FPIN's Clinical Inquiries

Micronutrient Supplementation During Pregnancy

 


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Am Fam Physician. 2015 Aug 1;92(3):222-223.

Clinical Question

What is the effect of multimicronutrient supplementation on birth outcomes in pregnant women?

Evidence-Based Answer

A multimicronutrient supplement is an oral tablet containing the recommended daily allowance of several vitamins and minerals: vitamin A, vitamin B1, vitamin B2, niacin, vitamin B6, vitamin B12, folic acid, vitamin C, vitamin D, vitamin E, iron, copper, selenium, and zinc. The use of multimicronutrient supplements in pregnant women reduces rates of low birth weight (by 11% to 14%) and small-for-gestational-age infants (by 9% to 17%). However, the World Health Organization does not recommend multimicronutrient supplementation because of the potential for increased neonatal mortality in some situations. (Strength of Recommendation: C, based on expert opinion and heterogeneous subgroup analyses.)

Evidence Summary

Five meta-analyses have evaluated the effects of multimicronutrient supplementation during pregnancy (eTable A).

View/Print Table

eTable A.

Meta-Analyses of Multimicronutrient Supplementation During Pregnancy

Outcomes
YearNumber of RCTs included (patients)Control interventionLow birth weight (95% CI)Small for gestational age (95% CI)Comments

2009A1

13 (61,705)

Placebo, or iron and folate

RR = 0.81 (0.73 to 0.91) vs. placebo

No difference

RR = 0.83 (0.74 to 0.93) vs. iron and folate

2009A2

12 (27,676)

Iron and folate

RR = 0.89 (0.83 to 0.97)*

RR = 0.91 (0.84 to 0.99)*

Increased rates of small-for-gestational-age births

2011A3

14 (67,213)

Iron and folate

NR

RR = 0.91 (0.86 to 0.96)

Increased neonatal mortality in areas with more than 60% home births

2012A4

21 (75,785)

Iron and folate

RR = 0.89 (0.83 to 0.94)

RR = 0.87 (0.81 to 0.95)

Decreased neonatal mortality if started after 20 weeks' gestation

2012A5

16 (61,972)

Less than three micronutrients (usually iron and folate)

RR = 0.86 (0.81 to 0.91)

RR = 0.83 (0.73 to 0.95)

Increased neonatal mortality if started after first trimester


note: Multimicronutrient supplementation includes vitamin A, vitamin B1, vitamin B2, niacin, vitamin B6, vitamin B12, folic acid, vitamin C, vitamin D, vitamin E, iron, copper, selenium, and zinc.

CI = confidence interval; NR = not reported; RCTs = randomized controlled trials; RR = relative risk.

*—Results reported as odds ratios, which were converted to RR assuming baseline rates of 10%.

Information from:

A1. Shah PS, Ohlsson A; Knowledge Synthesis Group on Determinants of Low Birth Weight and Preterm Births. Effects of prenatal multimicronutrient supplementation on pregnancy outcomes: a meta-analysis. CMAJ. 2009;180(12):E99–E108.

A2. Fall CH, Fisher DJ, Osmond C, Margetts BM; Maternal Micronutrient Supplementation Study Group. Multiple micronutrient supplementation during pregnancy in low-income countries: a meta-analysis of effects on birth size and length of gestation. Food Nutr Bull. 2009;30(4 suppl):S533–S546.

A3. Haider BA, Yakoob MY, Bhutta ZA. Effect of multiple micronutrient supplementation during pregnancy on maternal and birth outcomes. BMC Public Health. 2011;11(suppl 3):S19.

A4. Haider BA, Bhutta ZA. Multiple-micronutrient supplementation for women during pregnancy. Cochrane Database Syst Rev. 2012;(11):CD004905.

A5. Ramakrishnan U, Grant FK, Goldenberg T, Bui V, Imdad A, Bhutta ZA. Effect of multiple micronutrient supplementation on pregnancy and infant outcomes: a systematic review. Paediatr Perinat Epidemiol. 2012;26(suppl 1):153–167.

eTable A.

Meta-Analyses of Multimicronutrient Supplementation During Pregnancy

Outcomes
YearNumber of RCTs included (patients)Control interventionLow birth weight (95% CI)Small for gestational age (95% CI)Comments

2009A1

13 (61,705)

Placebo, or iron and folate

RR = 0.81 (0.73 to 0.91) vs. placebo

No difference

RR = 0.83 (0.74 to 0.93) vs. iron and folate

2009A2

12 (27,676)

Iron and folate

RR = 0.89 (0.83 to 0.97)*

RR = 0.91 (0.84 to 0.99)*

Increased rates of small-for-gestational-age births

2011A3

14 (67,213)

Iron and folate

NR

RR = 0.91 (0.86 to 0.96)

Increased neonatal mortality in areas with more than 60% home births

2012A4

21 (75,785)

Iron and folate

RR = 0.89 (0.83 to 0.94)

RR = 0.87 (0.81 to 0.95)

Decreased neonatal mortality if started after 20 weeks' gestation

2012A5

16 (61,972)

Less than three micronutrients (usually iron and folate)

RR = 0.86 (0.81 to 0.91)

RR = 0.83 (0.73 to 0.95)

Increased neonatal mortality if started after first trimester


note: Multimicronutrient supplementation includes vitamin A, vitamin B1, vitamin B2, niacin, vitamin B6, vitamin B12, folic acid, vitamin C, vitamin D, vitamin E, iron, copper, selenium, and zinc.

CI = confidence interval; NR = not reported; RCTs = randomized controlled trials; RR = relative risk.

*—Results reported as odds ratios, which were converted to RR assuming baseline rates of 10%.

Information from:

A1. Shah PS, Ohlsson A; Knowledge Synthesis Group on Determinants of Low Birth Weight and Preterm Births. Effects of prenatal multimicronutrient supplementation on pregnancy outcomes: a meta-analysis. CMAJ. 2009;180(12):E99–E108.

A2. Fall CH, Fisher DJ, Osmond C, Margetts BM; Maternal Micronutrient Supplementation Study Group. Multiple micronutrient supplementation during pregnancy in low-income countries: a meta-analysis of effects on birth size and length of gestation. Food Nutr Bull. 2009;30(4 suppl):S533–S546.

A3. Haider BA, Yakoob MY, Bhutta ZA. Effect of multiple micronutrient supplementation during pregnancy on maternal and birth outcomes. BMC Public Health. 2011;11(suppl 3):S19.

A4. Haider BA, Bhutta ZA. Multiple-micronutrient supplementation for women during pregnancy. Cochrane Database Syst Rev. 2012;(11):CD004905.

A5. Ramakrishnan U, Grant FK, Goldenberg T, Bui V, Imdad A, Bhutta ZA. Effect of multiple micronutrient supplementation on pregnancy and infant outcomes: a systematic review. Paediatr Perinat Epidemiol. 2012;26(suppl 1):153–167.

A Cochrane meta-analysis included 21 randomized controlled trials with nearly 76,000 pregnant women from developed and developing countries who were randomized to receive multimicronutrient supplements vs. iron/folate supplements. Multimicronutrient supplementation significantly decreased the number of low-birth-weight and small-for-gestational-age infants (by 11% and 13%, respectively).1 There were no significant effects on rates of preterm birth, miscarriage, maternal mortality, perinatal mortality, stillbirth, or overall neonatal mortality (relative risk [RR] = 1.01; 95% confidence interval [CI], 0.89 to 1.2).

A large international meta-analysis found a significant reduction in the incidence of low-birth-weight and small-for-gestational-age infants whose mothers received multi-micronutrient supplements (14% and 17%, respectively).2 Another large international meta-analysis found reductions in the incidence of low-birth-weight infants, but not in small-for-gestational-age infants.3 In both studies, overall neonatal mortality was unchanged. Two additional meta-analyses using studies from less-developed countries found reductions in small-for-gestational-age infants (9% in each), and one study evaluating low birth weight found a similar reduction (11%).4,5

One meta-analysis found no difference in the incidence of large-for-gestational-age infants in women who received multimicronutrient supplements (12 trials, N = 27,676; odds ratio = 1.1; 95% CI, 1.0 to 1.3).5 Overall mortality was not changed, but subgroup analyses in three of these studies suggested that supplementation may affect neonatal mortality in some situations.1,2,4 The Cochrane review found a decrease in neonatal mortality when supplementation was started after 20 weeks' gestation (three trials, N = 41,347; RR = 0.88; 95% CI, 0.8 to 0.97); however, the authors noted significant heterogeneity across the studies.1 Another meta-analysis found an increased risk of neonatal death when supplementation began after the first trimester (five trials, N = 7,835; RR = 1.4; 95% CI, 1.1 to 1.8)2; however, this meta-analysis excluded data from a large trial (n = 31,209) that was included in the Cochrane subanalysis. A third meta-analysis found an increased risk of neonatal mortality in studies in which more than 60% of births occurred at home (four trials, N = 11,583; RR = 1.5; 95% CI, 1.1 to 1.9).4

A separate meta-analysis evaluated the micronutrient intakes of pregnant women in developed countries and compared them with relevant national nutritional recommendations.6 Sixty-two studies were included, with nearly 109,000 pregnant women. Pregnant women in the United States consumed the most micronutrients at levels above national recommendations (vitamin A, vitamin B1, vitamin B2, niacin, vitamin B12, vitamin C, calcium, magnesium, and zinc), although intake of folate, iron, and vitamin D was below national recommendations.

Recommendations from Others

The World Health Organization recommends iron and folate supplementation in pregnant women.7 It acknowledges that multimicronutrient supplementation reduces the risk of low birth weight, but does not recommend it for general use because of neonatal mortality data. The Centers for Disease Control and Prevention recommends multivitamin supplementation in pregnant women who do not consume an adequate diet.8 In addition, it recommends that all women of reproductive age consume 0.4 mg of folic acid per day via fortified foods or supplements.

Copyright Family Physicians Inquiries Network. Used with permission.

Address correspondence to Jon O. Neher, MD, at jon_neher@valleymed.org. Reprints are not available from the authors.

Author disclosure: No relevant financial affiliations.

REFERENCES

show all references

1. Haider BA, Bhutta ZA. Multiple-micronutrient supplementation for women during pregnancy. Cochrane Database Syst Rev. 2012;(11):CD004905....

2. Ramakrishnan U, Grant FK, Goldenberg T, Bui V, Imdad A, Bhutta ZA. Effect of multiple micronutrient supplementation on pregnancy and infant outcomes: a systematic review. Paediatr Perinat Epidemiol. 2012;26(suppl 1):153–167.

3. Shah PS, Ohlsson A; Knowledge Synthesis Group on Determinants of Low Birth Weight and Preterm Births. Effects of prenatal multimicronutrient supplementation on pregnancy outcomes: a meta-analysis. CMAJ. 2009;180(12):E99–E108.

4. Haider BA, Yakoob MY, Bhutta ZA. Effect of multiple micronutrient supplementation during pregnancy on maternal and birth outcomes. BMC Public Health. 2011;11(suppl 3):S19.

5. Fall CH, Fisher DJ, Osmond C, Margetts BM; Maternal Micronutrient Supplementation Study Group. Multiple micronutrient supplementation during pregnancy in low-income countries: a meta-analysis of effects on birth size and length of gestation. Food Nutr Bull. 2009;30(4 suppl):S533–S546.

6. Blumfield ML, Hure AJ, Macdonald-Wicks L, Smith R, Collins CE. A systematic review and meta-analysis of micronutrient intakes during pregnancy in developed countries. Nutr Rev. 2013;71(2):118–132.

7. Kawai K, Spiegelman D, Shankar AH, Fawzi WW. Maternal multiple micronutrient supplementation and pregnancy outcomes in developing countries: meta-analysis and meta-regression. Bull World Health Organ. 2011;89(6):402–411B.

8. Moos MK, Dunlop AL, Jack BW, et al. Healthier women, healthier reproductive outcomes: recommendations for the routine care of all women of reproductive age. Am J Obstet Gynecol. 2008;199(6 suppl 2):S280–S289.

Clinical Inquiries provides answers to questions submitted by practicing family physicians to the Family Physicians Inquiries Network (FPIN). Members of the network select questions based on their relevance to family medicine. Answers are drawn from an approved set of evidence-based resources and undergo peer review. The strength of recommendations and the level of evidence for individual studies are rated using criteria developed by the Evidence-Based Medicine Working Group (http://www.cebm.net/?o=1025).

The complete database of evidence-based questions and answers is copyrighted by FPIN. If interested in submitting questions or writing answers for this series, go to http://www.fpin.org or email: questions@fpin.org.

This series is coordinated by John E. Delzell, Jr., MD, MSPH, Assistant Medical Editor.

A collection of FPIN's Clinical Inquiries published in AFP is available at http://www.aafp.org/afp/fpin.



 

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