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

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          Multiple micronutrient supplementation for pregnant women reduces low birth weight and has been recommended in low- and middle-income countries (LMICs) to improve child survival, growth and health. We aimed to review the evidence from long-term follow-up studies of multiple micronutrient supplementation beginning in the later first or second trimester.


          We searched systematically for follow-up reports from all trials in a 2015 Cochrane review of multiple micronutrient supplementation in pregnancy. The intervention comprised three or more micronutrients and the comparison group received iron (60 mg) and folic acid (400 μg), where possible. Median gestation of commencement varied from 9 to 23 weeks. Primary outcomes were offspring mortality, height, weight and head circumference, presented as unadjusted differences in means or proportions (intervention minus control). Secondary outcomes included other anthropometry, body composition, blood pressure, and cognitive and lung function.


          We found 20 follow-up reports from nine trials (including 88,057 women recruited), six of which used the UNIMMAP supplement designed to provide recommended daily allowances. The age of follow-up ranged from 0 to 9 years. Data for mortality estimates were available from all trials. Meta-analysis showed no difference in mortality (risk difference –0.05 per 1000 livebirths; 95 % CI, –5.25 to 5.15). Six trials investigated anthropometry and found no difference at follow-up in weight-for-age z score (0.02; 95 % CI, –0.03 to 0.07), height-for-age z score (0.01; 95 % CI, –0.04 to 0.06), or head circumference (0.11 cm; 95 % CI, –0.03 to 0.26). No differences were seen in body composition, blood pressure, or respiratory outcomes. No consistent differences were seen in cognitive function scores.


          There is currently no evidence that, compared with iron and folic acid supplementation, routine maternal antenatal multiple micronutrient supplementation improves childhood survival, growth, body composition, blood pressure, respiratory or cognitive outcomes.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s12916-016-0633-3) contains supplementary material, which is available to authorized users.

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          Standardisation of spirometry.

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            Maternal and child undernutrition: consequences for adult health and human capital

            Summary In this paper we review the associations between maternal and child undernutrition with human capital and risk of adult diseases in low-income and middle-income countries. We analysed data from five long-standing prospective cohort studies from Brazil, Guatemala, India, the Philippines, and South Africa and noted that indices of maternal and child undernutrition (maternal height, birthweight, intrauterine growth restriction, and weight, height, and body-mass index at 2 years according to the new WHO growth standards) were related to adult outcomes (height, schooling, income or assets, offspring birthweight, body-mass index, glucose concentrations, blood pressure). We undertook systematic reviews of studies from low-income and middle-income countries for these outcomes and for indicators related to blood lipids, cardiovascular disease, lung and immune function, cancers, osteoporosis, and mental illness. Undernutrition was strongly associated, both in the review of published work and in new analyses, with shorter adult height, less schooling, reduced economic productivity, and—for women—lower offspring birthweight. Associations with adult disease indicators were not so clear-cut. Increased size at birth and in childhood were positively associated with adult body-mass index and to a lesser extent with blood pressure values, but not with blood glucose concentrations. In our new analyses and in published work, lower birthweight and undernutrition in childhood were risk factors for high glucose concentrations, blood pressure, and harmful lipid profiles once adult body-mass index and height were adjusted for, suggesting that rapid postnatal weight gain—especially after infancy—is linked to these conditions. The review of published works indicates that there is insufficient information about long-term changes in immune function, blood lipids, or osteoporosis indicators. Birthweight is positively associated with lung function and with the incidence of some cancers, and undernutrition could be associated with mental illness. We noted that height-for-age at 2 years was the best predictor of human capital and that undernutrition is associated with lower human capital. We conclude that damage suffered in early life leads to permanent impairment, and might also affect future generations. Its prevention will probably bring about important health, educational, and economic benefits. Chronic diseases are especially common in undernourished children who experience rapid weight gain after infancy.
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              Evidence-based interventions for improvement of maternal and child nutrition: what can be done and at what cost?

              Maternal undernutrition contributes to 800,000 neonatal deaths annually through small for gestational age births; stunting, wasting, and micronutrient deficiencies are estimated to underlie nearly 3·1 million child deaths annually. Progress has been made with many interventions implemented at scale and the evidence for effectiveness of nutrition interventions and delivery strategies has grown since The Lancet Series on Maternal and Child Undernutrition in 2008. We did a comprehensive update of interventions to address undernutrition and micronutrient deficiencies in women and children and used standard methods to assess emerging new evidence for delivery platforms. We modelled the effect on lives saved and cost of these interventions in the 34 countries that have 90% of the world's children with stunted growth. We also examined the effect of various delivery platforms and delivery options using community health workers to engage poor populations and promote behaviour change, access and uptake of interventions. Our analysis suggests the current total of deaths in children younger than 5 years can be reduced by 15% if populations can access ten evidence-based nutrition interventions at 90% coverage. Additionally, access to and uptake of iodised salt can alleviate iodine deficiency and improve health outcomes. Accelerated gains are possible and about a fifth of the existing burden of stunting can be averted using these approaches, if access is improved in this way. The estimated total additional annual cost involved for scaling up access to these ten direct nutrition interventions in the 34 focus countries is Int$9·6 billion per year. Continued investments in nutrition-specific interventions to avert maternal and child undernutrition and micronutrient deficiencies through community engagement and delivery strategies that can reach poor segments of the population at greatest risk can make a great difference. If this improved access is linked to nutrition-sensitive approaches--ie, women's empowerment, agriculture, food systems, education, employment, social protection, and safety nets--they can greatly accelerate progress in countries with the highest burden of maternal and child undernutrition and mortality. Copyright © 2013 Elsevier Ltd. All rights reserved.

                Author and article information

                +44 (0)20 7905 2122 , +44 (0)20 7404 2062 ,
                BMC Med
                BMC Med
                BMC Medicine
                BioMed Central (London )
                16 June 2016
                16 June 2016
                : 14
                [ ]Institute for Global Health, University College London, 30 Guilford St, London, UK
                [ ]MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Tremona Road, Southampton, UK
                [ ]Pediatrics and Clinical Epidemiology at Sitaram Bhartia Institute of Science and Research, B-16, Qutab Institutional Area, New Delhi, India
                [ ]Faculty of Medicine, University of Southampton, Southampton General Hospital, Tremona Road, Southampton, UK
                [ ]Childhood Nutrition Research Centre, Institute of Child Health, University College London, 30 Guilford St, London, UK
                © The Author(s). 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.

                Funded by: Wellcome Trust (GB)
                Award ID: 091561/Z/10/Z
                Award Recipient :
                Funded by: Sitaram Bhartia Institute of Science and Research
                Funded by: FundRef, Research Trainees Coordinating Centre;
                Funded by: FundRef, Medical Research Council;
                Funded by: FundRef, Department for International Development;
                Funded by: Medical Research Council (GB)
                Funded by: Department for International Development (GB)
                Research Article
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                © The Author(s) 2016


                micronutrients, child, prenatal exposure delayed effects


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