Research Review By Dr. Ceara Higgins©


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Date Posted:

July 2013

Study Title:

Micronutrients and pregnancy; effect of supplementation on pregnancy and pregnancy outcomes: a systematic review


Zerfu AZ & Henok TA

Author's Affiliations:

College of Health Sciences and Referral Hospital, Dilla University, Dilla, Ethiopia & College of Natural Sciences, Addis Ababa University, Ethiopia

Publication Information:

Nutrition Journal 2013; 12:20.

Background Information:

More than 20 million infants worldwide are born with low birth weight each year. Further, approximately 3.6 million infants die during the neonatal period each year, with two thirds of those deaths occurring in sub-Saharan Africa and southern Asia. Of those deaths, more than one third are thought to be attributed to child and maternal under nutrition. It is also common to see multiple nutrient deficiencies in low socio-economic populations, so we must be concerned with the pre-natal nutritional status of those individuals (and all pregnant women, for that matter!).

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 (1). These deficiencies typically result from inadequate intake of meat, fruits and vegetables. Infections can also be a cause. Multiple micronutrient supplementation in pregnant women may be a promising strategy for reducing adverse pregnancy outcomes through improved maternal nutritional and immune status (2, 3). This concept has been studied and reviewed, but the literature is subject to some limitations. Many of the studies and literature reviews investigating maternal nutrition and birth outcomes have approached the issue by evaluating single nutrients in isolation. On one level, this is necessary for an in-depth study of the complex issues involved. However, as just mentioned, nutrient deficiencies are generally found in low-Socio-economic populations, where they are more likely to involve multiple rather than single deficiencies. Studies that address and bring together the broader picture of multiple nutrient intakes or deficiencies are lacking.

Currently, The World Health Organization (WHO) recommends supplementation with iron and folic acid during the pre-natal period and many developing countries currently have systems in place to deliver these supplements. This suggests that additional micronutrients could be delivered to expectant mothers in developing countries easily, with little additional cost.

The concepts of optimal prenatal and neonatal nutrition are obviously relevant worldwide. The goal of this systematic review was to evaluate the effect of supplementing various combinations and types of micronutrients on the course and outcomes of pregnancy.

Pertinent Results:

17 articles were included in the final review. 5 of these looked at the effect of Calcium and Vitamin D supplementation, 3 looked at iron and iron folic acid supplementation, and 9 looked at Multiple Micro Nutrient (MMN) supplementation.

Calcium and Vitamin D Supplementation:

Buppasiri et al. (4) found that calcium supplementation was associated with a significant protective effect in preventing pre-eclampsia and improving mean infant birth weight. Similarly, Hofmeyr and colleagues (5) showed that calcium supplementation appeared to reduce the risk of pre-eclampsia by almost 50%. They also showed a reduction in the rare occurrence of death or serious morbidity.

Dror et al. (6) showed that Vitamin D supplementation early in pregnancy could help modulate the risk of pregnancy complications, sustain fetal growth and bone development, and assist in immune maturation. Further studies by Melody (7) and Hollis (8) showed that Vitamin D supplementation had no effect on offspring bone mass at three years and expressed the need for further research on proper dosage of Vitamin D during pregnancy.

Iron and Iron Folic Acid Supplementation:

Christian et al. (9) showed that antenatal folic acid-iron supplementation modestly reduced the risk of low birth weight, while MMN showed no additional benefits.

MMN Supplementation:

Kapil (10) found no benefit to MMN supplementation with regards to reduced incidence of low birth weight and other pregnancy outcomes. Czeizel (11) showed that multivitamin supplementation taken periconceptionally could increase fertility but had no significant effect on the rate of fetal deaths, low birth weight, and preterm births. Contrarily, Prakesh and colleagues (12) found that prenatal MMN supplementation was associated with significantly reduced risk of low-birth weight, and improved birth weights when compared with iron-folic acid supplementation. Further, Bhutta et al. (13) found a significant benefit to MMN supplementation during pregnancy with respect to reducing small for gestational age (SGA) births. Abu-Saad (14) & Baker (15) both found that poor micronutrient status and intake can increase the risks of SGA births and concluded that since maternal nutrition is an easily modifiable risk factor, mothers should receive prenatal micronutrient supplementation. Finally, 3 studies (Baker et al. [15], Anjana [16], and Huybregts et al. [17]) showed that in poor populations maternal MMN supplementation not only had a positive effect on the fetus, but also showed increases in both weight and body size that persisted into childhood.

Clinical Application & Conclusions:

The majority of the reviewed studies showed MMN supplementation in the pre-natal period to be beneficial for the mother, the neonate, and even into early childhood. Although further studies are needed to determine the proper combinations and doses of micronutrients for mothers, particularly in areas with high levels of malnutrition, this study suggests that proper nutrient supplementation can be beneficial to our pregnant patients, especially those in lower socio-economic brackets.

Study Methods:

The authors included published studies, in English, which analyzed the effects of supplementing with Multiple Micro Nutrients (MMN) on the course of the pregnancy and pregnancy outcomes. MMNs were defined as single tablets which contained more that three distinct micronutrients. No fortified powders, foods, or beverages were considered. No limits were set on gestational age. A search was conducted using Medline, Pub Med, Health Internetwork Access to Research Initiative, and Google Scholar. The databases were searched to include articles published up to 2011. Observational studies, quasi-randomized trials, and prospective randomized controlled trials (RCTs) were included.

Study Strengths / Weaknesses:

The authors considered the most commonly recommended supplements and explored the benefits of additional supplementation.

By only including articles published in English and limiting their search to electronic databases it is highly possible that the authors may have missed a number of pertinent articles.

Additional References:

  1. Black RE, Allen LH, Bhutta ZA et al. Maternal and Child Undernutrition. Lancet 2008; 371: 243–260.
  2. Allen LH. MMN in pregnancy and lactation: an overview. Am J Clin Nutr 2005, 81:1206S–1212S.
  3. Bhutta ZA, Ahmed T, Black RE et al. Maternal and Child Undernutrition Study. Lancet 2008; 371: 417–440.
  4. Buppasiri P et al. Calcium supplementation (other than for preventing or treating hypertension) for improving pregnancy and infant outcomes (Review). The Cochrane Library 2011, (Issue 10).
  5. Hofmeyr GJ et al. Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems (Review). The Cochrane Library 2011, (Issue 2).
  6. 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 content. Nutrients 2012, 4: 68–77.
  7. Melody NG. Maternal Vitamin D Status during Pregnancy as a Predictor of Offspring Bone Mass At Three Years of Age. 2011, Open Access Dissertations and Theses. Paper 6326.
  8. Hollis BW, Wagner CL. Assessment of dietary vitamin D requirements during pregnancy and lactation. Am J Clin Nutr 2004; 79(5): 717–726.
  9. Christian P et al: Effects of alternative maternal micronutrient supplements on low birth weight in rural Nepal: double blind randomized community trial. BMJ 2003; 326: 571.
  10. Kapil U. Multiple micronutrient supplements will not reduce incidence of low birth weight. Indian J Community Med 2009; 34(2): 85-86.
  11. 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) 2004; 70: 853–861.
  12. Prakesh S & Arne O. Effects of prenatal MMN supplementation on pregnancy outcomes: a meta-analysis. CMAJ 2009; 180(12): E99–108.
  13. Bhutta ZA et al. Effect of multiple micronutrient supplementation during pregnancy on maternal and birth outcomes. BMC Public Health 2011; 11(Suppl 3): S19.
  14. Abu-Saad K: The Impact of micronutrient supplementation on malnourished HIV/AIDS- infected children in low-income countries. Available at
  15. Baker PN et al. A prospective study of micronutrient status in adolescent pregnancy. Am J Clin Nutr 2009, 89: 1114–1124.
  16. 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 trial. The Lancet 2008; 371: 492–499.
  17. Huybregts L et al. Prenatal food supplementation fortified with MMN increases birth length: a randomized controlled trial in rural Burkina Faso. Am J Clin Nutr 2009, 90:1593–1600.