Junk food use and neurodevelopmental and growth outcomes in infants in low-resource settings.

Introduction: Feeding infants a sub-optimal diet deprives them of critical nutrients for their physical and cognitive development. The objective of this study is to describe the intake of foods of low nutritional value (junk foods) and identify the association with growth and developmental outcomes in infants up to 18 months in low-resource settings. Methods: This is a secondary analysis of data from an iron-rich complementary foods (meat versus fortified cereal) randomized clinical trial on nutrition conducted in low-resource settings in four low- and middle-income countries (Democratic Republic of the Congo, Guatemala, Pakistan, and Zambia). Mothers in both study arms received nutritional messages on the importance of exclusive breastfeeding up to 6 months with continued breastfeeding up to at least 12 months. This study was designed to identify the socio-demographic predictors of feeding infants' complementary foods of low nutritional value (junk foods) and to assess the associations between prevalence of junk food use with neurodevelopment (assessed with the Bayley Scales of Infant Development II) and growth at 18 months. Results: 1,231 infants were enrolled, and 1,062 (86%) completed the study. Junk food feeding was more common in Guatemala, Pakistan, and Zambia than in the Democratic Republic of Congo. 7% of the infants were fed junk foods at 6 months which increased to 70% at 12 months. Non-exclusive breastfeeding at 6 months, higher maternal body mass index, more years of maternal and paternal education, and higher socioeconomic status were associated with feeding junk food. Prevalence of junk foods use was not associated with adverse neurodevelopmental or growth outcomes. Conclusion: The frequency of consumption of junk food was high in these low-resource settings but was not associated with adverse neurodevelopment or growth over the study period.

Infant and young child feeding indicators are positively associated with length and family care indicators in the children of the Women First trial participants.

This research describes the proportion of children in four low- and middle-income countries with adequate dietary practices at 6, 12, 18 and 24 months of age and how these practices changed over time using the World Health Organisation and UNICEF's infant young child feeding (IYCF) indicators. The associations between the IYCF indicators and anthropometric z-scores from 6 to 24 months, and between the IYCF indicators and the family care indicators (FCIs) at 24 months are described. This was a longitudinal study of offspring from participants in the Women First Preconception Maternal Nutrition Trial conducted in Sud-Ubangi, Democratic Republic of Congo; Chimaltenango, Guatemala; Belagavi, North Karnataka, India; and Thatta, Sindh Province, Pakistan. The frequency of the minimum dietary diversity (MDD), minimum meal frequency (MMF), and minimum adequate diet (MAD) increased between 6 and 24 months, but even at 24 months MAD remained below 50% at all sites. MDD (ß = 0.12; 95% CI = 0.04-0.22) and MMF (ß = 0.10; 95% CI = 0.03-0.17) were positively associated with length-for-age z-score at 24 months. All IYCF indicators were positively associated with mean total FCI score: MDD (proportion ratio [PR] = 1.04; 95% CI = 1.02-1.07), MMF (PR = 1.02; 95% CI = 1.01-1.04), MAD (PR = 1.05; 95% CI = 1.02-1.08). Although there are multiple barriers to young children having an adequate diet, our results support a positive association between familial interactions and improved IYCF feeding practices.

Zinc Kinetics Correlate With Length-for-Age z Scores in Bangladeshi Infants.

OBJECTIVES: Stunting [length-for-age z score (LAZ) <-2] has multiple causes and is prevalent in areas with low dietary zinc (Zn) intake. Zinc kinetics from non-stunted infants were used in a published model for predicting linear growth; here, we directly measure zinc kinetics in stunted infants. METHODS: Zinc kinetics were determined in 9-month-old Bangladeshi infants (n = 10), who were non-wasted [weight-for-length z score (WLZ) > -2], ranging in LAZ from -2.9 to -0.43. Stable isotopes were administered 2 hours after a meal as oral ( 70 Zn) and intravenous ( 67 Zn) tracers. After isotope administration, blood was sampled within 5 hours and all urine and feces were collected for 24 hours. Urine was sampled twice-daily out to 9 days. Data were analyzed by compartmental modeling. Daily zinc intake was estimated by the model as the sum of zinc used for growth plus that lost via urine and feces. Zinc absorbed (the amount required to maintain steady state) was the sum of zinc used for growth plus urine and endogenous fecal excretions. RESULTS: The LAZ score correlated with serum zinc concentration ( R = 0.77, P = 0.001), urinary zinc excretion ( R = 0.66, P = 0.010), and fractional zinc absorption from calculated daily intake ( R = 0.58, P = 0.030). In stunted infants (n = 8), the amount of zinc absorbed did not increase with calculated zinc intake unlike published values for non-stunted infants. CONCLUSIONS: Zinc kinetics in Bangladeshi infants correlate with LAZ and show that malabsorption of supplemental sources of zinc may occur in stunted infants.

Exchangeable Zinc Pool Size Reflects Form of Zinc Supplementation in Young Children and Is Not Associated with Markers of Inflammation.

A sensitive and reliable biomarker of zinc status has yet to be identified, but observational research suggests that the exchangeable zinc pool (EZP) size may be a possible biomarker. This randomized, placebo-controlled trial aimed to compare the change in EZP size from baseline to endline in 174 children who were preventatively supplemented with 10 mg of zinc as part of a multiple micronutrient power (MNP) or as a standalone dispersible tablet for 24 weeks versus a placebo powder. The effects of systemic inflammation on EZP size were also evaluated. Zinc stable isotopes were administered intravenously to children at baseline and endline, and the EZP was measured by the urine extrapolation method. A total of 156 children completed the study with the zinc dispersible tablet group having the greatest increase in EZP (14.1 mg) over 24 weeks when compared with the MNP group (6.8 mg) (p < 0.01) or placebo group (2.0 mg) (p < 0.001). Median EZP size was not different between children with normal or elevated serum inflammatory markers. EZP size was responsive to longitudinal zinc supplementation and reflected the expected difference in bioavailability for two forms of supplementation. The apparent absence of an effect of inflammation on EZP size may offer an advantage for use as a biomarker for group comparisons between different interventions.

Perceptions of women, their husbands and healthcare providers about anemia in rural Pakistan: Findings from a qualitative exploratory study.

BACKGROUND: In Pakistan, there is a dearth of literature on the perceptions of anemia among women of reproductive age (WRA). This study was undertaken to explore the perceptions of women, their husbands, and healthcare providers about anemia, its possible causes, and how anemia impacts maternal and child health in Thatta, Pakistan. METHODS: A qualitative study was conducted in Thatta, Pakistan from September to December 2018. Using a pre-tested semi-structured interview (SSI), we collected data to understand their definitions of anemia through ten focus group discussions (FGDs) with women and their partners and ten primary informant interviews (KIIs) with healthcare providers. We identified six major themes: (I) Knowledge and awareness of anemia, (II) Causes and consequences of Anemia, (III) Dietary practices, (IV) Knowledge and practices regarding the use of iron-folic acid supplements, (V) Factors influencing prevention and control of anemia and (VI) Women's health behavior. We analyzed the data through thematic analysis using NVivo 10 software. RESULTS: Most community members were not aware of the term anemia but described anemia as a condition characterized by 'blood deficiency' in the body. All study participants perceived anemia as an important health problem tending to cause adverse outcomes among WRA and their children. Study participants perceived gutka (chewable tobacco) consumption as an important cause of anemia. Healthcare providers identified short inter-pregnancy intervals, lack of family planning, poor health-seeking behavior, and consumption of unhealthy food as causes of anemia in the district. Consumption of unhealthy food might not be related to related to a poorer knowledge of iron-deficient foods, but economic constraints. This was further endorsed by the healthcare providers who mentioned that most women were too poor to afford iron-rich foods. All men and women were generally well versed with the sources of good nutrition to be consumed by WRA to prevent anemia. CONCLUSION: The findings suggest that the government should plan to develop strategies for poverty-stricken and vulnerable rural women and plan health awareness programs to improve dietary practices, compliance with supplements, and health-seeking behavior among women of reproductive age. There is a need to develop effective counseling strategies and context-specific health education sessions to improve the health-seeking behavior of women and men in the Thatta district of Pakistan. Besides, there is need to address social determinants of health such as poverty that pushes women of poorer socioeconomic strata to eat less nutritious foods and have more anaemia. Therefore, a comprehensive and robust strategic plan need to be adopted by government that focuses not only on the awareness programs, but also aim to reduce inequities that lead to pregnant women eat iron-poor foods, which, in turn, forces them to become anemic.

Use of Smokeless Tobacco Before Conception and Its Relationship With Maternal and Fetal Outcomes of Pregnancy in Thatta, Pakistan: Findings From Women First Study.

INTRODUCTION: Smokeless tobacco (SLT) consumption during pregnancy has adverse consequences for the mother and fetus. We aimed to investigate the effects of maternal pre-pregnancy SLT consumption on maternal and fetal outcomes in the district of Thatta, Pakistan. AIMS AND METHODS: We conducted a secondary data analysis of an individual randomized controlled trial of preconception maternal nutrition. Study participants were women of reproductive age (WRA) residing in the district of Thatta, Pakistan. Participants were asked questions regarding the usage of commonly consumed SLT known as gutka (exposure variable). Study outcomes included maternal anemia, miscarriage, preterm births, stillbirths, and low birth weight. We performed a cox-regression analysis by controlling for confounders such as maternal age, education, parity, working status, body mass index, and geographic clusters. RESULTS: The study revealed that 71.5% of the women reported using gutka, with a higher proportion residing in rural areas as compared with urban areas in the district of Thatta, Pakistan. In the multivariable analysis, we did not find a statistically significant association between gutka usage and anemia [(relative risk, RR: 1.04, 95% confidence interval, CI (0.92 to 1.16)], miscarriage [(RR: 1.08, 95% CI (0.75 to 1.54)], preterm birth [(RR: 1.37, 95% CI (0.64 to 2.93)], stillbirth [(RR: 1.02, 95% CI (0.39 to 2.61)], and low birth weight [(RR: 0.96, 95% CI (0.72 to 1.28)]. CONCLUSIONS: The study did not find an association between gutka usage before pregnancy and adverse maternal and fetal outcomes. In the future, robust epidemiological studies are required to detect true differences with a dose-response relationship between gutka usage both before and during pregnancy and adverse fetomaternal outcomes. IMPLICATIONS: While most epidemiological studies conducted in Pakistan have focused on smoking and its adverse outcomes among males, none of the studies have measured the burden of SLT among WRA and its associated adverse outcomes. In addition, previously conducted studies have primarily assessed the effect of SLT usage during pregnancy rather than before pregnancy on adverse fetal and maternal outcomes. The current study is unique because it provides an insight into the usage of SLT among WRA before pregnancy and investigates the association between pre-pregnancy SLT usage and its adverse fetomaternal outcomes in rural Pakistan.

Prevalence and determinants of anemia among women of reproductive age in Thatta Pakistan: Findings from a cross-sectional study.

BACKGROUND: Anemia is a major public health concern among women of reproductive age leading to high maternal mortality in low- and middle-income countries. Of the prior studies conducted in Pakistan, most focused on large urban areas and did not explore the determinants of anemia among women of reproductive age (WRA) across socio-demographic, dietary, reproductive, and biological domains. Thus, we aimed to study the prevalence and determinants of anemia among WRA in rural Pakistan. METHODS: We conducted a cross-sectional study in the Thatta district of Pakistan from September 2018 to January 2019 and enrolled 150 non-pregnant, married women. Data collectors administered a structured questionnaire to collect sociodemographic, reproductive and dietary data from women, who also provided stool and blood samples. We classified all WRA as anemic if their hemoglobin was <12.0 g/dl. We performed logistic regression analysis to calculate adjusted odds ratios (aOR) and their respective 95% CIs to assess the determinants of anemia. RESULTS: In our study, 61.3% of the enrolled women were anemic. In the multivariable analysis, we found that factors such as serum iron levels of less than 50 µg/dl (aOR: 7.17; 95% CI (2.94, 17.47)), history of breastfeeding (aOR: 2.43; 95% CI (1.04, 5.72)), living in a katcha house (aOR: 6.61; 95% CI (2.21, 19.87)), no consumption of meat (aOR: 4.18; 95% CI (1.66, 9.96)) were significantly associated with anemia among WRA. A history of more than one abortion (aOR: 0.06; 95% CI (0.01, 0.33) appeared protective for its association with anemia. CONCLUSION: Our findings demonstrate a high burden of anemia and its complex determinants among WRA in rural Pakistan. A combination of nutritional and educational strategies should be designed to encourage rural women to consume iron-rich foods in their diet with an access to adequate food. Breastfeeding women should be encouraged to consume extra calories with sufficient intake of the food to continue exclusive breastfeeding and reserve the iron stores through amenorrhea to prevent themselves from becoming anemic.

Longitudinal Changes of One-Carbon Metabolites and Amino Acid Concentrations during Pregnancy in the Women First Maternal Nutrition Trial.

BACKGROUND: Maternal dietary restriction and supplementation of one-carbon (1C) metabolites can impact offspring growth and DNA methylation. However, longitudinal research of 1C metabolite and amino acid (AA) concentrations over the reproductive cycle of human pregnancy is limited. OBJECTIVE: To investigate longitudinal 1C metabolite and AA concentrations prior to and during pregnancy and the effects of a small-quantity lipid-based nutrition supplement (LNS) containing >20 micronutrients and prepregnancy BMI (ppBMI). METHODS: This study was an ancillary study of the Women First Trial (NCT01883193, clinicaltrials.gov) focused on a subset of Guatemalan women (n = 134), 49% of whom entered pregnancy with a BMI ≥25 kg/m2. Ninety-five women received LNS during pregnancy (+LNS group), while the remainder did not (-LNS group). A subset of women from the Pakistan study site (n = 179) were used as a replication cohort, 124 of whom received LNS. Maternal blood was longitudinally collected on dried blood spot (DBS) cards at preconception, and at 12 and 34 wk gestation. A targeted metabolomics assay was performed on DBS samples at each time point using LC-MS/MS. Longitudinal analyses were performed using linear mixed modeling to investigate the influence of time, LNS, and ppBMI. RESULTS: Concentrations of 23 of 27 metabolites, including betaine, choline, and serine, changed from preconception across gestation after application of a Bonferroni multiple testing correction (P < 0.00185). Sixteen of those metabolites showed similar changes in the replication cohort. Asymmetric and symmetric dimethylarginine were decreased by LNS in the participants from Guatemala. Only tyrosine was statistically associated with ppBMI at both study sites. CONCLUSIONS: Time influenced most 1C metabolite and AA concentrations with a high degree of similarity between the 2 diverse study populations. These patterns were not significantly altered by LNS consumption or ppBMI. Future investigations will focus on 1C metabolite changes associated with infant outcomes, including DNA methylation. This trial was registered at clinicaltrials.gov as NCT01883193.

Preconception nutrition intervention improved birth length and reduced stunting and wasting in newborns in South Asia: The Women First Randomized Controlled Trial.

South Asia has >50% of the global burden of low birth weight (LBW). The objective was to determine the extent to which maternal nutrition interventions commenced before conception or in the 1st trimester improved fetal growth in this region. This was a secondary analysis of combined newborn anthropometric data for the South Asian sites (India and Pakistan) in the Women First Preconception Maternal Nutrition Trial. Participants were 972 newborn of mothers who were poor, rural, unselected on basis of nutritional status, and had been randomized to receive a daily lipid-based micronutrient supplement commencing ≥3 months prior to conception (Arm 1), in the 1st trimester (Arm 2), or not at all (Arm 3). An additional protein-energy supplement was provided if BMI <20 kg/m2 or gestational weight gain was less than guidelines. Gestational age was established in the 1st trimester and newborn anthropometry obtained <48-hours post-delivery. Mean differences at birth between Arm 1 vs. 3 were length +5.3mm and weight +89g. Effect sizes (ES) and relative risks (RR) with 95% CI for Arm 1 vs. 3 were: length-for-age Z-score (LAZ) +0.29 (0.11-0.46, p = 0.0011); weight-for-age Z-score (WAZ) +0.22 (0.07-0.37, p = 0.0043); weight-to-length-ratio-for-age Z-score (WLRAZ) +0.27 (0.06-0.48, p = 0.0133); LAZ<-2, 0.56 (0.38-0.82, p = 0.0032); WAZ <-2, 0.68 (0.53-0.88, p = 0.0028); WLRAZ <-2, 0.76 (0.64-0.89, p = 0.0011); small-for-gestational-age (SGA), 0.74 (0.66-0.83, p<0.0001); low birth weight 0.81 (0.66-1.00, p = 0.0461). For Arm 2 vs. 3, LAZ, 0.21 (0.04-0.38); WAZ <-2, 0.70 (0.53-0.92); and SGA, 0.88 (0.79-0.97) were only marginally different. ES or RR did not differ for preterm birth for either Arm 1 vs. 3 or 2 vs. 3. In conclusion, point estimates for both continuous and binary anthropometric outcomes were consistently more favorable when maternal nutrition supplements were commenced ≥3 months prior to conception indicating benefits to fetal growth of improving women's nutrition in this population.

Maternal Characteristics Affect Fetal Growth Response in the Women First Preconception Nutrition Trial.

The objective of this secondary analysis was to identify maternal characteristics that modified the effect of maternal supplements on newborn size. Participants included 1465 maternal-newborn dyads in Guatemala, India, and Pakistan. Supplementation commenced before conception (Arm 1) or late 1st trimester (Arm 2); Arm 3 received usual care. Characteristics included body mass index (BMI), stature, anemia, age, education, socio-economic status (SES), parity, and newborn sex. Newborn outcomes were z-scores for length (LAZ), weight (WAZ), and weight to length ratio-for-age (WLRAZ). Mixed-effect regression models included treatment arm, effect modifier, and arm * effect modifier interaction as predictors, controlling for site, characteristics, and sex. Parity (para-0 vs. para ≥1), anemia (anemia/no anemia), and sex were significant effect modifiers. Effect size (95% CI) for Arm 1 vs. 3 was larger for para-0 vs. ≥1 for all outcomes (LAZ 0.56 (0.28, 0.84, p < 0.001); WAZ 0.45 (0.20, 0.07, p < 0.001); WLRAZ 0.52 (0.17, 0.88, p < 0.01) but only length for Arm 2 vs. 3. Corresponding effects for para ≥1 were >0.02. Arm 3 z-scores were all very low for para-0, but not para ≥1. Para-0 and anemia effect sizes for Arm 1 were > Arm 2 for WAZ and WLRAZ, but not LAZ. Arm 1 and 2 had higher WAZ for newborn boys vs. girls. Maternal nulliparity and anemia were associated with impaired fetal growth that was substantially improved by nutrition intervention, especially when commenced prior to conception.

Different Gut Microbial Profiles in Sub-Saharan African and South Asian Women of Childbearing Age Are Primarily Associated With Dietary Intakes.

BACKGROUND: To compare and characterize the gut microbiota in women of childbearing age from sub-Saharan Africa (the Democratic Republic of the Congo, DRC) and South Asia (India), in relation to dietary intakes. METHODS: Women of childbearing age were recruited from rural DRC and India as part of the Women First (WF) preconception maternal nutrition trial. Findings presented include fecal 16S rRNA gene-based profiling of women in the WF trial from samples obtained at the time of randomization, prior to initiation of nutrition intervention and to conception. RESULTS: Stool samples were collected from 217 women (DRC n = 117; India n = 100). Alpha diversity of the gut microbiota was higher in DRC than in India (Chao1: 91 ± 11 vs. 82 ± 12, P = 6.58E-07). The gut microbial community structure was not significantly affected by any demographical or environmental variables, such as maternal BMI, education, and water source. Prevotella, Succinivibrio, and Roseburia were at relatively high abundance without differences between sites. Bifidobacterium was higher in India (4.95 ± 1.0%) than DRC (0.3 ± 0.1%; P = 2.71E-27), as was Lactobacillus (DRC: 0.2 ± 0.0%; India: 1.2 ± 0.1%; P = 2.39E-13) and Faecalibacterium (DRC: 6.0 ± 1.7%; India: 8.4 ± 2.9%; P = 6.51E-7). Ruminococcus was higher in DRC (2.3 ± 0.7%) than in India (1.8 ± 0.4%; P = 3.24E-5) and was positively associated with consumption of flesh foods. Succinivibrio was positively associated with dairy intake in India and fish/insects in DRC. Faecalibacterium was positively associated with vitamin A-rich fruits and vegetables. Overall, these observations were consistent with India being primarily vegetarian with regular fermented dairy consumption and DRC regularly consuming animal-flesh foods. CONCLUSION: Consumption of animal-flesh foods and fermented dairy foods were independently associated with the gut microbiota while demographic variables were not, suggesting that diet may have a stronger association with microbiota than demographic characteristics.

Challenges of Implementing an Individual Randomized Controlled Trial (Women First: Preconception Maternal Nutrition Study) in a Rural Study Site: A Case Study From Pakistan.

Persistent global disparities in maternal and neonatal outcomes associated with poor maternal nutrition provided the genesis of the Women First (WF) study, an individually randomized controlled trial on preconceptional maternal nutrition. This article describes the challenges that arose in implementing this trial related to nutrition or diet of the mother, in District Thatta-Pakistan. During different phases of the study, we encountered problems in identifying the eligible participants, taking consent from couples, randomizing participants in different arms, conducting biweekly follow-up visits on time, ensuring compliance to the intervention, and measuring the primary outcome within the 24 hours of birth. Each challenge was itself an opportunity for the research team to address the same through effective coordination and teamwork. Moreover, with adequate resources and dedicated staff with diverse backgrounds, it was possible to implement the WF study across the widely scattered geographic clusters of District Thatta. In addition, there are some broad strategies that could be applied to other studies such as very close contact either in person or at least by talking to mothers via phones and rapport with the study participants, the study leadership of country coordinator and the field supervisors to build trust between those on front lines and the study leadership. Moreover, continuous monitoring and supervision with frequent training and refreshers were also found to be more important to assure the data quality and to meet the study targets. Community meetings were also found to be very helpful and effective to follow the participants for a long time. Researchers conducting a similar type of studies particularly in rural areas can learn many lessons from such experiences. Thus, the process of implementing the study in one of the rural areas of Pakistan provides an insight into where and how similar individual randomized trials might be deployed.

Pregnant Women in Four Low-Middle Income Countries Have a High Prevalence of Inadequate Dietary Intakes That Are Improved by Dietary Diversity.

BACKGROUND: Up-to-date dietary data are required to understand the diverse nutritional challenges of pregnant women living in low-middle income countries (LMIC). To that end, dietary data were collected from 1st trimester pregnant women in rural areas of Guatemala, India, Pakistan, and Democratic Republic of the Congo (DRC) participating in a maternal lipid-based nutrient supplement (LNS) Randomized Controlled Trial to examine dietary diversity (DD), usual group energy and nutrient intakes, and prevalence of inadequate dietary intakes. METHODS: Two 24-h dietary recalls were conducted in ~240 pregnant women/site (total n = 966) prior to 12-week gestation. Adequate DD was assessed, i.e., ≥5 major food groups consumed within the past 24 h. Median, Q1, Q3 intakes (without LNS) of energy, macronutrients, 12 micronutrients, and phytate were examined. The "at risk" prevalence of inadequate intakes were based on international guidelines for pregnant women. RESULTS: Dietary patterns varied widely among sites, with adequate DD reported: 20% (Pakistan), 25% (DRC), 50% (Guatemala), and 70% (India). Significantly higher intakes of most key nutrients were observed in participants with adequate DD. More than 80% of women in all sites had inadequate intakes of folate, vitamin B12, and choline, and >80% of women in India and DRC also had inadequate intakes of calcium, thiamine, riboflavin, and vitamin B6. CONCLUSIONS: Our data highlight the likely need for micronutrient supplementation in pregnancy, specifically multi-micronutrient interventions, and support the value of increasing DD as part of sustainable long-term nutrition programs for women of reproductive age in these poor rural settings in LMIC.

Zinc Absorption and Endogenous Fecal Zinc Losses in Bangladeshi Toddlers at Risk for Environmental Enteric Dysfunction.

OBJECTIVES: Environmental enteric dysfunction (EED) impairs zinc absorption from food, and zinc deficiency may contribute to the poor growth associated with EED. We examined zinc absorption from a standardized aqueous zinc dose, and habitual daily endogenous fecal zinc excretion (EFZ) and compared these outcomes between children grouped by the lactulose to mannitol ratio (L:M). METHODS: Bangladeshi toddlers (18-24 months) with low (<0.09) and high (≥0.09) L:M were administered isotope-labeled 3 mg aqueous zinc in the fasted state. Fractional absorption of zinc (FAZ) and EFZ were measured by dual stable isotope tracer method and an isotope dilution method, respectively. Secondary aims included examining relationships of biomarkers of systemic and intestinal inflammation and gut function with FAZ and EFZ. RESULTS: Forty children completed the study; nearly all had evidence of EED. No differences in zinc homeostasis measurements (mean ±â€ŠSD) were observed between high and low L:M groups: FAZ was 0.38 ±â€Š0.19 and 0.31 ±â€Š0.19, respectively; both figures were within estimated reference range. Means of EFZ were 0.73 ±â€Š0.27 and 0.76 ±â€Š0.20 mg/day for high and low L:M, respectively, and were 10% to 15% above estimated reference range. Regression analyses indicated that biomarkers of systemic inflammation were directly associated with increasing FAZ, consistent with increased gut permeability. Biomarkers of intestinal inflammation were negatively associated with EFZ, consistent with low-zinc intake and chronic deficiency. CONCLUSIONS: In these children at risk of EED, endogenous zinc losses were not markedly increased. Results suggest that efforts to improve zinc status in EED should focus on substantially improving zinc intakes.

Factors associated with anemia among women of the reproductive age group in Thatta district: study protocol.

BACKGROUND: Maternal anemia is a leading public health issue placing pregnant women at higher risk of low birth weight, preterm birth, perinatal mortality, and neonatal mortality. Women in developing countries are at higher risk of anemia which could be either due to micronutrient deficiencies, hemoglobinopathies, infections or other socio-demographic factors. Thus, it is highly essential to explore the factors of anemia among women of the reproductive age group in order to design suitable interventions. The primary objective of this study is to assess the biological and socio-demographic factors that are associated with anemia among the women of the reproductive age group in Thatta district. METHODS: An exploratory mixed method study using quantitative and qualitative approaches will be conducted in district Thatta Pakistan from September 2018 to January 2019. In the qualitative phase, data will be collected through focus group discussions and key informant interviews to understand the perceptions of women, their husbands and healthcare providers about anemia. In addition, a quantitative approach using cross-sectional study will be conducted to determine biological and socio-demographic factors associated with anemia. Approximately 150 non-pregnant women and their spouses will be included in the quantitative component of the study. In addition to thematic analysis for the qualitative component, Logistic regression will be done to calculate adjusted Odds ratios with their respective 95% CIs to assess the factors associated with anemia. DISCUSSION: The better understanding of biological, socio-demographic factors and community perceptions of anemia will help us to design strategies and interventions to better address anemia during the reproductive cycle in rural areas of Pakistan. This will help the researchers and policymakers to take the appropriate action accordingly by designing suitable approaches to address the specific type of anemia in the rural population of Pakistan. This will, in turn, reduce the chances of adverse maternal and fetal outcomes associated with anemia.

A multicountry randomized controlled trial of comprehensive maternal nutrition supplementation initiated before conception: the Women First trial.

Background: Reported benefits of maternal nutrition supplements commenced during pregnancy in low-resource populations have typically been quite limited. Objectives: This study tested the effects on newborn size, especially length, of commencing nutrition supplements for women in low-resource populations ≥3 mo before conception (Arm 1), compared with the same supplement commenced late in the first trimester of pregnancy (Arm 2) or not at all (control Arm 3). Methods: Women First was a 3-arm individualized randomized controlled trial (RCT). The intervention was a lipid-based micronutrient supplement; a protein-energy supplement was also provided if maternal body mass index (kg/m2) was <20 or gestational weight gain was less than recommendations. Study sites were in rural locations of the Democratic Republic of the Congo (DRC), Guatemala, India, and Pakistan. The primary outcome was length-for-age z score (LAZ), with all anthropometry obtained <48 h post delivery. Because gestational ages were unavailable in DRC, outcomes were determined for all 4 sites from WHO newborn standards (non-gestational-age-adjusted, NGAA) as well as INTERGROWTH-21st fetal standards (3 sites, gestational age-adjusted, GAA). Results: A total of 7387 nonpregnant women were randomly assigned, yielding 2451 births with NGAA primary outcomes and 1465 with GAA outcomes. Mean LAZ and other outcomes did not differ between Arm 1 and Arm 2 using either NGAA or GAA. Mean LAZ (NGAA) for Arm 1 was greater than for Arm 3 (effect size: +0.19; 95% CI: 0.08, 0.30, P = 0.0008). For GAA outcomes, rates of stunting and small-for-gestational-age were lower in Arm 1 than in Arm 3 (RR: 0.69; 95% CI: 0.49, 0.98, P = 0.0361 and RR: 0.78; 95% CI: 0.70, 0.88, P < 0.001, respectively). Rates of preterm birth did not differ among arms. Conclusions: In low-resource populations, benefits on fetal growth-related birth outcomes were derived from nutrition supplements commenced before conception or late in the first trimester. This trial was registered at clinicaltrials.gov as NCT01883193.

Zinc Absorption from Micronutrient Powders Is Low in Bangladeshi Toddlers at Risk of Environmental Enteric Dysfunction and May Increase Dietary Zinc Requirements.

Background: Environmental enteric dysfunction (EED), a chronic inflammatory disorder of the small bowel, is suspected to impair absorption of micronutrients, including zinc. Objective: The objective of this study was to compare zinc absorption from micronutrient powder (MNP) over a range of zinc doses in young children screened for EED with use of the lactulose:mannitol ratio (L:M). Methods: Bangladeshi children aged 18-24 mo, grouped according to high and low L:M (≥0.09 and <0.09, respectively), were randomly assigned to MNP with 0, 5, 10, or 15 mg Zn/sachet (10 subjects per dose per L:M group). Over a day, fractional absorption of zinc was measured from an MNP-fortified meal and from unfortified meals with stable isotope tracers; total daily absorbed zinc (TAZ, milligrams per day) was determined as the primary outcome. Secondary outcomes included investigation of relations of TAZ to intake, to physiologic requirement, and to other variables, including biomarkers of systemic and intestinal inflammation, using nonlinear models. TAZ was also compared with published data on child zinc absorption. Results: In 74 subjects who completed the study, zinc absorption did not differ by L:M grouping. Most biomarkers of intestinal inflammation were elevated in both L:M groups. For combined L:M groups, mean ± SD TAZ for each MNP dose (0, 5, 10, and 15 mg/sachet) was 0.57 ± 0.30, 0.68 ± 0.31, 0.90 ± 0.43, and 1.0 ± 0.39 mg/d, respectively (P = 0.002), and exceeded the estimated physiologic requirement only for the 10- and 15-mg MNP doses. Zinc absorption was notably lower at all intake levels compared with published data (P < 0.0001) and was inversely related to serum α-1 acid glycoprotein and to fecal Entamoeba histolytica (P = 0.02). Conclusion: Results indicate impaired absorption of zinc, which may predispose to zinc deficiency in young children with evidence of enteropathy. These findings suggest that current doses of zinc in MNP may be insufficient to yield zinc-related preventative benefits in similar settings. This study is registered at clinicaltrials.gov as NCT02758444.

Preconception Micronutrient Supplementation Reduced Circulating Branched Chain Amino Acids at 12 Weeks Gestation in an Open Trial of Guatemalan Women Who Are Overweight or Obese.

Elevated branched chain amino acids (BCAAs: valine, leucine, and isoleucine) are well-established biomarkers of obesity-associated insulin resistance (IR). Mounting evidence suggests that low- and middle-income countries are suffering from a "double burden" of both undernutrition (growth stunting) and overnutrition (obesity) as these countries undergo a "nutrition transition". The purpose of this study was to examine if pre-pregnancy body mass index (BMI, kg/m²) and a daily lipid-based micronutrient supplement (LNS, Nutriset) would lead to cross-sectional differences in circulating levels of branched chain amino acids (BCAAs) in Guatemalan women experiencing short stature during early pregnancy. Using data from an ongoing randomized controlled trial, Women First, we studied women who were normal weight (NW, BMI range for this cohort = 20.1⁻24.1 kg/m²) or overweight/obese (OW/OB, BMI range for this cohort = 25.6⁻31.9 kg/m²), and divided into two groups: those who received daily LNS ≥ 3 months prior to conception through 12 weeks gestation (+LNS), or no LNS (-LNS) (n = 9⁻10/group). BCAAs levels were obtained from dried blood spot card samples (DBS) assessed at 12 weeks gestation. DBS cards provide a stable, efficient, and reliable means of collecting, transporting, and storing blood samples in low resource or field settings. Circulating maternal leptin, adiponectin, and insulin were determined by immunoassays from serum samples collected at 12 weeks gestation. We found maternal pre-pregnancy body mass index (ppBMI) was associated with higher circulating BCAAs (r² = 0.433, p = 0.002) and higher leptin/adiponectin ratio (r = 0.466, p = 0.044) in -LNS mothers at 12 weeks gestation. +LNS mothers demonstrated no correlations between BCAAs or leptin/adiponectin ratio across ppBMI suggesting LNS may be effective at improving metabolic status in OW/OB mothers during early pregnancy.

Exchangeable Zinc Pool Size at Birth in Pakistani Small for Gestational Age and Appropriate for Gestational Age Infants Do Not Differ But Are Lower Than in US Infants.

OBJECTIVES: Small for gestational age (SGA) infants are more susceptible to infectious morbidity and growth faltering compared to their appropriate for gestational age (AGA) counterparts. Zinc supplementation of SGA infants may be beneficial but the underlying susceptibility to zinc deficiency of SGA infants has not been examined. METHODS: In a community-based, observational, longitudinal study in a peri-urban settlement of Karachi, Pakistan, we compared the size of the exchangeable zinc pools (EZPs) in term SGA and AGA infants at birth and at 6 months of age, hypothesizing that the EZP would be lower in the SGA group. To measure EZP size, a zinc stable isotope was intravenously administered within 48 hours of birth (n = 17 and 22) at 6 months (n = 11 and 14) in SGA and AGA infants, respectively. Isotopic enrichment in urine was used to determine EZP. RESULTS: No significant difference was detected in the mean (±standard deviation) EZP between SGA and AGA infants at birth, with values of 9.8 ±â€Š3.5 and 10.1 ±â€Š4.1 mg/kg, respectively (P = 0.86), or at 6 months. Longitudinal EZP measurements demonstrated a significant decline in EZP relative to body weight in both groups at 6 months (P < 0.001). Mean EZP (adjusted for body weight) size at birth for the combined Pakistani groups was significantly lower than AGA infants at birth in the United States (P = 0.017). CONCLUSIONS: These results did not support a difference in zinc endowment between SGA and AGA Pakistani infants. They, however, do suggest lower in utero zinc transfer to the fetus in a setting where poor maternal nutritional status may confer a high susceptibility to postnatal zinc deficiency.

Anthropometric indices for non-pregnant women of childbearing age differ widely among four low-middle income populations.

BACKGROUND: Maternal stature and body mass indices (BMI) of non-pregnant women (NPW) of child bearing age are relevant to maternal and offspring health. The objective was to compare anthropometric indices of NPW in four rural communities in low- to low-middle income countries (LMIC). METHODS: Anthropometry and maternal characteristics/household wealth questionnaires were obtained for NPW enrolled in the Women First Preconception Maternal Nutrition Trial. Body mass index (BMI, kg/m2) was calculated. Z-scores were determined using WHO reference data. RESULTS: A total of 7268 NPW participated in Equateur, DRC (n = 1741); Chimaltenango, Guatemala (n = 1695); North Karnataka, India (n = 1823); and Thatta, Sindh, Pakistan (n = 2009). Mean age was 23 y and mean parity 1.5. Median (P25-P75) height (cm) ranged from 145.5 (142.2-148.9) in Guatemala to 156.0 (152.0-160.0) in DRC. Median weight (kg) ranged from 44.7 (39.9-50.3) in India to 52.7 (46.9-59.8) in Guatemala. Median BMI ranged from 19.4 (17.6-21.9) in India to 24.9 (22.3-28.0) in Guatemala. Percent stunted (<-2SD height for age z-score) ranged from 13.9% in DRC to 80.5% in Guatemala; % underweight (BMI <18.5) ranged from 1.2% in Guatemala to 37.1% in India; % overweight/obese (OW, BMI ≥25.0) ranged from 5.7% in DRC to 49.3% in Guatemala. For all sites, indicators for higher SES and higher age were associated with BMI. Lower SES women were underweight more frequently and higher SES women were OW more frequently at all sites. Younger women tended to be underweight, while older women tended to be OW. CONCLUSIONS: Anthropometric data for NPW varied widely among low-income rural populations in four countries located on three different continents. Global comparisons of anthropometric measurements across sites using standard reference data serve to highlight major differences among populations of low-income rural NPW and assist in evaluating the rationale for and the design of optimal intervention trials. TRIAL REGISTRATION: ClinicalTrials.gov # NCT01883193 (18 June 2013, retrospectively registered).