Preventing low birthweight through maternal multiple micronutrient supplementation: a cluster-randomized, controlled trial in Indramayu, West Java. A comparative evaluation of multiple micronutrient and iron-folic acid supplementation during pregnancy in Pakistan: impact on pregnancy outcomes. Impact of micronutrient supplementation during pregnancy on birth weight, duration of gestation, and perinatal mortality in rural western China: double blind cluster randomised controlled trial. Prenatal multiple micronutrient supplementation has greater impact on birthweight than supplementation with iron and folic acid: a cluster-randomized, double-blind, controlled programmatic study in rural Niger. Effects of alternative maternal micronutrient supplements on low birth weight in rural Nepal: double blind randomised community trial. Effect of multiple-micronutrient supplementation on maternal nutrient status, infant birth weight and gestational age at birth in a low-income, multi-ethnic population. Effects of maternal micronutrient supplementation on fetal loss and infant mortality: a cluster-randomized trial in Nepal. A micronutrient-fortified beverage prevents iron deficiency, reduces anemia and improves the hemoglobin concentration of pregnant Tanzanian women. Multiple micronutrient supplementation during pregnancy does not lead to greater infant birth size than does iron-only supplementation: a randomized controlled trial in a semirural community in Mexico.
Micronutrient deficiencies may contribute to a higher incidence of low birthweight (LBW). UNICEF/United Nations University/World Health Organization jointly proposed a formulation for a multiple micronutrient supplement for pregnant women, and several effectiveness trials were conducted to assess its impact.
                To evaluate the efficacy of prenatal multiple micronutrient supplementation for improving birth size, pregnancy outcome, and maternal micronutrient status in comparison with iron-folic acid supplementation.
                We carried out a cluster-randomized, controlled trial in Indramayu, Indonesia, involving 843 pregnant women. Of these, 432 received multiple micronutrients and 411 received iron-folic acid. Fieldworkers visited the women daily to observe supplement consumption and record fetal loss and mortality.
                The mean number of supplements consumed during pregnancy and 30 days postpartum was high (136 in the group receiving multiple micronutrients and 140 in the iron-folic acid group). The women consumed the supplements on average 5 days per week. Although there were no significant differences between the groups in the percentage of infants with LBW there was a trend toward a lower incidence of LBW in the group receiving multiple micronutrients (6.3% vs. 7.3%), and the mean birthweight was 40 g higher in the group receiving multiple micronutrients than in the iron-folic acid group, although the difference was not significant. Among those who consumed 90 or more supplements during pregnancy, women taking multiple micronutrients had a 3.3% combined rate of miscarriage, stillbirth, or neonatal death, as compared with 6.9% for those taking iron-folic acid only (p < .049). The anemia rates in the two groups were similar after supplementation, even though the amount of iron in the multiple micronutrient supplement was half that in the iron-folic acid supplement. Serum retinol was higher in the group receiving multiple micronutrients.
                Multivitamin supplementation use among pregnant women is as effective as iron-folic acid in improving anemia status and appears to have other benefits for maternal and child nutritional status. Maternal micronutrient deficiencies are widespread in Pakistan and are potentially associated with maternal undernutrition and intrauterine growth retardation. Intervention strategies largely consist of administration of iron-folic acid supplements during pregnancy.
                We evaluated the acceptability of multiple micronutrient supplementation and its potential benefits on pregnancy outcomes and maternal micronutrient status in a cohort of pregnant women in rural and urban Sindh through a cluster-randomized design.
                We randomly assigned 2378 pregnant women to receive either iron-folic acid or multiple micronutrient supplements. The supplements were administered fortnightly by community health workers who performed home visits to assess tolerance and observe the mothers.
                The women in both groups consumed about 75% of the supplements provided, and few reported adverse effects such as vomiting, abdominal pain, etc. There was a small (70 g) but significant increase in birthweight among infants of mothers receiving multiple micronutrients as compared with infants of mothers receiving iron-folic acid supplements (2.95 +/- 0.6 vs. 2.88 +/- 0.5 kg, p = .01). This translated into a 10% reduction (p < 0.17) in the proportion of low-birthweight infants among infants of mothers receiving multiple micronutrients. Although stillbirth rates were comparable in the two groups, the early neonatal mortality rate in the group receiving multiple micronutrients was higher, although not significantly, than that in the group receiving iron-folic acid (43.2 vs. 23.5 deaths per 1000 live births; RR = 1.64; 95% CI, 0.94 to 2.87). Comparable reductions in anemia (hemoglobin < 11 g/dL) were observed, although the proportion with low iron stores (assessed by serum ferritin) was lower in the iron-folic acid group in the postnatal period. Although the proportion of women with subclinical vitamin A deficiency after supplementation did not differ between the two groups, the iron-folic acid group had a higher proportion with lower serum zinc levels in the immediate postpartum period.
                These data suggest that multiple micronutrient supplements are well tolerated during pregnancy, but the effect on birthweight is modest. The observed effect on early neonatal mortality suggests the need for further studies and careful assessment of the intervention in health system settings. To examine the impact of antenatal supplementation with multiple micronutrients or iron and folic acid compared with folic acid alone on birth weight, duration of gestation, and maternal haemoglobin concentration in the third trimester.
                Cluster randomised double blind controlled trial.
                Two rural counties in north west China.
                5828 pregnant women and 4697 live births.
                Villages were randomised for all pregnant women to take either daily folic acid (control), iron with folic acid, or multiple micronutrients with a recommended allowance of 15 vitamins and minerals.
                Birth weight, length, and head circumference measured within 72 hours after delivery. Neonatal survival assessed at the six week follow-up visit.
                Birth weight was 42 g (95% confidence interval 7 to 78 g) higher in the multiple micronutrients group compared with the folic acid group. Duration of gestation was 0.23 weeks (0.10 to 0.36 weeks) longer in the iron-folic acid group and 0.19 weeks (0.06 to 0.32 weeks) longer in the multiple micronutrients group. Iron-folic acid was associated with a significantly reduced risk of early preterm delivery (<34 weeks) (relative risk 0.50, 0.27 to 0.94, P=0.031). There was a significant increase in haemoglobin concentration in both iron-folic acid (5.0 g/l, 2.0 to 8.0 g/l, P=0.001) and multiple micronutrients (6.9 g/l, 4.1 to 9.6 g/l, P<0.001) groups compared with folic acid alone. In post hoc analyses there were no significant differences for perinatal mortality, but iron-folic acid was associated with a significantly reduced early neonatal mortality by 54% (relative risk 0.46, 0.21 to 0.98).
                In rural populations in China antenatal supplementation with iron-folic acid was associated with longer gestation and a reduction in early neonatal mortality compared with folic acid. Multiple micronutrients were associated with modestly increased birth weight compared with folic acid, but, despite this weight gain, there was no significant reduction in early neonatal mortality. Pregnant women in developing countries need sufficient doses of iron in nutrient supplements to maximise reductions in neonatal mortality. Trial registration ISRCTN08850194. Micronutrient deficiencies during pregnancy are associated with adverse pregnancy outcomes, including reduced birthweight. Low birthweight is associated with increased risk of infant mortality and growth failure.
                To assess the effects of prenatal supplementation with UNIMMAP (United Nations International Multiple Micronutrient Preparation) compared with iron/folic acid on average birthweight and incidence of low birthweight.
                Pregnant women from 78 villages in Niger were included in a cluster-randomized, double-blinded, controlled supplementation trial. Baseline, monthly follow-up, and birth data were collected. Cluster analysis was conducted to assess differences in mean birthweight and incidence of low birthweight between groups using multiple linear regression models. Analyses were stratified by nutrition status and duration of supplementation.
                Of the 3,670 women recruited, 2,550 completed the study and provided complete birthweight data (1,328 received multiple micronutrients and 1,222 received iron/folic acid). Mean birthweight was significantly higher (67 g, p < .001) with multiple micronutrients (3,092 +/- 190 g) than with iron/folic acid (3,025 +/- 205 g); this corresponded to a 14% fall in the incidence of low birthweight (from 8.4% with multiple micronutrients to 7.2% with folic acid fortification). The impact of multiple micronutrients was greater when the supplements were taken for more than 150 days. The incidence of low birthweight was further reduced in women who entered pregnancy with a poorer nutrition status.
                Prenatal supplementation with multiple micronutrients had a greater positive impact on birthweight than supplementation with iron/folic acid. Our data suggest that prenatal supplementation with multiple micronutrients as part of a prenatal care package in addition to interventions to promote improved maternal prepregnancy nutrition status is an important strategy to increase birthweight and reduce the incidence of low birthweight. To assess the impact on birth size and risk of low birth weight of alternative combinations of micronutrients given to pregnant women.
                Double blind cluster randomised controlled trial.
                Rural community in south eastern Nepal.
                4926 pregnant women and 4130 live born infants.
                426 communities were randomised to five regimens in which pregnant women received daily supplements of folic acid, folic acid-iron, folic acid-iron-zinc, or multiple micronutrients all given with vitamin A, or vitamin A alone (control).
                Birth weight, length, and head and chest circumference assessed within 72 hours of birth. Low birth weight was defined <2500 g.
                Supplementation with maternal folic acid alone had no effect on birth size. Folic acid-iron increased mean birth weight by 37 g (95% confidence interval -16 g to 90 g) and reduced the percentage of low birthweight babies (<2500 g) from 43% to 34% (16%; relative risk=0.84, 0.72 to 0.99). Folic acid-iron-zinc had no effect on birth size compared with controls. Multiple micronutrient supplementation increased birth weight by 64 g (12 g to 115 g) and reduced the percentage of low birthweight babies by 14% (0.86, 0.74 to 0.99). None of the supplement combinations reduced the incidence of preterm births. Folic acid-iron and multiple micronutrients increased head and chest circumference of babies, but not length.
                Antenatal folic acid-iron supplements modestly reduce the risk of low birth weight. Multiple micronutrients confer no additional benefit over folic acid-iron in reducing this risk. Poor nutrient intake during pregnancy can adversely affect both infant and maternal health. The aim was to investigate the efficacy of multiple-micronutrient supplementation during pregnancy in a socially deprived population in the developed world. We conducted a randomised, double-blind, placebo-controlled trial of multiple-micronutrient supplementation including 20 mg Fe and 400 microg folic acid, from the first trimester of pregnancy in 402 mothers, in East London, UK. Nutrient status was measured at recruitment, and at 26 and 34 weeks of gestation. Infants were weighed at birth. At recruitment the prevalence of anaemia was 13 %, vitamin D insufficiency 72 %, thiamin deficiency 12 % and folate deficiency 5 %, with no differences between groups. Only 39 % of women completed the study; rates of non-compliance were similar in both groups. Intention-to-treat analysis showed that participants receiving treatment had higher mean Hb at 26 weeks of gestation (110 (sd 10) v.108 (sd 10) g/l; P = 0.041) and 34 weeks of gestation (113 (sd 12) v.109 (sd 10) g/l; P = 0.003) and packed cell volume concentrations at 26 weeks of gestation (0.330 (sd 0.025) v. 0.323 (sd 0.026) l/l; P = 0.011) and 34 weeks of gestation (0.338 (sd 0.029) v. 0.330 (sd 0.028) l/l; P = 0.014) compared with controls. Analysis of compliant women showed supplemented women had higher median concentrations of serum ferritin, erythrocyte folate and 25-hydroxyvitamin D later in gestation than controls. In the compliant subset (n 149), placebo mothers had more small-for-gestational age (SGA) infants (eight SGA v. thirteen; P = 0.042) than treatment mothers. Baseline micronutrient deficiencies were common; the multiple-micronutrient supplement was well-tolerated and improved nutrient status. Multiple-micronutrient supplements from early pregnancy may be beneficial and larger studies are required to assess impact on birth outcomes and infant development. We previously reported that maternal micronutrient supplementation in rural Nepal decreased low birth weight by approximately 15%.
                We examined the effect of daily maternal micronutrient supplementation on fetal loss and infant mortality.
                The study was a double-blind, cluster-randomized, controlled trial among 4926 pregnant women and their 4130 infants in rural Nepal. In addition to vitamin A (1000 microg retinol equivalents), the intervention groups received either folic acid (FA; 400 microg), FA + iron (60 mg), FA + iron + zinc (30 mg), or multiple micronutrients (MNs; the foregoing plus 10 microg vitamin D, 10 mg vitamin E, 1.6 mg thiamine, 1.8 mg riboflavin, 2.2 mg vitamin B-6, 2.6 microg vitamin B-12, 100 mg vitamin C, 64 microg vitamin K, 20 mg niacin, 2 mg Cu, and 100 mg Mg). The control group received vitamin A only.
                None of the supplements reduced fetal loss. Compared with control infants, infants whose mothers received FA alone or with iron or iron + zinc had a consistent pattern of 15-20% lower 3-mo mortality; this pattern was not observed with MNs. The effect on mortality was restricted to preterm infants, among whom the relative risks (RRs) were 0.36 (95% CI: 0.18, 0.75) for FA, 0.53 (0.30, 0.92) for FA + iron, 0.77 (0.45, 1.32) for FA + iron + zinc, and 0.70 (0.41, 1.17) for MNs. Among term infants, the RR for mortality was close to 1 for all supplements except MNs (RR: 1.74; 95% CI: 1.00, 3.04).
                Maternal micronutrient supplementation failed to reduce overall fetal loss or early infant mortality. Among preterm infants, FA alone or with iron reduced mortality in the first 3 mo of life. MNs may increase mortality risk among term infants, but this effect needs further evaluation. Maternal malnutrition continues to be a major contributor to adverse reproductive outcomes in developing countries, despite longstanding efforts to fortify foods or to distribute medicinal supplements to pregnant women. The objective of this study was to test the effect of a micronutrient-fortified beverage containing 11 micronutrients (iron, iodine, zinc, vitamin A, vitamin C, niacin, riboflavin, folate, vitamin B-12, vitamin B-6 and vitamin E) on the hemoglobin, iron and vitamin A status of pregnant women in Tanzania. A group of 259 pregnant women with gestational ages of 8 to 34 wk were enrolled in a randomized double-blind controlled trial in which study women received 8 wk of supplementation. Hemoglobin, ferritin and dried blood spot retinol were measured at baseline and at the end of the supplementation period. The supplement resulted in a 4.16 g/L increase in hemoglobin concentration and a 3 micro g/L increase in ferritin and reduced the risk of anemia and iron deficiency anemia by 51 and 56%, respectively. The risk of iron deficiency was reduced by 70% among those who had iron deficiency at baseline and by 92% among those who had adequate stores. The micronutrient-fortified beverage may be a useful and convenient preventative measure, one that could help improve the nutritional status of women both before and during pregnancy and thereby help avoid some of the potential maternal and fetal consequences of micronutrient deficiencies. Little is known about the benefits of prenatal multivitamin and mineral supplements in reducing low birth weight.
                We conducted a randomized, double-blind clinical trial in semirural Mexico to compare the effects of multiple micronutrient (MM) supplements with those of iron supplements during pregnancy on birth size.
                Pregnant women (n = 873) were recruited before 13 wk of gestation and received supplements 6 d/wk at home, as well as routine antenatal care, until delivery. Both supplements contained 60 mg Fe, but the MM group also received 1-1.5 times the recommended dietary allowances of several micronutrients.
                At recruitment, the women in the 2 groups were not significantly different in age, parity, economic status, height, or hemoglobin concentration but differed significantly in marital status (4.6% and 2.0% of women in the MM and iron-only groups, respectively, were single mothers) and mean (+/- SD) body mass index (in kg/m(2); 24.6 +/- 4.3 and 23.8 +/- 3.9 in the iron-only and MM groups, respectively). Losses to follow-up (25%) and compliance (95%) did not differ significantly between the groups. In intent-to-treat analyses (MM group: n = 323; iron-only group: n = 322), mean (+/- SD) birth weight (2.981 +/- 0.391 and 2.977 +/- 0.393 kg in the MM and iron-only groups, respectively) and birth length (48.61 +/- 1.82 and 48.66 +/- 1.83 cm in the MM and iron-only groups, respectively) did not differ significantly between the groups.
                These findings suggest that MM supplementation during pregnancy does not lead to greater infant birth size than does iron-only supplementation.
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.