Background: Few data are available on the effectiveness of large-scale food fortification programs.Objective: We assessed the impact of mandatory wheat flour fortification on micronutrient status in Yaoundé and Douala, Cameroon.Methods:... more
Background: Few data are available on the effectiveness of large-scale food fortification programs.Objective: We assessed the impact of mandatory wheat flour fortification on micronutrient status in Yaoundé and Douala, Cameroon.Methods: We conducted representative surveys 2 y before and 1 y after the introduction of fortified wheat flour. In each survey, 10 households were selected within each of the same 30 clusters (n = ∼300 households). Indicators of inflammation, malaria, anemia, and micronutrient status [plasma ferritin, soluble transferrin receptor (sTfR), zinc, folate, and vitamin B-12] were assessed among women aged 15-49 y and children 12-59 mo of age.Results: Wheat flour was consumed in the past 7 d by ≥90% of participants. Postfortification, mean total iron and zinc concentrations of flour samples were 46.2 and 73.6 mg/kg (target added amounts were 60 and 95 mg/kg, respectively). Maternal anemia prevalence was significantly lower postfortification (46.7% compared with 39....
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Human milk is recommended as the sole food source for infants 0-6 mo. Its micronutrient (MN) content is used as basis for making intake recommendations for breast-fed infants and lactating women. P...
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Anaemia has serious effects on human health and has multifactorial aetiologies. This study aimed to determine putative risk factors for anaemia in children 6–59 months and 15‐ to 49‐year‐old non‐pregnant women living in Ghana. Data from a... more
Anaemia has serious effects on human health and has multifactorial aetiologies. This study aimed to determine putative risk factors for anaemia in children 6–59 months and 15‐ to 49‐year‐old non‐pregnant women living in Ghana. Data from a nationally representative cross‐sectional survey were analysed for associations between anaemia and various anaemia risk factors. National and stratum‐specific multivariable regressions were constructed separately for children and women to calculate the adjusted prevalence ratio (aPR) for anaemia of variables found to be statistically significantly associated with anaemia in bivariate analysis. Nationally, the aPR for anaemia was greater in children with iron deficiency (ID; aPR 2.20; 95% confidence interval [CI]: 1.88, 2.59), malaria parasitaemia (aPR 1.96; 95% CI: 1.65, 2.32), inflammation (aPR 1.26; 95% CI: 1.08, 1.46), vitamin A deficiency (VAD; aPR 1.38; 95% CI: 1.19, 1.60) and stunting (aPR 1.26; 95% CI: 1.09, 1.46). In women, ID (aPR 4.33; 9...
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Increased first-trimester low-density lipoprotein (LDL-C) concentration has been associated with adverse pregnancy outcomes, such as gestational diabetes. The B vitamins folate, B-6, and total B-12 are key for the methyl group-dependent... more
Increased first-trimester low-density lipoprotein (LDL-C) concentration has been associated with adverse pregnancy outcomes, such as gestational diabetes. The B vitamins folate, B-6, and total B-12 are key for the methyl group-dependent endogenous synthesis of phosphatidylcholine, which is needed for lipoprotein synthesis, e.g., very low-density lipoprotein (VLDL), the precursor of circulating LDL-C. Maternal B-vitamin concentration usually declines across trimesters. Whether changes in maternal B-vitamin concentrations are associated with total cholesterol (TC), triglycerides (TG), and lipoprotein concentrations is unknown. Therefore, we explored the association between plasma folate, vitamin B-6 in the form of pyridoxal 5′-phosphate (PLP), and total B-12 with serum TC, LDL-C, HDL-C, and TG concentrations across trimesters. This secondary analysis used data of a prospective pregnancy cohort study included apparently healthy adult women (n = 179) from Rio de Janeiro, Brazil. The bio...
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Choline and related metabolites are key factors in many metabolic processes, and insufficient supply can adversely affect reproduction and fetal development. Choline status is mainly regulated by intake, and human milk is the only choline... more
Choline and related metabolites are key factors in many metabolic processes, and insufficient supply can adversely affect reproduction and fetal development. Choline status is mainly regulated by intake, and human milk is the only choline source for exclusively breastfed infants. Further, maternal status, genotype, and phenotype, as well as infant outcomes, have been related to milk choline concentrations. In order to enable the rapid assessment of choline intake for exclusively breastfed infants and to further investigate the associations between milk choline and maternal and infant status and other outcomes, we have developed a simplified method for the simultaneous analysis of human milk choline, glycerophosphocholine, phosphocholine, and the less abundant related metabolites betaine, carnitine, creatinine, dimethylglycine (DMG), methionine, and trimethylamine N-oxide (TMAO) using ultraperformance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS). These analytes have mi...
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Our previously reported, first validated, UPLC-MS/MS-based simultaneous analysis of five human milk B-vitamins revealed severe matrix effects. High levels of endogenous lactose fouled the electrospray ionization source affecting the... more
Our previously reported, first validated, UPLC-MS/MS-based simultaneous analysis of five human milk B-vitamins revealed severe matrix effects. High levels of endogenous lactose fouled the electrospray ionization source affecting the analysis. We evaluated solid-phase extraction (SPE), liquid-solid extraction (LSE), protein precipitation (PPT), and liquid chromatography effluent diversion for lactose-removal. SPE failed to separate lactose from vitamins; LSE using 2-propanol reduced lactose and vitamin recoveries. PPT-solvent, milk volume, and reconstitution solvent influenced flavin adenine dinucleotide, pyridoxal and nicotinamide recoveries. Using an optimized LC-gradient enabled chromatographic separation of lactose from vitamins and its removal using a post-column switch-valve. Only 40 µL milk was subjected to methanol-PPT and non-polar matrix removal by methyl tert-butyl ether. B-vitamin recoveries were established (81.9-118.6%; CV ≤ 11.9%; precision: 4.9-13.7%) with greatly reduced matrix effects, and improved process efficiency, and recovery.
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Background Infantile beriberi–related mortality is still common in South and Southeast Asia. Interventions to increase maternal thiamine intakes, and thus human milk thiamine, are warranted; however, the required dose remains unknown.... more
Background Infantile beriberi–related mortality is still common in South and Southeast Asia. Interventions to increase maternal thiamine intakes, and thus human milk thiamine, are warranted; however, the required dose remains unknown. Objectives We sought to estimate the dose at which additional maternal intake of oral thiamine no longer meaningfully increased milk thiamine concentrations in infants at 24 wk postpartum, and to investigate the impact of 4 thiamine supplementation doses on milk and blood thiamine status biomarkers. Methods In this double-blind, 4–parallel arm randomized controlled dose–response trial, healthy mothers were recruited in Kampong Thom, Cambodia. At 2 wk postpartum, women were randomly assigned to consume 1 capsule, containing 0, 1.2 (estimated average requirement), 2.4, or 10 mg of thiamine daily from 2 through 24 weeks postpartum. Human milk total thiamine concentrations were measured using HPLC. An Emax curve was plotted, which was estimated using a non...
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Background Little is known regarding the associations between maternal factors and B-vitamin and choline concentrations in early milk and the trajectories of these vitamins during lactation. Objectives In this hypothesis-generating study,... more
Background Little is known regarding the associations between maternal factors and B-vitamin and choline concentrations in early milk and the trajectories of these vitamins during lactation. Objectives In this hypothesis-generating study, we modeled the association between maternal and offspring factors and longitudinal changes in milk B-vitamin and choline concentrations throughout lactation. Methods A hundred women were studied in a prospective birth cohort and milk samples from 52 women were collected at 2–8 d, 76 women at 28–50 d, and 42 women at 88–119 d postpartum. Maternal dietary intake during pregnancy and lactation was assessed by an FFQ. Linear mixed-effects models with interaction terms were used to evaluate changes in milk B-vitamin and choline concentrations over time based on maternal factors and the early postpartum concentrations of these micronutrients. Results The women with higher early postpartum milk concentrations of niacin (βinteraction = −0.02; SE = 0.00; P ...
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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... more
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 ...
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Background Maternal supplementation during lactation could increase milk B-vitamin concentrations, but little is known about the kinetics of milk vitamin responses. Objectives We compared acute effects of maternal lipid-based nutrient... more
Background Maternal supplementation during lactation could increase milk B-vitamin concentrations, but little is known about the kinetics of milk vitamin responses. Objectives We compared acute effects of maternal lipid-based nutrient supplement (LNS) consumption (n = 22 nutrients, 175%–212% of the RDA intake for the nutrients examined), as a single dose or at spaced intervals during 8 h, on milk concentrations and infant intake from milk of B-vitamins. Methods This randomized crossover trial in Quetzaltenango, Guatemala included 26 mother–infant dyads 4–6 mo postpartum who were randomly assigned to receive 3 treatments in a random order: bolus 30-g dose of LNS (Bolus); 3 × 10-g doses of LNS (Divided); and no LNS (Control), with control meals. Mothers attended three 8-h visits during which infant milk consumption was measured and milk samples were collected at every feed. Infant intake was assessed as $\mathop \sum \nolimits_{i\ = \ 1}^n ( {{\rm{milk\ volum}}{{\rm{e}}_{{\rm{feed\ }}...
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Objectives Choline and related metabolites play important roles in metabolic processes. Inadequate provision of these nutrients to the exclusively breast-fed infant can negatively impact its healthy growth and development. Methods We... more
Objectives Choline and related metabolites play important roles in metabolic processes. Inadequate provision of these nutrients to the exclusively breast-fed infant can negatively impact its healthy growth and development. Methods We developed an UPLC-MS/MS method for analyzing choline (Cho), phospho-choline (PCho), glycerophospho-choline (GPCho), total choline (tCho = Cho + PCho + GPCho), betaine, carnitine, creatinine, dimethyl glycine (DMG), methionine, and trimethylamine N-oxide (TMAO) in human milk. Results Optimized results were obtained using a Phenomenex Luna Silica (2) column, 100 × 2 mm, 3 µm, and a gradient of 0.1% aqueous propionic acid (A) and acetonitrile (B) from 60% to 90% A over 2 min (Waters ACQUITY UPLC I-Class - SCIEX 4500TQ mass spectrometer). Sample preparation required only 5–10µL of milk, diluted 1:80 in methanol/water, 4:1, v/v, prior to analysis. Quantification was done using isotopically labeled internal standards and an external standard curve. Pooled hum...
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Background Except for low thiamin content, little is known about vitamins or macronutrients in milk from Cambodian mothers, and associations among milk nutrients. Objectives We measured fat-soluble vitamins (FSVs) and water-soluble... more
Background Except for low thiamin content, little is known about vitamins or macronutrients in milk from Cambodian mothers, and associations among milk nutrients. Objectives We measured fat-soluble vitamins (FSVs) and water-soluble vitamins (WSVs), and macronutrients, and explored internutrient associations in milk from Cambodian mothers. Methods Milk from women (aged 18–45 y, 3–27 wk postpartum, n = 68) who participated in a thiamin-fortification trial were analyzed for vitamins B-2 (riboflavin, FAD), B-3 (nicotinamide), B-5, B-6 (pyridoxal, pyridoxine), B-7, B-12, A, E [α-tocopherol and γ-tocopherol (γ-TPH)], carotenoids, carbohydrate (CHO), fat, and protein. Milk vitamin B-1 [thiamin, thiamin monophosphate (TMP), thiamin pyrophosphate (TPP)] was previously assessed for fortification effects. Milk nutrient concentrations were compared with the Adequate Intake (AI) values for infants aged 0–6 mo. Pearson correlation was used to examine internutrient associations after excluding nut...
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Objectives Little is known about the influence of maternal micronutrient (MN) supplementation during pregnancy/lactation on human milk (HM) MN concentrations. We evaluated B-vitamin (BV) concentrations in milk from mothers in Ghana and... more
Objectives Little is known about the influence of maternal micronutrient (MN) supplementation during pregnancy/lactation on human milk (HM) MN concentrations. We evaluated B-vitamin (BV) concentrations in milk from mothers in Ghana and Malawi who participated in the International Lipid-Based Nutrient Supplements (iLiNS) Project. Methods Women (<20 wk gestation) were randomized to receive: 1 x daily iron/folic acid (IFA) during pregnancy only, or a multiple micronutrient (MMN) tablet or LNS containing equal amounts of vitamins during pregnancy and 6 mo of lactation. HM at 6mo postpartum was analyzed for vitamins B1, B2, B3 (nicotinamide only), B5, B6, and B12 and compared to the recommended Adequate Intakes (AI) for infants 0–6 mo, which are based on values from milk from well-nourished mothers, assuming 780 mL/d milk intake. Results Concentrations and responses to supplementation differed greatly between countries. Comparing the IFA groups’ concentrations (geom. mean), women in G...
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Objectives Targeted metabolomics are commercially available for human plasma, but not for human milk. However, metabolite analyses could provide a novel and efficient approach to understanding human milk composition and relationships to... more
Objectives Targeted metabolomics are commercially available for human plasma, but not for human milk. However, metabolite analyses could provide a novel and efficient approach to understanding human milk composition and relationships to maternal and infant status. Methods Pooled human milk was used to evaluate and validate the Biocrates AbsoluteIDQ® p180 kit for human milk metabolomics (40 acylcarnitines, 42 acids/biogenic amines, 91 phospholipids, 15 sphingolipids, sum of hexoses) using an ABSciex 5500QTRAP mass spectrometer in LC-MS/MS and flow injection analysis (FIA) mode. In a feasibility study, milk collected <6 mo lactation from A) Bangladeshi healthy mothers (BMI >18.5, n = 12) and from B) mothers with stunted infants (HAZ-score
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Human-milk-targeted metabolomics analysis offers novel insights into milk composition and relationships with maternal and infant phenotypes and nutritional status. The Biocrates AbsoluteIDQ® p180 kit, targeting 40 acylcarnitines, 42 amino... more
Human-milk-targeted metabolomics analysis offers novel insights into milk composition and relationships with maternal and infant phenotypes and nutritional status. The Biocrates AbsoluteIDQ® p180 kit, targeting 40 acylcarnitines, 42 amino acids/biogenic amines, 91 phospholipids, 15 sphingolipids, and sum of hexoses, was evaluated for human milk using the AB Sciex 5500 QTRAP mass-spectrometer in liquid chromatography-tandem mass-spectrometry (LC-MS/MS) and flow-injection analysis (FIA) mode. Milk (<6 months lactation) from (A) Bangladeshi apparently healthy mothers (body mass index (BMI) > 18.5; n = 12) and (B) Bangladeshi mothers of stunted infants (height-for-age Z (HAZ)-score 18.5 was lower in 6 amino acids/biogenic amines but higher in isovalerylcarnitine, two phospholipids, and one sphingomyelin (p < 0.05 for all). Associations between milk metabolites differed between groups. The AbsoluteIDQ® p180 kit is a rapid analysis tool suitable for human milk analysis and reduce...
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Background Anemia in young children is a global health problem. Risk factors include poor nutrient intake and poor water quality, sanitation, or hygiene. Objective We evaluated the effects of water quality, sanitation, handwashing, and... more
Background Anemia in young children is a global health problem. Risk factors include poor nutrient intake and poor water quality, sanitation, or hygiene. Objective We evaluated the effects of water quality, sanitation, handwashing, and nutrition interventions on micronutrient status and anemia among children in rural Kenya and Bangladesh. Design We nested substudies within 2 cluster-randomized controlled trials enrolling pregnant women and following their children for 2 y. These substudies included 4 groups: water, sanitation, and handwashing (WSH); nutrition (N), including lipid-based nutrient supplements (LNSs; ages 6–24 mo) and infant and young child feeding (IYCF) counseling; WSH+N; and control. Hemoglobin and micronutrient biomarkers were measured after 2 y of intervention and compared between groups using generalized linear models with robust SEs. Results In Kenya, 699 children were assessed at a mean ± SD age of 22.1 ± 1.8 mo, and in Bangladesh 1470 participants were measured...
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Little valid information is available on human milk nutrient concentrations, especially for micronutrients (MN), and there are no valid Reference Values (RVs) across lactation. In this multi-center collaborative study, RVs will be... more
Little valid information is available on human milk nutrient concentrations, especially for micronutrients (MN), and there are no valid Reference Values (RVs) across lactation. In this multi-center collaborative study, RVs will be established for human milk nutrients across the first 8.5 months postpartum. Well-nourished, unsupplemented women in Bangladesh, Brazil, Denmark, and The Gambia (n = 250/site) were recruited during the third trimester of pregnancy. Milk, blood, saliva, urine, and stool samples from mothers and their infants are collected identically at three visits (1–3.49, 3.5–5.99, 6.0–8.49 months postpartum). Milk analyses include macronutrients, selected vitamins, trace- elements and minerals, iodine, metabolomics, amino acids, human milk oligosaccharides, and bioactive peptides. We measure milk volume; maternal and infant diets, anthropometry, and morbidity; infant development, maternal genome, and the infant and maternal microbiome. RVs will be constructed based on m...
It is uncertain whether vitamin B-12 supplementation can improve neurophysiologic function in asymptomatic elderly with low vitamin B-12 status or whether folate status affects responses to vitamin B-12 supplementation. We assessed the... more
It is uncertain whether vitamin B-12 supplementation can improve neurophysiologic function in asymptomatic elderly with low vitamin B-12 status or whether folate status affects responses to vitamin B-12 supplementation. We assessed the effects of a single intramuscular injection of 10 mg vitamin B-12 (which also contained 100 mg vitamin B-6 and 100 mg vitamin B-1) on vitamin B-12 status and neurophysiologic function in elderly community-dwelling Chileans with low serum vitamin B-12 concentrations who were consuming bread fortified with folic acid. A pretreatment and posttreatment study was conducted in 51 participants (median ± SD age: 73 ± 3 y; women: 47%) with serum vitamin B-12 concentrations <120 pmol/L at screening. Vitamin B-12 status was defined by combining vitamin B-12, plasma total homocysteine (tHcy), methylmalonic acid (MMA), and holotranscobalamin into one variable [i.e., a combined indicator of vitamin B-12 status (cB-12)]. The response to treatment was assessed by ...
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Representative data on folate and vitamin B-12 dietary intake and status in low-income countries are rare, despite the widespread adoption of folic acid fortification. The purpose was to evaluate folate and vitamin B-12 intake, status,... more
Representative data on folate and vitamin B-12 dietary intake and status in low-income countries are rare, despite the widespread adoption of folic acid fortification. The purpose was to evaluate folate and vitamin B-12 intake, status, and risk factors for deficiency before a national fortification program in Cameroon. A nationally representative cross-sectional cluster survey was conducted in 3 ecologic zones of Cameroon (South, North, and the 2 largest cities, Yaoundé/Douala), and information on dietary intake was collected from 10 households in each of 30 randomly selected clusters per zone. In a subset of women and their 12- to 59-mo-old children (n = 396 pairs), plasma folate and vitamin B-12, as well as breast milk vitamin B-12, were analyzed. Vitamin B-12 and folate dietary intake patterns and plasma concentrations were similar for women and children. In the subsample, 18% and 29% of women and 8% and 30% of children were vitamin B-12 (≤221 pmol/L) and folate (<10 nmol/L) d...
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Given the importance of breast milk for providing micronutrients (MN) in the first 624 mo our objective is to determine if its MN content is adequate in populations with poor dietary quality and how it is affected by maternal... more
Given the importance of breast milk for providing micronutrients (MN) in the first 624 mo our objective is to determine if its MN content is adequate in populations with poor dietary quality and how it is affected by maternal supplementation. We developed methods, including HPLC-MS/MS, to analyze multiple MN simultaneously in the milk matrix improving accuracy and efficiency of older methods. Available samples collected at 24 mo lactation were identified from multiple countries. Average population concentrations were expressed as % of those accepted by the IOM when setting DRIs for infants and lactation. Examples of the large differences in composition include: B1, 60% in India; riboflavin, 70% India, 30% Malawi, 20% Philippines and 10% in Bangladesh; niacin, 1020% (including California); B6, 220% California, 80% India, Malawi and Bangladesh, and 20% Philippines; B12, 60% Malawi, 30% India, and a very low 20% in Guatemala. Supplementation of HIV+ women in Malawi with 1X RDA from 06 ...
The purpose of this research was to compare and validate methods for the analysis of vitamin B12 in human milk. The Adequate Intake (AI) for infants is 0.4 μg based on an assumed milk concentration of 378pM. However, some older... more
The purpose of this research was to compare and validate methods for the analysis of vitamin B12 in human milk. The Adequate Intake (AI) for infants is 0.4 μg based on an assumed milk concentration of 378pM. However, some older concentration values were determined with inaccurate and non-validated methods. Poor maternal B12 intake or status causes low milk B12 and subsequent challenges for detection. Also, haptocorrin (HC) in human milk can produce falsely elevated or decreased values. We evaluated two assays (SimulTRAC-SNC and IMMULITE) for their suitability for analyzing B12 in human milk. SimulTRAC-SNB gave poor results and was highly influenced by HC, while IMMULITE can be applied without HC removal with an overall recovery rate of 78.9 % ± 9.1 (standard addition: 100 – 900 pg/mL). Diluted milk samples (24 – 193pM) were linearly correlated (r > 0.992). Analysis of milk samples from supplemented vs. unsupplemented women respectively in Bangladesh (± 250μg/d; milk concentration...
Maternal supplementation in lactation could be an effective approach for improving breast milk quality in populations consuming poor quality diets. To determine acute effects of micronutrient (MN) supplementation on concentrations in milk... more
Maternal supplementation in lactation could be an effective approach for improving breast milk quality in populations consuming poor quality diets. To determine acute effects of micronutrient (MN) supplementation on concentrations in milk during a 24h period, we recruited 18 healthy Bangladeshi women at 2-4 mo lactation for a 3d supplementation study. On d 1, no supplements were given, while in the morning of d 2 and 3 the participants received a dose of ~1x and 2x RDA respectively. Aliquots of a full breast milk expression were collected during every feed from the same breast on each study day and analyzed for vitamins A, E, B1, B2, B3, B6, and B12. All but vitamin A showed differences in mean concentrations based on collection day (P < 0.05, n = 448). To explore kinetics of vitamin secretion into milk, samples were grouped into 2h time intervals/d and mean values of the same intervals across days were compared. B2 and B6 concentrations both spiked after supplement consumption. ...
Vitamin B12 is important for infant growth and supplementation to lactating mothers could increase intakes to exclusively breastfed (EBF) infants in areas where maternal diet is poor in B12. HIV+ mothers in the Breastfeeding,... more
Vitamin B12 is important for infant growth and supplementation to lactating mothers could increase intakes to exclusively breastfed (EBF) infants in areas where maternal diet is poor in B12. HIV+ mothers in the Breastfeeding, Antiretrovirals, and Nutrition study were randomized to receive a lipid-based nutrient supplement (LNS), containing the RDA for B12 (2.6μg), or no LNS. We examined the relationships among maternal and infant plasma (MP, IP) and breastmilk (BM) concentrations of B12 in a sub-sample (n=521) at 2 or 6 wk (baseline) and 24 wk. At baseline MP B12 was positively correlated with BM (r=0.36) and IP (r=0.42), and IP and BM B12 were correlated (r=0.32) (all p<0.001). At 24 wk the relationships remained significant: MP B12 with BM (r=0.42) and IP (r=0.32), and IP with BM (r=0.29). At baseline there were no differences between LNS and no LNS in MP, BM or IP B12 concentrations. At 24 wk MP and BM B12 were higher in the LNS vs. no LNS group (p<0.005).However IP B12 was...
In resource-limited settings without safe alternatives to breastfeeding, the WHO recommends exclusive breastfeeding and antiretroviral (ARV) prophylaxis. Given the high prevalence of anemia among HIV-infected women, mothers and their... more
In resource-limited settings without safe alternatives to breastfeeding, the WHO recommends exclusive breastfeeding and antiretroviral (ARV) prophylaxis. Given the high prevalence of anemia among HIV-infected women, mothers and their infants (via fetal iron accretion) may be at risk of iron deficiency. We assessed the effects of maternal micronutrient-fortified lipid-based nutrient supplements (LNS) and maternal ARV treatment or infant ARV prophylaxis on maternal and infant iron status during exclusive breastfeeding from birth to 24 weeks. The Breastfeeding, Antiretrovirals, and Nutrition Study was a randomized controlled trial conducted in Lilongwe, Malawi from 2004-2010. HIV-infected mothers (CD4&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;200 cells/ul) and their infants were randomly assigned to 28-week interventions: maternal-LNS/maternal-ARV (n=424), maternal-LNS/infant-ARV (n=426), maternal-LNS (n=334), maternal-ARV (n=425), infant-ARV (n=426), or control (n=334). Longitudinal models tested intervention effects on hemoglobin (Hb). In a subsample (n=537) with multiple iron indicators, intervention effects on Hb, transferrin receptors (TfR) and ferritin were tested with linear and Poisson regression. In longitudinal models, LNS effects on maternal and infant Hb were minimal. In subsample mothers, maternal ARVs were associated with tissue iron depletion (TfR&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;8.3 mg/L) (Risk ratio (RR): 3.1, p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01), but not in ARV-treated mothers receiving LNS (p=0.17). LNS without ARVs, was not associated with iron deficiency or anemia (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;0.1). In subsample infants, interventions were not associated with impaired iron status (all p-values&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;0.1). Maternal ARV treatment with protease inhibitors is associated with maternal tissue iron depletion; but LNS mitigates adverse effects. ARVs do not appear to influence infant iron status; however, extended use needs to be evaluated.