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

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

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

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

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

Child Aflatoxin Exposure is Associated with Poor Child Growth Outcomes : A Prospective Cohort Study in Rural Malawi

Background: Aflatoxin (AF) exposure is associated with child growth faltering in cross-sectional studies, with limited findings from longitudinal studies. Objectives: To evaluate the relationship between maternal AF B1-lysine adduct concentration, child AF B1-lysine adduct concentration, and child growth in the first 30 mo of life. Methods: AF B1-lysine adduct was measured in mother-child dyad plasma samples using isotope dilution mass spectrometry. Using linear regression, we assessed the relationship between AF B1-lysine adduct concentration and child weight, height, and head and mid-upper arm circumferences at 1 wk, 6, 12, 18, 24, and 30 mo of age. Results: In adjusted models, maternal prenatal AF B1-lysine adduct (pg/μL) was positively associated with newborn anthropometric outcomes; largest beta coefficients for associations between standardized values were for newborn weight-for-age z-score [β = 0.13; 95% confidence interval (CI): 0.02, 0.24; P < 0.05 and β = 0.11; 95% CI: 0.00, 0.22; P < 0.05 for second and third trimester AF, respectively]. Child AF B1-lysine adduct (pg/μL) at 6 mo was negatively associated with head circumference-for-age z-score at 6, 18, 24, and 30 mo, with beta coefficients ranging from β = –0.15; 95% CI: –0.28, –0.02 to β = –0.17; 95% CI: –0.31, –0.03; P < 0.05); 18-mo AF was negatively associated with anthropometric outcomes at 18, 24, and 30 mo, most consistently with length-for-age z-score (β = –0.18; 95% CI: –0.32, –0.04, β = –0.21; 95% CI: –0.35, –0.07, β = –0.18; 95% CI: –0.32, –0.03 at 18, 24 and 30 mo, respectively). Conclusions: Child AF exposure was associated with impaired child growth, but maternal AF exposure was not. Exposure during infancy was linked to persistent deficit in head circumference, implying reduced brain size lasting beyond the age of 2 years. Exposure at 18 mo was linked to persistent linear growth deficit. Further research should elucidate mechanisms through which AF affects child growth.Peer reviewe

Longitudinal Assessment of Prenatal, Perinatal, and Early-Life Aflatoxin B1 Exposure in 828 Mother–Child Dyads from Bangladesh and Malawi

Background: In utero or early-life exposure to aflatoxin, which contaminates staple crops in disadvantaged settings, may compromise pregnancy and infant outcomes, but investigations into the extent, persistence, and determinants of aflatoxin exposure at these life stages have lacked longitudinal data collection and broad geographic representation. Objectives: Aflatoxin exposure and selected determinants thereof were characterized in mother–child dyads with serial plasma/serum samples in prenatal, perinatal, and early life in Malawi and Bangladesh. Methods: Circulating aflatoxin B1 (AFB1)–lysine albumin adducts were measured in dyads from Bangladesh (n = 573; maternal first and third trimester, 3 mo postpartum, cord blood, infant 24 mo) and Malawi (n = 255; maternal second and third trimester, 6 mo postpartum, infant 6 and 18 mo) with isotope dilution mass spectrometry. We examined AFB1-lysine adduct magnitude, persistence, seasonality, and associations with infant feeding, and estimated daily AFB1 intake. Results: Maternal AFB1-lysine was higher in Malawi (98% detectable; median: 0.469, IQR: 0.225–1.027 pg/μL) than in Bangladesh (59%; 0.030, nondetectable [nd]–0.077 pg/μL). Although estimated dietary exposure in Malawi was temporally stable (648 ng AFB1/day), estimated intake in Bangladesh was reduced by 94% between rainy and winter seasons (98 to 6 ng/day). AFB1-lysine was low in cord blood from Bangladesh (15% detectable; 0.045, 0.031–0.088 pg/μL among detectable) and in Malawian infants at 6 mo of age (0.072, nd–0.236 pg/μL), but reached maternal concentrations by 18 or 24 mo (Bangladesh: 0.034, nd–0.063 pg/μL; Malawi: 0.370, 0.195–0.964 pg/μL). In Malawian infants, exclusive breastfeeding at 3 mo was associated with 58% lower AFB1-lysine concentrations at 6 mo compared with other feeding modes (P = 0.010). Conclusions: Among pregnant women, aflatoxin exposure was persistently high in Malawi, while lower and seasonal in Bangladesh. Infants were partially protected from exposure in utero and with exclusive breastfeeding, but exposures reached adult levels by 18–24 mo of age. The Bangladesh and Malawi trials are registered at clinicaltrials.gov as NCT00860470 and NCT01239693. Curr Dev Nutr 2022;6:nzab153.publishedVersionPeer reviewe

JWST detection of heavy neutron capture elements in a compact object merger

The mergers of binary compact objects such as neutron stars and black holes are of central interest to several areas of astrophysics, including as the progenitors of gamma-ray bursts (GRBs), sources of high-frequency gravitational waves and likely production sites for heavy element nucleosynthesis via rapid neutron capture (the r-process). These heavy elements include some of great geophysical, biological and cultural importance, such as thorium, iodine and gold. Here we present observations of the exceptionally bright gamma-ray burst GRB 230307A. We show that GRB 230307A belongs to the class of long-duration gamma-ray bursts associated with compact object mergers, and contains a kilonova similar to AT2017gfo, associated with the gravitational-wave merger GW170817. We obtained James Webb Space Telescope mid-infrared (mid-IR) imaging and spectroscopy 29 and 61 days after the burst. The spectroscopy shows an emission line at 2.15 microns which we interpret as tellurium (atomic mass A=130), and a very red source, emitting most of its light in the mid-IR due to the production of lanthanides. These observations demonstrate that nucleosynthesis in GRBs can create r-process elements across a broad atomic mass range and play a central role in heavy element nucleosynthesis across the Universe.Comment: Submitted. Comments welcome! Nature (2023