Placental growth is a strong predictor of fetal growth, but little is known about maternal predictors of placental growth in malnourished populations. Our objective was to investigate in a ...prospective study the associations of maternal weight and body composition total body water (TBW) estimated by bioelectrical impedance and fat and fat-free mass derived from upper arm fat and muscle areas (UAFA, UAMA) and changes in these with placental and birth weights. Within a cluster-randomized trial of maternal micronutrient supplementation, a subsample of 350 women was measured 3 times across gestation. Longitudinal analysis was used to examine independent associations of ∼10-wk measurements and ∼10-20 wk and ∼20-32 wk changes with birth outcomes. Weight, TBW, and UAMA, but not UAFA, at ∼10 wk were each positively and independently associated with placental weight and birth weight (P < 0.05). Of the maternal ∼10-20 wk changes in measurements, only TBW change and placental weight, and maternal weight and birth weight were positively associated (P < 0.05). Gains in weight, TBW, and UAMA from 20 to 32 wk were positively and UAFA gain was negatively associated with placental weight (P ≤ 0.01). Gains in weight and UAMA from 20 to 32 wk were positively associated with birth weight (P ≤ 0.01). Overall, higher maternal weight and measures of fat-free mass at ∼10 wk gestation and gains from 20 to 32 wk are independently associated with higher placental and birth weight.
Inflammation-induced hyporetinolemia (IIH), a reduction in serum retinol (SR) during inflammation, may bias population estimates of vitamin A deficiency (VAD). The optimal adjustment for IIH depends ...on the type and extent of inflammation. In rural Zambian children (4–8 years, N = 886), we compared three models for defining inflammation: α-1-acid glycoprotein (AGP) only (inflammation present if > 1 g/L or normal if otherwise), C-reactive protein (CRP) only (moderate inflammation, 5–15 mg/L; high inflammation, > 15 mg/L; or normal if otherwise) and a combined model using both AGP and CRP to delineate stages of infectious episode. Models were compared with respect to 1) the variance in SR explained and 2) comparability of inflammation-adjusted VAD estimated in low and high malaria seasons. Linear regression was used to estimate the variance in SR explained by each model and in estimating the adjustment factors used in generating adjusted VAD (retinol < 0.7 μmol/L). The variance in SR explained were 2% (AGP-only), 11% (CRP-only), and 11% (AGP–CRP) in the low malaria season; and 2% (AGP-only), 15% (CRP-only), and 12% (AGP–CRP) in the high malaria season. Adjusted VAD estimates in the low and high malaria seasons differed significantly for the AGP (8.2 versus 13.1%) and combined (5.5 versus 9.1%) models but not the CRP-only model (6.1 versus 6.3%). In the multivariate regression, a decline in SR was observed with rising CRP (but not AGP), in both malaria seasons (slope = −0.06; P < 0.001). In this malaria endemic setting, CRP alone, as opposed to CRP and AGP, emerged as the most appropriate model for quantifying IIH.
Undernutrition may affect fecundability, but few studies have quantified this relationship. In rural Bangladesh, where newlywed couples face strong pressures to become pregnant, we assessed ...fecundability, estimated by time to pregnancy (TTP), and its association with preconceptional thinness among nulligravid, newlywed female adolescents. During 2001–2002, 5,516 newlywed women aged 12–19 years participated in a home‐based, 5‐weekly surveillance system for 5–6 years to enrol pregnant women into an antenatal vitamin A or β‐carotene supplementation trial. Thinness was defined as a left mid‐upper arm circumference (MUAC) ≤21.5 versus >21.5 cm. At each visit, staff obtained a monthly history of menstruation. Report of amenorrhea prompted a human chorionic gonadotropin urine test to confirm pregnancy. We derived hazard ratios (with 95% confidence intervals CI) for pregnancy and Kaplan–Meier curves for TTP. Ages of women at marriage and pregnancy detection (mean ± standard deviation) were 15.3 ± 1.9 and 17.0 ± 1.9 years, respectively. A total of 82.7% of thinner and 87.3% of better nourished women became pregnant. The unadjusted and multivariable relative hazard of ever becoming pregnant was 0.84 (95% CI 0.78, 0.89) and 0.86 (95% CI 0.81, 0.92), respectively, and TTP was 12 weeks longer (median 95% CI: 63 58–68 vs. 51 49–54) in women whose MUAC was ≤21.5 versus >21.5 cm. In rural Bangladesh, thin adolescent newlywed girls have a lower probability of becoming pregnant and experience a longer time to pregnancy.
Plasma volume expansion has been associated with fetal growth. Our objective was to examine the associations between maternal nutritional status in early pregnancy and extracellular water (ECW), ...total body water (TBW), and percentage plasma volume change across pregnancy. In a subsample of 377 pregnant women participating in a cluster-randomized trial of micronutrient supplementation, hemoglobin, hematocrit, and multi-frequency bioelectrical impedance were measured at ~10, 20, and 32 wk of gestation. In early pregnancy, women were short (mean ± SD, 148.9 ± 5.3 cm) and thin (19.5 ± 2.5 kg/m(2)). In mixed-effects multiple regression models, a 1-unit higher BMI at ~10 wk was associated with higher ECW and TBW (0.27 and 0.66 kg per kg/m(2), respectively; P < 0.01) at ~10, ~20, and ~32 wk. Height was also positively associated with ECW and TBW at each time point. Early pregnancy BMI was negatively associated with gains in ECW and TBW (-0.06 and -0.14 kg per kg/m(2), respectively; P < 0.01) from 10 to 20 wk, but not with 20- to 32-wk gains after accounting for weight gain. BMI was positively associated with percentage changes in plasma volume from 20 to 32 wk (0.57% per kg/m(2); P < 0.05). Height was not associated with changes in body water or plasma volume. Women with low BMI and height in early pregnancy have lower ECW and TBW in early, mid, and late pregnancy and lower late pregnancy plasma volume expansion, potentially increasing risk of fetal growth restriction.
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.
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.
Circulating aflatoxin B
(AFB
)-lysine albumin adducts were measured in dyads from Bangladesh (
= 573; maternal first and third trimester, 3 mo postpartum, cord blood, infant 24 mo) and Malawi (
= 255; maternal second and third trimester, 6 mo postpartum, infant 6 and 18 mo) with isotope dilution mass spectrometry. We examined AFB
-lysine adduct magnitude, persistence, seasonality, and associations with infant feeding, and estimated daily AFB
intake.
Maternal AFB
-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 AFB
/day), estimated intake in Bangladesh was reduced by 94% between rainy and winter seasons (98 to 6 ng/day). AFB
-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 AFB
-lysine concentrations at 6 mo compared with other feeding modes (
= 0.010).
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.
Anemia is estimated to affect one-half of school-age children in developing countries. The school years are an opportune time to intervene, and interventions must be based on sound epidemiologic ...understanding of the problem in this age group. We report on the distribution of iron deficiency and anemia across age, sex, anthropometric indexes, and parasitic infections in a representative sample of 3595 schoolchildren from Pemba Island, Zanzibar. Iron status was assessed by hemoglobin, erythrocyte protoporphyrin (EP), and serum ferritin concentrations from a venous blood sample. Overall, 62.3% of children were anemic (hemoglobin < 110 g/L), and 82.7% of anemia was associated with iron deficiency. The overall prevalence of iron-deficient erythropoiesis (EP > 90 mumol/mol heme) was 48.5%, and the prevalence of exhausted iron stores (serum ferritin < 12 micrograms/L) was 41.3%. In bivariate analyses, iron status was slightly better in girls than in boys, and was better in children aged 7–11 y than in those older or younger. Hemoglobin but not EP or serum ferritin concentrations were lower in stunted children. Infection with malaria, Trichuris trichiura, Ascaris lumbricoides, and hookworms were all associated with worse iron status; the association with hookworms was strongest by far. In multivariate analyses, hookworm infection intensity was the strongest explanatory variable for hemoglobin, EP, and serum ferritin. Sex, malarial parasitemia, A. lumbricoides infection, and stunting were also retained in the multivariate model for hemoglobin. Twenty-five percent of all anemia, 35% of iron deficiency anemia, and 73% of severe anemia were attributable to hookworm infection; < 10% of anemia was attributable to A. lumbricoides, malaria infection, or stunting. We conclude that anthelminthic therapy is an essential component of anemia control in schoolchildren in whom hookworms are endemic, and should be complemented with school-based iron supplementation.
Pregnancy exacerbates vitamin A (VA) deficiency and anaemia among women in developing countries. Improving circulating haemoglobin (Hb) requires erythrocyte production and availability of iron. ...Insulin-like growth factor- 1 (IGF-1) functions in erythropoiesis, but its association with VA status and pregnancy-associated anaemia has not been studied. The aim of this study was to examine the relationship between serum retinol, IGF-1, and Hb among pregnant women in extant samples collected during a placebo-controlled trial of VA and beta-carotene (BC) supplementation in rural Nepal conducted from 1994 to 1997. Mid-pregnancy serum IGF-1 was measured in serum from n=589 randomly selected women of n=1186 in whom anthropometric, VA (retinol) and iron (Hb, erythrocyte zinc protoporphyrin (ZP), and ferritin) status data were available. Associations of IGF-1 with retinol, Hb or anaemia, and iron status were determined using multiple linear and logistic regression. Path analysis was used to explore the role of IGF-1 as a mediator between retinol and Hb, accounting for iron status. A 2.6 g/L increase in IGF-1 was observed per 0.1 mol/L increment in retinol (p<0.0001). Hb increased with each quartile of IGF-1, and odds of anaemia declined 68.8% from the 1st to 4th quartile. Improved iron status indicators explained only 29.1% of the association between IGF-1 and Hb, while IGF-1 explained 25.6% of the association between retinol and Hb. Increasing IGF-1 was likely one mechanism by which retinol improved circulating Hb in pregnant women of rural Nepal, although IGF-1 worked primarily through pathways independent of improved iron status indicators, perhaps by stimulating erythrocyte production.
Vitamin K (VK) is a fat-soluble vitamin whose deficiency disrupts coagulation and may disturb bone and cardiovascular health. However, the scale and systems affected by VK deficiency in pediatric ...populations remains unclear. We conducted a study of the plasma proteome of 500 Nepalese children 6–8 years of age (male/female ratio = 0.99) to identify proteins associated with VK status. We measured the concentrations of plasma lipids and protein induced by VK absence-II (PIVKA-II) and correlated relative abundance of proteins quantified by mass spectrometry with PIVKA-II. VK deficiency (PIVKA-II >2 μg/L) was associated with a higher abundance of low-density lipoproteins, total cholesterol, and triglyceride concentrations (
p
< 0.01). Among 978 proteins observed in >10% of the children, five proteins were associated with PIVKA-II and seven proteins were differentially abundant between VK deficient versus sufficient children, including coagulation factor-II, hemoglobin, and vascular endothelial cadherin, passing a false discovery rate (FDR) threshold of 10% (q < 0.10). Among 27 proteins associated with PIVKA-II or VK deficiency at a less stringent FDR (q < 0.20), a network comprised of hemoglobin subunits and erythrocyte anti-oxidative enzymes were highly and positively correlated each other (all r > 0.7). Untargeted proteomics offers a novel systems approach to elucidating biological processes of coagulation, vascularization, and erythrocyte oxidative stress related to VK status. The results may help elucidate subclinical metabolic disturbances related to VK deficiency in populations.
Although hepcidin, a recently discovered peptide hormone, is considered a major regulator of iron metabolism and anemia in chronic inflammation, its role in anemia during pregnancy has not been ...characterized. Our objective was to characterize the role of hepcidin in anemia during pregnancy. We examined the relationships between urinary hepcidin, iron status indicators, hemoglobin, erythropoietin, alpha-1 acid glycoprotein, and C-reactive protein in a cross-sectional study conducted among 149 pregnant rural Bangladeshi women with biospecimens obtained during home visits. Urinary hepcidin was measured using surface-enhanced laser desorption/ ionization time-of-flight mass spectrometry. Urinary hepcidin, as log(intensity per mmol/L creatinine), was correlated with log ferritin (r = 0.33, p <0.001), the transferrin receptor index (r = -0.22, p = 0.007), and log alpha-1 acid glycoprotein (r = 0.20, p = 0.01), but not hemoglobin (r = 0.07, p= 0.40), log transferrin receptor (r = -0.07, p = 0.41), log erythropoietin (r = -0.01, p = 0.88) or log C-reactive protein (r = 0.06, p = 0.48). The strength of the relationship between hepcidin and ferritin was maintained in multiple linear regression analyses after enhancing the sample with data from women selected for low iron stores (n = 41). Among pregnant women in a community-based study in rural Bangladesh, urinary hepcidin levels were related to iron status and AGP but not hemoglobin, erythropoietin, or C-reactive protein.
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