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.

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.

Prediction Equations for Body-fat Percentage in Indian Infants and Young Children Using Skinfold Thickness and Mid-arm Circumference.

The objective of the study was to develop prediction equations for fat-mass percentage in infants in India based on skinfold thickness, mid-arm circumference, and age. Skinfold thicknesses and mid-arm circumference of 46 apparently-healthy infants (27 girls and 19 boys), aged 6-24 months, from among the urban poor attending a well baby clinic of a hospital in Kolkata were measured. Their body-fat percentage was measured using the D2O dilution technique as the reference method. Equations for body-fat percentage were developed using a stepwise forward regression model using skinfold thicknesses, mid-arm circumference, and age as independent variables, and the body-fat percentage was derived by D2O dilution as the dependent variable. The new prediction equations are: body-fat percentage=-69.26+5.76×B- 0.33×T2+5.40×M+0.01×A2 for girls and body-fat percentage=-8.75+3.73×B+2.57×S for boys, where B=biceps skinfold thickness, T=triceps skinfold thickness, and S=suprailiac skinfold thickness all in mm, M=mid-arm circumference in cm, and A=age in month. Using the D2O dilution technique, the means (SD) of the calculated body-fat percentage were 17.11 (7.25) for girls and 16.93 (6.62) for boys and, using the new prediction equations, these were 17.11 (6.25) for girls and 16.93 (6.02) for boys. The mean of the differences of paired values in body-fat percentage was zero. The mean (SD) of the differences of paired values for body-fat percentage derived by the D2O technique and the new equations, applied on an independent sample of 23 infants (11 girls and 12 boys) were -0.93 (6.56) for girls and 1.14 (2.43) for boys; the 95% confidence limits of the differences of paired values for body-fat percentage were -2.03 to +3.89 for girls and -0.26 to +2.54 for boys. Given that the trajectories of growth during infancy and childhood are a major risk factor for a group of diseases in adulthood, including coronary heart disease and diabetes, these predictive equations should be useful in field studies.