Underweight in the first 2 years of life and nutrition risk in later childhood: a prospective cohort study.

BACKGROUND: Children with underweight in the first 2 years have lower body mass index z-score (zBMI) and height-for-age z-score (HAZ) in later childhood. It is not known if underweight in the first 2 years is associated with nutrition risk in later childhood. OBJECTIVE: (1) Determine the relationship between underweight (zBMI < -2) in the first 2 years and nutrition risk measured by the Nutrition Screening for Toddlers and Preschoolers (NutriSTEP) score from 18 months to 5 years. (2) Explore the relationship between underweight in the first 2 years and the NutriSTEP subscores for eating behaviours and dietary intake from 18 months to 5 years. METHODS: This was a prospective study, including healthy full-term children in Canada aged 0-5 years. zBMI was calculated using measured heights and weights and the WHO growth standards. NutriSTEP score was measured using a parent-completed survey and ranged from 0 to 68. Nutrition risk was defined as a score ≥21. Linear mixed effects models were used. RESULTS: Four thousand nine hundred twenty-nine children were included in this study. At enrolment, 51.9% of participants were male. The prevalence of underweight children was 8.8%. Underweight in the first 2 years was associated with higher NutriSTEP (0.79, 95% CI: 0.29,1.29), higher eating behaviour subscore (0.24, 95% CI: 0.03, 0.46) at 3 years and higher odds of nutrition risk (OR: 1.39, 95% CI: 1.07,1.82) at 5 years. CONCLUSIONS: Children with underweight in the first 2 years had higher nutrition risk in later childhood. Further research is needed to understand the factors which influence these relationships.

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.

Fortification of salt with iron and iodine versus fortification of salt with iodine alone for improving iron and iodine status.

BACKGROUND: Iron deficiency is an important micronutrient deficiency contributing to the global burden of disease, and particularly affects children, premenopausal women, and people in low-resource settings. Anaemia is a possible consequence of iron deficiency, although clinical and functional manifestations of anemia can occur without iron deficiency (e.g. from other nutritional deficiencies, inflammation, and parasitic infections). Direct nutritional interventions, such as large-scale food fortification, can improve micronutrient status, especially in vulnerable populations. Given the highly successful delivery of iodine through salt iodisation, fortifying salt with iodine and iron has been proposed as a method for preventing iron deficiency anaemia. Further investigation of the effect of double-fortified salt (i.e. with iron and iodine) on iron deficiency and related outcomes is warranted.  OBJECTIVES: To assess the effect of double-fortified salt (DFS) compared to iodised salt (IS) on measures of iron and iodine status in all age groups. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, five other databases, and two trial registries up to April 2021. We also searched relevant websites, reference lists, and contacted the authors of included studies. SELECTION CRITERIA: All prospective randomised controlled trials (RCTs), including cluster-randomised controlled trials (cRCTs), and controlled before-after (CBA) studies, comparing DFS with IS on measures of iron and iodine status were eligible, irrespective of language or publication status. Study reports published as abstracts were also eligible. DATA COLLECTION AND ANALYSIS: Three review authors applied the study selection criteria, extracted data, and assessed risk of bias. Two review authors rated the certainty of the evidence using GRADE. When necessary, we contacted study authors for additional information. We assessed RCTs, cRCTs and CBA studies using the Cochrane RoB 1 tool and Cochrane Effective Practice and Organisation of Care (EPOC) tool across the following domains: random sequence generation; allocation concealment; blinding of participants and personnel; blinding of outcome assessment; incomplete outcome data; selective reporting; and other potential sources of bias due to similar baseline characteristics, similar baseline outcome assessments, and declarations of conflicts of interest and funding sources. We also assessed cRCTs for recruitment bias, baseline imbalance, loss of clusters, incorrect analysis, and comparability with individually randomised studies. We assigned studies an overall risk of bias judgement (low risk, high risk, or unclear).  MAIN RESULTS: We included 18 studies (7 RCTs, 7 cRCTs, 4 CBA studies), involving over 8800 individuals from five countries. One study did not contribute to analyses. All studies used IS as the comparator and measured and reported outcomes at study endpoint.  With regards to risk of bias, five RCTs had unclear risk of bias, with some concerns in random sequence generation and allocation concealment, while we assessed two RCTs to have a high risk of bias overall, whereby high risk was noted in at least one or more domain(s). Of the seven cRCTs, we assessed six at high risk of bias overall, with one or more domain(s) judged as high risk and one cRCT had an unclear risk of bias with concerns around allocation and blinding. The four CBA studies had high or unclear risk of bias for most domains. The RCT evidence suggested that, compared to IS, DFS may slightly improve haemoglobin concentration (mean difference (MD) 0.43 g/dL, 95% confidence interval (CI) 0.23 to 0.63; 13 studies, 4564 participants; low-certainty evidence), but DFS may reduce urinary iodine concentration compared to IS (MD -96.86 µg/L, 95% CI -164.99 to -28.73; 7 studies, 1594 participants; low-certainty evidence), although both salts increased mean urinary iodine concentration above the cut-off deficiency. For CBA studies, we found DFS made no difference in haemoglobin concentration (MD 0.26 g/dL, 95% CI -0.10 to 0.63; 4 studies, 1397 participants) or urinary iodine concentration (MD -17.27 µg/L, 95% CI -49.27 to 14.73; 3 studies, 1127 participants). No studies measured blood pressure. For secondary outcomes reported in RCTs, DFS may result in little to no difference in ferritin concentration (MD -3.94 µg/L, 95% CI -20.65 to 12.77; 5 studies, 1419 participants; low-certainty evidence) or transferrin receptor concentration (MD -4.68 mg/L, 95% CI -11.67 to 2.31; 5 studies, 1256 participants; low-certainty evidence) compared to IS. However, DFS may reduce zinc protoporphyrin concentration (MD -27.26 µmol/mol, 95% CI -47.49 to -7.03; 3 studies, 921 participants; low-certainty evidence) and result in a slight increase in body iron stores (MD 1.77 mg/kg, 95% CI 0.79 to 2.74; 4 studies, 847 participants; low-certainty evidence). In terms of prevalence of anaemia, DFS may reduce the risk of anaemia by 21% (risk ratio (RR) 0.79, 95% CI 0.66 to 0.94; P = 0.007; 8 studies, 2593 participants; moderate-certainty evidence). Likewise, DFS may reduce the risk of iron deficiency anaemia by 65% (RR 0.35, 95% CI 0.24 to 0.52; 5 studies, 1209 participants; low-certainty evidence).  Four studies measured salt intake at endline, although only one study reported this for both groups. Two studies reported prevalence of goitre, while one CBA study measured and reported serum iron concentration. One study reported adverse effects. No studies measured hepcidin concentration. AUTHORS' CONCLUSIONS: Our findings suggest DFS may have a small positive impact on haemoglobin concentration and the prevalence of anaemia compared to IS, particularly when considering efficacy studies. Future research should prioritise studies that incorporate robust study designs and outcome measures (e.g. anaemia, iron status measures) to better understand the effect of DFS provision to a free-living population (non-research population), where there could be an added cost to purchase double-fortified salt. Adequately measuring salt intake, both at baseline and endline, and adjusting for inflammation will be important to understanding the true effect on measures of iron status.

Effect of Correcting the Postnatal Age of Preterm-Born Children on Measures of Associations Between Infant Length-for-Age z Scores and Mid-Childhood Outcomes.

Child growth standards are commonly used to derive age- and sex-standardized anthropometric indices but are often inappropriately applied to preterm-born children (<37 weeks of gestational age (GA)) in epidemiology studies. Using the 2004 Pelotas Birth Cohort, we examined the impact of correcting for GA in the application of child growth standards on the magnitude and direction of associations in 2 a priori-selected exposure-outcome scenarios: infant length-for-age z score (LAZ) and mid-childhood body mass index (scenario A), and infant LAZ and mid-childhood intelligence quotient (scenario B). GA was a confounder that had a strong (scenario A) or weak (scenario B) association with the outcome. Compared with uncorrected postnatal age, using GA-corrected postnatal age attenuated the magnitude of associations, particularly in early infancy, and changed inferences for associations at birth. Although differences in the magnitude of associations were small when GA was weakly associated with the outcome, model fit was meaningfully improved using corrected postnatal age. When estimating population-averaged associations with early childhood growth in studies where preterm- and term-born children are included, incorporating heterogeneity in GA at birth in the age scale used to standardize anthropometric indices postnatally provides a useful strategy to reduce standardization errors.

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.

Recovery and relapse from severe acute malnutrition after treatment: a prospective, observational cohort trial in Pakistan.

OBJECTIVE: Millions of children suffer from severe acute malnutrition (SAM) in low- and middle- income countries. Much is known about the effectiveness of community treatment programmes (CMAM) but little is known about post-discharge outcomes after successful treatment. The present study aimed to evaluate post-discharge outcomes of children cured of SAM. DESIGN: Prospective, observational cohort study. Children with SAM who were discharged as cured were followed monthly for 6 months or until they experienced relapse to SAM. 'Cure' was defined as a child achieving a mid-upper arm circumference (MUAC) of ≥115 mm with ≥15 % weight gain after loss of oedema. Relapse was defined as a child with MUAC<115 mm and/or oedema at any monthly visit. SETTING: Save the Children CMAM programme in Swabi, Pakistan, from January 2012 to December 2014. SUBJECTS: Children aged 6-59 months (n 117) discharged as cured from the CMAM programme were eligible for the study and followed for 6 months. RESULTS: One hundred children (92·6 %) remained free of SAM, eight (7·4 %) relapsed to SAM, nine (8·3 %) were lost to follow-up and none died. Most relapses occurred within 3 months of discharge (mean time to relapse 73·4 (sd 36·2) d). At enrolment, 90 % had moderate acute malnutrition (MAM) and 10 % were not malnourished. By the end of 6 months, 35 % persisted with MAM and the remaining were not malnourished. CONCLUSIONS: In rural Pakistan, fewer than 10 % of children cured of SAM relapsed. The first 3 months is the most vulnerable time.

Geo-spatial factors associated with infection risk among young children in rural Ghana: a secondary spatial analysis.

BACKGROUND: Determining the spatial patterns of infection among young children living in a malaria-endemic area may provide a means of locating high-risk populations who could benefit from additional resources for treatment and improved access to healthcare. The objective of this secondary analysis of baseline data from a cluster-randomized trial among 1943 young Ghanaian children (6-35 months of age) was to determine the geo-spatial factors associated with malaria and non-malaria infection status. METHODS: Spatial analyses were conducted using a generalized linear geostatistical model with a Matern spatial correlation function and four definitions of infection status using different combinations of inflammation (C-reactive protein, CRP > 5 mg/L) and malaria parasitaemia (with or without fever). Potentially informative variables were included in a final model through a series of modelling steps, including: individual-level variables (Model 1); household-level variables (Model 2); and, satellite-derived spatial variables (Model 3). A final (Model 4) and maximal model (Model 5) included a set of selected covariates from Models 1 to 3. RESULTS: The final models indicated that children with inflammation (CRP > 5 mg/L) and/or any evidence of malaria parasitaemia at baseline were more likely to be under 2 years of age, stunted, wasted, live further from a health facility, live at a lower elevation, have less educated mothers, and higher ferritin concentrations (corrected for inflammation) compared to children without inflammation or parasitaemia. Similar results were found when infection was defined as clinical malaria or parasitaemia with/without fever (definitions 3 and 4). Conversely, when infection was defined using CRP only, all covariates were non-significant with the exception of baseline ferritin concentration. In Model 5, all infection definitions that included parasitaemia demonstrated a significant interaction between normalized difference vegetation index and land cover type. Maps of the predicted infection probabilities and spatial random effect showed defined high- and low-risk areas that tended to coincide with elevation and cluster around villages. CONCLUSIONS: The risk of infection among young children in a malaria-endemic area may have a predictable spatial pattern which is associated with geographical characteristics, such as elevation and distance to a health facility. Original trial registration clinicaltrials.gov (NCT01001871).

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.

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.

Prevalence of malnutrition at the time of admission among patients admitted to a Canadian tertiary-care paediatric hospital.

BACKGROUND: Malnutrition among hospitalized children is known to negatively influence their response to therapy and to prolong their admission. It also has short- and long-term consequences for growth, development and well-being. It is commonly regarded as a condition affecting children in low-income countries; however, malnutrition has been found to be variably prevalent among hospitalized children in higher-income countries. At the time the present study was conducted, it had been >30 years since the nutritional status of Canadian hospitalized children was last published. OBJECTIVES: To determine and communicate the prevalence of malnutrition among children in a Canadian tertiary-care paediatric hospital at the time of their admission. METHODS: In the present cross-sectional study, anthropometric measures were obtained from 322 children admitted to The Hospital for Sick Children in Toronto, Ontario. Nutritional indexes (BMI for age, weight for age, weight for length/height and length/height for age) were generated from anthropometric measures using the WHO igrowup software, and summarized according to WHO definitions. RESULTS: The overall prevalence of malnutrition using BMI for age was 39.6% (95% CI 33% to 46%), of which 8.8% and 30.8% of participants were under- and overnourished, respectively. Furthermore, 6.9% (95% CI 3% to 13%) were determined to be acutely malnourished (weight for length/height <-2 SD) and 13.4% (95% CI 10% to 18%) chronically malnourished (length/height for age <-2 SD). CONCLUSION: The high prevalence of overall malnutrition observed among study participants suggests that initial screening using simple anthropometric measures should be conducted on hospital admission so that patients can receive appropriate nutrition-specific care.

HISTORIQUE: On sait que la malnutrition chez les enfants hospitalisés nuit à leur réponse au traitement et prolonge leur hospitalisation. Elle a également des conséquences à court et à long terme sur la croissance, le développement et le bien-être. Elle est souvent considérée comme un problème chez les enfants de pays à faible revenu, mais sa prévalence est variable chez les enfants hospitalisés dans les pays à revenu élevé. Au moment de la présente étude, les dernières publications sur l'état nutritionnel des enfants canadiens hospitalisés remontaient à plus de 30 ans. OBJECTIFS: Déterminer et communiquer la prévalence de malnutrition chez les enfants au moment de leur admission dans un hôpital pédiatrique canadien de soins tertiaires. MÉTHODOLOGIE: Dans la présente étude transversale, les mesures anthropométriques ont été recensées auprès de 322 enfants admis à The Hospital for Sick Children de Toronto, en Ontario. Les indices nutritionnels (IMC par rapport à l'âge, poids par rapport à l'âge, poids par rapport à la taille et taille par rapport à l'âge) étaient tirés de mesures anthropométriques calculées au moyen du logiciel igrowup de l'OMS. Ces indices étaient résumés d'après les définitions de l'OMS. RÉSULTATS: D'après l'IMC en fonction de l'âge, la prévalence globale de malnutrition s'élevait à 39,6 % (95 % IC 33 % à 46 %). Ainsi, 8,8 % et 30,8 % des participants étaient sous-alimentés et suralimentés, respectivement. De plus, il a été établi que 6,9 % (95 % IC 3 % à 13 %) souffraient de malnutrition aiguë (poids par rapport à la taille <−2 ÉT), et 13,4 % (95 % IC 10 % à 18 %), de malnutrition chronique (taille par rapport à l'âge <−2 ÉT). CONCLUSION: D'après la forte prévalence de malnutrition globale chez les participants à l'étude, le dépistage initial faisant appel à des mesures anthropométriques simples devrait être effectué au moment de l'admission à l'hôpital, afin que les patients puissent recevoir des soins pertinents en matière de nutrition.

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.

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.

Underweight in the First 2 Years of Life and Growth in Later Childhood.

Importance: Few studies have examined the association between underweight in the first 2 years and growth in later childhood in high-income countries. Objective: To evaluate the associations of underweight in the first 2 years of life with body mass index (calculated as weight in kilograms divided by height in meters squared) z score (zBMI), weight-for-age z score (WAZ), and height-for-age z score (HAZ) from ages 2 to 10 years. Design, Setting, and Participants: This prospective cohort study was conducted between February 2008 to September 2020 in The Applied Research Group for Kids! practice-based research network in Toronto, Canada. Participants included healthy children aged 0 to 10 years. Data were analyzed from October 2020 to December 2021. Exposures: Underweight (ie, zBMI less than -2, per the World Health Organization) in the first 2 years of life. Main Outcomes and Measures: The primary outcome was zBMI from ages 2 to 10 years. Linear mixed-effects models were used to account for multiple growth measures over time. Results: A total of 5803 children were included in the primary analysis. At baseline, the mean (SD) age was 4.07 (5.62) months, 2982 (52.2%) were boys, and 550 children (9.5%) were underweight. Underweight in the first 2 years was associated with lower zBMI (difference, -0.39 [95% CI, -0.48 to -0.31]) at 10 years and lower HAZ (difference, -0.24 [95% CI, -0.34 to -0.14]) at age 2 years. Stratified by sex, at age 10 years, girls and boys with underweight in the first 2 years both had lower zBMI (girls: difference, -0.47 [95% CI, -0.59 to -0.34]; boys: difference, -0.32 [95% CI, -0.44 to -0.20]). At age 10 years, children with underweight and a lower zBMI growth rate in the first 2 years had lower zBMI (difference, -0.64 [95% CI, -0.77 to -0.53) and HAZ (difference, -0.12 [-0.24 to -0.01]), while children with underweight and a higher zBMI growth rate in the first 2 years had similar zBMI (difference, -0.11 [95% CI, -0.22 to 0.001]) and higher HAZ (difference, 0.16 [95% CI, 0.05 to 0.27]) compared with children who did not have underweight in the first 2 years. Conclusions and Relevance: In this prospective cohort study, children with underweight in the first 2 years of life had lower zBMI and HAZ in later childhood. These associations were attenuated among children with a higher growth rate in the first 2 years.

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.

Identification of EpCAM as the gene for congenital tufting enteropathy.

BACKGROUND & AIMS: Congenital tufting enteropathy (CTE) is a rare autosomal recessive diarrheal disorder presenting in the neonatal period. CTE is characterized by intestinal epithelial cell dysplasia leading to severe malabsorption and significant morbidity and mortality. The pathogenesis and genetics of this disorder are not well understood. The objective of this study was to identify the gene responsible for CTE. METHODS: A family with 2 children affected with CTE was identified. The affected children are double second cousins providing significant statistical power for linkage. Using Affymetrix 50K single nucleotide polymorphism (SNP) chips, genotyping was performed on only 2 patients and 1 unaffected sibling. Direct DNA sequencing of candidate genes, reverse-transcription polymerase chain reaction, immunohistochemistry, and Western blotting were performed on specimens from patients and controls. RESULTS: SNP homozygosity mapping identified a unique 6.5-Mbp haplotype of homozygous SNPs on chromosome 2p21 where approximately 40 genes are located. Direct sequencing of genes in this region revealed homozygous G>A substitution at the donor splice site of exon 4 in epithelial cell adhesion molecule (EpCAM) of affected patients. Reverse-transcription polymerase chain reaction of duodenal tissue demonstrated a novel alternative splice form with deletion of exon 4 in affected patients. Immunohistochemistry and Western blot of patient intestinal tissue revealed decreased expression of EpCAM. Direct sequencing of EpCAM from 2 additional unrelated patients revealed novel mutations in the gene. CONCLUSIONS: Mutations in the gene for EpCAM are responsible for CTE. This information will be used to gain further insight into the molecular mechanisms of this disease.

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.

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.