Multiple Micronutrient Supplementation during Pregnancy in Developing-Country Settings: Policy and Program Implications of the Results of a Meta-Analysis

Institute of Child Health, London, UK.
Food and nutrition bulletin (Impact Factor: 1.15). 12/2009; 30(4 Suppl):S556-73. DOI: 10.1177/15648265090304S410
Source: PubMed


An independent Systematic Review Team performed a meta-analysis of 12 randomized, controlled trials comparing multiple micronutrients with daily iron-folic acid supplementation during pregnancy.
To provide an independent interpretation of the policy and program implications of the results of the meta-analysis.
A group of policy and program experts performed an independent review of the meta-analysis results, analyzing internal and external validity and drawing conclusions on the program implications.
Although iron content was often lower in the multiple micronutrient supplement than in the iron-folic acid supplement, both supplements were equally effective in tackling anemia. Community-based supplementation ensured high adherence, but some mothers still remained anemic, indicating the need to concomitantly treat infections. The small, significant increase in mean birthweight among infants of mothers receiving multiple micronutrients compared with infants of mothers receiving iron-folic acid is of similar magnitude to that produced by food supplementation during pregnancy. Larger micronutrient doses seem to produce greater impact. Meaningful improvements have also been observed in height and cognitive development of the children by 2 years of age. There were no significant differences in the rates of stillbirth, early neonatal death, or neonatal death between the supplemented groups. The nonsignificant trend toward increased early neonatal mortality observed in the groups receiving multiple micronutrients may be related to differences across trials in the rate of adolescent pregnancies, continuing iron deficiency, and/or adequacy of postpartum health care and merits further investigation.
Replacing iron-folic acid supplements with multiple micronutrient supplements in the package of health and nutrition interventions delivered to mothers during pregnancy will improve the impact of supplementation on birthweight and on child growth and development.

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Available from: Roger Shrimpton, Aug 25, 2014
    • "Replacing IFA supplements with multiple micronutrient supplements during pregnancy has been reported to improve both birth weight and child growth. Furthermore, meaningful improvements have been shown in height and cognitive development of children by 2 years of age.[16] Multiple micronutrient supplements from week 12 to 16 of gestation to delivery resulted in a significant increase in birth size compared with placebo, but did not affect head circumference.[29] "
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    ABSTRACT: Increased requirement and decreased dietary intakes of micronutrients during pregnancy might affect maternal health and pregnancy outcomes. This study was aimed to examine the effects of two types of multiple micronutrient supplementations on pregnancy outcomes in Kashan, Iran. In a randomized single-blind controlled clinical trial, 104 primigravid singleton pregnant women aged 18-30 years were randomly assigned to receive either a multivitamin (n = 51) or a multivitamin-mineral (n = 53) supplements for 20 weeks. Participants consumed supplements once a day at week 16 of gestation. Maternal anthropometric data as well as newborn's weight, height, head circumference and 5-min Apgar score were also determined. Independent samples t-test was used for comparing between-group means. Multivariate linear regression analysis was used to identify determinants of newborn's weight, height and head circumference. Women taking multivitamin-mineral supplements gained marginally less weight until week 28 than those taking multivitamin supplements (weight at week 28 of gestation: 67.5 ± 11.4 vs. 71.6 ± 10.3 kg, P = 0.06). Mean body mass index at week 28 (25.8 ± 4.0 vs. 28.4 ± 3.7 kg/m(2), P = 0.001) as well as at delivery (28.0 ± 3.9 vs. 30.1 ± 3.8 kg/m(2), P = 0.006) was lower among women taking multivitamin-mineral supplements than those taking multivitamin supplements. Although no significant difference was seen in newborns' height and Apgar score between the two groups, mean birth weight (3.3 ± 0.4 vs. 3.1 ± 0.4 kg, P = 0.04) and head circumference (35 ± 1.4 vs. 34 ± 1.3 cm, P < 0.0001) of the infants whose mothers receiving multivitamin-mineral supplements were higher than those whose mothers received multivitamins. Multivitamin-mineral use by pregnant women was a significant predictor of infants' weight (β =0.191, P = 0.03) and head circumference (β =0.907, P = 0.005). In conclusion, we found that birth weight and head circumference was increased in infants whose mothers received multivitamin-mineral supplements for 5 months during pregnancy compared with infants whose mothers received multivitamin supplements.
    No preview · Article · Apr 2014 · International journal of preventive medicine
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    • "The UL was doubled from 2000 IU/day, as recommended by the IOM in 1997 [10], despite a lack of new pregnancy trial safety data published between 1997 and 2010. Uncertainty surrounding vitamin D requirements in pregnancy has led to divergent dose recommendations; for example, the UNICEF antenatal micronutrient formulation contains 200 IU/day [11], the Canadian Paediatric Society has suggested 2000 IU/day [12], and Hollis et al. advised an intake of 4000 IU/day [13]. Similarly, the 25(OH)D threshold to define vitamin D sufficiency is debated; the IOM set 50 nmol/L as a lower limit of sufficiency [7], yet other expert bodies such as the American Academy of Pediatrics have suggested that pregnant women attain serum 25(OH)D >80 nmol/L [14]. "
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    ABSTRACT: BACKGROUND: Antenatal vitamin D status may be associated with the risk of adverse pregnancy and neonatal outcomes; however, the benefits of vitamin D supplementation during pregnancy remain unknown. METHODS: We conducted a double-blind placebo-controlled randomized trial to evaluate the effect of high-dose prenatal 3rd trimester vitamin D3 supplementation on maternal and neonatal (cord blood) serum 25-hydroxyvitamin D (25(OH)D) concentration (primary biochemical efficacy outcome) and maternal serum calcium concentration (primary safety measure). Eligibility criteria were pregnant women aged 18 to <35 years, at 26 to 29 weeks gestation, and residing in Dhaka, Bangladesh. 160 women were randomized by 1:1 allocation to one of two parallel intervention groups; placebo (n = 80) or 35,000 IU/week of vitamin D3 (n = 80) until delivery. All participants, study personnel and study investigators were blind to treatment allocation. RESULTS: Mean maternal 25(OH)D concentration was similar in the vitamin D and placebo groups at baseline (45 vs. 44 nmol/L; p = 0.66), but was significantly higher in the vitamin D group vs. placebo group among mothers at delivery (134 vs. 38 nmol/L; p < 0.001) and newborns (cord blood: 103 vs. 39; p < 0.001). In the vitamin D group, 95% of neonates and 100% of mothers attained 25(OH)D >50 nmol/L, versus 21% mothers and 19% of neonates in the placebo group. No participants met criteria for hypercalcemia, there were no known supplement-related adverse events, and major pregnancy outcomes were similar between groups. CONCLUSIONS: Antenatal 3rd-trimester vitamin D3 supplementation (35,000 IU/week) significantly raised maternal and cord serum 25(OH)D concentrations above 50 nmol/L in almost all participants without inducing hypercalcemia or other observed safety concerns. Doses up to 35,000 IU/week may be cautiously used in further research aimed at establishing the clinical effects and safety of vitamin D3 supplementation in pregnancy.Trial registration: This trial was registered at (NCT01126528).
    Full-text · Article · Apr 2013 · Nutrition Journal
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    • "It is surprising to note that the participants remained anemic in the included studies, even though they were taking seemingly adequate amounts of supplemental iron. There is no exact reason for this but this has been seen in many effectiveness trials over the years [40]. An important aspect to consider is the timing of initiation of multiple micronutrient supplements. "
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    ABSTRACT: Given the widespread prevalence of micronutrient deficiencies in developing countries, supplementation with multiple micronutrients rather than iron-folate alone, could be of potential benefit to the mother and the fetus. These benefits could relate to prevention of maternal complications and reduction in other adverse pregnancy outcomes such as small-for-gestational age (SGA) births, low birth weight, stillbirths, perinatal and neonatal mortality. This review evaluates the evidence of the impact of multiple micronutrient supplements during pregnancy, in comparison with standard iron-folate supplements, on specific maternal and pregnancy outcomes of relevance to the Lives Saved Tool (LiST). DATA SOURCES/REVIEW METHODS: A systematic review of randomized controlled trials was conducted. Search engines used were PubMed, the Cochrane Library, the WHO regional databases and hand search of bibliographies. A standardized data abstraction and Child Health Epidemiology Reference (CHERG) adaptation of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) technique were used for data abstraction and overall quality of evidence. Meta-analyses were performed to calculate summary estimates of utility to the LiST model for the specified outcome of incidence of SGA births. We also evaluated the potential impact of multiple micronutrients on neonatal mortality according to the proportion of deliveries occurring in facilities (using a threshold of 60% to indicate functionality of health systems for skilled births). We included 17 studies for detailed data abstraction. There was no significant benefit of multiple micronutrients as compared to iron folate on maternal anemia in third trimester [Relative risk (RR) = 1.03; 95% confidence interval (CI): 0.87 - 1.22 (random model)]. Our analysis, however, showed a significant reduction in SGA by 9% [RR = 0.91; 95% CI: 0.86 - 0.96 (fixed model)]. In the fixed model, the SGA outcome remained significant only in women with mean body mass index (BMI) ≥ 22 kg/m2. There was an increased risk of neonatal mortality in studies with majority of births at home [RR = 1.47, 95% CI: 1.13-1.92]; such an effect was not evident where ≥ 60% of births occurred in facility settings [RR = 0.94, 95% CI: 0.81-1.09]. Overall there was no increase in the risk of neonatal mortality [RR = 1.05, 95% CI: 0.92 - 1.19 (fixed model)]. This review provides evidence of a 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. Given comparability of impacts on maternal anemia, the decision to replace iron-folate with multiple micronutrients during pregnancy may be taken in the context of available services in health systems and birth outcomes monitored.
    Full-text · Article · Apr 2011 · BMC Public Health
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