Title:
Multiple-micronutrient supplementation for women during pregnancy.

Abstract:
Multiple-micronutrient deficiencies often coexist in low- to middle-income countries. They are exacerbated in pregnancy due to the increased demands, leading to potentially adverse effects on the mother. Substantive evidence regarding the effectiveness of multiple-micronutrient supplements (MMS) during pregnancy is not available.
To evaluate the benefits to both mother and infant of multiple-micronutrient supplements in pregnancy and to assess the risk of adverse events as a result of supplementation.
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (17 February 2012) and reference lists of retrieved articles and key reviews. We also contacted experts in the field for additional and ongoing trials.
All prospective randomised controlled trials evaluating multiple-micronutrient supplementation during pregnancy and its effects on the pregnancy outcome, irrespective of language or publication status of the trials. We included cluster-randomised trials but quasi-randomised trials were excluded.
Two review authors independently assessed trials for inclusion and trial quality. Two review authors independently extracted the data. Data were checked for accuracy.
Twenty-three trials (involving 76,532 women) were identified as eligible for inclusion in this review but only 21 trials (involving 75,785 women) contributed data to the review.When compared with iron and folate supplementation, MMS resulted in a statistically significant decrease in the number of low birthweight babies (risk ratio (RR) 0.89; 95% confidence interval (CI) 0.83 to 0.94) and small-for-gestational age (SGA) babies (RR 0.87; 95% CI 0.81 to 0.95). No statistically significant differences were shown for other maternal and pregnancy outcomes: preterm births RR 0.99 (95% CI 0.96 to 1.02), miscarriage RR 0.90 (95% CI 0.79 to 1.02), maternal mortality RR 0.97 (95% CI 0.63 to 1.48), perinatal mortality RR 0.99 (95% CI 0.84 to 1.16), stillbirths RR 0.96 (95% CI 0.86 to 1.07) and neonatal mortality RR 1.01 (95% CI 0.89 to 1.15).A number of prespecified clinically important outcomes could not be assessed due to insufficient or non-available data. These include placental abruption, congenital anomalies including neural tube defects, premature rupture of membranes, neurodevelopmental delay, very preterm births, cost of supplementation, side-effects of supplements, maternal well being or satisfaction, and nutritional status of children.
Though multiple micronutrients have been found to have a significant beneficial impact on SGA and low birthweight babies, we still need more evidence to guide a universal policy change and to suggest replacement of routine iron and folate supplementation with a MMS. Future trials should be adequately powered to evaluate the effects on mortality and other morbidity outcomes. Trials should also assess the effect of variability between different combinations and dosages of micronutrients, keeping within the safe recommended levels. In regions with deficiency of a single micronutrient, evaluation of each micronutrient against a placebo in women already receiving iron with folic acid would be especially useful in justifying the inclusion of that micronutrient in routine antenatal care.