Iodine in Human Milk: A Systematic Review.

Because infants are born with small amounts of stored intrathyroidal iodine, they depend on human-milk iodine for normal physical and neurologic growth and development. The mammary gland concentrates iodide; however, there is a lack of consensus on the concentrations of breast-milk iodine necessary to achieve equilibrium in the infant. The objectives of the present review are to consider trends in breast-milk iodine concentrations over the course of lactation, to determine which maternal factors or interventions influence breast-milk iodine concentrations, to examine the association between breast-milk iodine concentrations and infant iodine status, and to identify how newer data contribute to the literature and inform recommendations for achieving optimal breast-milk iodine concentrations. A systematic search of the published literature was undertaken by using the US National Library of Medicine's MEDLINE/PubMed bibliographic search engine. Observational and intervention studies were included if the research was original, the study had not been included in a previous review, and iodine concentration in human milk was measured at ≥1 time point during the first 12 mo of lactation. Results of the systematic review indicate that breast-milk iodine concentrations vary widely between populations but are highest in colostrum and decrease gradually throughout the lactation period. Included studies did not replicate earlier findings of an inverse correlation between breast-milk iodine and perchlorate concentrations. Supplementation with high-dose or daily iodine during lactation was effective in increasing breast-milk iodine concentrations with some evidence of a dose-response relationship, which is consistent with findings of earlier supplementation trials in pregnancy and lactation. Although additional and globally representative research is needed, data suggest that breast-milk iodine concentrations in the range of 150 µg/L during the first 6 mo of lactation would achieve or exceed infant iodine equilibrium and prevent the developmental consequences of iodine deficiency.

Retinol-to-Fat Ratio and Retinol Concentration in Human Milk Show Similar Time Trends and Associations with Maternal Factors at the Population Level: A Systematic Review and Meta-Analysis.

Vitamin A in human milk is critical for meeting infant requirements and building liver stores needed after weaning. A number of studies have measured milk retinol, but only a subset have corrected for fat, which serves as the retinol carrier in breast milk. The purpose of the present work was to review and analyze studies in which human-milk retinol concentrations were reported in relation to milk fat and to compare these results with unadjusted breast-milk retinol concentrations in terms of time trends over the course of lactation, influences of maternal nutritional and constitutional factors, and effects of maternal vitamin A supplementation. A systematic approach was used to search the available literature by using the US National Library of Medicine's MEDLINE/PubMed bibliographic search engine. Observational and intervention studies were included if the research was original and the retinol-to-fat ratio (retinol:fat) in human milk was measured at ≥1 time point during the first 12 mo of lactation. Retinol:fat and retinol were highest in colostrum, declined rapidly in early lactation, and achieved statistical stability by 2 and 4 wk lactation, respectively. In mature milk, retinol concentration was positively correlated with milk fat (r = 0.61, P = 0.008). Breast-milk retinol:fat and retinol were positively associated with maternal vitamin A intake but were associated with plasma retinol only when dietary intake was inadequate. Postpartum supplementation with high-dose vitamin A (200,000-400,000 IU) resulted in significantly higher breast-milk retinol:fat for 3 mo and retinol for 6 mo (P < 0.05). In populations, the 2 indexes show similar trends and associations with maternal factors. Future studies should monitor how the uptake of retinol into the mammary gland affects maternal vitamin reserves, particularly in women who are at risk of vitamin A deficiency.

Vitamin B-12 in Human Milk: A Systematic Review.

Despite the critical role of vitamin B-12 in infant development, existing recommendations for infant and maternal intake during lactation are based on milk vitamin B-12 concentrations analyzed with outdated methods in a sample of 9 Brazilian women. Accurate quantification of vitamin B-12 in the milk matrix requires effective hydrolysis of the vitamin from haptocorrin, its binding protein. The objective of the present systematic review is to consider and critique evidence of associations between milk vitamin B-12 concentration and time postpartum, maternal vitamin B-12 consumption, maternal vitamin B-12 status, and sample collection methodology. A systematic search of published literature was undertaken using the US National Library of Medicine's MEDLINE/PubMed bibliographic search engine. Observational and intervention studies were included if research was original and vitamin B-12 concentration in human milk was measured using an appropriate method during the first 12 mo of lactation. Eleven studies met inclusion criteria. Vitamin B-12 concentration was highest in colostrum and decreased in a poorly delineated trajectory over the first 3-4 mo of lactation. There was some evidence of a positive association between habitual maternal vitamin B-12 intake and milk vitamin B-12 concentration in marginally nourished women. Supplementation with 50-250 µg vitamin B-12/d during pregnancy and lactation raised human milk vitamin B-12 concentrations while intervention was ongoing, whereas supplementation with 2.6-8.6 µg/d was effective in a population with poor baseline vitamin B-12 status but not in other populations. Whether milk vitamin B-12 concentration varies with maternal circulating vitamin B-12 concentrations or sampling methodology requires further research as existing data are conflicting. Additional research is needed to bridge knowledge gaps in the understanding of human milk vitamin B-12 concentrations. Reference values for vitamin B-12 in human milk and recommended intakes during infancy and lactation should be reevaluated using modern methods of analysis.

Limitations of the Evidence Base Used to Set Recommended Nutrient Intakes for Infants and Lactating Women.

Reported values for concentrations of micronutrients in human milk form the basis of the majority of micronutrient intake recommendations for infants and the additional maternal requirements for lactation. The infant recommendations may also be extrapolated to provide estimates for young children. The purpose of this review is to evaluate the adequacy of the milk micronutrient concentration data used by the Institute of Medicine to set recommendations for the United States and Canada, by FAO/WHO, the United Kingdom, and the European Food Safety Authority. The concentrations accepted by each agency are presented for each micronutrient accompanied by the source of information and comments on the number, location, status, and stage of lactation of the sample population, where known. These summaries show the small number of participants from which samples were collected in most studies, the wide range of concentrations within studies, the lack of longitudinal data, and the variability in collection methods. These factors contribute to the variability in nutrient intake recommendations among committees, although this variability is reduced by some committees that accept milk-composition values proposed by others. Values are also summarized from milk collected in studies in which mothers or infants were known to be deficient on the basis of clinical symptoms, biomarkers of inadequacy, or both, to show the extent to which milk micronutrients can be reduced by poor maternal nutritional status. We conclude that a new, multicenter study is needed to establish reference values for milk constituents across lactation.

Overview of Nutrients in Human Milk.

The WHO recommends exclusive breastfeeding for the first 6 mo of life to promote optimal infant health and development. Understanding the micro- and macronutrient concentrations of human milk and how each nutrient fluctuates with lactational stage, maternal factors, and supplementation is imperative for supporting good breastfeeding practices. Where maternal undernutrition compromises human milk quality, a thorough awareness of the effectiveness of interventions can direct efforts to achieve both maternal and infant nutrient sufficiency. This review of current knowledge covers trends in nutrient concentrations over the course of lactation and describes the influence of maternal intake, status, supplementation, and other factors on human milk concentrations of each nutrient.

Micronutrients in Human Milk: Analytical Methods.

Exclusive breastfeeding is recommended by the WHO for the first 6 mo of life because human milk protects against gastrointestinal infections and supplies balanced and adequate nutrient contents to the infant. However, reliable data on micronutrient concentrations in human milk are sparse, especially because some micronutrients are affected by maternal diet. Microbiological and competitive protein-binding assays, nuclear magnetic resonance or inductively coupled plasma spectroscopy, and chromatographic analyses are among the methods that have been applied to human-milk micronutrient analysis. However, the validation or evaluation of analytical methods in terms of their suitability for the complex human-milk matrix has been commonly ignored in reports, even though the human-milk matrix differs vastly from blood, plasma, or urine matrixes. Thus, information on the validity, accuracy, and sensitivity of the methods is essential for the estimation of infant and maternal intake requirements to support and maintain adequate milk micronutrient concentrations for healthy infant growth and development. In this review, we summarize current knowledge on methods used for analyzing water- and fat-soluble vitamins as well as iron, copper, zinc, iodine, and selenium in human milk and their different forms in milk; the tools available for quality control and assurance; and guidance for preanalytical considerations. Finally, we recommend preferred methodologic approaches for analysis of specific milk micronutrients.

Multiple-Micronutrient Fortified Non-Dairy Beverage Interventions Reduce the Risk of Anemia and Iron Deficiency in School-Aged Children in Low-Middle Income Countries: A Systematic Review and Meta-Analysis (i-iv).

Multiple-micronutrient (MMN) fortification of beverages may be an effective option to deliver micronutrients to vulnerable populations. The aim of the present systematic review and meta-analysis is to evaluate the nutritional impacts of MMN fortified beverages in the context of low-middle income countries. A systematic search of published literature yielded 1022 citations, of which 10 randomized controlled trials (nine in school-aged children and one in pregnant women) met inclusion criteria. Results of school-aged children were included in the meta-analysis. Compared to iso-caloric controls, children who received MMN fortified beverages for 8 weeks to 6 months showed significant improvements in hemoglobin (+2.76 g/L, 95% CI [1.19, 4.33], p = 0.004; 8 studies) and serum ferritin (+15.42 pmol/L, [5.73, 25.12], p = 0.007; 8 studies); and reduced risk of anemia (RR 0.58 [0.29, 0.88], p = 0.005; 6 studies), iron deficiency (RR 0.34 [0.21, 0.55], p = 0.002; 7 studies), and iron deficiency anemia (RR 0.17 [0.06, 0.53], p = 0.02; 3 studies). MMN fortified beverage interventions could have major programmatic implications for reducing the burden of anemia and iron deficiency in school-aged children in low-middle income countries. Additional research is needed to investigate effects on other biochemical outcomes and population subgroups.

Dairy product intake in children and adolescents in developed countries: trends, nutritional contribution, and a review of association with health outcomes.

Despite its contribution to nutrient intake and status, consumption of milk and dairy products by children and adolescents in many countries has waned in recent decades, with a substantial proportion of youth failing to meet intake recommendations. Dairy products remain an important dietary source of multiple micronutrients, including calcium, phosphorus, magnesium, zinc, iodine, potassium, vitamin A, vitamin D, vitamin B12 , and riboflavin (vitamin B2 ). In addition, dairy products provide children with energy, high-quality protein, and essential and nonessential fatty acids. A review of evidence was conducted to evaluate associations between milk or dairy product intake and health outcomes in children and adolescents. Results suggest a neutral or inverse association between consumption of milk and dairy products in children and adolescents and indicators of adiposity, incidence of dental caries, and hypertension. Available data indicate that dairy products are important for linear growth and bone health during childhood. Additional research--in particular, controlled intervention trials and long-term prospective cohort studies--is warranted to better understand how dairy intake affects health outcomes in children and adolescents.

The importance of using food and nutrient intake data to identify appropriate vehicles and estimate potential benefits of food fortification in Uganda.

BACKGROUND: Concern over micronutrient inadequacies in Uganda has prompted the introduction of mass fortification. OBJECTIVE: To use food intake to determine nutrient inadequacies in children aged 24 to 59 months and nonpregnant women of reproductive age, and to model the adequacy of mass fortification. METHODS: Data were collected by the 24-hour recall method in three regions. Usual nutrient intakes were calculated by adjusting actual intake distribution for the intraindividual variance. The impact of fortification on intake adequacy was simulated. RESULTS: The nutrients with the highest prevalence of inadequate intake across regions were vitamin A (30% to 99%), vitamin B12 (32% to 100%), iron (55% to 89%), zinc (18% to 82%), and calcium (84% to 100%). According to simulations, fortification of vegetable oil and sugar with vitamin A would reduce the prevalence of vitamin A inadequacy in the Western and Northern regions; in Kampala it would eliminate vitamin A inadequacy but would cause 2% to 48% of children to exceed the Tolerable Upper Intake Level (UL). The proposed fortification of wheat flour would reduce the prevalence of inadequate intakes of thiamine, riboflavin, folate, and niacin in Kampala, but would have little impact in the other two regions due to low flour consumption. CONCLUSIONS: Micronutrient fortification of vegetable oil and sugar in all regions and of wheat flour in Kampala would reduce the prevalence of micronutrient inadequacies. However, the wheat flour formulation should be modified to better meet requirements, and the vitamin A content in sugar should be reduced to minimize the risk of high intakes. Maize flour may be suitable for targeted fortification, but prior consolidation of the industry would be required for maize flour to become a good vehicle for mass fortification.

Interventions with vitamins B6, B12 and C in pregnancy.

The water-soluble vitamins B6, B12 and C play important roles in maternal health as well as fetal development and physiology during gestation. This systematic review evaluates the risks and benefits of interventions with vitamins B6, B12 and C during pregnancy on maternal, neonatal and child health and nutrition outcomes. Relevant publications were identified by searching PubMed, Popline and Web of Science databases. Meta-analyses were conducted for outcomes where results from at least three controlled trials were available. Potential benefits of vitamin B6 supplementation were reduction in nausea and vomiting, improvement in dental health, and treatment of some cases of anaemia. In meta-analysis based on three small studies, vitamin B6 supplementation had a significant positive effect on birthweight (d = 217 g [95% confidence interval (CI) 130, 304]). Interventions with vitamin C alone or combined with vitamin E did not systematically reduce the incidence of pre-eclampsia, premature rupture of membranes, or other adverse pregnancy outcomes. In meta-analyses, vitamins C and E increased the risk of pregnancy-related hypertension (relative risk 1.10 [95% CI 1.02, 1.19]). Effects of vitamin B6 or C intervention on other neonatal outcomes, including preterm birth, low birthweight, and perinatal morbidity and mortality, were not significant. Data on child health outcomes were lacking. Despite the prevalence of vitamin B12 deficiency amongst populations with limited intake of animal source foods, no intervention trials have evaluated vitamin B12 supplementation before or during pregnancy. In conclusion, existing evidence does not justify vitamin C supplementation during pregnancy. Additional studies are needed to confirm positive effects of vitamin B6 supplementation on infant birthweight and other outcomes. While vitamin B12 supplementation may reduce the incidence of neural tube defects in the offspring based on theoretical considerations, research is needed to support this hypothesis.

Evidence of associations between feto-maternal vitamin D status, cord parathyroid hormone and bone-specific alkaline phosphatase, and newborn whole body bone mineral content.

In spite of a high prevalence of vitamin D inadequacy in pregnant women and neonates, relationships among vitamin D status (25(OH)D), parathyroid hormone (PTH), bone specific alkaline phosphatase (BALP), and whole body bone mineral content (WBBMC) in the newborn are poorly characterized. The purpose of the present study was to investigate the relationships between maternal and cord 25(OH)D, PTH, BALP, and WBBMC in newborns in a multiethnic population in Oakland, California and to evaluate the predictive value of the biochemical indices as indicators of WBBMC. Maternal and cord blood were collected from 80 mother-infant pairs and infant WBBMC was measured by dual energy X-ray absorptiometry 8-21 days post-birth. Cord PTH and BALP were each inversely correlated with infant WBBMC (r = -0.28, p = 0.01 and r = -0.26, p = 0.02) and with cord 25(OH)D (r = -0.24, p = 0.03 and r = -0.34, p = 0.002), while cord 25(OH)D and unadjusted or weight-adjusted WBBMC were not significantly correlated with one other. In multivariate regression modeling, infant WBBMC was most strongly predicted by infant weight (p < 0.0001), while either PTH or BALP contributed modestly but significantly to the model (p = 0.006 and p = 0.03 respectively). Cord 25(OH)D was not a significant predictor of infant WBBMC. This study provides evidence of associations between feto-maternal 25(OH)D, cord PTH and BALP, and early infant WBBMC, though neither feto-maternal 25(OH)D nor the measured biochemical indices were suitable indicators of WBBMC.

Vitamin E deficiency in developing countries.

In addition to its role as a potent antioxidant, vitamin E is involved in a wide range of physiological processes, ranging from immune function and control of inflammation to regulation of gene expression and cognitive performance. Results from multiple studies suggest that poor nutritional status and higher prevalence of other oxidative stressors such as malaria and HIV infection predispose populations in developing countries for vitamin E deficiency. Although direct comparison between study outcomes is complicated by varied definitions of vitamin E deficiency, data trends indicate that children and the elderly are more vulnerable age groups and that men may be at higher risk for deficiency than women. Public health initiatives aimed at improving the vitamin E status of high-risk populations in developing countries would be prudent to counteract oxidative stress, improve immune function, and protect against neurologic and cognitive deficits. Additional research is needed to establish dose-response relationships of various interventions and to develop cost-effective, culturally-appropriate, and targeted programs.

The importance of milk and other animal-source foods for children in low-income countries.

BACKGROUND: Milk and other animal-source foods are concentrated dietary sources of macro- and micronutrients. Despite a global increase in milk production and consumption over the past decades, milk and other animal-source foods are often lacking in the diets of children in developing countries. OBJECTIVE: To evaluate the importance of milk and other animal-source food intake in promoting the growth, development, and health of children in low-income countries. METHODS: Original research articles describing observational and intervention studies with unfortified milk, fortified milk, and other animal-source foods in children were identified by searching the PubMed database. RESULTS: Consumption of milk and other animal-source foods by undernourished children improves anthropometric indices and cognitive function and reduces the prevalence of biochemical and functional nutritional deficiencies, reducing morbidity and mortality. Unfortified and fortified milk used in supplementation trials has been well tolerated and widely accepted by parents and children. CONCLUSIONS: To improve the dietary quality of children in low-income countries and further the effort to eradicate extreme poverty and hunger in accordance with the United Nations Millennium Development Goals, additional research is necessary to identify and implement programs and policy supporting increased intake of milk and other animal-source foods.

Vitamin D status during pregnancy: maternal, fetal, and postnatal outcomes.

PURPOSE OF REVIEW: To consider evidence from recent studies linking maternal vitamin D status during pregnancy with maternal, fetal, and postnatal outcomes. RECENT FINDINGS: Several studies have demonstrated an association between poor maternal vitamin D status and severe preeclampsia, though results are inconsistent and cannot be generalized to nonsevere preeclampsia. Pregnant women with gestational diabetes, intrahepatic cholestasis of pregnancy, and periodontal disease had lower vitamin D status at mid-gestation or delivery compared with controls. Maternal vitamin D status early in pregnancy was associated with risk of low birth weight and small-for-gestational age infants in one study, whereas another study found this relation only among white women. Polymorphisms in the vitamin D receptor gene may contribute to vitamin D-related disparities in fetal growth. Evidence from recent studies suggests an early prenatal influence of maternal vitamin D status on fetal skeletal development, with lasting postnatal effects. Cord blood vitamin D status was associated with tolerogenic immune regulation and fewer respiratory infections in the newborn. SUMMARY: Recent evidence supports a role of maternal vitamin D status, particularly early in pregnancy, in modulating the risk of pregnancy complications and in sustaining fetal growth, bone development, and immune maturation.

Effects of animal source foods, with emphasis on milk, in the diet of children in low-income countries.

This review evaluates evidence for benefits of including animal source foods (ASF) in the diets of children in developing countries. In observational studies, a higher usual intake of ASF in such countries is associated with better growth, status of some micronutrients, cognitive performance, motor development and activity. Only three randomized trials supplemented children with milk and compared outcomes with a nonintervention control group. Both height and weight growth were improved, although in Kenya height was increased only in younger schoolers who were stunted at baseline. Meat supplements have been evaluated in only two randomized controlled trials, in Kenya and Guatemala (mean baseline age 8 years and 1 year, respectively); growth was no better than in an equicaloric control group. Meat improved cognitive function and activity in Kenya; milk was less effective than meat for improving cognitive function and physical activity, perhaps due to its lower content of iron, zinc, or riboflavin. Meat and especially cow's milk are excellent sources of vitamin B(12), a micronutrient commonly deficient in populations which consume low amounts of ASF. Other micronutrients such as iron have been added to cow's milk and resulted in improved nutritional outcomes for children.

Association of modifiable and nonmodifiable factors with vitamin D status in pregnant women and neonates in Oakland, CA.

There is little information on the contribution of modifiable vs nonmodifiable factors to maternal and neonatal vitamin D status in temperate regions of the United States. The purpose of this cross-sectional observation study conducted between December 2006 and February 2008 was to identify associations between observed and measured maternal characteristics and vitamin D status at term in pregnant women and their infants in a multiethnic community in Oakland, CA. Two hundred seventy-five pregnant women aged 18 to 45 years and carrying a singleton fetus were recruited and data from 210 mother-infant pairs were included in analyses. Analysis of covariance identified predictors of maternal and cord serum 25-hydroxyvitamin D [25(OH)D] in a multivariate model considering vitamin D intake, lifestyle factors, and skin pigmentation. Maternal serum 25(OH)D was significantly associated with season of delivery (P=0.0002), average daily D intake (P=0.0008), right upper inner arm pigmentation (P=0.0035), and maternal pre- or early-pregnancy body mass index (calculated as kg/m²) (P=0.0207). The same factors were significant for cord serum 25(OH)D, which was highly correlated with maternal serum 25(OH)D (r=0.79; P<0.0001). During the year, 54% of mothers and 90% of neonates had 25(OH)D <30 ng/mL (<75 nmol/L). Of women taking daily prenatal vitamin/mineral supplements (400 IU vitamin D), 50.7% had serum 25(OH)D <30 ng/mL (<75 nmol/L). In conclusion, 25(OH)D <30 ng/mL (<75 nmol/L) was prevalent in mothers and neonates across racial groups and seasons, and vitamin D status was associated with both modifiable and nonmodifiable risk factors.

Vitamin D inadequacy in pregnancy: biology, outcomes, and interventions.

A high prevalence of maternal vitamin D inadequacy during pregnancy and at delivery has been demonstrated in various ethnic populations living at different latitudes. Because placental transfer of 25(OH)D is the major source of vitamin D to the developing human fetus, there is growing concern about adverse health impacts that hypovitaminosis D during pregnancy may have on the mother as well as the offspring in utero, in infancy, and later in life. While there is lack of consensus regarding the optimal circulating 25(OH)D concentration in pregnancy, it is evident that prior levels used to establish intake recommendations and vitamin D content of prenatal vitamin supplements were too conservative. This review summarizes vitamin D metabolism in the perinatal period, examines evidence regarding outcomes of insufficiency in the mother and offspring, discusses risk factors and prevalence of insufficiency, and considers strategies for public health intervention.

Effect of vitamin B12 deficiency on neurodevelopment in infants: current knowledge and possible mechanisms.

Severe vitamin B(12) deficiency produces a cluster of neurological symptoms in infants, including irritability, failure to thrive, apathy, anorexia, and developmental regression, which respond remarkably rapidly to supplementation. The underlying mechanisms may involve delayed myelination or demyelination of nerves; alteration in the S-adenosylmethionine:S-adenosylhomocysteine ratio; imbalance of neurotrophic and neurotoxic cytokines; and/or accumulation of lactate in brain cells. This review summarizes the current knowledge concerning infantile vitamin B(12) deficiency, including a pooled analysis of case studies of infants born to mothers with untreated pernicious anemia or a strict vegetarian lifestyle and a discussion of the mechanisms that may underlie the manifestations of deficiency.