Maternal Micronutrient Supplementation Research Articles

Effect of antenatal and infant micronutrient supplementation on middle childhood and early adolescent development outcomes in Tanzania

Background:There is growing evidence that nutritional interventions in the first 1,000 days of life may influence long-term health and development outcomes. Few studies have examined the effect of maternal and infant micronutrient supplementation on development outcomes in sub-Saharan Africa.Methods:We conducted a follow-up study of two randomized trials of antenatal and infant micronutrient supplementation conducted in Dar es Salaam, Tanzania. We assessed the effect of maternal multiple micronutrient (MMN) supplementation in pregnancy on development of children at 11–14 years of age. We also examined the effect of infant zinc and MMN supplementation on development at 6–8 years of age. We use generalized linear models to assess standardized mean differences (SMDs) in general intelligence, executive function and mental health scores.Results:We followed-up 446 children whose mothers were enrolled in the maternal MMN supplementation trial and 365 children who were enrolled in the infant zinc and MMN supplementation trial. We found no effect of maternal MMN supplementation on general intelligence (SMD: −0.03; 95% CI: −0.15, 0.09), executive function (SMD: 0.00; 95% CI: −0.11, 0.11) and mental health scores (SMD: 0.06; 95% CI: −0.10, 0.22). We also found no effect of either infant zinc or MMN supplementation on any of the three development domains (p-values >0.05).Conclusions:We found that antenatal MMN supplementation and infant zinc and MMN supplementation did not have a large effect on development outcomes in middle childhood and early adolescence in Tanzania.

Poverty and immigration as a barrier to iodine intake and maternal adherence to iodine supplementation.

Iodine deficiency still remains a significant health issue worldwide. Pregnant and lactating women are at risk for iodine deficiency when living in mild iodine-deficient areas such as Italy. This study aims at evaluating the consumption of iodized salt, iodine-rich-foods and maternal micronutrient supplements in a group of women with limited access to the Italian National Health System. A cross-sectional survey was conducted among immigrant and Italian women living in poverty and referring to 40 Non-Governmental Organization throughout Italy for their health needs. 3483 women answered the ad hoc questionnaire between January 2017 and February 2018. The consumption of iodized salt was very low, and even lower among immigrant women. Determinants of iodized salt consumption were the period spent in Italy for immigrant women and living in a family-type setting, parity and, particularly, the degree of education for Italian ones. 17.5% of immigrant women and 8.6% of the Italian ones reported a diagnosis of thyroid disease. 521 women, 75.4% of whom were immigrants, were pregnant or breast-feeding. The majority (57.3%) had no specific maternal supplementation. Both Italian and immigrating women with a low income or without access to the public health system have a poor adherence both to the salt iodization policy and to folic acid and iodine supplements in preconception and pregnancy. They also referred a low-frequency intake of iodine-rich-foods. The identification of barriers to health care access could be useful to promote specific health interventions in this target population.

Modifiers of the effect of maternal multiple micronutrient supplementation on stillbirth, birth outcomes, and infant mortality: a meta-analysis of individual patient data from 17 randomised trials in low-income and middle-income countries.

Micronutrient deficiencies are common among women in low-income and middle-income countries. Data from randomised trials suggest that maternal multiple micronutrient supplementation decreases the risk of low birthweight and potentially improves other infant health outcomes. However, heterogeneity across studies suggests influence from effect modifiers. We aimed to identify individual-level modifiers of the effect of multiple micronutrient supplements on stillbirth, birth outcomes, and infant mortality in low-income and middle-income countries. This two-stage meta-analysis of individual patient included data from 17 randomised controlled trials done in 14 low-income and middle-income countries, which compared multiple micronutrient supplements containing iron-folic acid versus iron-folic acid alone in 112 953 pregnant women. We generated study-specific estimates and pooled subgroup estimates using fixed-effects models and assessed heterogeneity between subgroups with the χ2 test for heterogeneity. We did sensitivity analyses using random-effects models, stratifying by iron-folic acid dose, and exploring individual study effect. Multiple micronutrient supplements containing iron-folic acid provided significantly greater reductions in neonatal mortality for female neonates compared with male neonates than did iron-folic acid supplementation alone (RR 0·85, 95% CI 0·75-0·96 vs 1·06, 0·95-1·17; p value for interaction 0·007). Multiple micronutrient supplements resulted in greater reductions in low birthweight (RR 0·81, 95% CI 0·74-0·89; p value for interaction 0·049), small-for-gestational-age births (0·92, 0·87-0·97; p=0·03), and 6-month mortality (0·71, 0·60-0·86; p=0·04) in anaemic pregnant women (haemoglobin <110g/L) as compared with non-anaemic pregnant women. Multiple micronutrient supplements also had a greater effect on preterm births among underweight pregnant women (BMI <18·5 kg/m2; RR 0·84, 95% CI 0·78-0·91; p=0·01). Initiation of multiple micronutrient supplements before 20 weeks gestation provided greater reductions in preterm birth (RR 0·89, 95% CI 0·85-0·93; p=0·03). Generally, the survival and birth outcome effects of multiple micronutrient supplementation were greater with high adherence (≥95%) to supplementation. Multiple micronutrient supplements did not significantly increase the risk of stillbirth or neonatal, 6-month, or infant mortality, neither overall or in any of the 26 examined subgroups. Antenatal multiple micronutrient supplements improved survival for female neonates and provided greater birth-outcome benefits for infants born to undernourished and anaemic pregnant women. Early initiation in pregnancy and high adherence to multiple micronutrient supplements also provided greater overall benefits. Studies should now aim to elucidate the mechanisms accounting for differences in the effect of antenatal multiple micronutrient supplements on infant health by maternal nutrition status and sex. None.

PERTUMBUHAN ANAK DARI IBU YANG MENDAPAT SUPLEMEN MULTI-MIKRONUTRIEN DAN ANAK DARI IBU YANG MENDAPAT SUPLEMEN BESI FOLAT SELAMA HAMIL (Studi follow up di Kabupaten Probolinggo, Jawa Timur)

Recent studies have shown that maternal multiple micronutrient (MMN) supplementation improved birth weight but there is insufficient evidence that postnatal growth of children from mothers who received MMN are better than children from mother who received iron folic acid (IFA) during pregnancy. The aim of this study was to compare the growth of children aged 16–39 months from mother who received MMN and children from mother who received IFA during pregnancy. The design of this study was nested case control study from cohort study of reconceptional multiple micronutrient supplementation to Improve Maternal Iron Status and Pregnancy Outcomes (Laduni Program). The subject were 30 children randomly selected from the children of mothers who received MMN, and 30 other children randomly selected from children of mothers who received IFA. Variables observed in this study were birth weight from the health records, height-for-age z-scores (HAZ), weight-for-age z-scores (WAZ), and body mass index-for-age z-scores (BMIAZ) through direct measurements; nutrient intake from 2 x 24 hours dietary recalls. The average of children’s age in this study (±SD) was 28 ± 5,3 months. There is no difference in HAZ, WAZ, BMIAZ, and nutrient intake between the children of mothers who received MMN and children of mothers who received IFA. Most of the nutrient intake were inadequate as the diet were unbalanced and monotonous. Conclusion: maternal MMN supplementation during pregnancy has no effect on growth of 16–39 month old children if the nutrient intake is inadequate. Children should eat a variety of diet sufficienly for an optimal growth.Keywords:growth, maternal multiple-micronutrient, iron folic acid, children

Modifiers of the Effect of Maternal Multiple Micronutrient Supplementation: an individual patient data meta‐analysis of 17 randomized trials

ObjectiveTo identify individual‐level effect modifiers of the effect of multiple micronutrient supplementation (MMS) containing iron and folic acid (IFA) during pregnancy, compared to IFA alone, on the risk of stillbirth, infant mortality, and birth outcomes.MethodsWe performed an individual patient data meta‐analysis. Study‐specific estimates were generated, and we pooled subgroup estimates using fixed effects models.FindingsWe included 17 randomized controlled trials (including 112,953 pregnancies). MMS resulted in greater reductions in low birthweight (RR 0.81; 95% CI: 0.74–0.89), small‐for‐gestational age births (RR 0.91; 95% CI: 0.87–0.96), and six‐month mortality (RR: 0.71; 95% CI: 0.60–0.86) among anemic (hemoglobin &lt;110g/L) as compared with non‐anemic pregnant women. MMS had a greater impact on preterm birth among underweight pregnant women (body mass index &lt;18.5kg/m2) (RR: 0.84; 95% CI: 0.78–0.90) compared to those with BMI ≥18.5 (RR: 0.94; 95% CI 0.90–0.98) (p value heterogeneity 0.01). MMS provided significantly greater reductions in infant mortality for female (RR: 0.87; 95% CI: 0.77–0.99) as compared to male infants (RR: 1.05; 95% CI: 0.93–1.18) (p value heterogeneity 0.04). In general, the survival and birth outcome effects of MMS were greater with high adherence (≥95%) to supplementation.ConclusionMMS produced greater birth outcome benefits for pregnant women with indicators of nutritional deficiency and improved survival for female infants.Support or Funding InformationNone.

Vitamin Concentrations in Human Milk Vary with Time within Feed, Circadian Rhythm, and Single-Dose Supplementation

Background: Human milk is the subject of many studies, but procedures for representative sample collection have not been established. Our improved methods for milk micronutrient analysis now enable systematic study of factors that affect its concentrations.Objective: We evaluated the effects of sample collection protocols, variations in circadian rhythms, subject variability, and acute maternal micronutrient supplementation on milk vitamin concentrations.Methods: In the BMQ (Breast-Milk-Quality) study, we recruited 18 healthy women (aged 18–26 y) in Dhaka, Bangladesh, at 2–4 mo of lactation for a 3-d supplementation study. On day 1, no supplements were given; on days 2 and 3, participants consumed ∼1 time and 2 times, respectively, the US-Canadian Recommended Dietary Allowances for vitamins at breakfast (0800–0859). Milk was collected during every feeding from the same breast over 24 h. Milk expressed in the first 2 min (aliquot I) was collected separately from the remainder (aliquot II); a third aliquot (aliquot III) was saved by combining aliquots I and II. Thiamin, riboflavin, niacin, and vitamins B-6, B-12, A, and E and fat were measured in each sample.Results: Significant but small differences (14–18%) between aliquots were found for all vitamins except for vitamins B-6 and B-12. Circadian variance was significant except for fat-adjusted vitamins A and E, with a higher contribution to total variance with supplementation. Between-subject variability accounted for most of the total variance. Afternoon and evening samples best reflected daily vitamin concentrations for all study days. Acute supplementation effects were found for thiamin, riboflavin, and vitamins B-6 and A at 2–4 h postdosing, with 0.1–6.17% passing into milk. Supplementation was reflected in fasting, 24-h postdose samples for riboflavin and vitamin B-6. Maximum amounts of dose-responding vitamins in 1 feeding ranged from 4.7% to 21.8% (day 2) and 8.2% to 35.0% (day 3) of Adequate Intake.Conclusions: In the milk of Bangladeshi mothers, differences in vitamin concentrations between aliquots within feedings and by circadian variance were significant but small. Afternoon and evening collection provided the most-representative samples. Supplementation acutely affects some breast-milk micronutrient concentrations. This trial was registered at clinicaltrials.gov as NCT02756026.

Maternal multiple micronutrient supplementation and other biomedical and socioenvironmental influences on children's cognition at age 9-12 years in Indonesia: follow-up of the SUMMIT randomised trial.

Brain and cognitive development during the first 1000 days from conception are affected by multiple biomedical and socioenvironmental determinants including nutrition, health, nurturing, and stimulation. An improved understanding of the long-term influence of these factors is needed to prioritise public health investments to optimise human development. We did a follow-up study of the Supplementation with Multiple Micronutrients Intervention Trial (SUMMIT), a double-blind, cluster-randomised trial of maternal supplementation with multiple micronutrients (MMN) or iron and folic acid (IFA) in Indonesia. Of 27 356 live infants from birth to 3 months of age in 2001-04, we re-enrolled 19 274 (70%) children at age 9-12 years, and randomly selected 2879 from the 18 230 who were attending school at a known location. Of these, 574 children were oversampled from mothers who were anaemic or malnourished at SUMMIT enrolment. We assessed the effects of MMN and associations of biomedical (ie, maternal and child anthropometry and haemoglobin and preterm birth) and socioenvironmental determinants (ie, parental education, socioeconomic status, home environment, and maternal depression) on general intellectual ability, declarative memory, procedural memory, executive function, academic achievement, fine motor dexterity, and socioemotional health. The SUMMIT trial was registered, number ISRCTN34151616. Children of mothers given MMN had a mean score of 0·11 SD (95% CI 0·01-0·20, p=0·0319) higher in procedural memory than those given IFA, equivalent to the increase in scores with half a year of schooling. Children of anaemic mothers in the MMN group scored 0·18 SD (0·06-0·31, p=0·0047) higher in general intellectual ability, similar to the increase with 1 year of schooling. Overall, 18 of 21 tests showed a positive coefficient of MMN versus IFA (p=0·0431) with effect sizes from 0·00-0·18 SD. In multiple regression models, socioenvironmental determinants had coefficients of 0·00-0·43 SD and 22 of 35 tests were significant at the 95% CI level, whereas biomedical coefficients were 0·00-0·10 SD and eight of 56 tests were significant, indicating larger and more consistent impact of socioenvironmental factors (p<0·0001). Maternal MMN had long-term benefits for child cognitive development at 9-12 years of age, thereby supporting its role in early childhood development, and policy change toward MMN. The stronger association of socioenvironmental determinants with improved cognition suggests present reproductive, maternal, neonatal, and child health programmes focused on biomedical determinants might not sufficiently enhance child cognition, and that programmes addressing socioenvironmental determinants are essential to achieve thriving populations. Grand Challenges Canada Saving Brains Program.

1744 Effects of different sources and routes of administration of copper and vitamins A and D on piglets gut microbiota

Placental and colostral transfers of copper and vitamins A and D micronutrients from dams to neonates are limited in pig species (Matte et al., 2014, JAS 92-Suppl. 2:153). The aim of the study was to evaluate the influence of different perinatal micronutrient supplementation strategies on piglets’ gut microbiota. Within each litter from 5 sows, 10 newborn piglets were allocated to one of the following combinations of sources and routes of micronutrient administrations: oral vitamin D3, retinol-acetate and CuSO4 (T1); oral 25-OH-vitamin D3, β-carotene and Cu-yeast (T2); exposure to UVB light (20 min every second day), oral retinol-palmitate and Cu-gluconate (T3); intramuscular vitamin D3 and retinol-propionate and oral Cu-acetate (T4); oral saline (CTL). Oral or intramuscular provisions corresponded to 12 mg of copper and 70 and 12 MIU of vitamins A and D, respectively. This design was repeated with 5 other sows fed daily extra supplements of 25-OH-vitamin D3 (4 MIU), β-carotene (24 MIU) and Cu-yeast (45 mg) from 90 d of gestation to 21 d of lactation. At 21 d of age, feces were collected and piglets were weaned. At 23 d of age, 5 repetitions of a combination of sow and piglet factorial treatments were sacrificed and feces and content from mid-jejunum, ileum, mid-colon, and rectum were collected to characterize gut microbiota. Bacterial communities were analyzed by sequencing the V3-V4 regions of 16S rRNA genes on an Illumina MiSeq. Bioinformatic analyses were performed on our internal data analysis pipeline and statistics were performed in R. The analysis of bacterial community composition at the class level revealed that sow supplementation significantly increased the relative abundance of Bacilli in feces at d 21 (P = 0.04) but not at d 23. Gut microbiota diversity significantly differed (P = 0.03) according to supplemental treatments provided to piglets. However there was no piglet treatment effect on gut microbiota based on PCoA analyses. The Shannon diversity of jejunal and ileal microbiota was significantly (P ≺ 0.05) decreased when supplementation was given to sows. Sow supplementation also significantly increased Bacilli in both jejunum and ileum (P≺ 0.001, both). The study demonstrated that piglet gut microbiota can be modulated by daily extra supplementation of vitamins A and D and organic copper to sows during late pregnancy and lactation periods. Further studies are thus warranted to study mechanisms of action explaining the impact of such maternal micronutrient supplementation on bacterial colonization in piglets gut.

Maternal Micronutrient Supplementation and Long Term Health Impact in Children in Rural Bangladesh.

BackgroundLimited data is available on the role of prenatal nutritional status on the health of school-age children. We aimed to determine the impact of maternal micronutrient supplementation on the health status of Bangladeshi children.MethodsChildren (8.6–9.6 years; n = 540) were enrolled from a longitudinal mother-child cohort, where mothers were supplemented daily with either 30mg iron and 400μg folic acid (Fe30F), or 60mg iron and 400μg folic acid (Fe60F), or Fe30F including 15 micronutrients (MM), in rural Matlab. Blood was collected from children to determine the concentration of hemoglobin (Hb) and several micronutrients. Anthropometric and Hb data from these children were also available at 4.5 years of age and mothers at gestational week (GW) 14 and 30.ResultsMM supplementation significantly improved (p≤0.05) body mass index-for-age z-score (BAZ), but not Hb levels, in 9 years old children compared to the Fe30F group. MM supplementation also reduced markers of inflammation (p≤0.05). About 28%, 35% and 23% of the women were found to be anemic at GW14, GW30 and both time points, respectively. The prevalence of anemia was 5% and 15% in 4.5 and 9 years old children, respectively. The adjusted odds of having anemia in 9 year old children was 3-fold higher if their mothers were anemic at both GW14 and GW30 [Odds Ratio (OR) = 3.05; 95% Confidence Interval (CI) 1.42, 6.14, P = 0.002] or even higher if they were also anemic at 4.5 years of age [OR = 5.92; 95% CI 2.64, 13.25; P<0.001].ConclusionMaternal micronutrient supplementation imparted beneficial effects on child health. Anemia during pregnancy and early childhood are important risk factors for the occurrence of anemia in school-age children.

Maternal antenatal multiple micronutrient supplementation for long-term health benefits in children: a systematic review and meta-analysis.

BackgroundMultiple micronutrient supplementation for pregnant women reduces low birth weight and has been recommended in low- and middle-income countries (LMICs) to improve child survival, growth and health. We aimed to review the evidence from long-term follow-up studies of multiple micronutrient supplementation beginning in the later first or second trimester.MethodsWe searched systematically for follow-up reports from all trials in a 2015 Cochrane review of multiple micronutrient supplementation in pregnancy. The intervention comprised three or more micronutrients and the comparison group received iron (60 mg) and folic acid (400 μg), where possible. Median gestation of commencement varied from 9 to 23 weeks. Primary outcomes were offspring mortality, height, weight and head circumference, presented as unadjusted differences in means or proportions (intervention minus control). Secondary outcomes included other anthropometry, body composition, blood pressure, and cognitive and lung function.ResultsWe found 20 follow-up reports from nine trials (including 88,057 women recruited), six of which used the UNIMMAP supplement designed to provide recommended daily allowances. The age of follow-up ranged from 0 to 9 years. Data for mortality estimates were available from all trials. Meta-analysis showed no difference in mortality (risk difference –0.05 per 1000 livebirths; 95 % CI, –5.25 to 5.15). Six trials investigated anthropometry and found no difference at follow-up in weight-for-age z score (0.02; 95 % CI, –0.03 to 0.07), height-for-age z score (0.01; 95 % CI, –0.04 to 0.06), or head circumference (0.11 cm; 95 % CI, –0.03 to 0.26). No differences were seen in body composition, blood pressure, or respiratory outcomes. No consistent differences were seen in cognitive function scores.ConclusionsThere is currently no evidence that, compared with iron and folic acid supplementation, routine maternal antenatal multiple micronutrient supplementation improves childhood survival, growth, body composition, blood pressure, respiratory or cognitive outcomes.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-016-0633-3) contains supplementary material, which is available to authorized users.

Maternal supplementation of omega-3 fatty acids and micronutrients reduces cardiometabolic variables in pregnancy induced hypertension rats

AimsReports indicate that during pregnancy hypertension is known to have long term adverse effects both in the mother and offspring. However, the effect of maternal micronutrient supplementation on this association of in utero exposure and risk of non-communicable diseases in the later life remains unclear. The present study examines the effect of maternal micronutrient and omega-3 fatty acid supplementation either individual or in combination on cardiometabolic risk factors both in the mother and offspring using an animal model of hypertension. Main methodsPregnant Wistar rats were randomly assigned to the following groups; control, PIH (Pregnancy induced hypertention) Induced, PIH+vitamin B12, PIH+ folic acid, PIH+omega-3 fatty acids and PIH+combined smicronutrient supplementation (vitamin B12+folic acid + omega-3 fatty acids). The dams and their offspring were shifted to a control diet after delivery and the offspring continued on these diets till 3mo of age. Hypertension during pregnancy was induced using l-Nitroarginine methylester (50mg/kgbody weight/day). Key findingsOmega-3 fatty acid supplementation during pregnancy demonstrated lower levels (p<0.05) of plasma cholesterol while a combined supplementation of folic acid, vitamin B12 and omega 3 fatty acids demonstrated lower (p<0.05) triglyceride levels as compared to PIH induced dams. PIH induction increased (p<0.01) the triglyceride levels in the offspring at 3mo of age and maternal supplementation of either individual or combined micronutrients demonstrated lower (p<0.01) triglyceride levels. SignificanceOur findings have implications for planning intervention studies in women with pregnancy induced hypertension.

Patterns of Fetal Growth Based on Ultrasound Measurement and its Relationship with Small for Gestational Age at Birth in Rural Vietnam.

Small for gestational age (SGA) is a global health problem. Identifying the timing of fetal growth faltering is critical for developing preventive interventions. We aim to describe patterns of fetal growth and to predict SGA at birth using fetal ultrasound measurements. We studied 1412 pregnant women enrolled in a randomised-controlled trial evaluating maternal micronutrient supplementation in Thai Nguyen province, Vietnam. Ultrasound examinations included biparietal diameter (BPD), head circumference (HC) and abdominal circumference (AC), and femur length (FL). Measures were assessed using the new international fetal growth standards (INTERGROWTH-21st Project). Generalised linear mixed logit regression models were used to examine the association between ultrasound measures and SGA at birth. Overall fetal growth restriction began in early pregnancy and continued through delivery, but the timing of growth faltering varied by measure: it began by 20 weeks for HC, BPD and AC, earlier as compared to FL growth that started >30 weeks. SGA infants had significantly lower mean fetal growth parameters as early as 14 weeks. Ultrasound measures below the 10th percentile were associated with a two to four times higher risk of SGA at birth compared to fetuses greater than the 50th percentile, with the largest odds ratios for AC (OR 3.9, 95% confidence interval (CI) 2.7, 5.7). Fetal growth faltering by ultrasound begins in early gestation among rural Vietnamese populations; these patterns clearly identified those to be born SGA. Efforts to prevent fetal growth faltering must begin early in pregnancy and perhaps even before pregnancy.

Blood pressure and the capacity-load model in 8-year-old children from Nepal: Testing the contributions of kidney size and intergenerational effects.

ObjectivesGrowth patterns in early life are increasingly linked with subsequent cardio-metabolic risk, but the underlying mechanisms require elucidation. We have developed a theoretical model of blood pressure, treating it as a function of homeostatic metabolic capacity, and antagonistic metabolic load. We sought to differentiate prenatal and postnatal components of metabolic capacity, and to identify intergenerational contributions to offspring capacity and load.MethodsWe followed up at 8 years a cohort of children originally recruited into a randomized trial of maternal micronutrient supplementation in pregnancy. Maternal anthropometry was measured at recruitment. Offspring anthropometry was measured at birth, 2 years and 8 years. Offspring blood pressure, kidney size, and body composition were measured at 8 years. Regression analysis was used to investigate potential associations of maternal phenotype, birth phenotype, and current body composition with kidney size and blood pressure.ResultsBlood pressure was positively associated with body fat, but negatively associated with birth weight and relative leg length. Kidney size was positively associated with birth weight but not with relative leg length. Adjusting for adiposity, blood pressure was independently negatively associated with birth weight, relative leg length, and kidney length. Maternal height and BMI predicted offspring size at birth and at 8 years, but not blood pressure.ConclusionsOur data provide support for the capacity-load model of blood pressure in Nepalese children. Fetal and postnatal growth and kidney dimensions all contribute to metabolic capacity. Maternal phenotype contributed to offspring capacity and load, but these associations did not propagate to blood pressure.

A Plasma α-Tocopherome Can Be Identified from Proteins Associated with Vitamin E Status in School-Aged Children of Nepal1–3

Background: The term vitamin E describes a family of 8 vitamers, 1 of which is α-tocopherol, that is essential for human health. Vitamin E status remains largely unknown in low-income countries because of the complexity and cost of measurement. Quantitative proteomics may offer an approach for identifying plasma proteins for assessing vitamin E status in these populations.Objective: To improve options for vitamin E status assessment, we sought to detect and quantify a set of plasma proteins associated with α- and γ-tocopherol concentrations in a cohort of 500 rural Nepalese children aged 6–8 y and, based on nutrient-protein associations, to predict the prevalence of vitamin E deficiency (α-tocopherol <12 μmol/L).Methods: Study children were born to mothers enrolled in an earlier antenatal micronutrient trial in Sarlahi District, Nepal. Plasma α- and γ-tocopherol concentrations were measured by high-performance liquid chromatography. Plasma aliquots were depleted of 6 high-abundance proteins, digested with trypsin, labeled with isobaric mass tags, and assessed for relative protein abundance by tandem mass spectrometry. Linear mixed-effects models were used to evaluate the association between α-tocopherol status and relative protein abundance and to predict deficiency.Results: We quantified 982 plasma proteins in >10% of all child samples, of which 119 correlated with α-tocopherol (false discovery rate,q < 0.10). Proteins were primarily involved in lipid transport, coagulation, repair, innate host defenses, neural function, and homeostasis. Six proteins [apolipoprotein (apo)C-III; apoB; pyruvate kinase, muscle; forkhead box 04; unc5 homolog C; and regulator of G-protein signaling 8] explained 71% of the variability in plasma α-tocopherol, predicting an in-sample population prevalence of vitamin E deficiency of 51.4% (95% CI: 46.4%, 56.3%) compared with a measured prevalence of 54.8%. Plasma γ-tocopherol was associated with 12 proteins (q < 0.10), 2 of which (apoC-III and Misato 1) explained 20% of its variability.Conclusions: In this undernourished population of children in South Asia, quantitative proteomics identified a large plasma α-tocopherome from which 6 proteins predicted the prevalence of vitamin E deficiency. The findings illustrate that protein biomarkers, once absolutely quantified, can potentially predict micronutrient deficiencies in populations. The maternal micronutrient supplementation trial from which data were derived as a follow-up activity was registered withclinicaltrials.gov as NCT00115271.

The association between third trimester multivitamin/mineral supplements and gestational length in uncomplicated pregnancies.

Widespread use of maternal micronutrient supplements have been correlated to gestational length and outcome in women predisposed to pre-eclampsia and preterm birth. However, research is yet to be conducted examining the influence of micronutrient supplements on outcomes at term in uncomplicated pregnancies. To analyse the relationship between third trimester micronutrient supplementation and gestation length at birth, demographics and maternal birthing outcomes in well women at term in a South East Queensland representative population. This research retrospectively analysed existing data pertaining to 427 uncomplicated, pregnancies birthing at the Gold Coast and Logan Hospitals using information gathered through the Environments for Healthy Living Study and Queensland perinatal data collection. Data were analysed using SPSS v20 by Chi square, ANOVA and regression analysis. Women in the third trimester taking individual zinc, folic acid or iron supplements in combination with a multivitamin were twice as likely to birth beyond 41 completed weeks (AOR 2.054, 95% CI 1.310-7.383, p=0.038) then those who did not take any supplement when controlled for established confounders. Non supplement users were found to experience a lower rate of post dates labour and requirements for induction (AOR 0.483, 95% CI 0.278-0.840, p=0.01). Length of gestation demonstrates significant associations with micronutrient supplementation practices. Well women consuming third trimester individual micronutrient supplements in addition to multivitamins experienced a longer gestation at term compared to women taking no micronutrients, increasing their risk for postdates induction of labour.

The long term impact of maternal multiple micronutrient supplementation, infant nutrition and health on visual acuity of 9‐12 year old children in Indonesia

The impact of the prenatal nutrition and neonatal health on visual acuity (VA) remains unknown. We investigated the long term relative impact of maternal multiple micronutrient (MMN) versus iron‐folic acid (IFA) supplementation on VA of 9‐12 years old school children, and explored the long term effects of birth weight, preterm birth, and stunting on VA. We assessed VA of 3,398 children of mothers who had participated in the Supplementation with Multiple Micronutrients Intervention Trial (SUMMIT), a cluster‐randomized trial of MMN versus IFA in Indonesia. Multivariate logistic regression was used to assess whether of MMN, child age, gender, socio‐economic status (SES), preterm birth, birth weight or stunting were related to VA. There was no siginificant long term impact of maternal MMN supplementation on VA in school age children. We found significant effects of birth weight on VA of the left eye (p=0.03) and left eye with pinhole assessments (p=0.01), and effects of stunting on VA of the left eye (p=0.04) and for both eyes (p=0.04), and of SES on VA for the right eye (p=0.04). No significant effects were observed for preterm birth, age and gender. There were no siginificant effects of maternal MMN and IFA supplementation on VA in 9‐12 years old school children, but there were significant effects of birth weight, stunting and SES on VA.

Maternal Multiple Micronutrient Supplementation and Children's Cognition at Age 9‐12 Years in Indonesia

Many micronutrients, including zinc, iodine, and B‐vitamins, are needed for the rapid brain development that occurs during gestation and infancy, laying a foundation for lifelong brain function. Few studies have examined the long‐term cognitive effects of maternal multiple micronutrient (MMN) supplements, compared to the current practice in many countries of iron and folic acid (IFA) supplementation. In 2001‐2004, in the SUMMIT trial, midwives in Indonesia were randomly assigned to distribute daily IFA or MMN from pregnancy through three months postpartum. We tested 3687 children of SUMMIT participants at 9‐12 years of age. Adjusting for midwife cluster, data collector, child age and gender, and home environment, children of mothers given MMN scored higher in visual attention (B=0.11, p &lt; .01) and arithmetic (B=0.10, p=.05) compared to IFA. We observed positive effects on verbal ability (B=0.17, p=.02) in children of mothers who were undernourished at enrollment and on sustained attention (B=0.10, p=.04) and letter/word recognition (B=0.23, p=.04) in children of mothers who were anemic, consistent with previously observed effects on pre‐school cognition in these groups. We found positive effects on speed of sentence reading in children of well‐nourished mothers (B=0.11, p = .04), consistent with effects on birth weight in this group. No effects were found on fine motor ability, socio‐emotional scores, or several measures of executive function.Funded by Grand Challenges Canada

Can Prevention of Low Birth Weight in Newborn may be Associated with Primordial Prevention of Cardiovascular Diseases and Type 2 Diabetes in Adult Life?

Poor nutrition during pregnancy may be a risk factor for low birth weight and for irreversible health issues including obesity, type 2 diabetes, hypertension and hypercholesterolemia in adult life. Low birth weight has also been related to greater mortality from coronary artery disease(CAD) and type 2 diabetes in adult life. One earlier study from Northern Europe proposed that poor social conditions in childhood may be risk factor for obesity, diabetes and cardiovascular diseases (CVDs) in later life. It is possible that multiple confounders related to energy and micronutrient deficiencies may be interacting in the process of adaptations in critical time periods, during fetal, postnatal and child development. A review of literature on the effects on birth size and length of babies and of multiple micronutrient supplementation during pregnancy in low-income countries indicates that incidence of low birth weight may be decreased by supplementation of about 15 micronutrients. This finding poses the possibility that for prevention of low birth weight, maternal micronutrient supplementation (15-20 nutrients) may be an important strategy. It is proposed that this strategy may lead the prevention of CVDs and type 2 diabetes in adult life. Cohort studies and long term follow up population based trials are needed to confirm this hypothesis.

Effect of maternal multiple micronutrient vs iron-folic acid supplementation on infant mortality and adverse birth outcomes in rural Bangladesh: the JiVitA-3 randomized trial.

Maternal micronutrient deficiencies may adversely affect fetal and infant health, yet there is insufficient evidence of effects on these outcomes to guide antenatal micronutrient supplementation in South Asia. To assess effects of antenatal multiple micronutrient vs iron-folic acid supplementation on 6-month infant mortality and adverse birth outcomes. Cluster randomized, double-masked trial in Bangladesh, with pregnancy surveillance starting December 4, 2007, and recruitment on January 11, 2008. Six-month infant follow-up ended August 30, 2012. Surveillance included 127,282 women; 44,567 became pregnant and were included in the analysis and delivered 28,516 live-born infants. Median gestation at enrollment was 9 weeks (interquartile range, 7-12). Women were provided supplements containing 15 micronutrients or iron-folic acid alone, taken daily from early pregnancy to 12 weeks postpartum. The primary outcome was all-cause infant mortality through 6 months (180 days). Prespecified secondary outcomes in this analysis included stillbirth, preterm birth (<37 weeks), and low birth weight (<2500 g). To maintain overall significance of α = .05, a Bonferroni-corrected α = .01 was calculated to evaluate statistical significance of primary and 4 secondary risk outcomes (.05/5). Among the 22,405 pregnancies in the multiple micronutrient group and the 22,162 pregnancies in the iron-folic acid group, there were 14,374 and 14,142 live-born infants, respectively, included in the analysis. At 6 months, multiple micronutrients did not significantly reduce infant mortality; there were 764 deaths (54.0 per 1000 live births) in the iron-folic acid group and 741 deaths (51.6 per 1000 live births) in the multiple micronutrient group (relative risk [RR], 0.95; 95% CI, 0.86-1.06). Multiple micronutrient supplementation resulted in a non-statistically significant reduction in stillbirths (43.1 vs 48.2 per 1000 births; RR, 0.89; 95% CI, 0.81-0.99; P = .02) and significant reductions in preterm births (18.6 vs 21.8 per 100 live births; RR, 0.85; 95% CI, 0.80-0.91; P < .001) and low birth weight (40.2 vs 45.7 per 100 live births; RR, 0.88; 95% CI, 0.85-0.91; P < .001). In Bangladesh, antenatal multiple micronutrient compared with iron-folic acid supplementation did not reduce all-cause infant mortality to age 6 months but resulted in a non-statistically significant reduction in stillbirths and significant reductions in preterm births and low birth weight. clinicaltrials.gov Identifier: NCT00860470.

Perinatal maternal feeding with an energy dense diet and/or micronutrient mixture drives offspring fat distribution depending on the sex and growth stage.

Maternal nutrition during pregnancy and lactation influences offspring development and health. Novel studies have described the effects on next generation obesity-related features depending on maternal macro- and micro-nutrient perinatal feeding. We hypothesized that the maternal obesogenic diet during pregnancy and lactation programs an obese phenotype, while maternal micronutrient supplementation at these stages could partially prevent these features. Thus, the aim was to assess the influence of a perinatal maternal feeding with an obesogenic diet enriched in fat and sucrose and a micronutrient supplementation during pregnancy and lactation on offspring growth and obese phenotypical features during life course. Female Wistar rats were assigned to four dietary groups during pregnancy and lactation: control, control supplemented with micronutrients (choline, betaine, folic acid and vitamin B12 ), high-fat sucrose (HFS) and HFS supplemented. At weaning, the offspring were transferred to a chow diet, and weight and fat mass were measured at weeks 3, 12 and 20. At birth, both male and female offspring from mothers fed the obesogenic diet showed lower body weight (-5 and -6%, respectively), while only female offspring weight decreased by maternal micronutrient supplementation (-5%). During lactation, maternal HFS diet was associated with increased body weight, while micronutrient supplementation protected against body weight gain. Whole body fat mass content increased at weeks 3, 12 and 20 (from 16 to 65%) due to maternal HFS diet. Maternal micronutrient supplementation decreased offspring fat mass content at week 3 (-8%). Male offspring showed higher adiposity than females at weeks 12 and 20. In conclusion, maternal HFS feeding during pregnancy and lactation was associated with a low offspring weight at birth and obese phenotypical features during adult life in a sex- and time-dependent manner. Furthermore, maternal methyl donor supplementation protected against body weight gain in male offspring during lactation and in female offspring also during juvenile period.