Effect of multiple micronutrient supplementation during pregnancy on maternal and birth outcomes

Abstract

Objectives/backgroundGiven 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 methodsA 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).ResultsWe 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)].ConclusionThis 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.

Effect of Different Iron-Folic Acid (IFA) Formulations, Doses, and Frequencies on Pregnancy and Neonatal Outcomes compared to Multiple Micronutrients (MMN) among Pregnant Women: A Systematic Review and Meta-analysis

“…Although these ndings may have occurred by chance, they cannot be disregarded and have important policy implications. Our ndings align with earlier versions of the Cochrane review and other systematic reviews by Haider (2011) [57], Ronsmans (2009)[58] and Christian (2018) [59]…”

Effect of Different Iron-Folic Acid (IFA) Formulations, Doses, and Frequencies on Pregnancy and Neonatal Outcomes compared to Multiple Micronutrients (MMN) among Pregnant Women: A Systematic Review and Meta-analysis

“…Although these ndings may have occurred by chance, they cannot be disregarded and have important policy implications. Our ndings align with earlier versions of the Cochrane review and other systematic reviews by Haider (2011) [57], Ronsmans (2009)[58] and Christian (2018) [59]…”

Micronutrient Supplementation and Pregnancy Outcomes

“…34,35 Unlike one meta-analysis 36 that found a trend toward higher early neonatal mortality in the group receiving MMN vs iron-folic acid alone, we found no difference between these groups. A recent meta-analysis 34 showed an increased risk of neonatal mortality with MMN compared with iron-folic acid in settings where less than 60% of births occurred in facilities; however, consistent with our trial, there was no increased risk in settings where most births occurred in facilities. Thus, our results should be interpreted in the context of the existing burden of micronutrient deficiencies, adverse pregnancy, and fetal outcomes, and the setting.…”

Effect of Multiple Micronutrient versus Iron-Folate Supplementation during Pregnancy on Intrauterine Growth

“…Our findings confirm earlier conclusions that prenatal MM supplements are efficacious in reducing the incidence of LBW and SGA when compared to providing only IFA. The direction and magnitude of effect sizes for LBW, SGA, and birthweight are similar to those reported by Fall et al [29] who included the trials that compared the UNIMMAP MM supplements with IFA, and that reported by Haider et al [8] for SGA. Shah and Ohlsson [30] reported similar reductions in LBW but did not find significant differences in the risk of delivering SGA infants; we used similar methods but included findings from seven additional trials (n = 16,839).…”

Effect of Different Iron-Folic Acid (IFA) Formulations, Doses, and Frequencies on Pregnancy and Neonatal Outcomes compared to Multiple Micronutrients (MMN) among Pregnant Women: A Systematic Review and Meta-analysis

“…Although these ndings may have occurred by chance, they cannot be disregarded and have important policy implications. Our ndings align with earlier versions of the Cochrane review and other systematic reviews by Haider (2011) [57], Ronsmans (2009)[58] and Christian (2018) [59]…”

Micronutrient Supplementation and Pregnancy Outcomes

“…34,35 Unlike one meta-analysis 36 that found a trend toward higher early neonatal mortality in the group receiving MMN vs iron-folic acid alone, we found no difference between these groups. A recent meta-analysis 34 showed an increased risk of neonatal mortality with MMN compared with iron-folic acid in settings where less than 60% of births occurred in facilities; however, consistent with our trial, there was no increased risk in settings where most births occurred in facilities. Thus, our results should be interpreted in the context of the existing burden of micronutrient deficiencies, adverse pregnancy, and fetal outcomes, and the setting.…”

Effect of Multiple Micronutrient versus Iron-Folate Supplementation during Pregnancy on Intrauterine Growth

“…Our findings confirm earlier conclusions that prenatal MM supplements are efficacious in reducing the incidence of LBW and SGA when compared to providing only IFA. The direction and magnitude of effect sizes for LBW, SGA, and birthweight are similar to those reported by Fall et al [29] who included the trials that compared the UNIMMAP MM supplements with IFA, and that reported by Haider et al [8] for SGA. Shah and Ohlsson [30] reported similar reductions in LBW but did not find significant differences in the risk of delivering SGA infants; we used similar methods but included findings from seven additional trials (n = 16,839).…”

Effect of Different Iron-Folic Acid (IFA) Formulations, Doses, and Frequencies on Pregnancy and Neonatal Outcomes compared to Multiple Micronutrients (MMN) among Pregnant Women: A Systematic Review and Meta-analysis

“…Although these ndings may have occurred by chance, they cannot be disregarded and have important policy implications. Our ndings align with earlier versions of the Cochrane review and other systematic reviews by Haider (2011) [57], Ronsmans (2009)[58] and Christian (2018) [59]…”

Micronutrient Supplementation and Pregnancy Outcomes

“…34,35 Unlike one meta-analysis 36 that found a trend toward higher early neonatal mortality in the group receiving MMN vs iron-folic acid alone, we found no difference between these groups. A recent meta-analysis 34 showed an increased risk of neonatal mortality with MMN compared with iron-folic acid in settings where less than 60% of births occurred in facilities; however, consistent with our trial, there was no increased risk in settings where most births occurred in facilities. Thus, our results should be interpreted in the context of the existing burden of micronutrient deficiencies, adverse pregnancy, and fetal outcomes, and the setting.…”

Effect of Multiple Micronutrient versus Iron-Folate Supplementation during Pregnancy on Intrauterine Growth

“…Our findings confirm earlier conclusions that prenatal MM supplements are efficacious in reducing the incidence of LBW and SGA when compared to providing only IFA. The direction and magnitude of effect sizes for LBW, SGA, and birthweight are similar to those reported by Fall et al [29] who included the trials that compared the UNIMMAP MM supplements with IFA, and that reported by Haider et al [8] for SGA. Shah and Ohlsson [30] reported similar reductions in LBW but did not find significant differences in the risk of delivering SGA infants; we used similar methods but included findings from seven additional trials (n = 16,839).…”