Document Detail

Vitamins and minerals for women: recent programs and intervention trials.
Jump to Full Text
MedLine Citation:
PMID:  21487490     Owner:  NLM     Status:  PubMed-not-MEDLINE    
Abstract/OtherAbstract:
Women's nutrition has received little attention in nutrition programming, even though clinical trials and intervention trials have suggested that dietary improvement or supplementation with several nutrients may improve their health, especially in low-income settings, the main focus of this paper. Most attention so far has focused on how improvements in maternal nutrition can improve health outcomes for infants and young children. Adequate vitamin D and calcium nutrition throughout life may reduce the risk of osteoporosis, and calcium supplementation during pregnancy may reduce preeclampsia and low birth weight. To reduce neural tube defects, additional folic acid and possibly vitamin B(12) need to be provided to non-deficient women before they know they are pregnant. This is best achieved by fortifying a staple food. It is unclear whether maternal vitamin A supplementation will lead to improved health outcomes for mother or child. Iron, iodine and zinc supplementation are widely needed for deficient women. Multimicronutrient supplementation (MMS) in place of the more common iron-folate supplements given in pregnancy in low-income countries may slightly increase birth weight, but its impact on neonatal mortality and other outcomes is unclear. More sustainable alternative approaches deserve greater research attention.
Authors:
Ted Greiner
Publication Detail:
Type:  Journal Article     Date:  2011-02-28
Journal Detail:
Title:  Nutrition research and practice     Volume:  5     ISSN:  2005-6168     ISO Abbreviation:  Nutr Res Pract     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-04-13     Completed Date:  2011-07-14     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  101311052     Medline TA:  Nutr Res Pract     Country:  Korea (South)    
Other Details:
Languages:  eng     Pagination:  3-10     Citation Subset:  -    
Affiliation:
Department of Food and Nutrition, College of Human Ecology, Hanyang University, 17 Haengdang-dong, Seoul 133-791, Korea.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Full Text
Journal Information
Journal ID (nlm-ta): Nutr Res Pract
Journal ID (publisher-id): NRP
ISSN: 1976-1457
ISSN: 2005-6168
Publisher: The Korean Nutrition Society and the Korean Society of Community Nutrition
Article Information
Download PDF
©2011 The Korean Nutrition Society and the Korean Society of Community Nutrition
open-access:
Print publication date: Month: 2 Year: 2011
Electronic publication date: Day: 28 Month: 2 Year: 2011
Volume: 5 Issue: 1
First Page: 3 Last Page: 10
ID: 3061267
PubMed Id: 21487490
DOI: 10.4162/nrp.2011.5.1.3

Vitamins and minerals for women: recent programs and intervention trials
Ted GreinerA1
Department of Food and Nutrition, College of Human Ecology, Hanyang University, 17 Haengdang-dong, Seoul 133-791, Korea.
Correspondence: Corresponding Author: Ted Greiner, Tel. 82-2-2220-1208, Fax. 82-2-2292-1226, tgreiner@hanyang.ac.kr

Introduction

Nature has given women additional challenges in their role as the bearers and early nurturers of children-which in some sense act as sizable parasites. This places women more at nutritional risk, especially where fertility rates are high, as they tend to be in low-income countries. Poor nutritional status, infection, and a heavy and stressful workload all contribute to increasing a woman's risk of health problems.

Interest in women's nutrition has grown rapidly in recent years but this is mainly because of its relation to child growth, especially nutritional stunting once it was realized that this begins at birth, with most of the insult in height growth taking place in infancy. In Malawi for example, 40% of the growth stunting that occurrs by three years of life has already taken place by 6 months of age [1]. Some have suggested that maternal nutrition during gestation and breastfeeding may be involved [2]. This has led to speculation that treating women with multivitamin and mineral supplements during and after pregnancy might reduce this process of stunting in infants.

Greiner suggested an alternative hypothesis, that early infant retardation in linear growth could to a great extent, be caused by the nearly universal lack of exclusive breastfeeding [3]. This is because in low income countries the foods and fluids given in the early months of life (which always displace breast milk to a large extent), even if they are adequate in energy, lack the other nutrients needed for height growth. In wealthier settings, milk, infant formula or fortified baby foods are more commonly given, and nutritional stunting is not among the known health consequences of the failure to breast feed exclusively. Particularly important for height growth are proteins and minerals, levels of which vary quite little in breast milk, except for the soluble and often endemically deficient minerals iodine and selenium [4].

We know that suboptimal nutrient intakes among women can have an impact on health, including pregnancy outcomes, bone development, immune function, and, in the elderly, neurological function [5]. This review will examine experience in addressing women's nutrient deficiencies at public health level. Ideally, this should be done by reviewing evaluations of public health programs. However, few such programs exist and evaluations of them are rare. Thus, the main focus here will be on intervention research that has been conducted during the past decade or so in women of about 15-45 years of age. This kind of research has been conducted mainly in low-income settings.

Some indirect interventions may have the greatest influence on maternal vitamin and mineral status such as delaying the first conception in young women, increased birth spacing, extending the period of paid maternity leave for working women, and better and earlier treatment of maternal infections. And of course women will benefit from overall strategies to improve vitamin and mineral nutrition such as the Global Alliance for Improved Nutrition (GAIN)-led Ten Year Strategy for the Reduction of Vitamin and Mineral Deficiencies [6]. However, this review focuses on specific interventions or intervention research aiming to improve vitamin and/or mineral status among women, first for their own health and then for that of their offspring.


Nutrient deficiencies linked to public health problems in women
Calcium and vitamin D

Calcium (1,200 mg elemental Ca/d) was found to reduce all four premenstrual syndrome symptoms examined in an older clinical trial [7]. It has even been suggested that PMS may be a marker for inadequate calcium intake [8].

Calcium supplementation during pregnancy (≥ 1 g/d) appears to reduce maternal blood pressure, approximately halve the risk of pre-eclampsia, and reduce the risk of preterm birth, with no evidence of doing harm [9]. This appears to be due to correcting deficiency (suboptimal calcium intake is common in women, even in rich countries) rather than a pharmaceutical effect.

Adequate vitamin D and calcium nutrition throughout the life-course appear to reduce the risk of osteoporosis [10]. So far there is no conclusive evidence that supplementation with any other nutrients has a beneficial impact on bone health [11].

Iron

Women tend to be more susceptible to iron deficiency than men because of monthly blood losses during their reproductive years, and the 10% who lose the most (> 80 ml/mo) are most at risk [12]. Intrauterine contractive devises may increase monthly losses by 30-50%, though levonorgestrel-releasing intrauterine systems reduce this problem [13]. Oral contraceptives and intensive breastfeeding [14] tend to reduce maternal iron losses during reproduction.

Pregnancy and delivery are the source of the greatest iron losses and hemorrhaging during delivery is a major cause of maternal mortality, with women suffering from anemia at increased risk [15]. Iron supplementation during pregnancy can improve maternal iron status, but only if begun early enough and where adherence is high [16]. While deficiencies of several nutrients besides iron can cause anemia, and some nutrients like vitamin A are often linked to iron status, a recent review found no greater impact of a multimicronutrient supplement on iron status than supplementing with iron alone [17].

Anemia increases the risk of preterm delivery and low birth weight (LBW). But high maternal iron levels are associated with an increased risk of fetal growth restriction, preterm delivery, and preeclampsia. High iron levels cause oxidative stress and are also linked to gestational diabetes [18]. Thus in general, where infrastructure will allow it would probably be wiser to ensure that a pregnant woman is iron deficient before giving her iron supplementation during pregnancy, at least in large doses.

Vitamin A

Vitamin A policymaking has focused on providing large doses, either to young children or to women soon after delivery [19], actively reducing the attention given to alternative approaches [20]. (Giving a dose larger than 10,000 IU, less than a two-day supply, at any other time to women in the reproductive age group is considered unethical, since higher doses may be associated with birth defects in women who do not yet know they are pregnant.) While women do receive large doses soon after delivery in some countries, the purpose of this is to increase levels in their breast milk. A recent systematic analysis failed to find any other benefit [21]. One trial in Nepal found that giving pregnant women frequent small doses of vitamin A reduced maternal mortality by 44% [22]. Later trials within less vitamin A deficient populations in Bangladesh [23] and Ghana [24] failed to find any impact.

Kirkwood argues that even the Nepal study provides inconclusive evidence, and thus, there is presently inadequate support for including low-dose vitamin-A supplementation for women in safe motherhood programs [25].

Vitamin E

One older placebo controlled trial found that a daily dose of 400 IU/d for three months led to a reduction in symptoms of premenstrual syndrome [26]. Results have been inconsistent for other supplements such as large doses of vitamin B6 and evening primrose oil.

Zinc

There is some evidence that zinc deficiency may be involved in some maternal mental health problems. In one study, 25 mg/d of zinc, along with medical treatment, improved depression more rapidly than medical treatment alone. Anorexia nervosa patients also improved more rapidly with zinc therapy [27].

Multivitamins

In one study, the use of prenatal multivitamins was found to lead to easier pregnancies (such as less morning sickness) [8].


Health problems of the fetus or child linked to maternal nutrient deficiency

Most vitamin and many mineral deficiencies in the mother, if serious enough, are likely to have any of a range of impacts on her offspring. But major attention must be placed on mortality, as well as birth defects and LBW, both major causes of infant morbidity and mortality. We begin with single nutrient interventions and then move to the major issue attracting research attention in recent years, multimicronutrient supplementation (MMS) of pregnant women.

Single nutrients
Birth defects

Some studies have found a number of apparent benefits from taking prenatal vitamins, including reductions in heart, neural tube, and other birth defects [8]. However, the focus here will be on the outcome that has been most strongly confirmed and acted on, neural tube defects. Additional folic acid needs to be provided to women at the very beginning of pregnancy to reduce the incidence of neural tube defects (recognizing that other birth defects may be affected as well). Programs to improve folate nutrition have been introduced in 40 countries, but they represent only about 10% of the neural tube defects that could be prevented [28]. In particular, advising women to take prenatal supplements is ineffective [29]. This is partly because once a woman knows she is pregnant, the neural tube has already folded, and partly because, even with encouragement, too few women take them regularly enough. Thus impact can best be accomplished through mandatory fortification of a universally consumed food. While most staple food fortification has focused on wheat (and to a lesser extent on maize), when rice is the staple food, it can be fortified at low cost with no impact on taste or appearance [30].

Recent research suggests that vitamin B12 deficiency may also be involved in the causation of neural tube defects [31]. Among other arguments for combining B12 with folate in fortification programs, there is some evidence that high folate combined with low B12 levels in pregnant women predisposes children to insulin resistance [32].

Infant morbidity

A study in West Java found that zinc supplementation in pregnant mothers led to a decreased incidence of diarrhea but an increase in episodes of cough during the first six months of infancy. Both zinc and β-carotene appeared to have an impact on the infant immune system [33]. Prenatal zinc supplementation was also found to reduce infant diarrhea in Indonesia [33] and Peru [34].

Birthweight

Even countries with high rates of low birthweight rarely have any defined programs to reduce it [35]. At the end of the 1990s, there were no known interventions with single vitamins and minerals that would decrease rates of intrauterine growth retardation [36], but the lack of good research was noted by the investigators.

Since then a great deal of additional research on this issue has been done. With respect to single nutrients, a systematic review found good evidence that calcium supplementation at > 1 g/day during pregnancy resulted in an average 17% reduction in LBW [37]. This effect may be due both to a prolongation of gestation and an increase in fetal growth. This same review found that the impact of magnesium supplementation during pregnancy may be even greater, but sample sizes so far have been slightly too small to be certain. The review found no significant impact of supplementation with other single nutrients on fetal growth.

However in deficient mothers, supplementation with iodine [38] and iron [39] can increase birthweight. For iodine, this is associated with neonatal survival [40] as well as IQ. One study found that zinc (with routine iron-folate) did not increase birthweight [41]. But among African American women with low levels of serum zinc at baseline, supplementation with 25 mg of zinc (in women taking non-zinc containing prenatal MMS) resulted in a 285 g increase in birthweights [42].

Iron-folate supplementation during pregnancy has sometimes been found to improve a number of developmental outcomes in young children [43], and sometimes not [44]; also, zinc has not [45].

Multimicronutrient supplementation during pregnancy
Birthweight

During the past decade, the most extensive relevant research has involved supplementation of pregnant women with multimicronutrients, including a multi-site UNICEF study using approximately the recommended daily intakes of iron, folic acid, zinc, copper, selenium, iodine, and vitamins A, B1, B2, B3, B6, B12, C, D, and E. (Note that this MMS did not include calcium or magnesium and used 30 mg of iron half the dose of what is often given in iron-folic acid supplements. However, a 60 mg dose is probably higher than necessary [46].) This research has focused on relatively large and "normal" populations, rather than on patients with clinical deficiencies.

A Cochrane review of MMS during pregnancy in 2006 found that it worked better than placebo but not better than iron-folate supplementation to reduce LBW (this is already commonly the standard of care and given to the control group in most studies) [47].

Use of MMS supplementation in pregnancy modestly increased birthweight in China (42 g compared to folate and 18 g compared to iron-folate) but did not have iron's impact in reducing mortality [48]. In West Java, is supplement resulted in a non-significant 40 g increase birthweight compared to iron-folate supplementation [49]; as well as increases of 52 g in Burkina Faso [50]; 70 g in Pakistan [51]; and 67 g in Niger [52]. In Vietnam, one district (A) received iron-folate, a second (B) received MMS and a third (C) received MMS and gender training. Birthweights were 105 g higher in C and 166 g higher in B, with A having about twice the rate of LBW. At age 2 years, children in B were about 2 cm taller and those in C were 1 cm taller than those in A [53].

A meta-analysis of 12 MMS trials found that the pooled estimate of increased birthweight was 24 g compared to supplementation iron-folate alone. There was about a 10% reduction in LBW, presumably due to an equal reduction in small for gestational age births. However, there was an equally large increase in gestational age births that were excessively large [54].

It is possible that the levels of nutrients used in the MMS were too low. One study in Guinea Bissau used a supplement with 15 nutrients at either one or two RDAs [55]. Among women for whom birth weights were available (who had had fewer births and more education), one RDA, resulted in a 53 g increase in birth weight and two RDAs, a 95 g increase (the latter was somewhat lower when potential confounders were adjusted for). There was no impact on the proportion born with LBWs or on mortality.

A few such trials have also taken place in industrialized countries. A recent trial of women who commonly had micronutrient deficiencies in East London, UK, though rather seriously flawed (about half the women did not complete the trial), suggested that MMS might reduce the incidence of small for gestational age deliveries [56]. A French study (1/3 loss to follow up) among apparently healthy mothers, found that MMS (which did not include iron but added Mg and Ca) increased birthweights from 3,049 to 3,300 g and resulted in a decrease in low birthweights (< 2,700 g) [57]. Maternal vitamin C levels seemed particularly important for birth weight along with zinc for birth length. In the USA, one prospective study in a low-income city for over a decade (which measured adherence to the prenatal vitamins prescribed to all participants) found substantially lower rates of preterm delivery in women who used the supplements (which contained 1 mg of folate, 25 mg zinc, 65 mg iron and 200 mg of calcium) [58]. However, there was no difference in the proportion that was small for gestational age.

Height growth

Shrimpton [59] argues that even modest reductions in LBW would substantially reduce stunting by two years of age. In one study in Vietnam, height at two years was one cm higher and rates of stunting were 8 percentage points lower (from a baseline of 29%) in two districts that received MMS compared to one that did not [53]. In France, maternal zinc supplementation alone was associated with birth length [57]. However, these studies appear to be exceptions. There was no effect of MMS on birth length in any of the 12 studies included in a meta-analysis and there was no overall impact when the data were combined [54]. Nor was such an impact seen in an MMS trial in Mexico, though in a per protocol analysis, the investigators noted that high adherence appeared more likely to lead to impact [60].

Young child morbidity

Maternal supplementation with folic acid with or without iron and zinc reduced the risk of kidney dysfunction and, to a lesser extent, metabolic syndrome among children at 6-8 y of age, however, MMS did not [61].

Neonatal mortality

In Lombok Indonesia, a large trial found that MMS through pregnancy and until 90 days after delivery reduced early infant mortality by 18% compared to iron-folate [62], with an impact of 38% among women who were anemic at baseline. LBW was decreased by 14% and 33% respectively. In a small trial of Indian women who were both undernourished (BMI < 18.5) and anemic (Hb 7-9 mg/dl), a supplement with 29 nutrients given through pregnancy resulted in substantial decreases in LBW and early neonatal morbidity [63].

In Burkina Faso [50], perinatal death was higher in the group receiving the MMS (OR: 1.78; 95% CI: 0.95, 3.32; P < 0.07), particularly among primiperas (OR: 3.44; 95% CI: 1.1, 10.7). Similarly, in Pakistan [51], MMS increased the neonatal mortality rate from 23.5 to 43.2 per thousand live births, though this was not statistically significant. A meta-analysis found no impact of MMS on any type of mortality [64].

Intellectual and motor function in young children

In Bangladesh, adding multiple micronutrients to food supplements for pregnant women led to better cognitive function in children at two years of age [65], although it failed to increase infant micronutrient levels, except for vitamin B12 [66]. In China, MMS increased raw scores in mental development at one year but not earlier, but it did not impact psychomotor development [67]. A study in Nepal found no such impact however [43].


Experience with actual programs aimed at improving women's vitamin and mineral status

Reviewing all the research done so far, the overall impact of MMS would appear to be quite variable, often unimpressive and sometimes apparently negative. Impacts on fetal growth and on young child growth and development appear to be of small to moderate effect sizes. However, it is unclear whether there is an overall positive or negative impact on early infant mortality rates. In addition, recent data suggest MMS may be associated with an increased risk of dysfunctional labor [68].

Some authors do feel that this accumulated evidence is enough to call on WHO to recommend that pregnant women routinely be given MMS [69,70]. Presumably, this is because MMS is so much simpler to implement than alternative interventions. However, others need to be studied even though they are complex, if only because they are likely to be less risky [71]. The period should come after the reference citation. An example of an effective alternative is conditional cash transfer programs; one in Mexico increased birthweights by 127 g [72].

We do not know whether successful food-based interventions will result in similar impacts on birth weight. While it is clear that all needed micronutrients can be obtained in diversified but relatively common diets [73], food-based programs often show improved micronutrient status without concomitant impacts on maternal and child health [74]. Diet-based approaches are complex; no particular food or nutrient manufacturer benefits from them; thus there are actually very few that have been undertaken. Bryce et al. [35] found that none of the largest 20 countries, in which a total 80% of global stunting takes place, have national food supplementation programs for women, though sub-national programs were found in 13 of them.

For addressing infant stunting, further attention should focus on exclusive breastfeeding. It is no doubt difficult to measure, since feeding patterns vary over time and most studies only measure current practices using a 24 hour recall [75], and exclusive breastfeeding with a duration of longer than several weeks is often rare, requiring large sample sizes. One study did examine the link and found an OR of nearly 4 for both stunting as well as wasting associated with exclusive breastfeeding for a duration of less than six months [76]. Even though one trial failed to find an impact [77], given how small the impact of MMS appears to be on early stunting, trials that examine the efficacy of efforts to increase exclusive breastfeeding in reducing infant stunting deserve more attention.

The only widely implemented vitamin or mineral program for women at national level is iron-folate supplementation during pregnancy. When maternal anemia during pregnancy is successfully corrected, it results in an average 20% decline in maternal mortality [78] and improves women's cognitive functioning [79] as well as their capacity to care for their children [80-82].

In countries where anemia levels are higher than 40% during pregnancy, it is recommended that these tablets be offered to all pregnant women [83]. In others, it is often provided only to those with anemia (cut-off points for this vary from serum hemoglobin (Hb) concentrations of 7 mg/dl to 9 mg/dl), on the assumption that much, if not most, of this is linked to iron deficiency. Iron-folate supplements are effective in clinical trials in improving status of these two nutrients during the supplementation periods (usually about 6 months, sometimes 9). A few Latin American and Asian countries have had reasonable success at implementing such programs [84]. Among others, experience in Thailand and Nicaragua suggests that iron-folate supplements can reduce maternal anemia by one-third over a ten-year period [85]. However poor access (great distance to a health facility; outages at health facilities; ineligibility of the health workers who meet the women to access the tablets and thus provide them) and to a somewhat less, but still important extent, poor adherence (side effects, rumors of side effects, and unfounded fears) have plagued these programs for decades and no clear solutions have been found, especially in the poorest countries where needs are greatest [86]. Side effects increase and adherence declines as dosage increases [87].

Methods for improving iron-folate programs exist, usually linked to community-based approaches [88,89], but do increase the cost of what is otherwise an extremely low-cost intervention. But providing iron tablets once per week to adolescents, reducing anemia from 73% to 25% in four years, cost only US $0.36/beneficiary/year [90]. The semi-annual counseling and deworming it included may be the reason it was more successful than previous attempts to reach adolescents with weekly iron supplements [91,92].

The use of bovine lactoferrin instead of ferrous sulfate also appears to greatly reduce the potential for side effects [93], as does the provision of riboflavin and retinol together with ferrous sulfate [94]. Even simply providing lower doses may be useful [95].


Conclusion

Why have so few other maternal nutrition programs emerged? One reason may be that the focus has been on mortality, and only iron deficiency anemia has a substantive impact. Micronutrient supplementation and adolescent and pre-pregnancy nutrition are not included in planning and budgeting for the reduction of maternal mortality [96]. In fact, there is very little normative guidance that provides prioritized advice to policy makers on what to do to improve maternal nutrition. Major attention has focused on child rather than maternal nutrition, perhaps in part due to UNICEF advocacy [59]. Nevertheless, Shrimpton believes that in many countries, the potential for scaling up community-based approaches that will benefit women's nutrition now exists [59].


References
1. Dewey KG,Huffman SL. Maternal, infant, and young child nutrition: combining efforts to maximize impacts on child growth and micronutrient statusFood Nutr BullYear: 200930S187S18920496610
2. Shrimpton R,Victora CG,de Onis M,Lima RC,Blossner M,Clugston G. Worldwide timing of growth faltering: implications for nutritional interventionsPediatricsYear: 2001107E7511331725
3. Greiner T. A New Theory: Breastmilk Displacement May be the Major Cause of Nutritional StuntingUN Standing Committee on Nutrition NewsYear: 2004286364
4. Greiner T. The Breastfeeding Mother's NutritionBreastfeeding TodayYear: 201011013
5. Underwood BA,Deckelbaum RJ,Akabas SR. Women and Micronutrients: Addressing the Gap Throughout the Life CycleAm J Clin NutrYear: 2005811187S
6. Zehner ER. Integrating maternal, infant, and young child nutrition: Report on the Ten Year Strategy Infant and Young Child Nutrition (IYCN) Working Group October 2008 WorkshopFood Nutr BullYear: 200930S190S19620496611
7. Thys-Jacobs S,Starkey P,Bernstein D,Tian J. Premenstrual Syndrome Study GroupCalcium carbonate and the premenstrual syndrome: effects on premenstrual and menstrual symptomsAm J Obstet GynecolYear: 19981794444529731851
8. Bendich A. Micronutrient's in womens health and immune functionNutritionYear: 20011785886711684393
9. Hofmeyr GJ,Lawrie T,Atallah A,Duley L. Calcium supplementation during pregnancy for preventing hypertensive disorders and related problemsCochrane Database Syst RevYear: 20104CD00105920687064
10. Earl S,Cole ZA,Holroyd C,Cooper C,Harvey NC. Session 2: Other diseases: Dietary management of osteoporosis throughout the life courseProc Nutr SocYear: 201069253319968903
11. Nieves JW. Osteoporosis: the role of micronutrientsAm J Clin NutrYear: 2005811232S1239S15883457
12. Pynaert I,De Bacquer D,Matthys C,Delanghe J,Temmerman M,De Backer G,De Henauw S. Determinants of ferritin and soluble transferrin receptors as iron status parameters in young adult womenPublic Health NutrYear: 2009121775178219105865
13. Fraser IS. Non-contraceptive health benefits of intrauterine hormonal systemsContraceptionYear: 20108239640320933112
14. Greiner T. Are lactating women a risk group for iron deficiency anemia?Paper presented at: the First National Workshop on the Control of Nutritional Anaemia in TanzaniaYear: 1992Dar es Salaam
15. Kavle JA,Stoltzfus RJ,Witter F,Tielsch JM,Khalfan SS,Caulfield LE. Association between anaemia during pregnancy and blood loss at and after delivery among women with vaginal births in Pemba Island, Zanzibar, TanzaniaJ Health Popul NutrYear: 20082623224018686556
16. Khambalia AZ,O'Connor DL,Macarthur C,Dupuis A,Zlotkin SH. Periconceptional iron supplementation does not reduce anemia or improve iron status among pregnant women in rural BangladeshAm J Clin NutrYear: 2009901295130219793860
17. Allen LH,Peerson JM. Maternal Micronutrient Supplementation Study GroupImpact of multiple micronutrient versus iron-folic acid supplements on maternal anemia and micronutrient status in pregnancyFood Nutr BullYear: 200930S527S53220120794
18. Scholl TO. Iron status during pregnancy: setting the stage for mother and infantAm J Clin NutrYear: 2005811218S1222S15883455
19. Latham M. The great vitamin A fiasco. [Commentary]World NutritionYear: 201011244
20. Greiner T. The case for universal supplementation is not well made. [Short communication]World NutritionYear: 20101275282
21. Oliveira-Menegozzo JM,Bergamaschi DP,Middleton P,East CE. Vitamin A supplementation for postpartum womenCochrane Database Syst RevYear: 20106CD00594420927743
22. West KP Jr,Katz J,Khatry SK,LeClerq SC,Pradhan EK,Shrestha SR,Connor PB,Dali SM,Christian P,Pokhrel RP,Sommer A. The NNIPS-2 Study GroupDouble blind, cluster randomised trial of low dose supplementation with vitamin A or beta carotene on mortality related to pregnancy in NepalBMJYear: 199931857057510037634
23. Christian P,West KP,Labrique A. Effects of maternal vitamin A or beta-carotene supplementation on maternal and infant mortality in rural Bangladesh: the JiVitA-1 trialYear: 2007Micronutrient ForumIstanbul; Turkey
24. Kirkwood BR,Hurt L,Amenga-Etego S,Tawiah C,Zandoh C,Danso S,Hurt C,Edmond K,Hill Z,Ten Asbroek G,Fenty J,Owusu-Agyei S,Campbell O,Arthur P. ObaapaVitA Trial TeamEffect of vitamin A supplementation in women of reproductive age on maternal survival in Ghana (ObaapaVitA): a cluster-randomised, placebo-controlled trialLancetYear: 20103751640164920435345
25. Kirkwood B. ObaapaViTa Trial TeamEffect of vitamin A supplementation on maternal survival [Letter to the editor: Reply]LancetYear: 201037687420833301
26. London RS,Murphy L,Kitlowski KE,Reynolds MA. Efficacy of alpha-tocopherol in the treatment of the premenstrual syndromeJ Reprod MedYear: 1987324004043302248
27. DiGirolamo AM,Ramirez-Zea M. Role of zinc in maternal and child mental healthAm J Clin NutrYear: 200989940S945S19176735
28. Sanghvi T,Van Ameringen M,Baker J,Fiedler J. Vitamin and mineral deficiencies technical situation analysis: a report for the Ten Year Strategy for the Reduction of Vitamin and Mineral Deficiencies, SummaryFood Nutr BullYear: 200728S160S16417674508
29. Busby A,Abramsky L,Dolk H,Armstrong B,Addor MC,Anneren G,Armstrong N,Baguette A,Barisic I,Berghold A,Bianca S,Braz P,Calzolari E,Christiansen M,Cocchi G,Daltveit AK,De Walle H,Edwards G,Gatt M,Gener B,Gillerot Y,Gjergja R,Goujard J,Haeusler M,Latos-Bielenska A,McDonnell R,Neville A,Olars B,Portillo I,Ritvanen A,Robert-Gnansia E,Rösch C,Scarano G,Steinbicker V. Preventing neural tube defects in Europe: a missed opportunityReprod ToxicolYear: 20052039340215927445
30. Beinner MA,Soares ADN,Barros ALA,Monteiro MAM. Sensory evaluation of rice fortified with ironCiencia E Tecnologia De AlimentosYear: 201030516519
31. Thompson MD,Cole DE,Ray JG. Vitamin B-12 and neural tube defects: the Canadian experienceAm J Clin NutrYear: 200989697S701S19116334
32. Yajnik CS,Deshpande SS,Jackson AA,Refsum H,Rao S,Fisher DJ,Bhat DS,Naik SS,Coyaji KJ,Joglekar CV,Joshi N,Lubree HG,Deshpande VU,Rege SS,Fall CH. Vitamin B12 and folate concentrations during pregnancy and insulin resistance in the offspring: the Pune Maternal Nutrition StudyDiabetologiaYear: 200851293817851649
33. Wieringa FT,Dijkhuizen MA,Muhilal,Van der Meer JW. Maternal micronutrient supplementation with zinc and β-carotene affects morbidity and immune function of infants during the first 6 months of lifeEur J Clin NutrYear: 2010641072107920683457
34. Iannotti LL,Zavaleta N,León Z,Huasquiche C,Shankar AH,Caulfield LE. Maternal zinc supplementation reduces diarrheal morbidity in peruvian infantsJ PediatrYear: 201015696096420227716
35. Bryce J,Coitinho D,Darnton-Hill I,Pelletier D,Pinstrup-Andersen P. Maternal and Child Undernutrition Study GroupMaternal and child undernutrition: effective action at national levelLancetYear: 200837151052618206224
36. de Onis M,Villar J,Gülmezoglu M. Nutritional interventions to prevent intrauterine growth retardation: evidence from randomized controlled trialsEur J Clin NutrYear: 199852S83S939511024
37. Merialdi M,Carroli G,Villar J,Abalos E,Gülmezoglu AM,Kulier R,de Onis M. Nutritional interventions during pregnancy for the prevention or treatment of impaired fetal growth: an overview of randomized controlled trialsJ NutrYear: 20031331626S1631S12730476
38. Mason JB,Deitchler M,Gilman A,Gillenwater K,Shuaib M,Hotchkiss D,Mason K,Mock N,Sethuraman K. Iodine fortification is related to increased weight-for-age and birthweight in children in AsiaFood Nutr BullYear: 20022329230812362593
39. Cogswell ME,Parvanta I,Ickes L,Yip R,Brittenham GM. Iron supplementation during pregnancy, anemia, and birth weight: a randomized controlled trialAm J Clin NutrYear: 20037877378114522736
40. Semba RD,de Pee S,Hess SY,Sun K,Sari M,Bloem MW. Child malnutrition and mortality among families not utilizing adequately iodized salt in IndonesiaAm J Clin NutrYear: 20088743844418258636
41. Saaka M,Oosthuizen J,Beatty S. Effect of prenatal zinc supplementation on birthweightJ Health Popul NutrYear: 20092761963119902797
42. Goldenberg RL,Tamura T,Neggers Y,Copper RL,Johnston KE,DuBard MB,Hauth JC. The effect of zinc supplementation on pregnancy outcomeJAMAYear: 19952744634687629954
43. Christian P,Murray-Kolb LE,Khatry SK,Katz J,Schaefer BA,Cole PM,Leclerq SC,Tielsch JM. Prenatal micronutrient supplementation and intellectual and motor function in early school-aged children in NepalJAMAYear: 20103042716272321177506
44. Katz J,Khatry SK,Leclerq SC,Mullany LC,Yanik EL,Stoltzfus RJ,Siegel EH,Tielsch JM. Daily supplementation with iron plus folic acid, zinc, and their combination is not associated with younger age at first walking unassisted in malnourished preschool children from a deficient population in rural NepalJ NutrYear: 20101401317132120484548
45. Caulfield LE,Putnick DL,Zavaleta N,Lazarte F,Albornoz C,Chen P,Dipietro JA,Bornstein MH. Maternal gestational zinc supplementation does not influence multiple aspects of child development at 54 mo of age in PeruAm J Clin NutrYear: 20109213013620484451
46. Ekström EC,Hyder SM,Chowdhury AM,Chowdhury SA,Lönnerdal B,Habicht JP,Persson LA. Efficacy and trial effectiveness of weekly and daily iron supplementation among pregnant women in rural Bangladesh: disentangling the issuesAm J Clin NutrYear: 2002761392140012450908
47. Haider BA,Bhutta ZA. Multiple-micronutrient supplementation for women during pregnancyCochrane Database Syst RevYear: 200618CD00490517054223
48. Zeng L,Dibley MJ,Cheng Y,Dang S,Chang S,Kong L,Yan H. Impact of micronutrient supplementation during pregnancy on birth weight, duration of gestation, and perinatal mortality in rural western China: double blind cluster randomised controlled trialBMJYear: 2008337a200118996930
49. Sunawang,Utomo B,Hidayat A,Kusharisupeni,Subarkah. Preventing low birthweight through maternal multiple micronutrient supplementation: a cluster-randomized, controlled trial in Indramayu, West JavaFood Nutr BullYear: 200930S488S49520120790
50. Roberfroid D,Huybregts L,Lanou H,Henry MC,Meda N,Menten J,Kolsteren P. MISAME Study GroupEffects of maternal multiple micronutrient supplementation on fetal growth: a double-blind randomized controlled trial in rural Burkina FasoAm J Clin NutrYear: 2008881330134018996870
51. Bhutta ZA,Rizvi A,Raza F,Hotwani S,Zaidi S,Moazzam Hossain S,Soofi S,Bhutta S. A comparative evaluation of multiple micronutrient and iron-folic acid supplementation during pregnancy in Pakistan: impact on pregnancy outcomesFood Nutr BullYear: 200930S496S50520120791
52. Zagré NM,Desplats G,Adou P,Mamadoultaibou A,Aguayo VM. Prenatal multiple micronutrient supplementation has greater impact on birthweight than supplementation with iron and folic acid: a cluster-randomized, double-blind, controlled programmatic study in rural NigerFood Nutr BullYear: 20072831732717974365
53. Huy ND,Le Hop T,Shrimpton R,Hoa CV. An effectiveness trial of multiple micronutrient supplementation during pregnancy in Vietnam: impact on birthweight and on stunting in children at around 2 years of ageFood Nutr BullYear: 200930S506S51620120792
54. Fall CH,Fisher DJ,Osmond C,Margetts BM. Maternal Micronutrient Supplementation Study GroupT Multiple micronutrient supplementation during pregnancy in low-income countries: a meta-analysis of effects on birth size and length of gestationFood Nutr BullYear: 200930S533S54620120795
55. Kaestel P,Michaelsen KF,Aaby P,Friis H. Effects of prenatal multimicronutrient supplements on birth weight and perinatal mortality: a randomised, controlled trial in Guinea-BissauEur J Clin NutrYear: 2005591081108916015266
56. Brough L,Rees GA,Crawford MA,Morton RH,Dorman EK. Effect of multiple-micronutrient supplementation on maternal nutrient status, infant birth weight and gestational age at birth in a low-income, multi-ethnic populationBr J NutrYear: 201010443744520412605
57. Hininger I,Favier M,Arnaud J,Faure H,Thoulon JM,Hariveau E,Favier A,Roussel AM. Effects of a combined micronutrient supplementation on maternal biological status and newborn anthropometrics measurements: a randomized double-blind, placebo-controlled trial in apparently healthy pregnant womenEur J Clin NutrYear: 200458525914679367
58. Scholl TO,Hediger ML,Bendich A,Schall JI,Smith WK,Krueger PM. Use of multivitamin/mineral prenatal supplements: influence on the outcome of pregnancyAm J EpidemiolYear: 19971461341419230775
59. Shrimpton R. UNSCNMaternal nutrition and the intergenerational cycle of growth failureProgress in Nutrition, 6th Report on the World Nutrition SituationYear: 2010GenevaUnited Nations System Standing Committee on Nutrition
60. Ramakrishnan U,Neufeld LM,Flores R,Rivera J,Martorell R. Multiple micronutrient supplementation during early childhood increases child size at 2 y of age only among high compliersAm J Clin NutrYear: 2009891125113119225121
61. Stewart CP,Christian P,Schulze KJ,Leclerq SC,West KP Jr,Khatry SK. Antenatal micronutrient supplementation reduces metabolic syndrome in 6- to 8-year-old children in rural NepalJ NutrYear: 20091391575158119549749
62. Shankar AH,Jahari AB,Sebayang SK,Aditiawarman,Apriatni M,Harefa B,Muadz H,Soesbandoro SD,Tjiong R,Fachry A,Shankar AV,Atmarita,Prihatini S,Sofia G. Supplementation with Multiple Micronutrients Intervention Trial (SUMMIT) Study GroupEffect of maternal multiple micronutrient supplementation on fetal loss and infant death in Indonesia: a double-blind cluster-randomised trialLancetYear: 200837121522718207017
63. Gupta P,Ray M,Dua T,Radhakrishnan G,Kumar R,Sachdev HP. Multimicronutrient supplementation for undernourished pregnant women and the birth size of their offspring: a double-blind, randomized, placebo-controlled trialArch Pediatr Adolesc MedYear: 2007161586417199068
64. Ronsmans C,Fisher DJ,Osmond C,Margetts BM,Fall CH. Maternal Micronutrient Supplementation Study GroupMultiple micronutrient supplementation during pregnancy in low-income countries: a meta-analysis of effects on stillbirths and on early and late neonatal mortalityFood Nutr BullYear: 200930S547S55520120796
65. Tofail F,Persson LA,El Arifeen S,Hamadani JD,Mehrin F,Ridout D,Ekström EC,Huda SN,Grantham-McGregor SM. Effects of prenatal food and micronutrient supplementation on infant development: a randomized trial from the Maternal and Infant Nutrition Interventions, Matlab (MINIMat) studyAm J Clin NutrYear: 20088770471118326610
66. Eneroth H,El Arifeen S,Persson LA,Lönnerdal B,Hossain MB,Stephensen CB,Ekström EC. Maternal multiple micronutrient supplementation has limited impact on micronutrient status of Bangladeshi infants compared with standard iron and folic acid supplementationJ NutrYear: 201014061862420053938
67. Li Q,Yan H,Zeng L,Cheng Y,Liang W,Dang S,Wang Q,Tsuji I. Effects of maternal multimicronutrient supplementation on the mental development of infants in rural western China: follow-up evaluation of a double-blind, randomized, controlled trialPediatricsYear: 2009123E685E69219336358
68. Christian P,Khatry SK,LeClerq SC,Dali SM. Effects of prenatal micronutrient supplementation on complications of labor and delivery and puerperal morbidity in rural NepalInt J Gynaecol ObstetYear: 20091063719368922
69. Dalmiya N,Darnton-Hill I,Schultink W,Shrimpton R. Multiple micronutrient supplementation during pregnancy: a decade of collaboration in actionFood Nutr BullYear: 200930S477S47920120788
70. Shrimpton R,Huffman SL,Zehner ER,Darnton-Hill I,Dalmiya N. Multiple micronutrient supplementation during pregnancy in developing-country settings: policy and program implications of the results of a meta-analysisFood Nutr BullYear: 200930S556S57320120797
71. McLaren DS. Multiple Micronutrients and "Hidden Hunger"Sight and Live MagazineYear: 20089Basel, SwitzerlandSight and Life, DSM612
72. Barber SL,Gertler PJ. The impact of Mexico's conditional cash transfer programme, Oportunidades, on birthweightTrop Med Int HealthYear: 2008131405141418983270
73. Uauy-Dagach R,Hertrampf E. Bowman B,Russell RFood-based dietary recommendations: possibilities and limitationsPresent Knowledge in NutritionYear: 200198th edWashington DCILSI Press636649
74. Olney DK,Talukder A,Iannotti LL,Ruel MT,Quinn V. Assessing impact and impact pathways of a homestead food production program on household and child nutrition in CambodiaFood Nutr BullYear: 20093035536920496626
75. Aarts C,Kylberg E,Hörnell A,Hofvander Y,Gebre-Medhin M,Greiner T. How exclusive is exclusive breastfeeding? A comparison of data since birth with current status dataInt J EpidemiolYear: 2000291041104611101545
76. Hien NN,Kam S. Nutritional status and the characteristics related to malnutrition in children under five years of age in Nghean, VietnamJ Prev Med Public HealthYear: 20084123224018664729
77. Bhandari N,Bahl R,Mazumdar S,Martines J,Black RE,Bhan MK. Infant Feeding Study GroupEffect of community-based promotion of exclusive breastfeeding on diarrhoeal illness and growth: a cluster randomised controlled trialLancetYear: 20033611418142312727395
78. Bhutta ZA,Ahmed T,Black RE,Cousens S,Dewey K,Giugliani E,Haider BA,Kirkwood B,Morris SS,Sachdev HP,Shekar M. Maternal and Child Undernutrition Study GroupWhat works? Interventions for maternal and child undernutrition and survivalLancetYear: 200837141744018206226
79. Beard JL,Hendricks MK,Perez EM,Murray-Kolb LE,Berg A,Vernon-Feagans L,Irlam J,Isaacs W,Sive A,Tomlinson M. Maternal iron deficiency anemia affects postpartum emotions and cognitionJ NutrYear: 200513526727215671224
80. Perez EM,Hendricks MK,Beard JL,Murray-Kolb LE,Berg A,Tomlinson M,Irlam J,Isaacs W,Njengele T,Sive A,Vernon-Feagans L. Mother-infant interactions and infant development are altered by maternal iron deficiency anemiaJ NutrYear: 200513585085515795446
81. Frith AL,Naved RT,Ekström EC,Rasmussen KM,Frongillo EA. Micronutrient supplementation affects maternal-infant feeding interactions and maternal distress in BangladeshAm J Clin NutrYear: 20099014114819439457
82. Murray-Kolb LE,Beard JL. Iron deficiency and child and maternal healthAm J Clin NutrYear: 200989946S950S19158210
83. WHO/UNICEFFocusing on anemia: towards an integrated approach for effective anemia controlYear: 2004GenevaWorld Health Organization
84. Palmer AP,Stewart CP. Micronutrients, Health and Development: Evidence-Based ProgramsSight and Live MagazineYear: 2009Basel, SwitzerlandSight and Live, DSM2533
85. Sanghvi TG,Harvey PW,Wainwright E. Maternal iron-folic acid supplementation programs: evidence of impact and implementationFood Nutr BullYear: 201031S100S10720715594
86. Gillespie S,Kevany J,Mason J. Controlling Iron DeficiencyYear: 1991GenevaACC/SCN
87. Souza AI,Batista Filho M,Bresani CC,Ferreira LO,Figueiroa JN. Adherence and side effects of three ferrous sulfate treatment regimens on anemic pregnant women in clinical trialsCad Saude PublicaYear: 2009251225123319503953
88. Shankar AV,Asrilla Z,Kadha JK,Sebayang S,Apriatni M,Sulastri A,Sunarsih E,Shankar AH. SUMMIT Study GroupProgrammatic effects of a large-scale multiple-micronutrient supplementation trial in Indonesia: using community facilitators as intermediaries for behavior changeFood Nutr BullYear: 200930S207S21420496613
89. Ndiaye M,Siekmans K,Haddad S,Receveur O. Impact of a positive deviance approach to improve the effectiveness of an iron-supplementation program to control nutritional anemia among rural Senegalese pregnant womenFood Nutr BullYear: 20093012813619689091
90. Vir SC,Singh N,Nigam AK,Jain R. Weekly iron and folic acid supplementation with counseling reduces anemia in adolescent girls: a large-scale effectiveness study in Uttar Pradesh, IndiaFood Nutr BullYear: 20082918619418947031
91. Soekarjo DD,Pee Sd S,Kusin JA,Schreurs WH,Schultink W,Muhilal,Bloem MW. Effectiveness of weekly vitamin A (10,000 IU) and iron (60 mg) supplementation for adolescent boys and girls through schools in rural and urban East Java, IndonesiaEur J Clin NutrYear: 20045892793715164114
92. Ahmed F,Khan MR,Akhtaruzzaman M,Karim R,Marks GC,Banu CP,Nahar B,Williams G. Efficacy of twice-weekly multiple micronutrient supplementation for improving the hemoglobin and micronutrient status of anemic adolescent schoolgirls in BangladeshAm J Clin NutrYear: 20058282983516210713
93. Paesano R,Berlutti F,Pietropaoli M,Pantanella F,Pacifici E,Goolsbee W,Valenti P. Lactoferrin efficacy versus ferrous sulfate in curing iron deficiency and iron deficiency anemia in pregnant womenBiometalsYear: 20102341141720407805
94. Ma AG,Schouten EG,Zhang FZ,Kok FJ,Yang F,Jiang DC,Sun YY,Han XX. Retinol and riboflavin supplementation decreases the prevalence of anemia in Chinese pregnant women taking iron and folic Acid supplementsJ NutrYear: 20081381946195018806105
95. Gill SK,Nguyen P,Koren G. Adherence and tolerability of iron-containing prenatal multivitamins in pregnant women with pre-existing gastrointestinal conditionsJ Obstet GynaecolYear: 20092959459819757261
96. Darmstadt GL,Walker N,Lawn JE,Bhutta ZA,Haws RA,Cousens S. Saving newborn lives in Asia and Africa: cost and impact of phased scale-up of interventions within the continuum of careHealth Policy PlanYear: 20082310111718267961

Article Categories:
  • Invited Review Article

Keywords: Maternal nutrition, multimicronutrient supplementation, vitamins, minerals, low birth weight.

Previous Document:  Revisiting Information Technology tools serving authorship and editorship: a case-guided tutorial to...
Next Document:  Expression of eotaxin in 3T3-L1 adipocytes and the effects of weight loss in high-fat diet induced o...