficiencies, but few studies adjust for dietary intakes and systemic inflammation. Objective: We tested whether EED is associated with micronutrient deficiency risk independent of diet and systemic inflammation, and whether it mediates the relation between intake and micronutrient status. Methods: Using data from 1283 children in the MAL-ED (Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health) birth cohort we evaluated the risk of anemia, low retinol, zinc, and ferritin, and high transferrin receptor (TfR) at 15 mo. We characterized gut inflammation and permeability by myeloperoxidase (MPO), neopterin (NEO), and α-1-antitrypsin (AAT) concentrations from asymptomatic fecal samples averaged from 9 to 15 mo, and averaged the lactulose:mannitol ratio z-score (LMZ) at 9 and 15 mo. Nutrient intakes from complementary foods were quantified monthly from 9 to 15 mo and densities were averaged for analyses. α-1-Acid glycoprotein at 15 mo characterized systemic inflammation. Relations between variables were modeled using a Bayesian network. Results: A greater risk of anemia was associated with LMZ [1.15 (95% CI: 1.01, 1.31)] and MPO [1.16 (1.01, 1.34)]. A greater risk of low ferritin was associated with AAT [1.19 (1.03, 1.37)] and NEO [1.22 (1.04, 1.44)]. A greater risk of low retinol was associated with LMZ [1.24 (1.08, 1.45)]. However, MPO was associated with a lower risk of high transferrin receptor [0.86 (0.74, 0.98)], NEO with a lower risk of low retinol [0.75 (0.62, 0.89)], and AAT with a lower risk of low plasma zinc [0.83 (0.70, 0.99)]. Greater nutrient intake densities (vitamins A and B6, calcium, protein, and zinc) were negatively associated with EED. Inverse associations between nutrient densities and micronutrient deficiency largely disappeared after adjustment for EED, suggesting that EED mediates these associations. Conclusions: EED is independently associated with an increased risk of low ferritin, low retinol, and anemia. Greater nutrient density from complementary foods may reduce EED, and the control of micronutrient deficiencies may require control of EED

A cluster-randomized, placebo-controlled, maternal vitamin a or beta-carotene supplementation trial in bangladesh: design and methods

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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 <url>http://Clinicaltrials.gov</url> as protocol NCT00198822.</p