A Randomized Multiple Micronutrient Powder Point-of-Use Fortification Trial Implemented in Indian Preschools Increases Expressive Language and Reduces Anemia and Iron Deficiency.

BACKGROUND: Anemia is a global public health problem that undermines childhood development. India provides government-sponsored integrated nutrition/child development preschools. OBJECTIVES: This double-masked, cluster-randomized controlled trial examines whether point-of-use multiple micronutrient powder (MNP) compared with placebo fortification of preschool meals impacts child development and whether effects vary by preschool quality (primary outcome) and biomarkers of anemia and micronutrients (secondary outcomes). We also measured growth and morbidity. METHODS: We randomly assigned 22 preschools in rural India to receive MNP/placebo fortification. We administered baseline and endline blood sampling and measures of childhood development (Mullen Scales of Early Learning, inhibitory control, social-emotional), anthropometry, and morbidity to preschoolers (aged 29-49 mo). Preschools added MNP/placebo to meals 6 d/wk for 8 mo. We conducted linear mixed-effects regression models accounting for preschool clustering and repeated measures. We evaluated child development, examining effects in high- compared with low-quality preschools using the Early Childhood Environment Rating Scale-Revised and the Home Observation for the Measurement of the Environment Inventory, modified for preschools. RESULTS: At baseline, mean age ± SD was 36.6 ± 5.7 mo, with 47.8% anemic, 41.9% stunted, and 20.0% wasted. Baseline expressive/receptive language scores were higher in high-quality compared with low-quality preschools (P = 0.02 and P = 0.03, respectively). At endline (91% retention, n = 293/321), we found MNP compared with placebo effects in expressive language (Cohen's standardized effect d = 0.4), inhibitory control (d = 0.2), and social-emotional (d = 0.3) in low-quality, not high-quality, preschools. MNP had significantly greater reduction of anemia and iron deficiency compared with placebo (37% compared with 13.5% and 41% compared with 1.2%, respectively). There were no effects on growth or morbidity. CONCLUSIONS: Providing multiple micronutrient-fortified meals in government-sponsored preschools is feasible; reduced anemia and iron deficiency; and, in low-quality preschools, increased preschoolers' expressive language and inhibitory control and reduced developmental disparities. Improving overall preschool quality by incorporating multiple components of nurturing care (responsive care, learning, and nutrition) may be necessary to enhance preschoolers' development. This trial was registered at clinicaltrials.gov as NCT01660958.

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

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

Comparison of two forms of daily preventive zinc supplementation versus therapeutic zinc supplementation for diarrhea on young children's physical growth and risk of infection: study design and rationale for a randomized controlled trial.

BACKGROUND: Zinc is an essential nutrient that is required for children's normal growth and resistance to infections, including diarrhea and pneumonia, two major causes of child mortality. Daily or weekly preventive zinc supplementation has been shown to improve growth and reduce the risk of infection, while therapeutic zinc supplementation for 10-14 days is recommended for the treatment of diarrhea. The overall objective of the present study is to compare several regimens for delivering zinc to young children, both for the prevention of zinc deficiency and the treatment of diarrhea. METHODS: The present study is a community-based, randomized controlled trial in the Lao People's Democratic Republic (PDR). Three thousand, four hundred children 6-23 months of age will be randomized to one of four intervention groups (daily preventive zinc dispersible tablet, daily preventive multiple micronutrient powder, therapeutic zinc dispersible tablet for diarrhea, or placebo control); interventions will be delivered for 9 months and outcomes measured at pre-determined intervals. Primary outcomes include physical growth (length and weight), diarrhea incidence, hemoglobin and micronutrient status, and innate and adaptive immune function. Secondary outcomes include mid-upper-arm circumference, neuro-behavioral development, hair cortisol concentrations, markers of intestinal inflammation and parasite burden. Incidence of adverse events and the modifying effects of inherited hemoglobin disorders and iron status on the response to the intervention will also be examined. We will estimate unadjusted effects and effects adjusted for selected baseline covariates using ANCOVA. DISCUSSION: Many countries are now rolling out large-scale programs to include therapeutic zinc supplementation in the treatment of childhood diarrhea, but few have established programs demonstrated to be effective in the prevention of zinc deficiency. This study will address how best to deliver supplemental zinc to prevent zinc deficiency and reduce the severity of diarrhea-related health complications. TRIAL REGISTRATION: Trial registration identifier (NCT02428647) ; Date of registration: April 29, 2015.

Impact of preconceptional micronutrient supplementation on maternal mental health during pregnancy and postpartum: results from a randomized controlled trial in Vietnam.

BACKGROUND: Micronutrient malnutrition has been associated with maternal depressive symptoms (MDS), but little is known about the effects of preconceptional micronutrient supplementation. This paper examined the effects of preconceptional micronutrient supplementation on MDS during pregnancy and postpartum. METHODS: We used data from a double-blind controlled trial (PRECONCEPT) in which 5011 Vietnamese women were randomized to receive weekly supplements containing either a) multiple micronutrients (MM) b) iron and folic acid (IFA) or c) folic acid (FA) until conception (n = 1813). Maternal mental health was assessed using the Center for Epidemiologic Studies Depression Scale (CES-D) at baseline (preconception), and the Edinburgh Postnatal Depression Scale (EPDS) during pregnancy and 3 months postpartum. Elevated MDS was defined as EPDS score ≥ 4. All group comparisons were done using ANOVA or chi-square tests of proportions intention to treat and per protocol analyses (women consumed supplements ≥26 weeks before conception). We also conducted stratified analyses by preconception CES-D scores, underweight, or anemia status using generalized linear models. RESULTS: Baseline CES-D scores were similar across treatment groups. The proportion of women experiencing elevated MDS was 11.3, 8.1 and 4.9% at first, second and third trimesters of pregnancy, respectively, and 3.6% at 3 mo postpartum. Mean EPDS scores at first (1.5 ± 2.7), second (1.1 ± 2.4), and third trimester of pregnancy (0.7 ± 2.0) and early postpartum (0.6 ± 1.8) were low and did not differ by treatment group. However, among women in the highest tertile of CES-D scores at preconception, mean EPDS scores in the first and second trimesters of pregnancy were lower in the MM and IFA groups compared to FA only (P < 0.05). CONCLUSIONS: Weekly preconceptional micronutrient supplements containing iron did not improve depression measures relative to folic acid alone among all women, but may have benefitted women who were at risk for depression. TRIAL REGISTRATION: The trial was registered retrospectively at ClinicalTrials.Gov as NCT01665378 on August 13, 2012.

Predictors of adherence to micronutrient supplementation before and during pregnancy in Vietnam.

BACKGROUND: Poor adherence to micronutrient supplementation often limits the effectiveness of public health programs. While predictors of adherence to micronutrient supplementation during pregnancy are well documented, information on adherence to preconception supplements is scarce. The objective of this study was to describe the predictors of adherence to preconception and prenatal micronutrient supplementation among women participating in a randomized control trial in Vietnam. METHODS: Adherence data were collected prospectively from a double blind randomized controlled trial in rural Vietnam. Five thousand eleven women of reproductive age were randomized to receive preconception supplements for weekly consumption containing either: Folic Acid, Iron and Folic Acid (IFA), or Multiple Micronutrients. Women who became pregnant received prenatal IFA supplements for daily consumption through delivery. Village health workers visited participants' homes every two weeks to deliver supplements and record consumption and side effects. Multivariate logistic regression was used to assess individual, household, and programmatic predictors of supplement adherence. RESULTS: Adherence was high with 78 and 82% of the women consuming more than 80% of the preconception and prenatal supplements, respectively. Women of minority ethnicity (OR = 0.78 95% CI = 0.67, 0.91) and farmers (OR = 0.71 95% CI = 0.58, 0.88) were less likely to consume >80% of the preconception supplements while socioeconomic status (SES) (OR = 2.71 highest vs. lowest quintile; 95% CI = 2.10, 3.52) was positively associated with >80% adherence in the entire preconception sample with available information (n = 4417). Women in their first pregnancy had lower prenatal adherence compared to multiparous women. At the programmatic level, each village health worker visit was associated with higher odds of >80% adherence by 3-5% before pregnancy and 18% during pregnancy. CONCLUSIONS: Key determinants of adherence included SES, ethnicity, occupation (farmer) and parity which may be helpful for targeting women for counseling on supplement adherence. Increased contact with village health workers was positively associated with adherence to micronutrient supplementation both before conception and during pregnancy indicating the need for resources to support community outreach to women of reproductive age. TRIAL REGISTRATION: NCT01665378 . Registered on August 12, 2012.

The effect of oral iron with or without multiple micronutrients on hemoglobin concentration and hemoglobin response among nonpregnant Cambodian women of reproductive age: a 2 x 2 factorial, double-blind, randomized controlled supplementation trial.

Background: Despite a high prevalence of anemia among nonpregnant Cambodian women, current reports suggest that iron deficiency (ID) prevalence is low. If true, iron supplementation will not be an effective anemia reduction strategy.Objective: We measured the effect of daily oral iron with or without multiple micronutrients (MMNs) on hemoglobin concentration in nonpregnant Cambodian women screened as anemic.Design: In this 2 × 2 factorial, double-blind, randomized trial, nonpregnant women (aged 18-45 y) with hemoglobin concentrations ≤117 g/L (capillary blood) were recruited from 26 villages in Kampong Chhnang province and randomly assigned to receive 12 wk of iron (60 mg; Fe group), MMNs (14 other micronutrients; MMN group), iron plus MMNs (Fe+MMN group), or placebo capsules. A 2 × 2 factorial intention-to-treat analysis with the use of a generalized mixed-effects model was used to assess the effects of iron and MMNs and the interaction between these factors. Results: In July 2015, 809 women were recruited and 760 (94%) completed the trial. Baseline anemia prevalence was 58% (venous blood). Mean (95% CI) hemoglobin concentrations at 12 wk in the Fe, MMN, Fe+MMN, and placebo groups were 121 (120, 121), 116 (116, 117), 123 (122, 123), and 116 (116, 117) g/L, with no iron × MMN interaction (P = 0.66). Mean (95% CI) increases in hemoglobin were 5.6 g/L (3.8, 7.4 g/L) (P < 0.001) among women who received iron (n = 407) and 1.2 g/L (-0.6, 3.0 g/L) (P = 0.18) among women who received MMNs (n = 407). The predicted proportions (95% CIs) of women with a hemoglobin response (≥10 g/L at 12 wk) were 19% (14%, 24%), 9% (5%, 12%), 30% (24%, 35%), and 5% (2%, 9%) in the Fe, MMN, Fe+MMN, and placebo groups, respectively.Conclusions: Daily iron supplementation for 12 wk increased hemoglobin in nonpregnant Cambodian women; however, MMNs did not confer additional significant benefit. Overall, ∼24% of women who received iron responded after 12 wk; even fewer would be likely to respond in the wider population. This trial was registered at clinicaltrials.gov as NCT02481375.

Iodine supplementation for women during the preconception, pregnancy and postpartum period.

BACKGROUND: Iodine is an essential nutrient required for the biosynthesis of thyroid hormones, which are responsible for regulating growth, development and metabolism. Iodine requirements increase substantially during pregnancy and breastfeeding. If requirements are not met during these periods, the production of thyroid hormones may decrease and be inadequate for maternal, fetal and infant needs. The provision of iodine supplements may help meet the increased iodine needs during pregnancy and the postpartum period and prevent or correct iodine deficiency and its consequences. OBJECTIVES: To assess the benefits and harms of supplementation with iodine, alone or in combination with other vitamins and minerals, for women in the preconceptional, pregnancy or postpartum period on their and their children's outcomes. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register (14 November 2016), and the WHO International Clinical Trials Registry Platform (ICTRP) (17 November 2016), contacted experts in the field and searched the reference lists of retrieved studies and other relevant papers. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials with randomisation at either the individual or cluster level comparing injected or oral iodine supplementation (such as tablets, capsules, drops) during preconception, pregnancy or the postpartum period irrespective of iodine compound, dose, frequency or duration. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility, risk of bias, extracted data and conducted checks for accuracy. We used the GRADE approach to assess the quality of the evidence for primary outcomes.We anticipated high heterogeneity among trials, and we pooled trial results using random-effects models and were cautious in our interpretation of the pooled results. MAIN RESULTS: We included 14 studies and excluded 48 studies. We identified five ongoing or unpublished studies and two studies are awaiting classification. Eleven trials involving over 2700 women contributed data for the comparisons in this review (in three trials, the primary or secondary outcomes were not reported). Maternal primary outcomesIodine supplementation decreased the likelihood of the adverse effect of postpartum hyperthyroidism by 68% (average risk ratio (RR) 0.32; 95% confidence interval (CI) 0.11 to 0.91, three trials in mild to moderate iodine deficiency settings, 543 women, no statistical heterogeneity, low-quality evidence) and increased the likelihood of the adverse effect of digestive intolerance in pregnancy by 15 times (average RR 15.33; 95% CI 2.07 to 113.70, one trial in a mild-deficiency setting, 76 women, very low-quality evidence).There were no clear differences between groups for hypothyroidism in pregnancy or postpartum (pregnancy: average RR 1.90; 95% CI 0.57 to 6.38, one trial, 365 women, low-quality evidence, and postpartum: average RR 0.44; 95% CI 0.06 to 3.42, three trials, 540 women, no statistical heterogeneity, low-quality evidence), preterm birth (average RR 0.71; 95% CI 0.30 to 1.66, two trials, 376 women, statistical heterogeneity, low-quality evidence) or the maternal adverse effects of elevated thyroid peroxidase antibodies (TPO-ab) in pregnancy or postpartum (average RR 0.95; 95% CI 0.44 to 2.07, one trial, 359 women, low-quality evidence, average RR 1.01; 95% CI 0.78 to 1.30, three trials, 397 women, no statistical heterogeneity, low-quality evidence), or hyperthyroidism in pregnancy (average RR 1.90; 95% CI 0.57 to 6.38, one trial, 365 women, low-quality evidence). All of the trials contributing data to these outcomes took place in settings with mild to moderate iodine deficiency. Infant/child primary outcomesCompared with those who did not receive iodine, those who received iodine supplements had a 34% lower likelihood of perinatal mortality, however this difference was not statistically significant (average RR 0.66; 95% CI 0.42 to 1.03, two trials, 457 assessments, low-quality evidence). All of the perinatal deaths occurred in one trial conducted in a severely iodine-deficient setting. There were no clear differences between groups for low birthweight (average RR 0.56; 95% CI 0.26 to 1.23, two trials, 377 infants, no statistical heterogeneity, low-quality evidence), neonatal hypothyroidism/elevated thyroid-stimulating hormone (TSH) (average RR 0.58; 95% CI 0.11 to 3.12, two trials, 260 infants, very low-quality evidence) or the adverse effect of elevated neonatal thyroid peroxidase antibodies (TPO-ab) (average RR 0.61; 95% CI 0.07 to 5.70, one trial, 108 infants, very low-quality evidence). All of the trials contributing data to these outcomes took place in areas with mild to moderate iodine deficiency. No trials reported on hypothyroidism/elevated TSH or any adverse effect beyond the neonatal period. AUTHORS' CONCLUSIONS: There were insufficient data to reach any meaningful conclusions on the benefits and harms of routine iodine supplementation in women before, during or after pregnancy. The available evidence suggested that iodine supplementation decreases the likelihood of postpartum hyperthyroidism and increases the likelihood of the adverse effect of digestive intolerance in pregnancy - both considered potential adverse effects. We considered evidence for these outcomes low or very low quality, however, because of study design limitations and wide confidence intervals. In addition, due to the small number of trials and included women in our meta-analyses, these findings must be interpreted with caution. There were no clear effects on other important maternal or child outcomes though these findings must also be interpreted cautiously due to limited data and low-quality trials. Additionally, almost all of the evidence came from settings with mild or moderate iodine deficiency and therefore may not be applicable to settings with severe deficiency.More high-quality randomised controlled trials are needed on iodine supplementation before, during and after pregnancy on maternal and infant/child outcomes. However, it may be unethical to compare iodine to placebo or no treatment in severe deficiency settings. Trials may also be unfeasible in settings where pregnant and lactating women commonly take prenatal supplements with iodine. Information is needed on optimal timing of initiation as well as supplementation regimen and dose. Future trials should consider the outcomes in this review and follow children beyond the neonatal period. Future trials should employ adequate sample sizes, assess potential adverse effects (including the nature and extent of digestive intolerance), and be reported in a way that allows assessment of risk of bias, full data extraction and analysis by the subgroups specified in this review.

Impact of Preconception Micronutrient Supplementation on Anemia and Iron Status during Pregnancy and Postpartum: A Randomized Controlled Trial in Rural Vietnam.

OBJECTIVE: Preconception micronutrient interventions may be a promising approach to reduce anemia and iron deficiency during pregnancy, but currently we have limited data to inform policies. We evaluated whether providing additional pre-pregnancy weekly iron-folic acid (IFA) or multiple micronutrient (MM) supplements compared to only folic acid (FA) improves iron status and anemia during pregnancy and early postpartum. METHODS: We conducted a double blind randomized controlled trial in which 5011 Vietnamese women were provided with weekly supplements containing either only 2800 µg FA (control group), IFA (60 mg Fe and 2800 µg FA) or MM (15 micronutrients with similar amounts of IFA). All women who became pregnant (n = 1813) in each of the 3 groups received daily IFA (60 mg Fe and 400 µg FA) through delivery. Hematological indicators were assessed at baseline (pre-pregnancy), during pregnancy, 3 months post-partum, and in cord blood. Adjusted generalized linear models were applied to examine the impact of preconception supplementation on anemia and iron stores, using both intention to treat and per protocol analyses (women consumed supplements ≥ 26 weeks before conception). RESULTS: At baseline, 20% of women were anemic, but only 14% had low iron stores (ferritin <30 µg/L) and 3% had iron deficiency (ferritin <12 µg/L). The groups were balanced for baseline characteristics. Anemia prevalence increased during pregnancy and post-partum but was similar among intervention groups. In intention to treat analyses, prenatal ferritin was significantly higher among women receiving MM (geometric mean (µg/L) [95% CI]: 93.6 [89.3-98.2]) and IFA (91.9 [87.6-96.3]) compared to control (85.3 [81.5-89.2]). In per protocol analyses, women receiving MM or IFA had higher ferritin 3 months postpartum (MM 118.2 [109.3-127.8]), IFA 117.8 [108.7-127.7] vs control 101.5 [94.0-109.7]) and gave birth to infants with greater iron stores (MM 184.3 [176.1-192.9]), IFA 189.9 [181.6-198.3] vs control 175.1 [167.9-182.6]). CONCLUSION: Preconception supplementation with MM or IFA resulted in modest increases in maternal and infant iron stores but did not impact anemia. Further research is needed to characterize the etiology of anemia in this population and identify effective interventions for reducing prenatal anemia. TRIAL REGISTRATION: ClinicalTrials.Gov NCT01665378.

Neither Preconceptional Weekly Multiple Micronutrient nor Iron-Folic Acid Supplements Affect Birth Size and Gestational Age Compared with a Folic Acid Supplement Alone in Rural Vietnamese Women: A Randomized Controlled Trial.

BACKGROUND: Maternal nutritional status before and during early pregnancy plays a critical role in fetal growth and development. The benefits of periconception folic acid (FA) supplementation in the prevention of neural tube defects is well recognized, but the evidence for preconception micronutrient interventions for improving pregnancy outcomes is limited. OBJECTIVE: This study aimed to evaluate whether preconception supplementation with weekly iron and folic acid (IFA) or multiple micronutrients (MMs) improves birth outcomes compared with FA alone. METHODS: We recruited 5011 women of reproductive age in a double-blind, randomized controlled trial in Vietnam and provided weekly supplements containing either 2800 µg FA, 60 mg Fe and 2800 µg FA (IFA), or the same amount of FA and iron plus other MMs until they conceived (n = 1813). All pregnant women received daily IFA through delivery, and were followed up for birth outcomes, including birth weight, gestational age, preterm delivery and small for gestational age (SGA). Group comparisons were done with the use of ANOVA or chi-square tests for both intention-to-treat (n = 1599) and per-protocol analyses (women consumed supplements ≥26 wk before conception; n = 824). Effect modification by baseline underweight or anemia status was tested with the use of generalized linear models. RESULTS: The mean age of the women was 26 y, 30% were underweight, and <10% were nulliparous. The groups were similar for most baseline characteristics. The mean ± SD duration of the preconception intervention was 33 ± 25 wk and compliance was high (>90%). Infants born to the 3 groups of women did not differ (P ≥ 0.05) on mean ± SD birth weight (3076.8 ± 444.5 g) or gestational age (39.2 ± 2.0 wk), or prevalence of SGA (12%), low birth weight (5%) and preterm delivery (10%). There were no significant differences in women who consumed supplements ≥26 wk before conception or by baseline underweight or anemia. CONCLUSION: Weekly supplementation with MMs or IFA before conception did not affect birth outcomes compared with FA in rural Vietnamese women. The trial was registered at clinicaltrials.gov as NCT01665378.

Integrating nutrition and early child-development interventions among infants and preschoolers in rural India.

This article describes the development, design, and implementation of an integrated randomized double-masked placebo-controlled trial (Project Grow Smart) that examines how home/preschool fortification with multiple micronutrient powder (MNP) combined with an early child-development intervention affects child development, growth, and micronutrient status among infants and preschoolers in rural India. The 1-year trial has an infant phase (enrollment age: 6-12 months) and a preschool phase (enrollment age: 36-48 months). Infants are individually randomized into one of four groups: placebo, placebo plus early learning, MNP alone, and MNP plus early learning (integrated intervention), conducted through home visits. The preschool phase is a cluster-randomized trial conducted in Anganwadi centers (AWCs), government-run preschools sponsored by the Integrated Child Development System of India. AWCs are randomized into MNP or placebo, with the MNP or placebo mixed into the children's food. The evaluation examines whether the effects of the MNP intervention vary by the quality of the early learning opportunities and communication within the AWCs. Study outcomes include child development, growth, and micronutrient status. Lessons learned during the development, design, and implementation of the integrated trial can be used to guide large-scale policy and programs designed to promote the developmental, educational, and economic potential of children in developing countries.

Iodine and mental development of children 5 years old and under: a systematic review and meta-analysis.

Several reviews and meta-analyses have examined the effects of iodine on mental development. None focused on young children, so they were incomplete in summarizing the effects on this important age group. The current systematic review therefore examined the relationship between iodine and mental development of children 5 years old and under. A systematic review of articles using Medline (1980-November 2011) was carried out. We organized studies according to four designs: (1) randomized controlled trial with iodine supplementation of mothers; (2) non-randomized trial with iodine supplementation of mothers and/or infants; (3) prospective cohort study stratified by pregnant women's iodine status; (4) prospective cohort study stratified by newborn iodine status. Average effect sizes for these four designs were 0.68 (2 RCT studies), 0.46 (8 non-RCT studies), 0.52 (9 cohort stratified by mothers' iodine status), and 0.54 (4 cohort stratified by infants' iodine status). This translates into 6.9 to 10.2 IQ points lower in iodine deficient children compared with iodine replete children. Thus, regardless of study design, iodine deficiency had a substantial impact on mental development. Methodological concerns included weak study designs, the omission of important confounders, small sample sizes, the lack of cluster analyses, and the lack of separate analyses of verbal and non-verbal subtests. Quantifying more precisely the contribution of iodine deficiency to delayed mental development in young children requires more well-designed randomized controlled trials, including ones on the role of iodized salt.

Rationale, design, methodology and sample characteristics for the Vietnam pre-conceptual micronutrient supplementation trial (PRECONCEPT): a randomized controlled study.

BACKGROUND: Low birth weight and maternal anemia remain intractable problems in many developing countries. The adequacy of the current strategy of providing iron-folic acid (IFA) supplements only during pregnancy has been questioned given many women enter pregnancy with poor iron stores, the substantial micronutrient demand by maternal and fetal tissues, and programmatic issues related to timing and coverage of prenatal care. Weekly IFA supplementation for women of reproductive age (WRA) improves iron status and reduces the burden of anemia in the short term, but few studies have evaluated subsequent pregnancy and birth outcomes.The Preconcept trial aims to determine whether pre-pregnancy weekly IFA or multiple micronutrient (MM) supplementation will improve birth outcomes and maternal and infant iron status compared to the current practice of prenatal IFA supplementation only. This paper provides an overview of study design, methodology and sample characteristics from baseline survey data and key lessons learned. METHODS/DESIGN: We have recruited 5011 WRA in a double-blind stratified randomized controlled trial in rural Vietnam and randomly assigned them to receive weekly supplements containing either: 1) 2800 µg folic acid 2) 60 mg iron and 2800 µg folic acid or 3) MM. Women who become pregnant receive daily IFA, and are being followed through pregnancy, delivery, and up to three months post-partum. Study outcomes include birth outcomes and maternal and infant iron status. Data are being collected on household characteristics, maternal diet and mental health, anthropometry, infant feeding practices, morbidity and compliance. DISCUSSION: The study is timely and responds to the WHO Global Expert Consultation which identified the need to evaluate the long term benefits of weekly IFA and MM supplementation in WRA. Findings will generate new information to help guide policy and programs designed to reduce the burden of anemia in women and children and improve maternal and child health outcomes in resource poor settings. TRIAL REGISTRATION: NCT01665378.

Iron deficiency and anemia control for infants and young children in malaria-endemic areas: a call to action and consensus among the research community.

WHO recommendations on iron supplementation for infants and young children in malaria-endemic areas changed dramatically from universal to targeted supplementation for iron-deficient children only, after a trial in a high malaria transmission area showed an increased risk of hospital admission and mortality among iron-replete children following iron and folic acid supplementation. Since this time, there has been much debate and little agreement among the nutrition research community on how to move forward, and country policy and program decision makers have been left with incomplete guidance on how to address young child iron deficiency and anemia in their countries. The focus of a recent symposium during the American Society for Nutrition annual meeting, held in Washington, DC, in April 2011, was on exploring options for addressing iron deficiency and anemia among infants and young children in malaria-endemic areas, now, with safe, effective, and feasible interventions that provide iron. Papers based on the invited presentations are included in this supplement. The first paper is a review of the relationship between iron and malaria. The second is an analysis of theoretical and practical considerations regarding the targeted approach of providing iron and includes results from field testing noninvasive screening devices. This is followed by a review of the safety of universal provision of iron through home-fortification products in malaria-endemic areas. The final papers provide a call to action by highlighting pending research issues (fourth paper) and feasible strategies to move programs forward (fifth paper).