Effect of food and micronutrient supplementation during pregnancy on subsequent development of infants in Bangladesh: a randomized trial

Background: The prevalence of low birth weight (LBW) is high in developing countries and is estimated to be 30% (UNICEF, 2001) in Bangladesh. Maternal under nutrition is an important cause of LBW is also highly prevalent in Bangladesh 50 % (March of Dimes, 2002). Public health programs of food-supplementation during pregnancy have been mounted to address the issue and it is important to determine the most effective way of providing the food. In addition it has been suggested that supplementation with multiple micronutrients may be more beneficial than supplementing with iron and folic acid alone, which is the present practise. Most studies of pregnancy supplementation have focused on the effect on birth outcomes whereas there is extremely little data on the effects on the offspring's' development. A large randomized-trial of the effect of 2 types of nutritional supplementation (food and micronutrients) in pregnant women on birth-outcomes was conducted in the Matlab field-site of ICDDR,B: Centre for Health and Population Research, Bangladesh. We took the opportunity to evaluate the effect of the supplements on children's development.;Aims: We aimed to determine the effect of giving pregnant women early (around 10 week of gestation) versus late (around 17 week of gestation) food-supplementation and multi-micronutrients or 30mg iron + 400 fig folate or 60mg iron + 400 fig folate on their infants' development.;Methods: A sub-sample of all singletons (n=2853) born between May 2002 and December 2003 in the main trial was selected to have developmental assessments at 7 months of age. The children were assessed using 2 problem-solving tests (cover and support), the Bayley motor-scale (PDI) and Wolke's behaviour ratings assessing approach, activity, emotionality, co-operation and vocalization during the test procedure. The children were also assessed for the age of attainment of motor milestones.;Intervention: 2 nutritional interventions were given: Food supplementation: Women were randomly assigned to begin the food supplementation program (a) immediately after diagnosis of pregnancy (early care) or (b) at the time of their choosing (usual care). Micronutrient supplementation: Within each food group, women were randomly assigned to receive a pill that contained (a) 30 mg iron and 400 Lig folate or (b) 60 mg iron and 400 Hg folate (usual care) or (c) 30 mg iron, 400 U-g folate and 13 additional micronutrients (UN1CEF/WHO/UNU, 1999 formulation of 15-micronutrients).;Results: There is no overall benefit of prenatal supplementation with early food or multiple-micronutrients compared with late food or iron and folate supplementation on any of the tests of children's development when assessed at 7 months of age. However infants of thin mothers (body mass index <18.5 kg/m ) showed a small but statistically significant benefit from both early food and multiple-micronutrients supplements whereas the children of better nourished mothers did not. Early food supplementation benefited children of malnourished mothers in the problem solving tests, support (BMI x early food p<0.03) and cover (BMI x early food p<0.05) and behaviour. The children were less fussy (BMI x early food p<0.04), more cooperative with the test situation (BMI x early food p<0.04) and vocalised more often (BMI x early food p<0.04) than children of similar mothers given late food supplementation. Small but significant benefits on motor development (BMI x micronutrients p=0.05) and activity (BMI x micronutrients p<0.05) were also observed among the infants of malnourished mothers who received multiple-micronutrient supplements. Mothers' BMI had an independent effect on children's development.;Conclusions: Early food and multiple micronutrient supplementation benefited development in children of undernourished mothers but not children of better nourished mothers. The findings support current practices in Bangladesh of targeting thin mothers and suggest that early food supplementation may be more beneficial than later supplementation. The findings also suggest that multiple micronutrients may be more beneficial to the child than iron and folate. However, the effect sizes were very small and their clinical and public health importance are not clear and can only be determined with longer follow-up. As there was no placebo group, the benefit of giving food supplementation throughout pregnancy could not be assessed. The relationship between mothers BMI and children's development emphasises the importance of maternal nutrition

Association of Postpartum Maternal Morbidities with Children's Mental, Psychomotor and Language Development in Rural Bangladesh

Little is known from developing countries about the effects of maternal morbidities diagnosed in the postpartum period on children's development. The study aimed to document the relationships of such morbidities with care-giving practices by mothers, children's developmental milestones and their language, mental and psychomotor development. Maternal morbidities were identified through physical examination at 6-9 weeks postpartum (n=488). Maternal care-giving practices and postnatal depression were assessed also at 6-9 weeks postpartum. Children's milestones of development were measured at six months, and their mental (MDI) and psychomotor (PDI) development, language comprehension and expression, and quality of psychosocial stimulation at home were assessed at 12 months. Several approaches were used for identifying the relationships among different maternal morbidities, diagnosed by physicians, with children's development. After controlling for the potential confounders, maternal anaemia diagnosed postpartum showed a small but significantly negative effect on children's language expression while the effects on language comprehension did not reach the significance level (p=0.085). Children's development at 12 months was related to psychosocial stimulation at home, nutritional status, education of parents, socioeconomic status, and care-giving practices of mothers at six weeks of age. Only a few mothers experienced each specific morbidity, and with the exception of anaemia, the sample-size was insufficient to make a conclusion regarding each specific morbidity. Further research with a sufficient sample-size of individual morbidities is required to determine the association of postpartum maternal morbidities with children's development

Integrating an early childhood development programme into Bangladeshi primary health-care services: an open-label, cluster-randomised controlled trial

BACKGROUND: Poor development in young children in developing countries is a major problem. Child development experts are calling for interventions that aim to improve child development to be integrated into health services, but there are few robust evaluations of such programmes. Previous small Bangladeshi trials that used individual play sessions with mothers and their children (at home or in clinics), which were predominantly run by employed women, found moderate improvements on child development. We aimed to integrate an early childhood development programme into government clinics that provide primary health care and to evaluate the effects of this intervention on child cognition, language, and motor development, growth, and behaviour in a subsample of the children. METHODS: In this open-label cluster-randomised controlled trial, we recruited individuals from community clinics in Narsingdi district, Bangladesh. These clinics were randomly selected from a larger sample of eligible clinics, and they were assigned (1:1) to either deliver an intervention of 25 sessions, in which mothers of eligible children were shown how to support their child's development through play and interactions, or to deliver no intervention (control group). Participants were underweight children, defined as a weight-for-age Z score of -2 SDs of the WHO standard, who were aged 5-24 months and who lived near the clinic (defined as a walk of less than 30 min). Government health workers ran these sessions at the clinics as part of their routine work, and mothers and children attended fortnightly in pairs (instead of individual weekly home visits that were specified in the original programme). A subsample of children from each clinic was randomly selected for impact evaluation, and these children were assessed on the Bayley Scales of Infant and Toddler Development for their cognitive, language, and motor performance and for their behaviour with Wolke's ratings, before and after implementation of the intervention. The primary outcomes were the performance of this evaluation subsample on the Bayley and Wolke scales and their anthropometric measurements (weight, length or height, and head circumference) after 1 year of the intervention. This study is registered with ClinicalTrials.gov, number NCT02208531. FINDINGS: Between Nov 29, 2014, and April 30, 2015, 12 054 children in 90 clinics were screened, and between six and 25 underweight children were enrolled from each clinic. From the 2423 (20%) underweight children, we excluded 656 (27%) children who lived more than 30-min walking distance from the community clinics, and 30 (1%) children whose mothers did not consent to participate. We therefore enrolled 1737 (72%) children from these 90 clinics. After randomisation, the control group clinics included 878 (51%) children (who all received no intervention) and the intervention group clinics included 859 (49%) children (who all received the child development programme sessions). Eight children from each clinic (360 [41%] children from the control group clinics and 358 [42%] children from the intervention group clinics) were randomly selected for inclusion in the evaluation subsample. Between Feb 24, 2016, and Sept 7, 2016, 344 (96%) children in control group clinics and 343 (96%) children in intervention group clinics were assessed for the primary outcome. 16 (5%) children in the control group clinics and 15 (4%) children in the intervention group clinics did not provide all data and were not included in final analyses. An intention-to-treat analysis showed that the intervention significantly improved children's cognition (effect size 1·3 SDs, 95% CI 1·1 to 1·5; p=0·006), language (1·1 SDs, 0·9 to 1·2; p=0·01), and motor composite scores (1·2 SDs, 1·0 to 1·3; p=0·006) and behaviour ratings (ranging from 0·7 SDs, 0·5 to 0·9; p=0·02; to 1·1 SDs, 1·0 to 1·2; p=0·007), but the intervention had no significant effect on growth (p values ranged from 0·05 to 0·74). Three (1%) children in the intervention group died, but their deaths were not related to the intervention. INTERPRETATION: The extent and range of benefits of our intervention are encouraging. Health workers ran most of the sessions effectively and attendance was good, which is promising for scale-up of the intervention model. However, researchers trained and supervised the health workers, and the next step will be to determine whether the Bangladeshi ministry of health can perform these tasks. In future programmes, more attention needs to be paid to the nutrition of the children. FUNDING: Grand Challenges Canada (Saving Brains)

Ferroelectric Polarization in Nanocrystalline Hydroxyapatite Thin Films on Silicon

Hydroxyapatite nanocrystals in natural form are a major component of bone- a known piezoelectric material. Synthetic hydroxyapatite is widely used in bone grafts and prosthetic pyroelectric coatings as it binds strongly with natural bone. Nanocrystalline synthetic hydroxyapatite films have recently been found to exhibit strong piezoelectricity and pyroelectricity. While a spontaneous polarization in hydroxyapatite has been predicted since 2005, the reversibility of this polarization (i.e. ferroelectricity) requires experimental evidence. Here we use piezoresponse force microscopy to demonstrate that nanocrystalline hydroxyapatite indeed exhibits ferroelectricity: a reversal of polarization under an electrical field. This finding will strengthen investigations on the role of electrical polarization in biomineralization and bone- density related diseases. As hydroxyapatite is one of the most common biocompatible materials, our findings will also stimulate systematic exploration of lead and rare-metal free ferroelectric devices for potential applications in areas as diverse as in vivo and ex vivo energy harvesting, biosensing and electronics

Does prenatal micronutrient supplementation improve children's mental development? A systematic review

<p>Abstract</p> <p>Background</p> <p>Although maternal nutrient status influences all aspects of fetal development including the brain, the impact of micronutrient supplementation on the baby's mental function is a topic of debate. This systematic review assesses the effect of single and multiple micronutrient supplementation during pregnancy on offspring mental development.</p> <p>Methods</p> <p>Eleven electronic literature databases were searched using key terms of various combinations and filter string terms. Reference lists of articles selected for review were scanned for citations fitting the same inclusion criteria. Each stage of the literature retrieval and review process was conducted independently by two reviewers. The CONSORT checklist was used to assess study quality.</p> <p>Results</p> <p>A total of 1316 articles were retrieved from the electronic database search, of which 18 met the inclusion criteria and were evaluated. The selected studies were randomized controlled trials published from 1983 to 2010, with high variance in sample size, intervention type, and outcome measures. The median CONSORT score was 15 (range 12 - 19). Due to inconsistent interventions and outcome measures among the studies, no conclusive evidence was found that enhancing the intrauterine environment through micronutrient supplementation was associated with child mental development in a number of dimensions. There was some evidence to support n-3 fatty acids or multi-micronutrients having some positive effect on mental development, but the evidence for single nutrients was much weaker.</p> <p>Conclusions</p> <p>The study of children's mental outcomes as a function of prenatal supplementation is still relatively new, but the results of this systematic review suggest that further work with multiple micronutrients and/or n-3 fatty acids should be conducted.</p

Cluster-randomised controlled trials of individual and combined water, sanitation, hygiene and nutritional interventions in rural Bangladesh and Kenya: the WASH Benefits study design and rationale.

INTRODUCTION: Enteric infections are common during the first years of life in low-income countries and contribute to growth faltering with long-term impairment of health and development. Water quality, sanitation, handwashing and nutritional interventions can independently reduce enteric infections and growth faltering. There is little evidence that directly compares the effects of these individual and combined interventions on diarrhoea and growth when delivered to infants and young children. The objective of the WASH Benefits study is to help fill this knowledge gap. METHODS AND ANALYSIS: WASH Benefits includes two cluster-randomised trials to assess improvements in water quality, sanitation, handwashing and child nutrition-alone and in combination-to rural households with pregnant women in Kenya and Bangladesh. Geographically matched clusters (groups of household compounds in Bangladesh and villages in Kenya) will be randomised to one of six intervention arms or control. Intervention arms include water quality, sanitation, handwashing, nutrition, combined water+sanitation+handwashing (WSH) and WSH+nutrition. The studies will enrol newborn children (N=5760 in Bangladesh and N=8000 in Kenya) and measure outcomes at 12 and 24 months after intervention delivery. Primary outcomes include child length-for-age Z-scores and caregiver-reported diarrhoea. Secondary outcomes include stunting prevalence, markers of environmental enteropathy and child development scores (verbal, motor and personal/social). We will estimate unadjusted and adjusted intention-to-treat effects using semiparametric estimators and permutation tests. ETHICS AND DISSEMINATION: Study protocols have been reviewed and approved by human subjects review boards at the University of California, Berkeley, Stanford University, the International Centre for Diarrheal Disease Research, Bangladesh, the Kenya Medical Research Institute, and Innovations for Poverty Action. Independent data safety monitoring boards in each country oversee the trials. This study is funded by a grant from the Bill & Melinda Gates Foundation to the University of California, Berkeley. REGISTRATION: Trial registration identifiers (http://www.clinicaltrials.gov): NCT01590095 (Bangladesh), NCT01704105 (Kenya)

Effects of Low-Dose Drinking Water Arsenic on Mouse Fetal and Postnatal Growth and Development

© The Author(s), 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS One 7 (2012): e38249, doi:10.1371/journal.pone.0038249.Arsenic (As) exposure is a significant worldwide environmental health concern. Chronic exposure via contaminated drinking water has been associated with an increased incidence of a number of diseases, including reproductive and developmental effects. The goal of this study was to identify adverse outcomes in a mouse model of early life exposure to low-dose drinking water As (10 ppb, current U.S. EPA Maximum Contaminant Level). C57B6/J pups were exposed to 10 ppb As, via the dam in her drinking water, either in utero and/or during the postnatal period. Birth outcomes, the growth of the F1 offspring, and health of the dams were assessed by a variety of measurements. Birth outcomes including litter weight, number of pups, and gestational length were unaffected. However, exposure during the in utero and postnatal period resulted in significant growth deficits in the offspring after birth, which was principally a result of decreased nutrients in the dam's breast milk. Cross-fostering of the pups reversed the growth deficit. Arsenic exposed dams displayed altered liver and breast milk triglyceride levels and serum profiles during pregnancy and lactation. The growth deficits in the F1 offspring resolved following separation from the dam and cessation of exposure in male mice, but did not resolve in female mice up to six weeks of age. Exposure to As at the current U.S. drinking water standard during critical windows of development induces a number of adverse health outcomes for both the dam and offspring. Such effects may contribute to the increased disease risks observed in human populations.This work was supported by National Institute of Environmental Health Sciences at the National Institutes of Health grants 1F32 ES019070 (CDK-H) and P42 ES007373 (BPJ, JWH, RIE and CDK-H, Dartmouth Superfund Research Program Project Grant, Project 2 and Pilot Project)

Effects of prenatal food and micronutrient supplementation on child growth from birth to 54 months of age: a randomized trial in Bangladesh

<p>Abstract</p> <p>Background</p> <p>There is a lack of information on the optimal timing of food supplementation to malnourished pregnant women and possible combined effects of food and multiple micronutrient supplementations (MMS) on their offspring's growth. We evaluated the effects of prenatal food and micronutrient interventions on postnatal child growth. The hypothesis was that prenatal MMS and early invitation to food supplementation would increase physical growth in the offspring during 0-54 months and a combination of these interventions would further improve these outcomes.</p> <p>Methods</p> <p>In the large, randomized MINIMat trial (Maternal and Infant Nutrition Interventions in Matlab), Bangladesh, 4436 pregnant women were enrolled between November 2001 and October 2003 and their children were followed until March 2009. Participants were randomized into six groups comprising 30 mg Fe and 400 μg folic acid (Fe30F), 60 mg Fe and 400 μg folic acid (Fe60F) or MMS combined with either an early (immediately after identification of pregnancy) or a later usual (at the time of their choosing, i.e., usual care in this community) program invitation to food supplementation. The anthropometry of 3267 children was followed from birth to 54 months, and 2735 children were available for analysis at 54 months.</p> <p>Results</p> <p>There were no differences in characteristics of mothers and households among the different intervention groups. The average birth weight was 2694 g and birth length was 47.7 cm, with no difference among intervention groups. Early invitation to food supplementation (in comparison with usual invitation) reduced the proportion of stunting from early infancy up to 54 months for boys (p = 0.01), but not for girls (p = 0.31). MMS resulted in more stunting than standard Fe60F (p = 0.02). There was no interaction between the food and micronutrient supplementation on the growth outcome.</p> <p>Conclusions</p> <p>Early food supplementation in pregnancy reduced the occurrence of stunting during 0-54 months in boys, but not in girls, and prenatal MMS increased the proportion of stunting in boys. These effects on postnatal growth suggest programming effects in early fetal life.</p> <p>Trial registration number</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN16581394">ISRCTN16581394</a></p