Impact of milk secretor status on the fecal metabolome and microbiota of breastfed infants.

Maternal secretor status has been shown to be associated with the presence of specific fucosylated human milk oligosaccharides (HMOs), and the impact of maternal secretor status on infant gut microbiota measured through 16s sequencing has previously been reported. None of those studies have confirmed exclusive breastfeeding nor investigated the impact of maternal secretor status on gut microbial fermentation products. The present study focused on exclusively breastfed (EBF) Indonesian infants, with exclusive breastfeeding validated through the stable isotope deuterium oxide dose-to-mother (DTM) technique, and the impact of maternal secretor status on the infant fecal microbiome and metabolome. Maternal secretor status did not alter the within-community (alpha) diversity, between-community (beta) diversity, or the relative abundance of bacterial taxa at the genus level. However, infants fed milk from secretor (Se+) mothers exhibited a lower level of fecal succinate, amino acids and their derivatives, and a higher level of 1,2-propanediol when compared to infants fed milk from non-secretor (Se-) mothers. Interestingly, for infants consuming milk from Se+ mothers, there was a correlation between the relative abundance of Bifidobacterium and Streptococcus, and between each of these genera and fecal metabolites that was not observed in infants receiving milk from Se- mothers. Our findings indicate that the secretor status of the mother impacts the gut microbiome of the exclusively breastfed infant.

Women in Selected Communities of Punjab, India Have a High Prevalence of Iron, Zinc, Vitamin B12, and Folate Deficiencies: Implications for a Multiply-Fortified Salt Intervention.

Dietary intake and biomarkers of micronutrient status of 100 non-pregnant women of reproductive age (NPWRA) were assessed to determine optimal levels of iron, zinc, vitamin B12, and folic acid to include in multiply-fortified salt (MFS) that will be evaluated in an upcoming trial. Weighed food records were obtained from participants to measure intake of micronutrients and discretionary salt, and to assess adequacy using Indian Nutrient Reference Values (NRVs). Statistical modeling was used to determine optimal fortification levels to reduce inadequate micronutrient intake while limiting intake above the upper limit. Fasting blood samples were obtained to assess iron, zinc, vitamin B12, and folate status. In usual diets, inadequate intake of iron (46%), zinc (95%), vitamin B12 (83%), and folate (36%) was high. Mean intake of discretionary salt was 4.7 g/day. Prevalence estimates of anemia (37%), iron deficiency (67%), zinc deficiency (34%), vitamin B12 insufficiency (37%), and folate insufficiency (70%) were also high. Simulating the addition of optimized MFS to usual diets resulted in percentage point (pp) reductions in inadequate intake by 29 pp for iron, 76 pp for zinc, 81 pp for vitamin B12, and 36 pp for folate. MFS holds potential to reduce the burden of micronutrient deficiencies in this setting.

Quintuply-fortified salt for the improvement of micronutrient status among women of reproductive age and preschool-aged children in Punjab, India: protocol for a randomized, controlled, community-based trial.

BACKGROUND: Multiple micronutrient (MN) deficiencies remain highly prevalent among women of reproductive age (WRA) and preschool-aged children (PSC) in many areas within India. Salt is an attractive vehicle for MN fortification in this context, as it is universally consumed in fairly consistent amounts and coverage of iodized salt (IS) is 94%. The overall objective of this trial is to evaluate the nutritional impact of quintuply-fortified salt with iron in the form of encapsulated ferrous fumarate, zinc, vitamin B12, folic acid, and iodine (eFF-Q5S) vs. quintuply-fortified salt with iron in the form of ferric pyrophosphate plus EDTA, zinc, vitamin B12, folic acid, and iodine (FePP-Q5S) vs. IS for the improvement of MN status among non-pregnant WRA and PSC. METHODS: The study is a community-based, randomized, controlled trial that will be conducted in Punjab, India. 780 non-pregnant WRA 18-49 years old and 468 PSC 12-59 months old will be enrolled and assigned to one of three intervention groups. Salt will be provided to participants monthly for 12 months. Primary outcomes include changes in mean concentration of biomarkers of iron, zinc, vitamin B12, folate and iodine. Secondary outcomes include changes in the composition of the gut microbiome, and discretionary salt intake of PSC. DISCUSSION: If proven efficacious, multiply-fortified salt (MFS) has the potential to drastically reduce the burden of MN deficiencies in India, and around the world. Although effectiveness research will be needed to examine the impact of MFS under programmatic conditions, salt fortification will piggy-back on existing platforms to produce IS and doubly-fortified salt (DFS), making it possible to scale-up the intervention quickly. TRIAL REGISTRATION: Clinicaltrials.gov: NCT05166980; date of registration: December 22, 2021. Clinical Trials Registry-India: CTRI/2022/040332 and CTRI/2022/02/040333; date of registration: February 15, 2022.

Selenium intakes and plasma selenium of New Zealand toddlers: secondary analysis of a randomised controlled trial.

Little is known about Se intakes and status in very young New Zealand children. However, Se intakes below recommendations and lower Se status compared with international studies have been reported in New Zealand (particularly South Island) adults. The Baby-Led Introduction to SolidS (BLISS) randomised controlled trial compared a modified version of baby-led weaning (infants feed themselves rather than being spoon-fed), with traditional spoon-feeding (Control). Weighed 3-d diet records were collected and plasma Se concentration measured using inductively coupled plasma mass spectrometry (ICP-MS). In total, 101 (BLISS n 50, Control n 51) 12-month-old toddlers provided complete data. The OR of Se intakes below the estimated average requirement (EAR) was no different between BLISS and Control (OR: 0·89; 95 % CI 0·39, 2·03), and there was no difference in mean plasma Se concentration between groups (0·04 µmol/l; 95 % CI -0·03, 0·11). In an adjusted model, consuming breast milk was associated with lower plasma Se concentrations (-0·12 µmol/l; 95 % CI -0·19, -0·04). Of the food groups other than infant milk (breast milk or infant formula), 'breads and cereals' contributed the most to Se intakes (12 % of intake). In conclusion, Se intakes and plasma Se concentrations of 12-month-old New Zealand toddlers were no different between those who had followed a baby-led approach to complementary feeding and those who followed traditional spoon-feeding. However, more than half of toddlers had Se intakes below the EAR.

Chicken liver and eggshell crackers as a safe and affordable animal source food for overcoming micronutrient deficits during pregnancy and lactation in Indonesia: a double-blind, randomised placebo-controlled trial (SISTIK Growth Study).

Background: Indonesia ranks fifth in terms of the number of stunted children and there has been little change in the stunting prevalence in the last decade. In earlier observational studies conducted in 2014-2015, we identified several key underlying problems with the potential to impact stunting in Sumedang district, West Java, Indonesia. Deficits in intakes of growth-limiting micronutrients were observed, most notably calcium, iron, zinc, and vitamin A, emphasizing the need for a food-based intervention to overcome these micronutrient deficits in the diets of mothers and their infants. Methods: A double-blind placebo-controlled cluster randomised trial comparing the effect of daily consumption of 75 grams of locally produced micronutrient-enriched crackers (MEC) (intervention group) compared to placebo crackers (control group) by mothers at two-time intervals: (i) from the 8-14 weeks of pregnancy to delivery (i.e., 28-34 weeks of consumption of MEC) on birth length, and (ii) from the 8-14 weeks of pregnancy to 5 months post-partum on attained linear growth and linear growth velocity of breast-fed infants. A total of 324 pregnant women from 28 clusters (villages) located in 3 sub-districts in Sumedang district, West Java, Indonesia, will be randomly assigned to either intervention (n=14 villages) or control (n=14 villages). Discussi on: This will be the first study in Indonesia to use crackers based on powdered eggshells and chicken liver, in a form which is acceptable, safe, and has a long shelf life. If daily consumption of MEC for 6 months during pregnancy can enhance birth length, or their continued daily consumption for 5 months postpartum improves both attained and incremental linear growth at 5 months of age, then scaling-up in Indonesia may be considered. Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04564222 ; 25 th September 2020.

Multiple Micronutrients, Including Zinc, Selenium and Iron, Are Positively Associated with Anemia in New Zealand Aged Care Residents.

Anemia is a significant comorbidity for older adults not fully attributable to iron deficiency. Low-grade inflammation and other micronutrient deficiencies also contribute. This cross-sectional study examined the relationships between nutrient and non-nutrient factors with hemoglobin and anemia in 285 residents (>65 years) of 16 New Zealand aged-care facilities. Blood samples were analyzed for hemoglobin, ferritin, sTfR, hepcidin, zinc, selenium, and interleukin-6 (IL-6), (with ferritin, sTfR, zinc and selenium adjusted for inflammation). Linear regression models examined the relationships between micronutrient biomarkers (iron, zinc, selenium, vitamin B-12 and D), age, sex, and health factors with hemoglobin. Thirty-two percent of participants exhibited anemia, although <2% had either depleted iron stores or iron deficiency. Plasma zinc and selenium deficiencies were present in 72% and 38% of participants, respectively. Plasma zinc and total body iron (TBI) were positively associated (p < 0.05) with hemoglobin, while gastric acid suppressing medications, hepcidin, and interleukin-6 were inversely associated. These relationships were maintained after the application of anemia cut-offs. These findings emphasize the importance of considering multiple micronutrient deficiencies as risk factors for anemia.

Multiple micronutrient supplementation improves micronutrient status in primary school children in Hai Phong City, Vietnam: a randomised controlled trial.

We aimed to determine the efficacy of multiple micronutrient supplementation on the biomarkers of iron, zinc, and vitamin A status across anthropometric status categories in Vietnamese school children. In this 22-week randomised controlled trial, 347 undernourished, normal weight, or overweight/obese children aged 6-9 years were allocated to receive every school day a multiple micronutrient supplement (10 mg iron, 10 mg zinc, 400 µg vitamin A) or a placebo. Haematological indices; circulating ferritin, zinc, and retinol (corrected for inflammation); and C-reactive protein were measured at baseline and 22 weeks. At week 22, linear mixed models showed that mean corpuscular volume increased by 0.3 fL, serum ferritin by 9.1 µg/L, plasma zinc by 0.9 µmol/L, and plasma retinol by 15%, and the prevalence of zinc deficiency decreased by 17.3% points in the intervention group compared to placebo. No intervention effects were found for other haematological indices, or the prevalence of anaemia. Multiple micronutrient supplementation for 22 weeks improved the biomarkers of zinc and vitamin A status and some biomarkers of iron status, and reduced the prevalence of zinc deficiency in Vietnamese school children.Trial registration: This trial was registered on 06/09/2016 at www.anzctr.org.au as ACTRN12616001245482.

Differences in Micronutrient Intakes of Exclusive and Partially Breastfed Indonesian Infants from Resource-Poor Households are Not Accompanied by Differences in Micronutrient Status, Morbidity, or Growth.

BACKGROUND: When maternal micronutrient intakes and statuses are compromised, reductions in micronutrient concentrations in neonatal stores and human milk may result in suboptimal micronutrient intakes, statuses, and functional outcomes of breastfed infants during the critical first 6-month period. OBJECTIVES: We compared the adequacy of micronutrient intakes and statuses at 2 and/or 5 months and morbidity and growth faltering at 2, 5, and 12 months in a cohort of exclusively breastfed (EBF) and partially breastfed (PBF) infants from low-resource Indonesian households. METHODS: At 2 and 5 months, the breastfeeding status and human milk intake of 212 infants were determined using the deuterium oxide dose-to-mother technique, and intakes were calculated from milk micronutrient concentrations and 3-d weighed food intakes. At 5 months, five infant micronutrient biomarkers, hemoglobin, C-reactive protein, and α-1-acid-glycoprotein were measured. Infant morbidity, weight, and length were measured at 2, 5, and 12 months. Means, medians, or proportions were reported for each group and differences between groups were statistically determined. RESULTS: Median intakes of iron, thiamin, niacin, and vitamin B-12 were higher in PBF than EBF infants at 5 months (all P values < 0.05), but intakes in all infants were below adequate intakes. At 5 months, anemia was <20% in both groups, although fewer PBF versus EBF infants had vitamin B-12 deficiency (11.5% vs. 28.6%, respectively; P = 0.011). The mean ± SD length-for-age z-scores for EBF versus PBF infants at 2 months were 0.7 ± 0.9 versus -0.5 ± 1.1, respectively  (P = 0.158), declining to -1.4 ± 0.9 versus -1.1 ± 1.2, respectively, at 12 months (P = 0.059). Reported morbidity rates were generally low, with no evidence of a difference between infant groups (all P values > 0.126). CONCLUSIONS: Irrespective of exclusive or partial breastfeeding status, micronutrient intakes of infants were low, statuses were compromised, and growth faltering during the critical 6 months period of early infancy was present. The findings highlight the importance of improving maternal nutritional statuses and evaluating their impacts on infant outcomes.

Qualitative and quantitative vibrational spectroscopic analysis of macronutrients in breast milk.

Raman and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy were used to analyze 208 breast milk samples as part of a larger research study. Comprehensive qualitative and quantitative analysis was carried out using chemometric methods: principal component analysis (PCA) and partial least squares (PLS) regression. The obtained information on the main macronutrients (protein, fat and carbohydrate) were primarily evaluated in relation to the available metadata of the samples, where study location and respective primary food sources revealed a stronger differentiation in fat composition than its absolute content. The limitations and challenges of using both spectroscopic techniques for the type of analysis are also highlighted.

Association of maternal diet, micronutrient status, and milk volume with milk micronutrient concentrations in Indonesian mothers at 2 and 5 months postpartum.

BACKGROUND: Maternal micronutrient deficits during preconception and pregnancy may persist during lactation and compromise human milk composition. OBJECTIVE: We measured micronutrient concentrations in human milk and investigated their association with maternal micronutrient intakes, status, and milk volume. METHODS: Infant milk intake (measured via a deuterium dose-to-mother technique), milk micronutrient and fat concentrations, and maternal micronutrient intakes were assessed at 2 and 5 mo postpartum in 212 Indonesian lactating mother-infant pairs. Maternal hemoglobin, ferritin, transferrin receptors, retinol binding protein (RBP), zinc, selenium, and vitamin B-12 were measured at 5 mo (n = 163). Multivariate or mixed effects regression examined associations of milk micronutrient concentrations with maternal micronutrient intakes, status, and milk volume. RESULTS: Prevalence of anemia (15%), and iron (15% based on body iron), selenium (2.5%), and vitamin B-12 deficiency (0%) were low compared with deficiencies of zinc (60%) and vitamin A (34%). The prevalence of inadequate intakes was >50% for 7 micronutrients at 2 and 5 mo. Median milk concentrations for most micronutrients were below reference values, and nearly all declined between 2 and 5 mo postpartum and were not associated substantially with milk volume (except for ß-carotene, α-carotene, and ß-cryptoxanthin). At 5 mo postpartum, associations between maternal micronutrient status and corresponding milk concentrations reported as mean percentage difference in human milk concentration for each unit higher maternal biomarker were significant for hemoglobin (1.9%), iron biomarkers (ranging from 0.4 to 7%), RBP (35%), selenium (70%), and vitamin B-12 (0.1%), yet for maternal intakes only a positive association with ß-carotene existed. CONCLUSIONS: Most milk micronutrient concentrations declined during lactation, independent of changes in human milk production, and few were associated with maternal micronutrient intakes. The significant associations between maternal biomarkers and milk micronutrient concentrations at 5 mo warrant further study to investigate whether the declines in milk micronutrients are linked to shifts in maternal status.

Diet and Nutrition Status of Mongolian Adults.

(1) Background: Aspects of the Mongolian food supply, including high availability of animal-source foods and few plant foods, are plausibly associated with disease in the population. Data on Mongolian diets are lacking, and these risks are poorly quantified. The purpose of this study was to provide a multifaceted nutritional analysis of the modern Mongolian diet. (2) Methods: The study population consisted of 167 male and 167 female healthy non-pregnant urban and nomadic adults (22-55 years) randomly selected from lists of residents in 8 regions. From 2011-2016, 3-day weighed diet records and serum were collected twice from each participant in summer and winter; anthropometry was collected once from each participant. Serum was analyzed for biomarkers, and nutrient intake computed using purpose-built food composition data and adjusted for within-person variation. Exploratory dietary patterns were derived and analyzed for associations with diet and nutrition measurements. (3) Results: We collected 1838 of an expected 1986 diet records (92.5%), 610/658 serum samples (92.7%), and 315/334 height and weight measurements (94.3%). Sixty-one percent of men and 51% of women were overweight or obese. Consumption of red meat, refined grains, and whole-fat dairy was high, while that of fruits, non-tuberous vegetables, eggs, nuts and seeds, fish and poultry, and whole grains was low. Dairy and red meat were more consumed in summer and winter, respectively. Dietary inadequacy of 10 of 21 assessed nutrients, including fiber, folate, and vitamin D were >50% prevalent, while protein, zinc, and vitamin B12 inadequacy were low. Biochemical evidence of iron and vitamin A deficiency was also low. Three dietary patterns (Urban, Transitional, Nomadic) explained 41% of variation in food consumption. The Urban pattern was positively associated with BMI in multivariate analysis. (4) Conclusions: Results indicate a high prevalence of key dietary inadequacies and overweight among Mongolian adults. Prior studies by our group have suggested that expanded supplementation and food fortification would be effective in addressing micronutrient inadequacies; these strategies should be coupled with measures to mitigate the growing burden of chronic disease.

Examination of Carbohydrate Products in Feces Reveals Potential Biomarkers Distinguishing Exclusive and Nonexclusive Breastfeeding Practices in Infants.

BACKGROUND: The stable isotope deuterium dose-to-mother (DTM) technique to estimate nonbreast milk water intake demonstrates that maternal self-report methods of infant feeding overestimate the true prevalence of exclusively breastfeeding practices. OBJECTIVE: We aimed to determine potential monosaccharide and oligosaccharide markers that distinguish between exclusively breastfed (EBF) versus nonexclusively breastfed (non-EBF) infants utilizing LC-MS-based methods. METHODS: Data for the analysis were collected as part of a larger, longitudinal study of 192 breastfed Indonesian infants aged 2 mo and followed up at 5 mo. Feces samples were collected from infants aged 2 mo (n = 188) and 5 mo (n = 184). EBF and non-EBF strata at each time point were determined via the DTM technique. Feces samples were analyzed to determine monosaccharide content using ultra-high-performance LC-triple quadrupole MS (UHPLC-QqQ MS). Relative abundances of fecal oligosaccharides were determined using nano-LC-Chip-quadrupole time-of-flight MS (nano-LC-Chip-Q-ToF MS). RESULTS: At age 2 mo, monosaccharide analysis showed the abundance of fructose and mannose were significantly higher (+377% and +388%, respectively) in non-EBF compared with EBF infants (P <0.0001). Fructose and mannose also showed good discrimination with areas under the curve (AUC) of 0.86 and 0.82, respectively. Oligosaccharide analysis showed that a 6-hexose (Hex6) isomer had good discrimination (AUC = 0.80) between EBF and non-EBF groups at 5 mo. CONCLUSION: Carbohydrate products, particularly fecal mono- and oligosaccharides, differed between EBF and non-EBF infants aged under 6 mo and can be used as potential biomarkers to distinguish EBF versus non-EBF feeding practices.

Suboptimal feeding and caring practices among young Indian children ages 12 to 24 mo living in the slums of New Delhi.

OBJECTIVES: Inappropriate infant and young child feeding and caring practices affect nutritional status, increases the risk for growth faltering, and ultimately, affect child survival. The aim of this study was to characterize the feeding and caring practices of disadvantaged urban Indian children 12 to 24 mo of age in relation to the World Health Organization (WHO) and Pan American Health Organization (PAHO) recommendations. METHODS: This cross-sectional study was conducted in self-selected households in a South Delhi slum. A household survey was administered to the mother/primary caregiver of 120 eligible children. We collected child anthropometry, 2-d weighed food records (n = 69), and compliance to WHO and PAHO recommended feeding, caring, food safety, and hygiene practices. RESULTS: Of the children, 39% were stunted, 31% underweight, and 10% wasted; none were overweight. Despite 88% achieving minimum meal frequency (more than three to four meals daily), only 50% consumed at least four food groups (minimum dietary diversity), and 44% a minimum acceptable diet (composite score of minimum meal frequency and minimum dietary diversity). Consumption of iron-rich or iron-fortified foods, vitamin A-rich fruits and vegetables, and eggs was low (<25%) and flesh foods were negligible (1.4%), whereas consumption of both sugary and snack foods was >60%. Reported compliance to responsive feeding indicators was generally ∼50%, but there was a wide range (13-98%) for food safety and hygiene practices, which were not always consistent with home observations. CONCLUSIONS: Complementary feeding and caregiving practices were suboptimal among these disadvantaged young Indian children and education interventions focused on infant and young child feeding, responsive feeding, food safety, and hygiene practices are urgently needed.

Anaemia and Its Relation to Demographic, Socio-economic and Anthropometric Factors in Rural Primary School Children in Hai Phong City, Vietnam.

Little is known about the prevalence of anaemia and associated factors in school children in Vietnam. In this cross-sectional study, we aimed to determine the prevalence of anaemia and its subtypes, and the associations of types of anaemia with demographic, socio-economic and anthropometric factors among 6-9-year-old primary school children in rural areas of Hai Phong City, Vietnam. Haemoglobin (Hb) and mean corpuscular volume (MCV) were measured, and demographic, socio-economic and anthropometric data were collected in 893 children from eight primary schools. The prevalence of anaemia (Hb < 115 g/L) was 12.9% (95% CI: 8.1%, 19.9%), microcytic anaemia (Hb < 115 g/L and MCV < 80 fL) was 7.9% (95% CI: 5.3%, 11.6%) and normocytic anaemia (Hb < 115 g/L and MCV 80-90 fL) was 5.3% (95% CI: 2.9%, 9.5%). No child presented with macrocytic anaemia (Hb < 115 g/L and MCV > 90 fL). Children who were underweight, wasted, or in anthropometric failure (either underweight, stunted or wasted) were more likely to be anaemic (all p ≤ 0.004), and specifically, to have normocytic anaemia (all p ≤ 0.006), than those who were not underweight, wasted or in anthropometric failure. Stunted children were more likely to be anaemic (p = 0.018) than those who were not stunted. Overweight/obese children were less likely to be anaemic (p = 0.026) or have normocytic anaemia (p = 0.038) compared with children who were not overweight/obese. No anthropometric status indicator was associated with the risk of microcytic anaemia. No demographic or socio-economic factor was associated with any type of anaemia. Anaemia remains a public health issue in rural areas in Hai Phong City, Vietnam, and future approaches for its prevention and control should target undernourished primary school children.

Breastmilk intake among exclusively breastfed Indonesian infants is negatively associated with maternal fat mass.

Excessive maternal fat mass may impair lactogenesis and lead to lower breastmilk volume. We investigated this relationship in rural Indonesian exclusively breastfeeding mother-infant (2-5.3 months) dyads (n = 112) by measuring breastmilk intake by deuterium oxide dose-to-mother technique (DDMT) and maternal fat mass by DDMT, bioelectrical impedance analysis (BIA), and body mass index (BMI). We also compared fat mass assessed by DDMT and BIA. In this population, we found a significant negative relationship between breastmilk intake and maternal fat mass measured by DDMT (ß = -5.04 mL, 95% CI: -9.36, -0.72, P = 0.023), and similar but slightly weaker negative trend with BIA and BMI, after adjusting for social-economic status, maternal age, infant age and sex. Maternal fat mass estimates by BIA and DDMT showed good agreement. In light of the trend for overweight and obesity worldwide, further research is needed into the underlying mechanisms of this negative relationship.

Micronutrient intakes of lactating mothers and their association with breast milk concentrations and micronutrient adequacy of exclusively breastfed Indonesian infants.

BACKGROUND: Breast milk is the sole source of nutrition for exclusively breastfed infants in the first 6 mo of life, yet few studies have measured micronutrient concentrations in breast milk in light of maternal diet and subsequent infant micronutrient intakes. OBJECTIVES: We evaluated the adequacy of micronutrient intakes of exclusively breastfed Indonesian infants by measuring milk volume and micronutrient concentrations and assessed maternal micronutrient intakes and their relationship with milk concentrations. METHODS: Mother-infant (2-5.3 mo) dyads (n = 113) were recruited for this cross-sectional study. Volume of breast-milk intake via the deuterium dose-to-mother technique over 14 d and analyzed micronutrient concentrations were used to calculate micronutrient intakes of exclusively breastfed infants. Maternal 3-d weighed food records were collected to assess median (IQR) micronutrient intakes. Multivariate regression analyses examined the association of usual maternal micronutrient intakes with milk micronutrient concentrations after adjustment for confounding variables. RESULTS: Mean ± SD intake of breast-milk volume was 787 ± 148 mL/d. Median daily infant intakes of iron, zinc, selenium, magnesium, sodium, and B-vitamins (thiamin, riboflavin, niacin, pantothenic acid, B-6, and B-12) were below their respective Adequate Intakes. Inadequacies in maternal intakes (as % < estimated average requirements) were >40% for calcium, niacin, and vitamins A, B-6, and B-12. Significant positive associations existed between maternal usual intakes of vitamin A, niacin and riboflavin and milk retinol, nicotinamide, and free riboflavin concentrations in both unadjusted and adjusted (for infant age, milk volume, and parity) analyses (all P < 0.05). CONCLUSIONS: The majority of micronutrient intakes for these exclusively breastfed infants and their mothers fell below recommendations, with associations between maternal intakes and breast-milk concentrations for 3 nutrients. Data on nutrient requirements of exclusively breastfed infants are limited, and a better understanding of the influence of maternal nutritional status on milk nutrient concentrations and its impact on the breastfed infant is needed.

Development of a Parsimonious Design for Optimal Classification of Exclusive Breastfeeding.

A deuterium oxide dose-to-mother (DTM) technique is used to determine if an infant is exclusive breastfeeding (EBF). However, the DTM method is intensive, requiring seven paired mother-infant samples during a 14-day study period. The purpose of this study was to develop a field-friendly protocol. Data from 790 mother-infant pairs from nine countries were analyzed using a Markov chain Monte Carlo method with Stan. The data were split into (i) model building (565 pairs) and (ii) design evaluation (225 pairs). EBF classification was based on a previously published cut-off for nonmilk water intake. Classification based on the full design was the reference (gold standard classification). The receiver operating characteristics of parsimonious designs were used to determine an optimal parsimonious classification method. The best two postdose windows (days 7-9 and 13-14) yielded optimal categorization with similar performance in the design evaluation data. This postdose two-sample design provided 95% sensitivity and specificity when compared with the full design.

Including 60 mg Elemental Iron in a Multiple Micronutrient Supplement Blunts the Increase in Serum Zinc after 12 Weeks of Daily Supplementation in Predominantly Anemic, Nonpregnant Cambodian Women of Reproductive Age.

BACKGROUND: Multiple micronutrient (MMN) supplementation may result in interaction effects due to competing absorptive pathways of trace elements. OBJECTIVES: The aim of this study was to investigate the effect of MMN supplementation with or without iron on serum zinc, selenium, and copper concentrations in Cambodian women. METHODS: In a 2 × 2 factorial double-blind randomized 12-wk trial, predominantly anemic, nonpregnant women (aged 18-45 y) received daily 60 mg of iron (Fe; n = 201); 14 other micronutrients including zinc (15 mg), selenium (65 µg), and copper (2 mg), but no iron (MMN; n = 202); 60 mg iron plus MMN (Fe + MMN; n = 206); or a placebo (n = 200). Fasting morning blood was collected at baseline and 12 wk from women in 26 villages in Kampong Chhnang province. Serum zinc, selenium, and copper concentrations (secondary outcomes of the randomized controlled trial) were measured using inductively coupled plasma mass spectrometry. Generalized linear regression was used to estimate intervention effects [ß coefficient (95% CI)] for Fe (with or without MMN) and MMN (with or without Fe) after testing for the presence of an Fe × MMN interaction. RESULTS: A total of 760 women completed the trial. Zinc deficiency prevalence at baseline was 45% (inflammation-adjusted serum zinc <10.7 µmol/L). A significant Fe × MMN interaction (P = 0.02) was detected in the 2 × 2 analysis with serum zinc concentration as the outcome: the MMN group had a higher mean serum zinc concentration at 12 wk (12.3 µmol/L; 95% CI: 12.2, 12.4 µmol/L) compared with all other groups, and the Fe + MMN group had a higher mean serum zinc concentration (11.6 µmol/L; 95% CI: 11.5, 11.7 µmol/L) compared with the Fe group (11.0 µmol/L; 95% CI: 10.9, 11.0 µmol/L) and the placebo group (11.2 µmol/L; 95% CI: 11.1, 11.4 µmol/L). CONCLUSIONS: The inclusion of 60 mg iron in the daily MMN formulation may be interfering with the absorption and/or metabolism of supplemental zinc in Cambodian women. This is of particular concern when MMN supplementation is implemented in populations with risk of zinc deficiency. This trial was registered at clinicaltrials.gov as NCT-02481375.

Multimicronutrient Biomarkers Are Related to Anemia during Infancy in Indonesia: A Repeated Cross-Sectional Study.

BACKGROUND: Anemia during infancy in Indonesia is common, with iron deficiency (ID) assumed to be the major cause. Other micronutrients besides iron may have a role in determining hemoglobin (Hb) but have not yet been explored in Indonesia. OBJECTIVE: We investigated 7 micronutrient biomarkers and selected nonnutritional factors as potential predictors of Hb and anemia at ages 6, 9, and 12 mo in a cohort of Indonesian infants at risk of coexisting micronutrient deficiencies. METHODS: Apparently healthy breastfed infants were randomly selected from birth registries at 6 mo (n = 230) and followed-up at 9 mo (n = 202) and 12 mo (n = 190). Hb, serum micronutrient biomarkers-iron [as ferritin and serum soluble transferrin receptor (sTfR)], zinc, selenium, folate, vitamin A [as retinol-binding protein (RBP)], vitamin B-12, and vitamin D (as 25-hydroxyvitamin D) (adjusted for inflammation, where appropriate)-and maternal sociodemographic status, health, BMI, heminthiasis, and selected Hb genetic disorders were measured. Multivariate analysis examined relations between micronutrient biomarkers and nonnutritional factors (except helminthiasis and genetic Hb disorders) with Hb and anemia at 6 and 12 mo. RESULTS: ID (based on ferritin) was a predictor of lower Hb and anemia at both 6 and 12 mo of age (P < 0.02). Additional predictors at 6 mo were tertiary education and higher maternal Hb for higher Hb, sex (being male) and inflammation (P < 0.05) for both lower Hb and anemia, and greater maternal height (P = 0.036) for anemia only. At 12 mo, a significant biomarker predictor besides ID was RBP (P = 0.035) for Hb. CONCLUSION: ID was a major contributor to lower Hb and anemia, although RBP was also associated.

Development of a nutrient quality score for the complementary diets of Indonesian infants and relationships with linear growth and stunting: a longitudinal analysis.

Reducing multifactorial stunting is a priority for the 2025 WHO Global Nutrition Target. In the plant-based complementary diets of low-income countries, deficits in several growth-limiting micronutrients may contribute to stunting. Hence the intercorrelation between multiple micronutrients in terms of their intake and impact is important. Therefore, our aim was to develop a nutrient quality score using principal component analysis (PCA) in a sample of Indonesian infants at 6, 9 and 12 months of age and to evaluate the association of the scores with linear growth and stunting. At 6 months, 217 infants were recruited from Sumedang District, West Java, with 195 and 189 followed at 9 and 12 months of age, respectively. Complementary food intakes were assessed using 2-d weighed food records. Eight correlated nutrients (vitamin A, ascorbic acid, thiamine, riboflavin, niacin, Ca, Fe and Zn) were summarised using PCA into a single nutrient pattern that explained 56-65 % of the total variability. Nutrient quality scores were related to demographic, inflammation and complementary food indicator variables in hypothesised directions. While no significant relationships were apparent with linear growth, the odds of being stunted at ages 9 and 12 months was lower for infants with a higher nutrient quality score at 9 months (OR 0·75, 95 % CI 0·59, 0·95 and OR 0·69, 95 % CI 0·55, 0·88), respectively, for the fully adjusted models. A data-driven nutrient quality score is a valid tool to assess the influence of nutrient quality on stunting in at-risk infants.