Effect of maternal vitamin D supplementation on nasal pneumococcal acquisition, carriage dynamics and carriage density in infants in Dhaka, Bangladesh.

BACKGROUND: Invasive pneumococcal disease is a major cause of infant morbidity and death worldwide. Vitamin D promotes anti-pneumococcal immune responses in vitro, but whether improvements in infant vitamin D status modify risks of nasal pneumococcal acquisition in early life is not known. METHODS: This is a secondary analysis of data collected in a trial cohort in Dhaka, Bangladesh. Acute respiratory infection (ARI) surveillance was conducted from 0 to 6 months of age among 1060 infants of women randomized to one of four pre/post-partum vitamin D dose combinations or placebo. Nasal swab samples were collected based on standardized ARI criteria, and pneumococcal DNA quantified by qPCR. Hazards ratios of pneumococcal acquisition and carriage dynamics were estimated using interval-censored survival and multi-state modelling. RESULTS: Pneumococcal carriage was detected at least once in 90% of infants by 6 months of age; overall, 69% of swabs were positive (2616/3792). There were no differences between any vitamin D group and placebo in the hazards of pneumococcal acquisition, carriage dynamics, or carriage density (p > 0.05 for all comparisons). CONCLUSION: Despite in vitro data suggesting that vitamin D promoted immune responses against pneumococcus, improvements in postnatal vitamin D status did not reduce the rate, alter age of onset, or change dynamics of nasal pneumococcal colonization in early infancy. Trial registration Registered in ClinicalTrials.gov with the registration number of NCT02388516 and first posted on March 17, 2015.

Randomized Trial of Oral Iron and Diet Advice versus Diet Advice Alone in Young Children with Nonanemic Iron Deficiency.

OBJECTIVE: To compare the effects of 2 treatment options on neurodevelopmental and laboratory outcomes in young children with nonanemic iron deficiency. STUDY DESIGN: A blinded, placebo-controlled, randomized trial of children 1-3 years with nonanemic iron deficiency (hemoglobin ≥110 g/L, serum ferritin <14 µg/L) was conducted in 8 primary care practices in Toronto, Canada. Interventions included ferrous sulfate or placebo for 4 months; all parents received diet advice. The primary outcome was the Early Learning Composite (ELC) using the Mullen Scales of Early Learning (mean 100, SD 15). Secondary outcomes included serum ferritin. Measurements were obtained at baseline and 4 and 12 months. Sample size was calculated to detect a between-group difference of 6-7 points in ELC. RESULTS: At enrollment (n = 60), mean age was 24.2 (SD 7.4) months and mean serum ferritin was 10.0 (SD 2.4) µg/L. For ELC, the mean between-group difference at 4 months was 1.1 (95% CI -4.2 to 6.5) and at 12 months was 4.1 (95% CI -1.9 to 10.1). For serum ferritin, at 4 months, the mean between-group difference was 16.9 µg/L (95% CI 6.5 to 27.2), and no child randomized to ferrous sulfate had a serum ferritin <14 µg/L (0% vs 31%, P = .003). CONCLUSIONS: For young children with nonanemic iron deficiency, treatment options include oral iron and/or diet advice. We remain uncertain about which option is superior with respect to cognitive outcomes; however, adding ferrous sulfate to diet advice resulted in superior serum ferritin outcomes after 4 months. Shared decision-making between practitioners and parents may be considered when selecting either option. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01481766.

Impact of iron fortification on the geospatial patterns of malaria and non-malaria infection risk among young children: a secondary spatial analysis of clinical trial data from Ghana.

OBJECTIVES: Patterns of infection among children with varying levels of iron status in a malaria endemic area may vary spatially in ways requiring integrated infection and iron deficiency control programmes. The objective of this secondary analysis was to determine the geospatial factors associated with malaria and non-malaria infection status among young Ghanaian children at the end of a 5-month iron intervention trial. DESIGN: Cluster-randomised controlled trial. SETTING: Rural Ghana PARTICIPANTS: 1943 children (6-35 months of age) with geocoded compounds. INTERVENTIONS: Point-of-use fortification with micronutrient powders containing vitamins and minerals with or without iron. PRIMARY AND SECONDARY OUTCOME MEASURES: Generalised linear geostatistical models with a Matern spatial correlation function were used to analyse four infection response variables, defined using different combinations of inflammation (C-reactive protein, CRP >5 mg/L) and malaria parasitaemia. Analyses were also stratified by treatment group to assess the independent effects of the iron intervention. RESULTS: The by-group and combined-group analyses both showed that baseline infection status was the most consistent predictor of endline infection risk, particularly when infection was defined using parasitaemia. In the No-iron group, age above 24 months and weight-for-length z-score at baseline were associated with high CRP at endline. Higher asset score was associated with a 12% decreased odds of endline infection, defined as CRP >5 mg/L and/or parasitaemia (OR 0.88, 95% credible interval 0.78 to 0.98), regardless of group. Maps of the predicted risk and spatial random effects showed a defined low-risk area around the District centre, regardless of how infection was defined. CONCLUSION: In a clinical trial setting of iron fortification, where all children receive treated bed nets and access to malaria treatment, there may be geographical variation in the risk of infection with distinct high-risk and low-risk areas, particularly around municipal centres. TRIAL REGISTRATION NUMBER: clinicaltrials.gov, NCT01001871.

Mineral- and vitamin-enhanced micronutrient powder reduces stunting in full-term low-birth-weight infants receiving nutrition, health, and hygiene education: a 2 × 2 factorial, cluster-randomized trial in Bangladesh.

BACKGROUND: The causes of stunting are complex but likely include prenatal effects, inadequate postnatal nutrient intake, and recurrent infections. Low-birth-weight (LBW) infants are at high risk of stunting. More than 25% of live births in low- and middle-income countries are at full term with low birth weight (FT-LBW). Evidence on the efficacy of specific interventions to enhance growth in this vulnerable group remains scant. OBJECTIVE: We investigated the independent and combined effects of a directed use of a water-based hand sanitizer (HS) and a mineral- and vitamin-enhanced micronutrient powder (MNP) (22 minerals and vitamins) to prevent infections and improve nutrient intake to reduce stunting in FT-LBW infants. DESIGN: The study was a prospective 2 × 2 factorial, cluster-randomized trial in 467 FT-LBW infants during 2 periods: from 0 to 5 mo postpartum (0-180 d postpartum) and from 6 to 12 mo postpartum (181-360 d postpartum) with the use of 48 clusters. All groups received the same general nutrition, health, and hygiene education (NHHE) at enrollment and throughout the 12 mo. Group assignments initially included the following 2 groups: no HS (control) group or HS from 0 to 5 mo postpartum. These assignments were followed by further divisions into the following 4 groups from 6 to 12 mo postpartum: 1) no HS and no MNP (control), 2) HS only, 3) MNP only, and 4) HS and MNP. RESULTS: When delivered in combination with NHHE, the use of an HS showed no additional benefit in reducing indicators of infection in the first or second half of infancy or the likelihood of stunting at 12 mo postpartum. FT-LBW infants who received the MNP (with or without the HS) were significantly less likely to be stunted at 12 mo than were controls (OR: 0.35; 95% CI: 0.15, 0.84; P = 0.017). CONCLUSIONS: The use of a mineral- and vitamin-enhanced MNP significantly reduced stunting in FT-LBW infants in this high-risk setting. The use of a water-based HS did not have an additive effect. This trial was registered at clinicaltrials.gov as NCT01455636.

Maternal vitamin D supplementation during pregnancy and lactation to promote infant growth in Dhaka, Bangladesh (MDIG trial): study protocol for a randomized controlled trial.

BACKGROUND: Vitamin D regulates bone mineral metabolism and skeletal development. Some observational studies have suggested that prenatal vitamin D deficiency increases the risk of adverse pregnancy and/or birth outcomes; however, there is scant evidence from controlled trials, leading the World Health Organization to advise against routine vitamin D supplementation in pregnancy. Importantly, little is known about the effect of maternal vitamin D status on infant linear growth in communities in South Asia where stunting is highly prevalent and maternal-infant vitamin D status is commonly suboptimal. METHODS/DESIGN: The Maternal Vitamin D for Infant Growth study is a randomized, placebo-controlled, dose-ranging trial of maternal vitamin D supplementation during pregnancy and lactation in Dhaka, Bangladesh. The primary aims are to estimate (1) the effect of maternal prenatal oral vitamin D3 supplementation (4200 IU/wk, 16,800 IU/wk, or 28,000 IU/wk, administered as weekly doses) versus placebo on infant length at 1 year of age and (2) the effect of maternal postpartum oral vitamin D3 supplementation (28,000 IU/wk) versus placebo on length at 1 year of age among infants born to women who received vitamin D 28,000 IU/wk during pregnancy. Generally healthy pregnant women (n = 1300) in the second trimester (17-24 weeks of gestation) are randomized to one of five parallel arms: placebo 4200 IU/wk, 16,800 IU/wk, or 28,000 IU/wk in the prenatal period and placebo in the postpartum period or 28,000 IU/wk in the prenatal period and 28,000 IU/wk in the postpartum period. Household- and clinic-based follow-up of mother-infant pairs is conducted weekly by trained personnel until 26 weeks postpartum and every 3 months thereafter. The primary trial outcome measure is length for age z-score at 1 year of age. Anthropometric measurements, clinical information, and biological specimens collected at scheduled intervals will enable the assessment of a range of maternal, perinatal, and infant outcomes. DISCUSSION: The role of vitamin D in maternal and infant health remains unresolved. This trial is expected to contribute unique insights into the effects of improving maternal-infant vitamin D status in a low-income setting where stunting and adverse perinatal outcomes represent significant public health burdens. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01924013. Registered on 13 August 2013.

An internal pilot study for a randomized trial aimed at evaluating the effectiveness of iron interventions in children with non-anemic iron deficiency: the OptEC trial.

BACKGROUND: The OptEC trial aims to evaluate the effectiveness of oral iron in young children with non-anemic iron deficiency (NAID). The initial sample size calculated for the OptEC trial ranged from 112-198 subjects. Given the uncertainty regarding the parameters used to calculate the sample, an internal pilot study was conducted. The objectives of this internal pilot study were to obtain reliable estimate of parameters (standard deviation and design factor) to recalculate the sample size and to assess the adherence rate and reasons for non-adherence in children enrolled in the pilot study. METHODS: The first 30 subjects enrolled into the OptEC trial constituted the internal pilot study. The primary outcome of the OptEC trial is the Early Learning Composite (ELC). For estimation of the SD of the ELC, descriptive statistics of the 4 month follow-up ELC scores were assessed within each intervention group. The observed SD within each group was then pooled to obtain an estimated SD (S2) of the ELC. Correlation (ρ) between the ELC measured at baseline and follow-up was assessed. Recalculation of the sample size was performed using analysis of covariance (ANCOVA) method which uses the design factor (1- ρ(2)). Adherence rate was calculated using a parent reported rate of missed doses of the study intervention. CONCLUSION: The new estimate of the SD of the ELC was found to be 17.40 (S2). The design factor was (1- ρ2) = 0.21. Using a significance level of 5%, power of 80%, S2 = 17.40 and effect estimate (Δ) ranging from 6-8 points, the new sample size based on ANCOVA method ranged from 32-56 subjects (16-28 per group). Adherence ranged between 14% and 100% with 44% of the children having an adherence rate ≥ 86%. Information generated from our internal pilot study was used to update the design of the full and definitive trial, including recalculation of sample size, determination of the adequacy of adherence, and application of strategies to improve adherence. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01481766 (date of registration: November 22, 2011).

Bioavailability of enteric-coated microencapsulated calcium during pregnancy: a randomized crossover trial in Bangladesh.

BACKGROUND: Prenatal calcium and iron supplements are recommended in settings of low dietary calcium intake and high prevalence of anemia. However, calcium administration may inhibit iron absorption. To overcome calcium-iron interactions, we developed a multi-micronutrient powder containing iron (60 mg), folic acid (400 µg), and calcium carbonate granules microencapsulated with a pH-sensitive enteric coating to delay intestinal release. OBJECTIVES: We aimed to establish in vivo evidence that enteric-coated (EC) calcium is bioavailable in pregnant women and to explore the dose-responsiveness of fractional calcium absorption (FCA) in pregnancy. DESIGN: This was a randomized crossover trial in pregnant women (26-28 wk of gestation) in Dhaka, Bangladesh. Participants were allocated to 1 of 3 dose groups (500, 1000, or 1500 mg elemental Ca). FCA was estimated in random order for EC and non-EC (control) granules by a dual-stable-isotope method ((44)Ca-labeled granules and intravenous (42)Ca) on the basis of the relative recovery of (44)Ca compared with (42)Ca in urine over 48 h. RESULTS: Forty-nine participants with FCA for both EC and non-EC granules were included in the primary analyses. FCA geometric means were as follows: 21.8% (500 mg), 9.2% (1000 mg), and 11.7% (1500 mg) for non-EC granules compared with 3.3% (500 mg), 1.2% (1000 mg), and 2.1% for EC granules. Cumulative 48-h FCA of EC calcium was 85% lower (P < 0.001) than that of non-EC calcium, after adjustment for dose. In comparison to 500 mg, the FCA for the 1000-mg dose was 61% lower (P < 0.001) and was 42% lower (P = 0.002) for the 1500-mg dose, after adjustment for formulation. CONCLUSIONS: A pH-sensitive enteric coating substantially reduced calcium absorption from a prenatal multi-micronutrient powder. In its current formulation, this novel supplement is not suitable for clinical use. FCA was highly dose-dependent, such that doses of 1000 and 1500 mg delivered only negligibly more bioavailable calcium than the 500-mg dose. This trial was registered at clinicaltrials.gov as NCT01678079.

Design and development of a combined calcium-iron-folic acid prenatal supplement to support implementation of the new World Health Organization recommendations for calcium supplementation during pregnancy.

BACKGROUND: Hypertensive diseases of pregnancy are important causes of maternal and perinatal mortality. Based on meta-analyses of efficacy trials of prenatal calcium supplementation to reduce the risk of hypertensive diseases of pregnancy, the World Health Organization recommends 1.5 to 2.0 g of elemental calcium per day for pregnant women with low dietary calcium intakes (as well as 60 mg of iron and 400 microg of folic acid). However, implementation of this recommendation is challenged by the size and number of calcium tablets required and the need to avoid concurrent ingestion of calcium and iron due to intraintestinal interactions. OBJECTIVE: We developed a novel micronutrient powder containing microencapsulated pH-sensitive calcium in addition to iron and folic acid, designed to facilitate early intestinal iron release and delayed calcium release. METHODS: Two pharmaceutical companies were contracted to develop a prototype, one of which was chosen for clinical testing. Calcium carbonate granules were coated with a trilayer pH-sensitive enteric coating using a fluid-bed spray coater. Iron and folic acid granules were encapsulated with a time-release coating. Iron and calcium dissolution profiles were assessed during exposure to acidic (pH 1.2) and/or basic (pH 5.8) media using a modified USP apparatus 1 (basket) method. RESULTS: At pH 1.2, calcium and iron release was < or = 10% and > 90% after 120 minutes, respectively. At pH 5.8, > 80% of total calcium was released after 90 minutes. CONCLUSIONS: Based on in vitro criteria, the supplement may be a promising approach for delivering calcium, iron, and folic acid as a single daily dose to pregnant women in settings of low dietary intake of calcium.

A 22-element micronutrient powder benefits language but not cognition in Bangladeshi full-term low-birth-weight children.

BACKGROUND: Low-birth-weight children are known to be at risk of both anemia and cognitive/language deficits in their early years. OBJECTIVE: The aim of the current study was to examine the effects of a 22-element multiple micronutrient powder (MNP) on the cognitive and language development of full-term low-birth-weight (LBW-T) children in Bangladesh. METHODS: The current study was a follow-up of children who were enrolled in a randomized cluster trial at 7-12 mo of age. Children in 12 intervention clusters (communities) were administered a daily 22-element MNP sachet with their food for 5 mo, and both intervention and control groups (also 12 clusters) received nutrition, health, and hygiene education. The current study involved the assessment of children at 16-22 mo of age (22-element MNP group: n = 96; control group: n = 82) on 3 subtests of the Bayley Scales of Infant and Toddler Development III test to measure cognitive, receptive language, and expressive language development. RESULTS: There was a significant effect of the 22-element MNP on children's expressive language scores (d = 0.39), and stunting moderated the effect on receptive language scores; there was no effect on cognitive development (d = 0.08). CONCLUSION: An MNP may thus offer one feasible solution to improve language development of LBW-T children in low-resource community settings. This trial was registered at clinicaltrials.gov as NCT01455636.

Tablets are preferred and more acceptable than powdered prenatal calcium supplements among pregnant women in Dhaka, Bangladesh.

Prenatal calcium supplementation is recommended by the WHO to decrease the risk of preeclampsia in women with low dietary calcium intake; yet, this recommendation has not been successfully implemented to date. One component of an effective population-based prenatal calcium intervention will be the selection of a widely accepted calcium vehicle to promote consistent, long-term consumption of the supplement. We aimed to evaluate preference and acceptability of 4 different options for delivering prenatal calcium (conventional tablets, chewable tablets, unflavored powder, and flavored powder) to pregnant women in urban Bangladesh. In a modified discrete-choice trial, pregnant women (n = 132) completed a 4-d "run-in period" in which each delivery vehicle was sampled once, followed by a 21-d "selection period" during which participants were instructed to freely select a single delivery vehicle of their choice each day. Preference was empirically defined as the probability that each delivery vehicle was selected on a given day, and measured from participants' daily delivery vehicle selections; acceptability was assessed by using mid- and post-trial questionnaires. Conventional tablets demonstrated the highest probability of selection (62%); the probability of selection of chewable tablets (19%), flavored powder (12%), and unflavored powder (5%) were all significantly lower than for conventional tablets (P < 0.001). The palatability and product characteristics of the conventional tablets were more acceptable than for the other 3 delivery vehicles. Our rigorous methodologic approach used both quantitative and self-reported measures that consistently identified the most preferred and accepted prenatal calcium delivery form. Through observation of pregnant women's actual supplement use, and perceptions of acceptability (i.e., ease of use, palatability), we demonstrated that conventional tablets are likely to be the most accepted and successful calcium delivery vehicle in future field studies and scale-up of the WHO recommendation in Bangladesh.

Home fortification with calcium reduces Hb response to iron among anaemic Bangladeshi infants consuming a new multi-micronutrient powder formulation.

OBJECTIVE: To investigate whether the recommended dietary intake of Ca in anaemic infants compromises the expected Hb response, via home fortification with a new Ca- and Fe-containing Sprinkles™ micronutrient powder (MNP). DESIGN: A double-blind, randomized controlled, 2-month trial was conducted in Bangladesh. Infants were randomized to one of two MNP intervention groups containing Fe and other micronutrients, with or without Ca. Hb, anthropometrics and dietary intake were measured pre- and post-intervention while family demographics were collected at baseline. SETTING: Twenty-six rural villages in the Kaliganj sub-district of Gazipur, Bangladesh. SUBJECTS: One hundred infants aged 6-11 months. RESULTS: A significant increase in Hb (MNP, 13·3 (sd 12·6) g/l v. Ca-MNP, 7·6 (sd 11·6) g/l; P < 0·0001) was noted in infants from both groups. However, infants receiving MNP without Ca had a significantly higher end-point Hb concentration (P = 0·024) and rate of anaemia recovery (P = 0·008). Infants receiving MNP with Ca were more likely to remain anaemic (OR 3·2; 95 % CI 1·4, 7·5). Groups did not differ in dietary intake or demographic and anthropometric indicators. CONCLUSIONS: Although both groups showed significant improvement in Hb status, the nutrient-nutrient interaction between Fe and Ca may have diminished the Hb response in infants receiving the Ca-containing MNP.

Relative efficacy of micronutrient powders versus iron-folic acid tablets in controlling anemia in women in the second trimester of pregnancy.

BACKGROUND: Iron deficiency is a major cause of anemia and the most prevalent nutrient deficiency among pregnant women in developing countries. The use of iron and folic acid supplements to treat and prevent iron-deficiency anemia has limited effectiveness, mainly due to poor adherence. Home fortification with a micronutrient powder for pregnant women may be an effective and acceptable alternative to traditional drug models. OBJECTIVE: To determine whether home fortification with micronutrient powders is at least as efficacious as iron and folic acid tablets for improving hemoglobin concentration in pregnant women. METHODS: A cluster-randomized noninferiority trial was conducted in the rural subdistrict of Kaliganj in central Bangladesh. Pregnant women (gestational age 14-22 weeks, n=478), were recruited from 42 community-based Antenatal Care Centres. Each centre was randomly allocated to receive either a micronutrient powder (containing iron,folic acid, vitamin C, and zinc) or iron and folic acid tablets. Changes in hemoglobin from baseline were compared across groups using a linear mixed-effects regression model. RESULTS: At enrolment, the overall prevalence of anemia was 45% (n = 213/478). After the intervention period, the mean hemoglobin concentrations among women receiving the micronutrient powder were not inferior to those among women receiving tablets (109.5 ± 12.9 vs. 112.0 ± 11.2 g/L; 95% CI, -0.757 to 5.716). Adherence to the micronutrient powder was lower than adherence to tablets (57.5 ± 22.5% vs. 76.0 ± 13.7%; 95% CI, -22.39 to -12.94); however, in both groups, increased adherence was positively correlated with hemoglobin concentration. CONCLUSIONS: The micronutrient powder was at least as efficacious as the iron and folic acid tablets in controlling moderate to severe anemia during pregnancy.

Iron deficiency anemia prevalence at first stroke or transient ischemic attack.

BACKGROUND: Iron deficiency anemia (IDA) has been implicated in the etiology of transient ischemic attack and ischemic stroke. This study aimed to: 1) document IDA prevalence in patients ≥ 65 years of age admitted to hospital with transient ischemic attack or first ischemic stroke, and 2) investigate dietary intake as a predictor of iron status. METHODS: Ninety-four patients were enrolled. An algorithm containing values for hemoglobin, ferritin, total iron binding capacity, transferrin saturation, and serum transferrin receptor measured at admission was used to identify IDA. Usual dietary intake was assessed with the Clue II food frequency questionnaire. RESULTS: Prevalence estimates were 6.4% for IDA, 2.1% for iron deficiency without anemia, and 6.4% for anemia from other causes. IDA prevalence was significantly higher than published National Health and Nutrition Examination Survey III (NHANES III) estimates for gender-specific age groups ≥ 70 years (One-Sample Proportion Test; males p = 0.038 [n= 37]; females p = 0.002 [n=44]). A comparison of IDA prevalence against selected controls from the NHANES III database yielded an odds ratio (OR) of 6.3, 95% confidence interval (CI) 0.8 to 53.7, which was not statistically significant (Fisher's Exact Test; n=94; p = 0.118). Multivariate linear regression analysis of dietary intake with indicators of iron status (n=58) revealed only iron supplements (p = 0.013) and heme iron intake (p = 0.038) as negative predictors of total iron binding capacity (p<0.05). CONCLUSIONS: These findings support the initiation of a prospective case control study to investigate IDA as a risk factor for ischemic stroke in elderly patients.

Unexpectedly high early prevalence of anaemia in 6-month-old breast-fed infants in rural Bangladesh.

OBJECTIVE: To determine the prevalence of anaemia and maternal and infant factors associated with Hb values in infants at 6 months of age in rural Bangladesh. DESIGN: Infants (born to mothers supplemented with Fe-folic acid from mid-pregnancy) were visited at birth and 6 months of age. Mothers' anthropometric status, and infants' birth weight, gestational age at birth, weight and Hb concentration at 6 months were measured. Household socio-economic and demographic data, infant feeding practices and health status were collected using a pre-tested structured questionnaire. SETTING: Rural Bangladesh. SUBJECTS: Four hundred and two infants. RESULTS: For the total cohort (n 402), the range of anaemia prevalence values was from 30.6 % using a cut-off value of Hb < 95 g/l to 71.9 % using a value of Hb < 110 g/l. Birth weight and month of birth were the only factors positively associated with infant Hb in a linear regression model (P = 0.008 and 0.011, respectively). CONCLUSIONS: There was an unexpectedly high prevalence of anaemia in infants at 6 months of age, before the assumed period of vulnerability. Hb at this age tended to be higher in those with higher birth weight. We also found a season effect on Hb, as it tended to be higher as the study progressed. The high prevalence of anaemia at such an early age needs to be addressed to minimize the disease's long-term consequences.

Periconceptional iron supplementation does not reduce anemia or improve iron status among pregnant women in rural Bangladesh.

BACKGROUND: There is a growing interest in periconceptional iron supplementation in developing countries by researchers and policy makers; however, there are no randomized controlled trials that examine the effectiveness of this strategy in decreasing anemia during pregnancy. OBJECTIVE: The aim was to determine whether periconceptional iron supplementation reduces anemia during pregnancy. DESIGN: A randomized, double-blind, controlled trial was conducted in rural Bangladesh. Married, nulliparous women were randomly assigned to receive daily iron and folic acid (IFA; 60 mg ferrous fumarate and 400 microg folic acid) (n = 134) or folic acid (FA; 400 microg) (n = 138) in the form of a powdered supplement added to food. Women were followed until pregnancy or the end of 9 mo. Primary outcomes included hemoglobin, plasma ferritin, and plasma transferrin receptor concentrations. RESULTS: Among 88 pregnant women, periconceptional IFA in comparison with FA did not affect anemia or iron status at 15 wk gestation. However, each 1% increase in adherence was associated with a 10-g/L increase in change in hemoglobin from baseline (P = 0.03), and those who initiated supplementation at a mean (+/-SD) time of 72.9 +/- 57.8 d before conception showed a 7.3-g/L increase in change in hemoglobin from baseline compared with those who initiated supplementation at 26.3 +/- 12.3 d after conception (P = 0.01). Among 146 nonpregnant women, IFA decreased anemia (odds ratio: 0.19; 95% CI: 0.04, 0.95) and improved iron stores (P = 0.001) more than did FA. CONCLUSION: Good adherence and initiation of supplementation before conception are needed to reduce anemia during early pregnancy. This trial was registered at www.clinicaltrials.gov as NCT00953134.

Omega 3 fatty acids (fish oil) for maintenance of remission in Crohn's disease.

BACKGROUND: The anti-inflammatory effects of n-3 (omega-3 fatty acids, fish oil) have been suggested to be beneficial in chronic inflammatory disorders such as inflammatory bowel disease. OBJECTIVES: To systematically review the efficacy and safety of n-3 for maintenance of remission in Crohn's disease (CD). SEARCH STRATEGY: The following databases were searched from their inception without language restriction: Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Healthstar, PubMed, and ACP journal club. Experts were contacted for unpublished data. SELECTION CRITERIA: Randomized placebo-controlled trials (RCT) of n-3 for maintenance of remission in CD were included. Studies must have enrolled patients of any age group, who were in remission at the time of recruitment, and were followed for at least six months. The intervention must have been fish oil or n-3 given in pre-defined dosage. Co-interventions were allowed only if they were balanced between the study groups. The primary outcome was the relapse rate and secondary outcomes included change in disease activity scores, time to first relapse and adverse events. DATA COLLECTION AND ANALYSIS: Two independent investigators reviewed studies for eligibility, extracted the data and assessed study quality using Jadad's criteria. Meta-analyses were performed using RevMan 4.2 software weighted by the Mantel-Haenszel method. Random or fixed effect models were used according to degree of heterogeneity and subgroup analyses were performed in an attempt to explore possible sources of heterogeneity. MAIN RESULTS: Six studies were eligible for inclusion. There was a marginal significant benefit of n-3 therapy for maintaining remission (RR 0.77 0.; 95%CI 0.61 to 0.98; P = 0.03). However, the studies were both clinically and statistically heterogeneous (P = 0.03, I(2) = 58%). Two large studies showed negative results. When considering the estimated rather than the observed 1-year relapse rate of these two studies, the benefit was no longer statistically significant (RR 0.59; 95% CI 0.34 to 1.03; P=0.06). A funnel plot suggested publication bias. No serious adverse events were recorded in any of the studies but in a pooled analyses there was a significantly higher rate of diarrhea (RR 1.36 95% CI 1.01 to 1.84) and symptoms of the upper gastrointestinal tract (RR 1.98 95% CI 1.38 to 2.85) in the n-3 treatment group. AUTHORS' CONCLUSIONS: Omega 3 fatty acids are safe but probably ineffective for maintenance of remission in CD. The existing data do not support routine maintenance treatment of Crohn's disease with omega 3 fatty acids.

Economics of preventing premature mortality and impaired cognitive development in children through home-fortification: a health policy perspective.

BACKGROUND: Home-fortification is a new strategy of adding micronutrients including zinc and iron to home-made foods. Zinc supplementation may prevent morbidity and mortality related to diarrheal illnesses, and iron supplementation may improve cognitive development, in children. OBJECTIVES: To project clinical and economic effects of home-fortification in children in an urban slum of Karachi, Pakistan. METHODS: This is a cost benefit analysis of 5,000 simulated male and female infants (6-12 months) assigned to micronutrients or placebo for 4 months and followed for 55 years. We linked the effect of zinc on longitudinal prevalence of diarrhea to mortality, and the effect of iron on hemoglobin to IQ scores and lifetime earnings. Cost estimates were based on volumes of resource utilization from the Pakistan Sprinkles Diarrhea study. Main outcome was incremental benefit defined as the gain in lifetime earnings after accounting for the incremental costs of micronutrients over placebo (societal perspective). RESULTS: Our model projected that the reduction in diarrhea and improvement in hemoglobin concentrations through home-fortification was associated with reduced child mortality, higher IQ scores, and higher earnings. The present value of incremental benefit was $106 (95 percent probability interval = $17 to $193) U.S. dollars, which corresponds to $464.79 ($74.54 to $846.27) international dollars using a purchasing power parity exchange rate. CONCLUSIONS: Home-fortification appears to improve clinical outcomes at a reasonable cost, and may actually be cost beneficial when lifetime earnings are considered.

Children with autism: effect of iron supplementation on sleep and ferritin.

To determine if there is a relationship between low serum ferritin and sleep disturbance in children with autism spectrum disorder, an 8-week open-label treatment trial with oral iron supplementation was conducted as a pilot study. At baseline and posttreatment visits, parents completed a Sleep Disturbance Scale for Children and a Food Record. Blood samples were obtained. Thirty-three children completed the study. Seventy-seven percent had restless sleep at baseline, which improved significantly with iron therapy, suggesting a relationship between sleep disturbance and iron deficiency in children with autism spectrum disorder. Sixty-nine percent of preschoolers and 35% of school-aged children had insufficient dietary iron intake. Mean ferritin increased significantly (16 microg/L to 29 microg/L), as did mean corpuscular volume and hemoglobin, suggesting that low ferritin in this patient group resulted from insufficient iron intake. Similar prevalence of low ferritin at school age as preschool age indicates that children with autism spectrum disorder require ongoing screening for iron deficiency.

Effect of daily versus once-weekly home fortification with micronutrient Sprinkles on hemoglobin and iron status among young children in rural Bangladesh.

BACKGROUND: The effectiveness of commonly suggested public health interventions to control childhood iron-deficiency anemia has been low. OBJECTIVE: To determine whether iron provided in Sprinkles daily or in a higher dose once weekly affected hemoglobin, serum ferritin levels, and serum transferrin receptor levels, and to determine whether there were differences in the effects of the two regimens. METHODS: In this cluster-randomized, community-based trial conducted in rural areas of Bangladesh, 136 children aged 12 to 24 months with mild to moderate anemia (hemoglobin 70-109 g/L) were randomly allocated to receive Sprinkles daily (12.5 mg of elemental iron, n = 79) or once weekly (30 mg of elemental iron, n = 73) for 8 weeks. Hemoglobin, serum ferritin, and serum transferrin receptor were assessed at the start and end of the intervention. RESULTS: In both groups, there were significant increases in hemoglobin and serum ferritin and a significant decrease in serum transferrin receptor (p < .01). There were no significant differences between the groups in the increases in hemoglobin (16.1 +/- 13.2 g/L for the group receiving Sprinkles daily and 12.3 +/- 13.3 g/L for the group receiving Sprinkles once weekly) and serum ferritin (10.6 and 5.7 microg/L, respectively). The decrease in serum transferrin receptor also did not significantly differ between the groups (median, -2.5 and -1.8 mg/L, respectively). The prevalence rates of iron-deficiency anemia, depleted iron stores, and tissue iron deficiency decreased significantly within each group (p < .01), with no significant differences between the groups. CONCLUSIONS: Home fortification of complementary foods with Sprinkles given either daily or once weekly improved iron-deficiency anemia and iron status among young children.

Home fortification in emergency response and transition programming: experiences in Aceh and Nias, Indonesia.

BACKGROUND: Improving the nutritional status of an emergency-affected population is essential, because undernutrition increases infection risk and is linked to more than 50% of childhood deaths in developing countries. Emergency food aid addresses nutritional needs, including micronutrient deficiencies, but is provided only for a limited time and uses few items, so the needs of specific target groups are often not fully met. OBJECTIVE: To describe the post-tsunami experience with distribution of Vitalita Sprinkles in Aceh and Nias and to analyze the monitoring data gathered for the emergency response. METHODS: International agencies such as Helen Keller International and partners provided micronutrients in response to the tsunami emergency in Aceh and Nias and to analyze the monitoring data gathered for the emergency response. RESULTS: In March and April 2006, the percentage of children aged 6 months to 59 months who had consumed Vitalita in the previous month was more than 70% in 5 of 11 districts evaluated, 40% to 70% in another five districts, and 32% in one district. An independent survey found 25% less anemia among recipients. Almost all mothers interviewed during March to April 2006 (96.3%) had heard about Vitalita and recognized its packaging, 69% said that Vitalita contained vitamins for under-fives, 86% knew the appropriate target group for Vitalita, and 83% said it had to be mixed with solid food. Of the 26% that reported not having given Vitalita to their child in the last month, 90.5% said that their child did not like it. CONCLUSIONS AND LESSONS LEARNED: Because the product, including its concept, was new, appropriate information and training was required as well as a thorough introduction to the beneficiaries, particularly on proper use, to ensure acceptance. This experience demonstrates that providing micronutrients as part of emergency relief and transition programming, as recently recommended by the World Health Organization/UNICEF/World Food Program, is feasible.