Rebecca D. Merrill

Aflatoxin exposure during the first 1000 days of life in rural South Asia assessed by aflatoxin B1-lysine albumin biomarkers

Aflatoxin B1 is a potent carcinogen, occurring from mold growth that contaminates staple grains in hot, humid environments. In this investigation, aflatoxin B1-lysine albumin biomarkers were measured by mass spectrometry in rural South Asian women, during the first and third trimester of pregnancy, and their children at birth and at two years of age. These subjects participated in randomized community trials of antenatal micronutrient supplementation in Sarlahi District, southern Nepal and Gaibandha District in northwestern Bangladesh. Findings from the Nepal samples demonstrated exposure to aflatoxin, with 94% detectable samples ranging from 0.45 to 2939.30 pg aflatoxin B1-lysine/mg albumin during pregnancy. In the Bangladesh samples the range was 1.56 to 63.22 pg aflatoxin B1-lysine/mg albumin in the first trimester, 3.37 to 72.8 pg aflatoxin B1-lysine/mg albumin in the third trimester, 4.62 to 76.69 pg aflatoxin B1-lysine/mg albumin at birth and 3.88 to 81.44 pg aflatoxin B1-lysine/mg albumin at age two years. Aflatoxin B1-lysine adducts in cord blood samples demonstrated that the fetus had the capacity to convert aflatoxin into toxicologically active compounds and the detection in the same 2-year-old children illustrates exposure over the first 1000 days of life.

Effect of fortified complementary food supplementation on child growth in rural Bangladesh: a cluster-randomized trial

Background: Growth faltering in the first 2 years of life is high in South Asia where prevalence of stunting is estimated at 40–50%. Although nutrition counselling has shown modest benefits, few intervention trials of food supplementation exist showing improvements in growth and prevention of stunting. Methods: A cluster-randomized controlled trial was conducted in rural Bangladesh to test the effect of two local, ready-to-use foods (chickpea and rice-lentil based) and a fortified blended food (wheat-soy-blend++, WSB++) compared with Plumpy’doz, all with nutrition counselling vs nutrition counselling alone (control) on outcomes of linear growth (length and length-for-age z-score, LAZ), stunting (LAZ < −2), weight-for-length z-score (WLZ) and wasting (WLZ < −2) in children 6–18 months of age. Children (n = 5536) were enrolled at 6 months of age and, in the food groups, provided with one of the allocated supplements daily for a year. Results: Growth deceleration occurred from 6 to 18 months of age but deceleration in LAZ was lower (by 0.02–0.04/month) in the Plumpy’doz (P = 0.02), rice-lentil (< 0.01), and chickpea (< 0.01) groups relative to control, whereas WLZ decline was lower only in Plumpy’doz and chickpea groups. WSB++ did not impact on these outcomes. The prevalence of stunting was 44% at 18 months in the control group, but lower by 5–6% (P ≤ 0.01) in those receiving Plumpy’doz and chickpea. Mean length and LAZ at 18 months were higher by 0.27–0.30 cm and 0.07–0.10 (all P < 0.05), respectively, in all four food groups relative to the control. Conclusions: In rural Bangladesh, small amounts of daily fortified complementary foods, provided for a year in addition to nutrition counselling, modestly increased linear growth and reduced stunting at 18 months of age.

Iron Status of Women Is Associated with the Iron Concentration of Potable Groundwater in Rural Bangladesh

Women of reproductive age are at a high risk of iron deficiency, often as a result of diets low in bioavailable iron. In some settings, the iron content of domestic groundwater sources is high, yet its contribution to iron intake and status has not been examined. In a rural Bangladeshi population of women deficient in dietary iron, we evaluated the association between groundwater iron intake and iron status. In 2008, participants (n = 209 with complete data) were visited to collect data on 7-d food frequency, 7-d morbidity history, 24-h drinking water intake, and rice preparation, and to measure the groundwater iron concentration. Blood was collected to assess iron and infection status. Plasma ferritin (μg/L) and body iron (mg/kg) concentrations were [median (IQR)] 67 (46, 99) and 10.4 ± 2.6, respectively, and the prevalence of iron deficiency (ferritin < 12 μg/L) was 0%. Daily iron intake from water [42 mg (18, 71)] was positively correlated with plasma ferritin (r = 0.36) and total body iron (r = 0.35) (P < 0.001 for both). In adjusted linear regression analyses, plasma ferritin increased by 6.1% (95% CI: 3.8, 8.4%) and body iron by 0.3 mg/kg (0.2, 0.4) for every 10-mg increase in iron intake from water (P < 0.001). In this rural area of northern Bangladesh, women of reproductive age had no iron deficiency likely attributable to iron consumed from drinking groundwater, which contributed substantially to dietary intake. These findings suggest that iron intake from water should be included in dietary assessments in such settings.

First-trimester plasma tocopherols are associated with risk of miscarriage in rural Bangladesh

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.

Plasma zinc, vitamin B 12 and α-tocopherol are positively and plasma γ-tocopherol is negatively associated with Hb concentration in early pregnancy in north-west Bangladesh

OBJECTIVE The objective of the current analysis was to explore the association of multiple micronutrients with Hb concentration among pregnant women in a South Asian setting, a topic that has not been adequately explored. DESIGN Sociodemographic, anthropometric and micronutrient status (plasma ferritin, transferrin receptor, retinol, a- and g-tocopherol, folate, vitamin B12, Zn) and Hb concentration were assessed at early pregnancy. SETTING The biochemical sub-study was nested within a double-blind, placebo-controlled, community-based vitamin A and b-carotene supplementation trial in rural north-western Bangladesh (JiVitA). All assessments were conducted before trial supplementation was initiated. SUBJECTS A systematic sample of 285 women was selected from those enrolled in the biochemical sub-study. RESULTS Seventeen per cent of women were mildly anaemic; moderate and severe anaemia was uncommon (2.1 %). a-Tocopherol, vitamin B12 and Zn deficiencies were common (43.5%, 19.7% and 14.7%, respectively); however, vitamin A, folate and Fe deficiencies were comparatively rare (7.4%, 2.8% and ,1%,respectively). Plasma Zn, vitamin B12 and a-tocopherol were positively associated and plasma g-tocopherol was negatively associated with Hb (P < 0.05) after adjustment for gestational age, inflammation status, season and nutritional status measured by mid-upper arm circumference. CONCLUSIONS Among pregnant women in rural Bangladesh with minimal Fe deficiency, plasma Zn, vitamin B12, and a- and g-tocopherol concentrations were associated with Hb concentration. Appreciating the influence on Hb of micronutrients in addition to those with known associations with anaemia, such as Fe, folate, and vitamin A, is important when addressing anaemia in similar settings.

Groundwater Iron Assessment and Consumption by Women in Rural Northwestern Bangladesh

In Bangladesh, approximately 97 % of the rural population uses groundwater as a drinking source. In many areas of the country this water is known to have elevated levels of iron. The contribution to iron intake that this exposure provides, and the impact on health, are unknown. In the pre- and post-monsoon seasons of 2008, we measured iron content of household tube well water, explored local water collection methods, and estimated iron intake through consumption of groundwater for 276 women of reproductive age in a rural setting in northwestern Bangladesh. Groundwater samples were analyzed for total iron (mg/L), arsenic (category of µg/L), pH, temperature (°C), and oxidation-reduction potential (Eh). Participants drank [mean (SD); 2.7 (0.8) L] of water per day, all of which was collected from domestic tube wells. Total iron concentration in groundwater was high, [median (IQR) 16.3 (6.9, 28.2) mg/L], and variable throughout the area. Using this value, estimated daily iron intake [median (IQR)] was 41.1 (16.0, 71.0) mg from drinking water alone. The amount of water consumed was unrelated to its iron concentration (r = - 0.06; p = 0.33) despite potentially unpleasant organoleptic qualities of high iron content in water. Groundwater contributes substantially to daily iron intake of rural Bangladeshi women and currently represents an under-assessed potential source of dietary iron.

Canonical Correlation Analysis of Infant's Size at Birth and Maternal Factors: A Study in Rural Northwest Bangladesh

This analysis was conducted to explore the association between 5 birth size measurements (weight, length and head, chest and mid-upper arm [MUAC] circumferences) as dependent variables and 10 maternal factors as independent variables using canonical correlation analysis (CCA). CCA considers simultaneously sets of dependent and independent variables and, thus, generates a substantially reduced type 1 error. Data were from women delivering a singleton live birth (n = 14506) while participating in a double-masked, cluster-randomized, placebo-controlled maternal vitamin A or β-carotene supplementation trial in rural Bangladesh. The first canonical correlation was 0.42 (P<0.001), demonstrating a moderate positive correlation mainly between the 5 birth size measurements and 5 maternal factors (preterm delivery, early pregnancy MUAC, infant sex, age and parity). A significant interaction between infant sex and preterm delivery on birth size was also revealed from the score plot. Thirteen percent of birth size variability was explained by the composite score of the maternal factors (Redundancy, RY/X = 0.131). Given an ability to accommodate numerous relationships and reduce complexities of multiple comparisons, CCA identified the 5 maternal variables able to predict birth size in this rural Bangladesh setting. CCA may offer an efficient, practical and inclusive approach to assessing the association between two sets of variables, addressing the innate complexity of interactions.

Low-birthweight rates higher among Bangladeshi neonates measured during active birth surveillance compared to national survey data

Birth size is an important gauge of fetal and neonatal health. Birth size measurements were collected within 72 h of life for 16 290 live born, singleton infants in rural Bangladesh from 2004 to 2007. Gestational age was calculated based on the date of last menstrual period. Newborns were classified as small-for-gestational age (SGA) based on a birthweight below the 10th percentile for gestational age, using three sets of US reference data. Birth size distributions were explored based on raw values as well as after z-score standardisation in reference to World Health Organization (WHO) 2006 growth standards. Mean (SD) birthweight (g), length (cm) and head circumference (cm) measurements, completed within [median (25th, 75th percentile)] 15 (8, 23) h of life, were 2433 (425), 46.4 (2.4) and 32.4 (1.6), respectively. Twenty-two per cent were born preterm. Over one-half (55.3%) of infants were born low birthweight; 46.6%, 37.0% and 33.6% had a weight, length and head circumference below -2 z-scores of the WHO growth standard at birth; and 70.9%, 72.2% and 59.8% were SGA for weight based on Alexander et al., Oken et al. and Olsen et al. references, respectively. Infants in this typical rural Bangladesh setting were commonly born small, reflecting a high burden of fetal growth restriction and preterm birth. Our findings, produced by active birth surveillance, suggest that low birthweight is far more common than suggested by cross-sectional survey estimates. Interventions that improve fetal growth during pregnancy may have the largest impact on reducing SGA rates.

Factors associated with inflammation in preschool children and women of reproductive age: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project

Background: In many settings, populations experience recurrent exposure to inflammatory agents that catalyze fluctuations in the concentrations of acute-phase proteins and certain micronutrient biomarkers such as C-reactive protein (CRP), α-1-acid glycoprotein (AGP), ferritin, and retinol. Few data are available on the prevalence and predictors of inflammation in diverse settings. Objective: We aimed to assess the relation between inflammation (CRP concentration >5 mg/L or AGP concentration >1 g/L) and covariates, such as demographics, reported illness, and anthropometric status, in preschool children (PSC) (age range: 6–59 mo) and women of reproductive age (WRA) (age range: 15–49 y). Design: Cross-sectional data from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project from 29,765 PSC in 16 surveys and 25,731 WRA in 10 surveys were used to model bivariable and multivariable relations. Results: The inflammation prevalence was 6.0–40.2% in PSC and 7.9–29.5% in WRA (elevated CRP) and 21.2–64.3% in PSC and 7.1–26.7% in WRA (elevated AGP). In PSC, inflammation was consistently positively associated with recent fever and malaria but not with other recent illnesses. In multivariable models that were adjusted for age, sex, urban or rural residence, and socioeconomic status, elevated AGP was positively associated with stunting (height-for-age z score <−2) in 7 of 10 surveys. In WRA, elevated CRP was positively associated with obesity [body mass index (in kg/m2) ≥30] in 7 of 9 surveys. Other covariates showed inconsistent patterns of association with inflammation. In a pooled analysis of surveys that measured malaria, stunting was associated with elevated AGP but not CRP in PSC, and obesity was associated with both elevated CRP and AGP in WRA. Conclusions: Recent morbidity and abnormal anthropometric status are consistently associated with inflammation across a range of environments, whereas more commonly collected demographic covariates were not. Because of the challenge of defining a general demographic population or environmental profile that is more likely to experience inflammation, inflammatory markers should be measured in surveys to account for their effects.

Preferred Delivery Method and Acceptability of Wheat-Soy Blend (WSB++) as a Daily Complementary Food Supplement in Northwest Bangladesh

Fortified blended foods (FBFs) are widely used to prevent undernutrition in early childhood in food-insecure settings. We field tested enhanced Wheat Soy Blend (WSB++)—a FBF fortified with micronutrients, milk powder, sugar, and oil—in preparation for a complementary food supplement (CFS) trial in rural northwestern Bangladesh. Formative work was conducted to determine the optimal delivery method (cooked vs. not) for this CFS, to examine mothers’ child feeding practices with and acceptance of the WSB++, and to identify potential barriers to adherence. Our results suggest WSB++ is an acceptable CFS in rural Bangladesh and the requirement for mothers to cook WSB++ at home is unlikely to be a barrier to its daily use as a CFS in this population.