Micronutrient Status during Pregnancy and Effects of Antenatal Supplementation with Multiple Micronutrients versus Iron-folic Acid in Rural Bangladesh.

Objectives: Women often enter pregnancy with micronutrient deficiencies, exacerbated by demands of pregnancy. Yet, gestational micronutrient status is uncommonly assessed, even as momentum builds toward preventing multiple micronutrient (MM) deficiencies. We assessed micronutrient status of women early in pregnancy in a rural setting in northern Bangladesh. Methods: In a substudy of women participating in a randomized trial of MM versus iron-folic acid (IFA) supplementation we identified a population-based subsample of n=1526 women from whom plasma samples were obtained in the 1st trimester (TM), prior to supplementation, and in the 3rd TM, to evaluate micronutrient status and response to supplementation. Results: In available 1st TM data (n=491-1448 per nutrient assay), 6.8% of women were vitamin A deficient (retinol < 0.70 μmol/L), 41.7% had low β-carotene (<0.09 μmol/L), and 57.7% were vitamin E deficient (α-tocopherol < 12 μmol/L). Folate deficiency (plasma folate < 6.8 nmol/L) was 2.6%, while prevalence of vitamin B12 deficiency (cobalamin < 150 pmol/L) was 29.8%. Anemia affected 20.6% of women, but iron deficiency by TfR (4.7% > 8.3 μg/L) and ferritin (1.8% < 12 μg/L) was uncommon. Plasma zinc was low (<10 μmol/L) in 30.6% of women. Inflammation, by α-1 acid glycoprotein (AGP > 1 g/L), was present in 8.1% of women. Baseline vitamin D and iodine status, and MM versus IFA effects on micronutrient status by the 3rd TM, are being determined. Conclusions: Women in rural Bangladesh experience a variety of micronutrient deficiencies in early pregnancy, supporting the need to address "hidden hunger" with multiple micronutrient supplementation during pregnancy.

The Effect of Antenatal Multiple Micronutrient Supplementation on Placental Angiogenesis and Fetal Growth Factors in Rural Bangladesh.

Objectives: Pathways by which micronutrients may influence birth size are not well understood. To elucidate these, we assessed markers of placental angiogenesis and fetal growth factors in a substudy of a community-based, double blinded, cluster-randomized trial of maternal multiple micronutrient (MM) supplementation versus iron and folic acid (IFA) in rural Bangladesh. Methods: We collected maternal blood (n=395) at 10 and 32 weeks gestation and cord blood (n=325) at home deliveries, where infant and placental weight were measured. Angiogenic factors assessed in maternal plasma were placental growth factor (PlGF), angiopoietin 2 (Ang-2), vascular endothelial growth factor (VEGF), and VEGF receptor 1 (VEGFR-1). Insulin, insulin-like growth factor-1 (IGF-1), and IGF binding protein-1 (IGFBP-1) were measured in cord plasma. Results: Mothers had a mean (SD) BMI in early pregnancy of 19.5 (2.5) kg/m2 and infants weighed 2.68 (0.41) kg at birth. Ang-2 at 32 weeks gestation was 3.1 (95% CI: 0.20, 6.0) ng/mL higher in mothers taking MM vs. IFA suggesting improved vascular remodeling. Other angiogenic factors and insulin, IGF-1, and IGFBP-1 did not differ by maternal supplementation, but significant interactions were observed with infant sex and maternal height. For male fetuses, change in VEGF from 10 to 32 weeks was lower by 7.5 (95% CI: -13.3, -1.7) pg/mL for MM vs. IFA groups reflecting improved angiogenesis across pregnancy. Among shorter women (<145 cm), MM increased insulin by 1.8 (95% CI: 1.0, 3.1) μIU/ML indicating improved fetal energy metabolism. Conclusions: MM supplementation has a biologic basis for improving fetal growth beyond improved micronutrient status of the fetus.

Dietary Diversity is Low and Associated with Nutritional Status of Women in Early Pregnancy in Rural Bangladesh.

Objectives: To evaluate the association between nutritional status and other risk factors with dietary diversity in the 1st trimester of pregnancy among women in rural Bangladesh. Methods: A cross-sectional analysis of data among women enrolled during the 1st trimester of pregnancy into the JiVitA-1 weekly vitamin A or beta-carotene supplementation trial in rural Bangladesh from 2001 to 2007. A dietary diversity score (DDS) based on 9-conventionally defined food groups was calculated based on data collected from a 7-day food frequency questionnaire. Mid-upper arm circumference (MUAC) from the main trial (n=67,690), and BMI and serum markers of micronutrient status from a substudy (n=1,869) of women were used as indicators of maternal nutritional status. Other individual, household and seasonality factors were examined for their association with DDS, and as potential confounders in the association between DDS and maternal nutritional status. Results: Overall mean (sd) DDS was low at 2.1 (1.1) (Max. Score=9). In a multivariate model, selected individual (maternal education, being a wage earner, and selected morbidity symptoms), household (living standard index, smaller household size, food security, and ownership of a fruit grove, home garden or fish pond) factors and seasonality (non-lean season) were positively associated with maternal DDS. Maternal MUAC, BMI and serum levels of lycopene (biomarker for vegetable/fruit intake) were also associated with DDS. Conclusions: In this rural setting of northern Bangladesh, dietary diversity is low and maternal nutritional status is poor. Dietary diversity, measured by a simple score summed over one week, was positively associated with maternal nutritional status in early pregnancy.

Effect of Vitamin D, Calcium and Multiple Micronutrients Supplementation on Lipid Profile in Pre-menopausal Bangladeshi Garment Factory Workers with Hypovitaminosis D.

Elevated total cholesterol and low-density lipoprotein cholesterol in sera are both well-known risk factors of coronary heart disease. Adequate vitamin D status is important for optimal function of many organs and tissues of our body. There is continuing controversy about the effect of adequate vitamin D consumption on serum lipids and lipoproteins. The present study assessed the effect of vitamin D, calcium and multiple micronutrients supplementation on the lipid profile in Bangladeshi young female garment factory workers who have hypovitaminosis D. This placebo-controlled intervention trial conducted over a period of one year randomly assigned a total of 200 apparently healthy subjects aged 16-36 years to 4 groups. The subjects received daily supplements of 400 IU of vitamin D (VD group) or 400 IU of vitamin D+600 mg of calcium lactate (VD-Ca group), or multiple micronutrients with 400 IU of vitamin-D+600 mg of calcium lactate (MMN-VD-Ca group), or the group consuming placebo (PL group). Serum concentrations of lipid and lipoprotein, 25-hydroxyvitamin D (25OHD) and intact parathyroid hormone (iPTH) were measured at baseline and after one year of follow-up. No significant changes in the serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), LDL-C/HDL-C ratio were observed in the supplemented groups compared to the placebo group. Supplementation had a positive effect (p<0.05) on very low-density lipoprotein cholesterol (VLDL-C) and triacylglycerol (TAG). A negative correlation between changes in serum iPTH and HDL-C was observed, which indicated that subjects with the greatest decline in S-iPTH had the greatest increase in HDL-C. The results suggest that consumption of adequate vitamin D with calcium or MMN for one-year may have no impact on serum lipid profile in the subjects studied. Longer-term clinical trials with different doses of supplemental vitamin D are warranted in evaluating the effect of intervention.

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 (≤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.

Constructing Indices of Rural Living Standards in Northwestern Bangladesh.

This study aimed to construct indices of living standards in rural Bangladesh that could be useful to study health outcomes or identify target populations for poverty-alleviation programmes. The indices were constructed using principal component analysis of data on household assets and house construction materials. Their robustness and use was tested and found to be internally consistent and correlated with maternal and infant health, nutritional and demographic indicators, and infant mortality. Indices derived from 9 or 10 household asset variables performed well; little was gained by adding more variables but problems emerged if fewer variables were used. A ranking of the most informative assets from this rural, South Asian context is provided. Living standards consistently and significantly improved over the six-year study period. It is concluded that simple household socioeconomic data, collected under field conditions, can be used for constructing reliable and useful indices of living standards in rural South Asian communities that can assist in the assessment of health, quality of life, and capabilities of households and their members.

Age of Onset, Nutritional Determinants, and Seasonal Variations in Menarche in Rural Bangladesh.

Menarche is an important milestone in the development of female adolescents. The study assessed the age at menarche using recall, its seasonality, and association with marital and nutritional status (using midupper arm circumference [MUAC]) among 3,923 female adolescents aged 12-19 years in a rural area of Bangladesh. At the time of assessment, most (88%) adolescents had attained menarche at the mean (standard deviation [SD]) age of 12.8 (1.4) years. Age of onset of menarche among married adolescents (13%) occurred earlier than in those who were unmarried (12.6±1.3 years vs 12.9±1.4 years, p<0.01). Age at menarche was negatively associated with MUAC after adjusting for age and marital status (β=-0.10, p<0.01). More than 50% of the adolescents had an onset of menarche during winter (χ2=634.97; p<0.001), with peaks in December and January. In this rural population, the current age at menarche was found to be slightly lower than the previous estimates of 13.0 years in Bangladesh. An early onset of menarche was associated with season and better nutritional status of the female adolescents and may be associated with early marriage.

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.

A low-cost method to identify tubewells for longitudinal research on arsenic in groundwater.

Exposure to high concentrations of arsenic in tubewell groundwater from the shallow aquifers of Bangladesh could result in up to 300,000 arsenic-related cancer cases over the next four decades. Understanding the magnitude and temporal dynamics of this exposure, via longitudinal studies, is imperative for planning effective mitigation and management strategies. Appropriate methods are needed to identify tubewells for longitudinal sampling. A plastic band marked with a unique identification number was developed, and various methods for attaching the band to the tubewell were tested, resulting in the choice of a galvanized-iron split-rivet. Two follow-up surveys at two and 14 months post-banding assessed the durability and longevity under field conditions in the JiVitA Project area in rural, northwestern Bangladesh. After two months, approximately 96.0% of the original bands on 1,063 tubewells were functional, although the rivets were partially corroded. After 14 months, approximately 65% of a subsample of the bands were functional. With further improvements to the rivets, these bands offer an inexpensive, durable, enumeration technology for longitudinal studies on groundwater arsenic.