Document Detail

Micronutrients and pregnancy; effect of supplementation on pregnancy and pregnancy outcomes: a systematic review.
Jump to Full Text
MedLine Citation:
PMID:  23368953     Owner:  NLM     Status:  Publisher    
ABSTRACT: INTRODUCTION: Every year more than 20 million infants are born with low birth weight worldwide. About 3.6 million infants die during the neonatal period. More than one third of child deaths are thought to be attributable to maternal and child under nutritionObjectives: To systematically review the effect of supplementing various combinations and types of micronutrients on the course and outcomes of pregnancy. METHODS: Electronic search of Medline, Pub Med, Health Internetwork access to Research Initiative, and Google Scholar databases was conducted. Outcomes of interest were birth weight, low birth weight, small size for gestational age, prenatal mortality and neonatal mortality. After exclusion of irrelevant /incomplete ones, 17 out of 115 articles were considered for the final analysis. FINDINGS: Majority of the articles reviewed favored the supplementation of micronutrients to pregnant mother. Some studies suggested calcium supplementation is associated with a significant protective benefit in the prevention of pre-eclampsia. The remaining articles reviewed, showed significant benefit of Multiple Micronutrients supplementation during pregnancy in reducing low birth weight, small for Gestational Age births as compared to the usual iron-folate supplements. CONCLUSIONS: Supplying micronutrients, mainly multiple micronutrients have beneficial effect in reducing the risk of low birth weight and other complications. Further studies at various combination and doses of micronutrient supplements are recommended.
Taddese Alemu Zerfu; Henok Taddese Ayele
Related Documents :
11808553 - Distribution of ozone and other air pollutants in forests of the carpathian mountains i...
21392403 - In vitro study on human cytomegalovirus affecting early pregnancy villous evt's invasio...
20931553 - Does timing of biochemistry in first-trimester aneuploidy risk assessment affect the ge...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-31
Journal Detail:
Title:  Nutrition journal     Volume:  12     ISSN:  1475-2891     ISO Abbreviation:  Nutr J     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-2-1     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101152213     Medline TA:  Nutr J     Country:  -    
Other Details:
Languages:  ENG     Pagination:  20     Citation Subset:  -    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

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

Full Text
Journal Information
Journal ID (nlm-ta): Nutr J
Journal ID (iso-abbrev): Nutr J
ISSN: 1475-2891
Publisher: BioMed Central
Article Information
Download PDF
Copyright ©2013 Zerfu and Ayele; licensee BioMed Central Ltd.
Received Day: 15 Month: 5 Year: 2012
Accepted Day: 25 Month: 1 Year: 2013
collection publication date: Year: 2013
Electronic publication date: Day: 31 Month: 1 Year: 2013
Volume: 12First Page: 20 Last Page: 20
PubMed Id: 23368953
ID: 3585818
Publisher Id: 1475-2891-12-20
DOI: 10.1186/1475-2891-12-20

Micronutrients and pregnancy; effect of supplementation on pregnancy and pregnancy outcomes: a systematic review
Taddese Alemu Zerfu12 Email:
Henok Taddese Ayele13 Email:
1College of Health Sciences and Referral Hospital, Dilla University, Dilla, Ethiopia
2Food Science and Nutrition Program, College of Natural Sciences, Addis Ababa University, , Ethiopia
3Department of Infectious Diseases Epidemiology, Devision of Julius Center for Health Sciences & Primary Care, University Medical Center, Heidelberglaan 100, Utrecht, 3584, CX, the Netherlands


Every year more than 20 million infants are born with low birth weight worldwide [1]. About 3.6 million infants die during the neonatal period [2]. Two thirds of these deaths occur in southern Asia and sub-Saharan Africa. More than one third of child deaths are thought to be attributable to maternal and child under nutrition [3]. Deficiencies in micronutrients such as folate, iron and zinc and vitamins A, B6, B12, C, E and riboflavin are highly prevalent and may occur concurrently among pregnant women [3]. Micronutrient deficiencies result from inadequate intake of meat, fruits and vegetables, and infections can also be a cause. Multiple micronutrient supplementations in pregnant women may be a promising strategy for reducing adverse pregnancy outcomes through improved maternal nutritional and immune status [4,5].

The World Health Organization (WHO) currently recommends iron and folic acid supplementation to reduce the risk of iron deficiency anemia among pregnant women. Since many developing countries already have systems in place for the delivery of iron and folic acid supplements, micronutrient supplements could be provided at little additional cost [6].

Several systematic reviews of trials examining the effects of maternal multiple micronutrient supplementation have been conducted [7-10] but they have had limitations. Although some researchers have raised concerns that micronutrient supplementation may increase perinatal mortality, none of the previous review articles has adequately addressed this issue [7-9,11]. None has examined the potential sources of heterogeneity in the effect of supplementation on perinatal mortality.

In addition, most of the studies and literature reviews dealing with maternal nutrition and birth outcomes have approached the issue by investigating single nutrients in isolation. On one level, this is necessary for an in-depth study of the complex issues involved. However, nutrient deficiencies are generally found in low-Socio-economic populations, where they are more likely to involve multiple rather than single deficiencies [4]; and studies that address and bring together the broader picture of multiple nutrient intakes or deficiencies are lacking [5].

The effects of maternal micronutrient supplementation on perinatal mortality and other pregnancy outcomes can differ depending on trial characteristics and study population. An updated systematic review is essential to provide the basis for future research and for a discussion of policy implications. Hence, this manuscript examines the effect of micronutrient supplements on the progress and outcomes of pregnancy by reviewing high quality literatures/articles.


The published results from high-quality human observational and experimental studies which analyzed the effects of supplying Multiple Micro Nutrients (MMN) on the course of pregnancy and pregnancy outcomes were all included to this literature based analysis. Electronic search of Medline, Pub Med, Health Internetwork Access to Research Initiative (HINARI), and Google Scholar databases up to the end of 2011 was conducted. Search was done in keywords: (“Mothers” OR “Pregnancy” OR mother* OR maternal OR pregnancy) AND (“Micronutrients” OR “multiple micronutrient*” OR multivitamin OR micronutrient*) AND (supplement*) AND (Observational OR studies OR clinical trials). A function extracting related articles as well as reference lists from research, reviews and editorials was used during the search process. The full version of the English-language analyzed articles and abstracts of most found papers were available during the selection process except for pubmed search.

All literatures, including: observational studies, quasi-randomized trials and prospective randomized controlled trials (RCTs) evaluating multiple micronutrient supplementation in women during pregnancy, published in English language, were included. There were no limits on gestational age at the time of enrolment in the study and the duration of supplementation. Other than the assessment of Small for Gestational Age and neonatal mortality, we did not specifically evaluate minor adverse effects of the supplements such as nausea and vomiting among the mothers and newborns.

In the primary search 115 records were found. After exclusion of studies/reviews which did not examine the effect of micronutrient supplements on pregnancy outcomes duplicated and outdated (published before 2005) data, 64 articles were selected. During the second selection we evaluated 17 of them as potentially relevant articles considering the effect of multiple micro nutrient supplementations on pregnancy and birth outcomes. Studies that failed to meet our criteria were not taken into consideration (Figure 1).

We defined a “multiple micronutrient supplement” as a single tablet containing more than three different micronutrients; however micronutrient-fortified powders, foods and beverages were not included in the definition.

Result and discussion

We identified 115 potentially relevant articles for detailed review (Figure 1). We excluded 51 articles during initial screening because they were not directly referring the effect of micronutrients on pregnancy. The remaining 64 articles were again analyzed for their internal consistency with the research objectives and some 47 of them were found not relevant and/or incomplete, hence excluded for the second time. The remaining 17 of were considered for final review and analysis. From these finally accommodated articles, five of them were related to the effect of Calcium and vitamin D supplementation, three of them were about Iron and iron folic acid supplementation, and the remaining majority [9] articles reviewed were about the effects of MMN supplementations on pregnancy and its outcomes.

Though some degrees of variation by type and amount of micronutrients supplied are observed, the results of the final analysis of the most articles reviewed, favored the supplementation of micronutrients to pregnant mothers.

The systematic review of clinical trials by Buppasiri P et al. from Thailand, with the objective of determining the effect of calcium supplementation on maternal, fetal and neonatal outcomes revealed that Calcium supplementation is associated with a significant protective benefit in the prevention of pre-eclampsia and improving mean infant birth weight. The same study also confirmed lack of additional benefits for calcium supplementation in prevention of preterm birth or low infant birth weight [12].

Another study with a similar finding by Hofmeyr GJ et al. concluded that Calcium supplementation appears to almost halve the risk of pre-eclampsia, and to reduce the rare occurrence of the composite outcome ‘death or serious morbidity’, with no other clear benefits, or harms [13].

The thesis based study by Melody B. on maternal vitamin D status during pregnancy as a predictor of offspring bone mass at three years of age shows that maternal vitamin D status during pregnancy did not predict for the child at 3 years of age [14]. Another systematic review by Bruce W. on dietary vitamin D requirements during pregnancy and lactation recommends further studies to determine optimal vitamin D intakes for pregnant and lactating women as a function of latitude and race [15].

Similarly, the study by Dror DK et al. shows the existence of recent evidence supporting the role of maternal vitamin D status, particularly early in pregnancy, in modulating the risk of pregnancy complications and in sustaining fetal growth, bone development, and immune maturation [16].

On the other hand, according to the findings of the many of the final articles reviewed; though few disfavored the beneficial outcomes of supplementing MMN to pregnant mothers; majority of the others in one way or another supported the presence of significant association and benefit of MMN supplementation with at least one birth outcome.

Among the studies against the added role of supplying MMN to pregnant mothers, the study by Parul Christian, which was about the Effects of alternative maternal micronutrient supplements on low birth weight in rural Nepal, revealed that Antenatal folic acid-iron supplements modestly reduce the risk of low birth weight but MMN confer no additional benefit over folic acid-iron in reducing this risk [17,18]. Another Indian study by Umesh Kapil et al. also said MMN Supplements will not Reduce Incidence of Low Birth weight and other pregnancy outcomes [19]. The Hungarian RCT study by Czeizel AE also revealed that Periconceptional multivitamin supplementation increased fertility but had no significant effect on the rate of different groups of fetal deaths, low birth weight and preterm birth in singletons [20].

Conversely, the remaining RCT and observational studies reviewed from various parts of the world confer that oral supplementation of MMN for pregnant woman benefits the mother and the growing fetus as well as the newborn.

In line with this, the reviews and RCT studies by Prakesh S., Zulfiqar A Bhutta, Michael B Zimmermann and other scholars across the globe unanimously reported that supplementing pregnant mothers with MMN immensely benefits both the mother and the growing fetus in reducing maternal morbidity conditions and morbid neonatal birth outcomes [21-23].

Similarly, the systematic review by Prakesh S. et al. also indicates that prenatal MMN supplementation is associated with a significantly reduced risk of low birth weight and with improved birth weight when compared with iron–folic acid supplementation. However, there was no significant effect of MMN supplementation on the risk of preterm birth or small-for-gestational-age infants [21,22].

Additionally, the review by Zulfiqar A Bhutta et al. also provides evidence on significant benefit of MMN supplementation during pregnancy on reducing SGA births as compared to iron-folate, with no significant increase in the risk of neonatal mortality in populations where skilled birth care is available and majority of births take place in facilities [22].

Furthermore, other review by Kosuke Kawai et al. discusses the safety, efficacy and effective delivery of maternal micronutrient supplementation requiring further research. The other study by Dr. Kathleen Abu-Saad on the other side, declares that maternal nutrition is a modifiable risk factor of public health importance that can be integrated into efforts to prevent adverse birth outcomes, particularly among economically developing/low-income populations [24,25].

On the other hand, RCT by Philip N Baker et al. revealed that Poor micronutrient intake and status increases the risk of SGA births in pregnant adolescents and hence mothers should get prenatal micronutrient supplementation in addition to the customary iron folic acid supplementation [26].

In addition, in a poor population, the effects of maternal MMN supplementation on the fetus persisted into childhood, with increases in both weight and body size. Maternal MMN supplementation might therefore be an important part of overall strengthening of prenatal-care programmes [26-28].

Therefore, it is clear to see that given comparability of impacts on maternal anemia, the decision to replace iron-folate with MMN during pregnancy may be taken in the context of available services in health systems and birth outcomes monitored.


It was possible to learn that almost all available studies of RCT and other observational studies conducted in various parts of the world revealed that it is beneficial for the mother and the neonate and even to childhood with supplementation of MMN than ordinarily iron folic acid supplementation; nonetheless, there are still some equivocal findings related to the effect of MMN supplementation on the risk of preterm birth, small-for-gestational-age infants and neonatal mortality. Therefore, further studies at various combination and doses of micronutrient supplements particularly in areas where there is high prevalence of malnutrition are recommended.

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

TA developed the review parameters and secured support. He also undertook partial literature search, data extraction and analysis. HT made detailed and extensive literature search and involved in the write up and synthesis of the findings. He also reviewed and standardized the study. Both authors read and approved the final manuscript.

Low Birthweight: Country, Regional and Global EstimatesYear: 2004New York: United Nations Children’s Fund & World Health Organization
Black RE,Cousens S,Johnson HL,Lawn JE,Rudan I,Bassani DG,Child Health Epidemiology Reference Group of WHO and UNICEFet al. Global, regional, and national causes of child mortality in 2008: a systematic analysisLancetYear: 20103751227
Black RE,Allen LH,Bhutta ZA,Caulfield LE,de Onis M,Ezzati M,et al. Maternal and Child UndernutritionLancetYear: 200837124326010.1016/S0140-6736(07)61690-018207566
Allen LH,MMN in pregnancy and lactation: an overviewAm J Clin NutrYear: 2005811206S1212S15883453
Bhutta ZA,Ahmed T,Black RE,Cousens S,Dewey K,Giugliani E,et al. Maternal and Child Undernutrition StudyLancetYear: 200837141744010.1016/S0140-6736(07)61693-618206226
Shrimpton R,Shrimpton R,Schultink W,Can supplements help meet the micronutrient needs of the developing world?Proc Nutr SocYear: 20026122322910.1079/PNS200216312133204
Haider BA,Bhutta ZA,Multiple-micronutrient supplementation for women during pregnancyCochrane Database Syst RevYear: 20064418
Shah PS,Ohlsson A,Knowledge synthesis group on determinants of Low birth weight and preterm births. Effects of prenatal MMN supplementation on pregnancy outcomes: a meta-analysisCMAJYear: 2009180E99E10810.1503/cmaj.08177719506270
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: 200930S547S55720120796
Fall CH,Fisher DJ,Osmond C,Margetts BM,Maternal Micronutrient Supplementation Study GroupMultiple micronutrient supplementation during pregnancy in low-income countries: a meta-analysis of effects on birth size and length of gestationFood Nutr BullYear: 200930S533S54620120795
Christian P,Osrin D,Manandhar DS,Khatry SK,de Costello LAM,West KP,Antenatal micronutrient supplements in NepalLancetYear: 2005366711712 16125578
Buppasiri P,et al. Calcium supplementation (other than for preventing or treating hypertension) for improving pregnancy and infant outcomes (Review)The Cochrane LibraryYear: 2011Issue 10
Hofmeyr GJ,Lawrie TA,Atallah AN,Duley L,Duley L,Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems (Review)The Cochrane LibraryYear: 2011Issue 2
Melody NG,Maternal Vitamin D Status during Pregnancy as a Predictor of Offspring Bone Mass At Three Years of AgeYear: 2011 Open Access Dissertations and Theses. Paper 6326.
Hollis BW,Wagner CL,Assessment of dietary vitamin D requirements during pregnancy and lactationAm J Clin NutrYear: 200479571772615113709
Dror DK,et al. Evidence of associations between feto-maternal vitamin D status, cord parathyroid hormone and bone-specific alkaline phosphatase, and newborn whole body bone mineral contentNutrientsYear: 201246877 10.3390/nu402006822413062
Tina G,et al. Maternal iron–folic acid supplementation programs: Evidence of impact and implementationFood Nutr BullYear:  312
Parul C,et al. Effects of alternative maternal micronutrient supplements on low birth weight in rural Nepal: double blind randomized community trialBMJYear: 2003326
Umesh K,Multiple micronutrient supplements will not reduce incidence of Low birth weightIndian J Community MedYear: 2009342
Czeizel AE,Dobo M,Vargha P,Hungarian cohort-controlled trial of periconceptional multivitamin supplementation shows a reduction in certain congenital Abnormalities Birth defects research (part a)Year: 200470853861
Prakesh S,Arne O,Effects of prenatal MMN supplementation on pregnancy outcomes: a meta-analysisCMAJYear: 200918012E9910810.1503/cmaj.08177719506270
Bhutta ZA,et al. Effect of multiple micronutrient supplementation during pregnancy on maternal and birth outcomesBMC Public HealthYear: 201111Suppl 3S1910.1186/1471-2458-11-S3-S1921501436
Zimmermann MB,Iodine deficiency in pregnancy and the effects of maternal iodine supplementation on the offspring: a reviewAm J Clin NutrYear: 200989668S672S10.3945/ajcn.2008.26811C19088150
Kawai KA,Spiegelman D,Shankar AH,Fawzi WW,Maternal multiple micronutrient supplementation and pregnancy outcomes in developing countries: meta-analysis and meta-regressionBulletin of the World Health OrganizationYear: 201189402411B10.2471/BLT.10.08375821673856
Abu-Saad K,The Impact of micronutrient supplementation on malnourished HIV/AIDS- infected children in low-income countries Available at
Baker PN,et al. A prospective study of micronutrient status in adolescent pregnancyAm J Clin NutrYear: 2009891114112410.3945/ajcn.2008.2709719244368
Anjana V,Effects of antenatal multiple micronutrient supplementation on children’s weight and size at 2 years of age in Nepal: follow-up of a double-blind randomized controlled trialThe LancetYear: 2008371961149249910.1016/S0140-6736(08)60172-5
Huybregts L,et al. Prenatal food supplementation fortified with MMN increases birth length: a randomized controlled trial in rural Burkina FasoAm J Clin NutrYear: 2009901593160010.3945/ajcn.2009.2825319812173


[Figure ID: F1]
Figure 1 

Selection of studies included in systematic review of randomized controlled trials and observational studies on maternal multiple micronutrient supplementation and pregnancy outcomes.

Article Categories:
  • Review

Previous Document:  Integrating the Overlap of Obstructive Lung Disorders with Obstructive Sleep Apnea: OLDOSA Syndrome.
Next Document:  Intra-coronary thrombus in an infant with Kawasaki disease and giant coronary aneurysm.