Supplementation with Fortified Lipid-Based and Blended Complementary Foods has Variable Impact on Body Composition Among Rural Bangladeshi Children: A Cluster-Randomized Controlled Trial.

BACKGROUND: Complementary food supplementation enhances linear growth and may affect body composition in children. OBJECTIVE: We aimed to determine the effect of complementary food supplements provided from the age of 6 to 18 mo on fat-free mass (FFM) and fat mass (FM) gain among children in rural Bangladesh. METHODS: In an unblinded, cluster-randomized, controlled trial we tested the effects of 4 complementary food supplements for 1 y [chickpea, rice lentil, Plumpy'doz, and wheat-soy-blend++ (WSB++)] compared with no supplements on linear growth. Body composition was estimated using weight-length-based, age- and sex-specific equations at 6, 9, 12, 15, and 18 mo and postintervention aged 24 mo. Generalized estimating equations (GEEs) were applied to estimate the effect of each complementary food on mean FFM and FM from 9 to 18 and 24 mo compared with the control, adjusting for baseline measures. Sex interactions were also explored. RESULTS: In total, 3592 (65.9% of enrolled) children completed all anthropometric assessments. Estimated FFM and FM (mean ± SD) were 5.3 ± 0.6 kg and 1.4 ± 0.4 kg, respectively, at the age of 6 mo. Mean ± SE FFM and FM from 9 to 18 mo were 75.4 ± 14.0 g and 32.9 ± 7.1 g, and 61.0 ± 16.6 g and 30.0 ± 8.4 g, higher with Plumpy'doz and chickpea foods, respectively, than the control (P < 0.001). Estimated FFM was 41.5 ± 16.6 g higher in rice-lentil-fed versus control (P < 0.05) children. WSB++ had no impact on FFM or FM. A group-sex interaction (P < 0.1) was apparent with Plumpy'doz and rice-lentil foods, with girls involved in the intervention having higher estimated FFM and FM than control girls compared with no significant effect in boys. At 24 mo, FFM and FM remained higher only in girls eating Plumpy'doz compared with the controls (P < 0.01). CONCLUSIONS: In this randomized trial, supplementation effected small shifts in apparent body composition in rural Bangladeshi children. Where seen, FFM increments were twice that of FM, in proportion to these compartments, and more pronounced in girls. FFM increased in line with reported improvements in length. This trial was registered at clinicaltrials.gov as NCT01562379.

Prenatal cortisol modifies the association between maternal trauma history and child cognitive development in a sex-specific manner in an urban pregnancy cohort.

Women's experience of trauma may cause lifelong alterations in physiological stress regulation, which can be transmitted to offspring in utero. We investigated, in a prospective pregnancy cohort, associations among maternal lifetime interpersonal trauma (IPT) history, prenatal cortisol dysregulation, and children's memory domains. Sex-specific effects were also explored. Pregnant women were enrolled from Brigham & Women's Hospital and affiliated clinics near Boston, MA, in 2002-2007. IPT was assessed with the Revised Conflict Tactics Scale, short form. Salivary cortisol was measured at five time points on each of three days in one week at 29.0 ± 5.1 weeks gestation, and morning rise and diurnal slope were calculated. The Wide Range Assessment of Memory & Learning, 2nd Edition was administered at 6.5 ± 1.0 years and scores were generated for general memory and three sub-domains: verbal, visual, and attention/concentration. In total, 258 maternal-child dyads provided memory and IPT and/or cortisol data. IPT was positively associated with verbal memory in boys (ß ± SE: 4.6 ± 2.6) and inversely associated with visual memory score in girls (-6.5 ± 3.2). IPT did not predict prenatal cortisol, but prenatal cortisol modified the association between IPT history and child memory in varying coefficient models allowing for non-linear effect modification. The strongest evidence of interaction was for visual memory in boys: IPT history was associated with poorer visual memory only in those with flatter prenatal diurnal slope (interaction p = .005). Maternal lifetime IPT that leads to prenatal HPA dysregulation may have consequences for child memory, more so than either trauma or elevated cortisol alone. Boys may be more vulnerable to effects. Sex- and timing-specific effects require further investigation.

Complementary Food Supplements Increase Dietary Nutrient Adequacy and Do Not Replace Home Food Consumption in Children 6-18 Months Old in a Randomized Controlled Trial in Rural Bangladesh.

Background: Inadequate complementary feeding is common in low- and middle-income countries, contributing to growth deficits. Complementary food supplements (CFSs) aim to fill dietary gaps, but few CFS studies have measured nutrient intake. In a community-based, randomized CFS trial in Bangladesh, we previously reported poor dietary diversity in 6-18-mo-old participants. Objective: We investigated, in a secondary analysis in the same trial, micronutrient intake adequacy in supplemented compared with control-arm children. Methods: At age 6 mo, children were assigned to 1 y of child-feeding counseling for mothers (control) or counseling plus 1 of 4 CFS formulations. Mothers were administered quantitative past 24-h diet questionnaires for their children at ages 6, 9, 12, 15, and 18 mo. Nutrient intakes were estimated with local recipes and food composition tables assuming average age-specific breastmilk intake. Adequacy was evaluated relative to estimated average requirements or adequate intakes. Multivariate analysis of variance and generalized estimating equation (GEE) regression models estimated the effect of each CFS on nutrient adequacy. GEE models tested dietary predictors of nutrient adequacy in the control arm. Results: A total of 25,964 dietary modules across 5 interviews were completed. Nutrient adequacy from home foods combined with assumed breastmilk intake was low. Only 5 of 16 micronutrients were adequately consumed by >60% of children at 18 mo of age. Daily CFSs did not affect energy-adjusted micronutrient intake from home foods at any follow-up age (P > 0.05). CFSs increased the mean adequacy ratio for all micronutrients (P < 0.001 at all ages), to ≥1 for 14 of 16 micronutrients at 18 mo. Dietary diversity predicted adequate iron, zinc and calcium intake at 15 mo in unsupplemented controls. Conclusions: Home foods did not meet the estimated micronutrient needs of 9-18-mo-old children in rural Bangladesh. Daily supplementation with fortified complementary foods filled many micronutrient intake gaps and did not displace home foods. Previously, CFSs were shown to also improve linear growth and reduce stunting in this cohort. Findings support the need for CFSs in similar settings to promote nutritional well being and growth. This trial was registered at clinicaltrials.gov as NCT01562379.

Environmental enteric dysfunction and systemic inflammation predict reduced weight but not length gain in rural Bangladeshi children.

Environmental enteric dysfunction (EED) and systemic inflammation (SI) are common in developing countries and may cause stunting. In Bangladesh, >40 % of preschool children are stunted, but EED and SI contributions are unknown. We aimed to determine the impact of EED and SI (assessed with multiple indicators) on growth in children (n 539) enrolled in a community-based randomised food supplementation trial in rural Bangladesh. EED was defined with faecal myeloperoxidase, α-1 antitrypsin and neopterin and serum endotoxin core antibody and glucagon-like peptide-2, consolidated into gut inflammation (GI) and permeability (GP) scores, and urinary lactulose:mannitol α-1 acid glycoprotein (AGP) characterised SI. Biomarker associations with anthropometry (15-, 18- and 24-month length-for-age (LAZ), weight-for-length (WLZ) and weight-for-age (WAZ) z scores) were examined in pairwise correlations and adjusted mixed-effects regressions. Stunting, wasting and underweight prevalence at 18 months were 45, 15 and 37 %, respectively, with elevated EED and SI markers common. EED and SI were not associated with 15-24-month length trajectory. Elevated (worse) GI and GP scores predicted reduced 18-24-month WLZ change (ß -0·01 (se 0·00) z score/month for both). Elevated GP was also associated with reduced 15-18-month WLZ change (ß -0·03 (se 0·01) z score/month) and greater 15-month WLZ (ß 0·16 (se 0·05)). Higher AGP was associated with reduced prior and increased subsequent WLZ change (ß -0·04 (se 0·01) and ß 0·02 (se 0·00) z score/month for 15-18 and 18-24 months). The hypothesised link from EED to stunting was not observed in this sample of Bangladeshi 18-month-olds, but the effects of EED on constrained weight gain may have consequences for later linear growth or for other health and development outcomes.

Association between stunting and early childhood development among children aged 36-59 months in South Asia.

Stunting (length-for-age z score < -2) before 2 years of age has shown associations with poor child developmental indicators, but information at the population level is scarce in South Asia, the region with the highest burden of stunting. We examined associations between z scores (i.e., height for age [HAZ], weight for age [WAZ], and weight for height [WHZ]) and undernutrition (i.e., stunting [HAZ < -2], wasting [WHZ < -2], and underweight [WAZ < -2]) with learning/cognition and social-emotional development among children 36-59 months of age. Data from Multiple Indicator Cluster Surveys in Bangladesh (n = 8,659), Bhutan (n = 2,038), Nepal (n = 2,253), and Pakistan (Punjab n = 11,369 and Sindh n = 6,718) were used. Children were considered developmentally "on-track" in learning/cognition or social-emotional domains if they met specific early child development criteria. Meta-analysis was conducted to examine regional associations, adjusting for socio-economic status, early childhood education, and quality of care. In a pooled sample, on-track learning/cognition development was positively associated with HAZ (OR = 1.17, 95% CI [1.07, 1.27]) and WAZ (OR = 1.18, 95% CI [1.07, 1.31]) and negatively associated with stunting (OR = 0.72, 95% CI [0.60, 0.86]) and underweight (OR = 0.75, 95% CI [0.66, 0.86]) but not associated with WHZ or wasting. On-track development of social-emotional domain was not associated with any z scores or undernutrition indicators. Across several countries of South Asia, stunted children were less likely to be developmentally "on track" for learning/cognition. It is likely that interventions that prevent stunting may benefit child development, leading to significant individual and societal gains given the large burden of child stunting in regions like South Asia.

Epidemiology of anaemia in children, adolescent girls, and women in Bhutan.

Anaemia inhibits health and development in Bhutan. We estimated anaemia prevalence and explored risk factors in children and women using data from Bhutan's National Nutrition Survey 2015. Prevalence was calculated using life-stage-specific cut-offs adjusted for altitude and survey design. Risk factors were evaluated in modified Poisson regressions. Anaemia affected 42%, 29%, 36%, and 28% of children, adolescent girls, and non-pregnant and pregnant women, respectively. Risk of anaemia was greater in children who were younger (RR 2.0, 95% CI [1.7, 2.3] and RR 1.9, 95% CI [1.6, 2.3], respectively, for 12-23 and 6-11 vs. 24-59 months), male (1.2, 1.1-1.4, ref.: female), and stunted (1.2, 1.0-1.3, ref.: height-for-age ≥ -2z). Older (15-19 years) versus younger (10-14 years) adolescents were at higher risk (1.5, 1.2-1.8), as were adolescents living at home versus at school (1.2, 0.9-1.6) and those working versus studying (1.3, 1.0-1.7). Among adult women, anaemia risk increased with age (1.2, 1.0-1.4 and 1.3, 1.1-1.5, for 30-39 and 40-49, respectively, vs. 20-29 years) and was higher for women without schooling (1.1, 1.0-1.3, vs. primary schooling), who were unmarried or separated (1.4, 1.2-1.7 and 1.3, 1.1-1.6, respectively, vs. married), without a child <5 years (1.1, 1.0-1.3), and lacking improved sanitation (1.1, 1.0-1.3). High coverage of antennal iron and folic acid supplementation may contribute to the lower prevalence of anaemia among pregnant women and women with young children. Expansion of iron supplementation programmes, fortification, and other strategies to improve dietary iron intake may reduce the prevalence of anaemia, but causes of anaemia other than iron deficiency (e.g., thalassemias) should also be investigated.

Infant and young child feeding practices and nutritional status in Bhutan.

In South Asia, childhood undernutrition persists while overweight is increasing. Internationally recommended infant and young child feeding (IYCF) practices promote healthy nutritional status; however, little is known about IYCF in Bhutan, investigated here using 2015 National Nutrition Survey data. WHO/UNICEF IYCF indicators, anthropometry and household socio-economic status were available for 441 children <24 months. Stunting, wasting, and underweight prevalence (<-2Z length-for-age [LAZ], weight-for-age, [WAZ] and weight-for-length [WLZ], respectively) were 15%, 9%, and 5%, respectively, whereas overweight (WLZ >2) prevalence was 6%. In survey-design-adjusted analyses, 52% of mothers of 0- to 5-month olds reported exclusive breastfeeding (EBF), with EBF less common for girls than boys (OR: 0.2 [95% CI: 0.1-0.9]). Although 61% of children were breastfed at 2 years and 75% of children >6 months met a minimum daily meal frequency, only 18% of children 6-23 months met minimum dietary diversity. IYCF was unassociated with risk of stunting, wasting, or underweight, possibly due to relatively low prevalence of anthropometric failure and small sample size. However, currently-breastfed children were less often overweight [OR: ~0.1 (95% upper limit ≤1.0)]. Neither breastfeeding nor most complementary feeding practices differed by socio-economic status, but children in the highest two fifth of a wealth index had 7.8 (1.3-46.9) and 5.3 (1.1-25.2) times greater odds than children in the lowest fifth of meeting minimum dietary diversity criteria. Low rates of EBF, given possible protection of breastfeeding against overweight, and inadequate dietary diversity offer evidence to guide future program interventions to improve nutritional status of young children.

Nutritional status and risk factors for stunting in preschool children in Bhutan.

Childhood malnutrition remains endemic in South Asia, although the burden varies by country. We examined the anthropometric status and risk factors for malnutrition among children aged 0-59 months through the 2015 National Nutrition Survey in Bhutan. We assessed in 1,506 children nutritional status (by z-scores of height-for-age [HAZ], weight-for-height [WHZ], and weight-for-age [WAZ]), estimating prevalence, adjusted for survey design, of stunting, wasting, underweight, and overweight (<-2 for HAZ, WHZ, and WAZ and >2 for WHZ). Children were also assessed for pedal oedema. We conducted multivariable linear/logistic regression analysis to identify child, maternal, and household risk factors for childhood undernutrition and overweight, excluding children with oedema (1.7%). Mean (SE) HAZ, WHZ, and WAZ were -0.82 (0.13), 0.10 (0.04), and -0.42 (0.05), respectively. Prevalence of stunting, wasting, underweight, and overweight were 21.2%, 2.6%, 7.4%, and 2.6%, respectively. In multivariable regressions, risk of stunting significantly increased by age: 5.3% at <6 months (reference), 16.8% at 6-23 months (OR = 3.06, 95% CI [0.63, 14.8]), and 25.0% at 24-59 months (OR = 5.07, [1.16, 22.2]). Risk of stunting also decreased in a dose-response manner with improved maternal education. None of the examined variables were significantly associated with wasting or overweight. Despite a WHZ distribution comparable with the World Health Organization reference (with ~2.6% vs. an expected 2.5% of children beyond 2 z in each tail), stunting persists in one fifth of preschool Bhutanese children, suggesting that other nutrient deficits or nonnutritional factors may be constraining linear growth for a substantial proportion of children.

Infant and young child feeding practices and nutritional status in Bhutan.

In South Asia, childhood undernutrition persists while overweight is increasing. Internationally recommended infant and young child feeding (IYCF) practices promote healthy nutritional status; however, little is known about IYCF in Bhutan, investigated here using 2015 National Nutrition Survey data. WHO/UNICEF IYCF indicators, anthropometry and household socio-economic status were available for 441 children <24 months. Stunting, wasting, and underweight prevalence (<-2Z length-for-age [LAZ], weight-for-age, [WAZ] and weight-for-length [WLZ], respectively) were 15%, 9%, and 5%, respectively, whereas overweight (WLZ >2) prevalence was 6%. In survey-design-adjusted analyses, 52% of mothers of 0- to 5-month olds reported exclusive breastfeeding (EBF), with EBF less common for girls than boys (OR: 0.2 [95% CI: 0.1-0.9]). Although 61% of children were breastfed at 2 years and 75% of children >6 months met a minimum daily meal frequency, only 18% of children 6-23 months met minimum dietary diversity. IYCF was unassociated with risk of stunting, wasting, or underweight, possibly due to relatively low prevalence of anthropometric failure and small sample size. However, currently-breastfed children were less often overweight [OR: ~0.1 (95% upper limit ≤1.0)]. Neither breastfeeding nor most complementary feeding practices differed by socio-economic status, but children in the highest two fifth of a wealth index had 7.8 (1.3-46.9) and 5.3 (1.1-25.2) times greater odds than children in the lowest fifth of meeting minimum dietary diversity criteria. Low rates of EBF, given possible protection of breastfeeding against overweight, and inadequate dietary diversity offer evidence to guide future program interventions to improve nutritional status of young children.

Biomarkers of Environmental Enteric Dysfunction Among Children in Rural Bangladesh.

OBJECTIVES: Environmental enteric dysfunction (EED) may inhibit growth and development in low- and middle-income countries, but available assessment methodologies limit its study. In rural Bangladesh, we measured EED using the widely used lactulose mannitol ratio (L:M) test and a panel of intestinal and systemic health biomarkers to evaluate convergence among biomarkers and describe risk factors for EED. METHODS: In 539 18-month-old children finishing participation in a randomized food supplementation trial, serum, stool, and urine collected after lactulose and mannitol dosing were analyzed for biomarkers of intestinal absorption, inflammation, permeability and repair, and systemic inflammation. EED scores for each participant were developed using principal component analysis and partial least squares regression. Associations between scores and L:M and with child sociodemographic and health characteristics were evaluated using regression analysis. RESULTS: EED prevalence (L:M > 0.07) was 39.0%; 60% had elevated acute phase proteins (C-reactive protein >5 mg/L or α-1 acid glycoprotein >100 mg/dL). Correlations between intestinal biomarkers were low, with the highest between myeloperoxidase and α-1 antitrypsin (r = 0.33, P < 0.01), and biomarker values did not differ by supplementation history. A 1-factor partial least squares model with L:M as the dependent variable explained only 8.6% of L:M variability. In adjusted models, L:M was associated with child sex and socioeconomic status index, whereas systemic inflammation was predicted mainly by recent illness, not EED. CONCLUSIONS: Impaired intestinal health is widespread in this setting of prevalent stunting, but a panel of serum and stool biomarkers demonstrated poor agreement with L:M. Etiologies of intestinal and systemic inflammation are likely numerous and complex in resource-poor settings, underscoring the need for a better case definition with corresponding diagnostic methods to further the study of EED.

Evaluation of a Novel Single-administration Food Frequency Questionnaire for Assessing Seasonally Varied Dietary Patterns among Women in Rural Nepal.

Novel dietary assessment methods are needed to study chronic disease risk in agrarian cultures where food availability is highly seasonal. In 16,320 rural Nepalese women, we tested a novel food frequency questionnaire, administered once, to assess past 7-day intake and usual frequency of intake throughout the year for year-round foods and when in season for seasonal foods. Spearman rank correlations between usual and past 7-day intakes were 0.12-0.85 and weighted kappa statistics, representing chance-corrected agreement, were 0.10-0.80, with better agreement for frequently consumed foods. The questionnaire performed well, but may require refinement for settings of extremely low dietary diversity.

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.

Seasonal dietary intakes and socioeconomic status among women in the Terai of Nepal.

Despite widespread nutritional deficiencies, investigations of usual diet in rural South Asia remain sparse. The present study characterizes year-round and seasonal dietary patterns of women in the Terai of Nepal by sociodemographic status, using a novel, weekly single-visit and usual food frequency questionnaire that links recall to the agricultural season. The study was conducted across seasons in 2006-2008 among 15,899 women of reproductive age in Sarlahi district. Intakes were tabulated for all foods, overall and by socioeconomic status (SES), and in and out of season, as appropriate. Foods consumed regularly [median (interquartile range) weekly frequency] were rice [13 (7-13)], potatoes [10 (5-13)], legumes [6 (2-9)], and vegetable oil [13 (13-13)]. Animal products were infrequently consumed [1 (0-2) time per week] as were fruits and vegetables, most with a median weekly intake frequency of 0. Higher SES was associated with more frequent consumption of most food-groups, including in-season fruits and vegetables. Diets of women in the Terai of Nepal lack diversity and, likely, nutrient adequacy, which may pose health risks.

Prevalence and Risk Factors of Iron Deficiency and Anemia in Women of Reproductive Age in the Hispanic Community Health Study/Study of Latinos.

Background: Women of reproductive age are at elevated risk of iron deficiency (ID) and anemia; in the United States, those of Hispanic/Latino background are at especially high risk. Causes of ID and anemia and variations in risk within Hispanic/Latino women of reproductive age are not well described. Objectives: To characterize ID and anemia and their risk factors/markers in Hispanic/Latina women. Methods: Data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) were used. HCHS/SOL enrolled participants in 2008-2011 at 4 sites: Bronx, Chicago, Miami, and San Diego; 5386 were non-pregnant women ages 18-49 y. Primary outcomes were ID (ferritin <30 µg/L) and anemia (hemoglobin <12 g/dL). Predictors were background/heritage, Short Acculturation Scale for Hispanics scores, years lived in the United States, and interview language, diet summarized in the Alternate Healthy Eating Index 2010, sociodemographic covariates, and study site. Main analyses used survey log binomial regressions adjusted for age, site, and smoking. Results: Almost half (42%) of participants were of Mexican background, 15% of Cuban background, and <15% each were of Puerto Rican, Dominican, Central American, or South American background. ID prevalence was 34.4% overall but differed by site-background pairings. The lowest and highest prevalence were 26% and 42% among women of Cuban background in Miami and women of Mexican background in Chicago, respectively. Anemia prevalence was 16% and ranged from 8.9% (Central American background/Miami) to 22% (Dominican background/Bronx). Acculturation, sociodemographic, and diet variables examined did not explain observed prevalence differences by site/background. Conclusions: Prevalence of ID and anemia were high among HCHS/SOL women and differed by field center and background. These differences highlight the importance of characterizing nutritional risk by background within Hispanic/Latino women.

Prevalence of and Risk Factors for Iron Deficiency in Twin and Singleton Newborns.

Iron deficiency (ID) in utero and in infancy can cause irreversible neurocognitive damage. Iron status is not routinely tested at birth, so the burden of neonatal ID in the United States is unknown. Infants born from twin or higher-order pregnancies may be at elevated risk of inadequate nutrient endowment at birth. The present study sought to compare the burden of neonatal ID in cord blood serum samples from twin (n = 54) and singleton pregnancies (n = 24). Iron status (serum ferritin (SF), soluble transferrin receptor (sTfR), hepcidin) and inflammation (C-reactive protein (CRP) and interleukin-6 (IL-6)) biomarker concentrations were measured by immunoassay. The prevalence of ID (SF < 76 ng/mL) among twins was 21% (23/108) and among singletons 20% (5/24). Gestational age at birth, maternal race and infant sex predicted SF levels. Maternal anemia (hemoglobin < 11 g/dL) was observed in 40% of mothers but was not associated with neonatal iron biomarkers. More research is needed to identify risk factors and regulatory mechanisms for inadequate fetal iron accrual to identify higher risk pregnancies and neonates for screening and intervention.

Characteristics that modify the effect of small-quantity lipid-based nutrient supplementation on child anemia and micronutrient status: an individual participant data meta-analysis of randomized controlled trials.

BACKGROUND: Small-quantity lipid-based nutrient supplements (SQ-LNSs) have been shown to reduce the prevalence of child anemia and iron deficiency, but effects on other micronutrients are less well known. Identifying subgroups who benefit most from SQ-LNSs could support improved program design. OBJECTIVES: We aimed to identify study-level and individual-level modifiers of the effect of SQ-LNSs on child hemoglobin (Hb), anemia, and inflammation-adjusted micronutrient status outcomes. METHODS: We conducted a 2-stage meta-analysis of individual participant data from 13 randomized controlled trials of SQ-LNSs provided to children 6-24 mo of age (n = 15,946). We generated study-specific and subgroup estimates of SQ-LNSs compared with control, and pooled the estimates using fixed-effects models. We used random-effects meta-regression to examine potential study-level effect modifiers. RESULTS: SQ-LNS provision decreased the prevalence of anemia (Hb < 110 g/L) by 16% (relative reduction), iron deficiency (plasma ferritin < 12 µg/L) by 56%, and iron deficiency anemia (IDA; Hb < 110 g/L and plasma ferritin <12 µg/L) by 64%. We observed positive effects of SQ-LNSs on hematological and iron status outcomes within all subgroups of the study- and individual-level effect modifiers, but effects were larger in certain subgroups. For example, effects of SQ-LNSs on anemia and iron status were greater in trials that provided SQ-LNSs for >12 mo and provided 9 (as opposed to <9) mg Fe/d, and among later-born (than among first-born) children. There was no effect of SQ-LNSs on plasma zinc or retinol, but there was a 7% increase in plasma retinol-binding protein (RBP) and a 56% reduction in vitamin A deficiency (RBP < 0.70 µmol/L), with little evidence of effect modification by individual-level characteristics. CONCLUSIONS: SQ-LNSs can substantially reduce the prevalence of anemia, iron deficiency, and IDA among children across a range of individual, population, and study design characteristics. Policy-makers and program planners should consider SQ-LNSs within intervention packages to prevent anemia and iron deficiency.This trial was registered at www.crd.york.ac.uk/PROSPERO as CRD42020156663.

Disentangling Associations Among Maternal Lifetime and Prenatal Stress, Psychological Functioning During Pregnancy, Maternal Race/Ethnicity, and Infant Negative Affectivity at Age 6 Months: A Mixtures Approach.

Purpose: Maternal stress and psychological dysfunction in pregnancy are independently linked with fetal neurodevelopment. Stress encompasses environmental stressors and psychological and physiological responses. Stressors and psychopathology co-occur with patterns differing by race/ethnicity. We aimed to extend environmental mixtures methodology to elucidate prenatal stress associations with infant negative affectivity (NA) in a racially/ethnically mixed cohort. Methods: Participants were mother/infant dyads (n=445) in a prospective pregnancy cohort study in two urban US settings in 2011-2018. During pregnancy, women completed the Life Stressor Checklist-Revised, Crisis in Family Systems-Revised, Edinburgh Postnatal Depression Scale, and post-traumatic stress disorder (PTSD) Checklist-Civilian version; the Infant Behavior Questionnaire-Revised assessed NA in 6-month olds. Using weighted quantile sum (WQS) regression, we developed a weighted maternal stress index encompassing lifetime and current life events and symptoms of depression and PTSD. Stress-by-race/ethnicity interactions allowed differential contributions of individual stress domains by maternal race/ethnicity. Results: Mothers were majority black (44%) or Hispanic (37%). Stress questionnaire and infant NA scores were similar by race/ethnicity. The WQS prenatal stress score was positively associated with infant NA (ß: 0.40 [95% confidence interval 0.16-0.64]). PTSD was the strongest contributor to the WQS score in Hispanic women (59%), whereas in black women, lifetime stress and depressive symptoms accounted for 38% and 35%, respectively, of the association with NA. Conclusions: Extending environmental mixtures methodology to stress research may disentangle complex associations among lifetime and current stressful life events and psychological symptomatology and their contributions to early childhood neurobehavioral outcomes. Consideration of effect modification by race/ethnicity may inform understanding of differing vulnerability across racial/ethnic groups.

Novel Method for Estimating Nutrient Intakes Using a Semistructured 24-Hour Diet Recall for Infants and Young Children in Rural Bangladesh.

BACKGROUND: Nutrient-level intakes from home-prepared complementary foods are rarely estimated among infants and young children in low-income settings. The major constraints are related to lack of standard recipes and ingredients and portion sizes. OBJECTIVES: This article describes the feasibility, applicability, and validity of a post hoc qualitative methodology to estimate nutrient intakes in children using 24-h dietary recall. METHODS: Semistructured, interviewer-administered caregiver 24-h diet recalls were conducted to assess food intake among children participating in a randomized trial of complementary food supplementation at ages 6, 9, 12, 15, 18, and 24 mo in rural Bangladesh. At the end of the diet data collection, focus group discussions with mothers (n = 6) and cooking activities (n = 5) were conducted to obtain standard recipes (and ingredients) and portion sizes for reported foods given at different ages. Nutrient intakes were calculated for children in the control group (n = 1438), and convergent validity of the data was tested by examining the association of energy and protein intakes with child age and socioeconomic status (SES). RESULTS: Focus group discussions generated standardized recipes for 21 commonly consumed mixed dishes being fed to children. These recipes were cooked, and portion sizes of standardized measures used in 24-h recalls were quantified in grams. For discrete foods, we quantified women's perceptions of "small," "medium," and "large" in grams. Across all ages, food groups consumed consisted mostly of staples, with the most common being rice, potatoes, and biscuits. Using portion size data and recipe ingredients, the 24-h dietary data, and Bangladeshi food composition tables, we successfully estimated nutrient intakes in children. Convergent validity analysis showed that energy and protein intakes were strongly associated with age and SES (both P < 0.001). CONCLUSIONS: We demonstrated the use of a validated, qualitative methodology for estimating nutrient intakes in young children from complementary foods in undernourished contexts. This trial was registered at clinicaltrials.gov as NCT01562379.

Micronutrient and Inflammation Status Following One Year of Complementary Food Supplementation in 18-Month-Old Rural Bangladeshi Children: A Randomized Controlled Trial.

Background: Four fortified complementary food supplements (CFSs) in a randomized controlled trial (RCT) were found to improve childhood linear growth in rural Bangladesh. We hypothesized children receiving these supplements would have improved micronutrient status. Methods: In the RCT, we assessed hemoglobin and serum ferritin, retinol, zinc, C-reactive protein (CRP), and α-1-acid glycoprotein (AGP) at endline (18 mo) in a subsample of children (n = 752). The impact of supplementation on mean concentrations and the prevalence of nutrient deficiency and inflammation were evaluated using adjusted generalized estimating equation (GEE) linear and log-binomial regression models. Results: In the control arm at age 18 months, 13% of children were anemic (hemoglobin < 110 g/L), and 6% were iron (inflammation-adjusted ferritin < 12 µg/L), 8% vitamin A (inflammation-adjusted retinol < 0.70 µmol/L), and 5% zinc (zinc < 9.9 µmol/L) deficient. The prevalence of inflammation by CRP (>5 mg/L) and AGP (>1 g/L) was 23% and 66%, respectively, in the control group. AGP trended lower in CFS groups (p = 0.04), while CRP did not. Mean ferritin (p < 0.001) and retinol (p = 0.007) were higher in all supplemented groups relative to control, whereas hemoglobin improved with two of the four CFSs (p = 0.001), and zinc was equal or lower in supplemented groups relative to control (p = 0.017). Conclusions: CFSs improved iron status and vitamin A concentrations and lowered inflammation in a context of low underlying nutrient deficiency but high inflammation.

Maternal Prenatal Psychosocial Stress and Prepregnancy BMI Associations with Fetal Iron Status.

BACKGROUND: Iron accrued in utero is critical for fetal and infant neurocognitive development. Psychosocial stress and obesity can each suppress fetal iron accrual. Their combined effects and differences by fetal sex are not known. In an observational pregnancy cohort study in Mexico City, we investigated associations of maternal prenatal life stressors, psychological dysfunction, and prepregnancy BMI with fetal iron status at delivery. OBJECTIVES: We hypothesized that greater maternal prenatal psychosocial stress and prepregnancy overweight and obesity are associated with lower cord blood ferritin and hemoglobin (Hb), with stronger associations in boys than girls. METHODS: Psychosocial stress in multiple domains of life stress (negative life events, perceived stress, exposure to violence) and psychological dysfunction symptoms (depression, generalized anxiety, and pregnancy-specific anxiety) were assessed with validated questionnaires during pregnancy. Prepregnancy BMI was predicted with a validated equation and categorized as normal/overweight/obese. Cord blood ferritin and Hb associations with prenatal psychosocial stress and BMI were modeled in multivariable linear regressions adjusted for maternal age, socioeconomic status, child sex, and prenatal iron supplementation. Interactions with child sex and 3-way stress-overweight/obesity-sex interactions were tested with product terms and likelihood ratio tests. RESULTS: In 493 dyads, median (IQR) cord blood ferritin and Hb concentrations were 185 µg/L (126-263 g/dL) and 16 g/dL (14.7-17.1 g/dL), respectively. Ferritin was lower in infants of mothers with higher prenatal perceived stress (-23%; 95% CI: -35%, -9%), violence exposure (-28%; 95% CI: -42%, -12%), anxiety symptoms (-16%; 95% CI: -27%, -4%), and obesity (-17%; 95% CI: -31%, 0.2%). Interaction models suggested sex differences and synergism between maternal stress and overweight/obesity. No associations were observed between stress or BMI and Hb. CONCLUSIONS: Multiple prenatal psychosocial stressors and excess prepregnancy BMI were each inversely associated with fetal iron status at birth. Pregnancies and infants at elevated risk of impaired fetal iron accrual may be identifiable according to observed synergism between maternal stress and obesity and differential associations with fetal iron status by infant sex.