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. Effect of multimicronutrient supplementation on gestational length and birth size: a randomized, placebo-controlled, double-blind effectiveness trial in Zimbabwe. 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. Vitamins and perinatal outcomes among HIV-negative women in Tanzania. Effect of supplementation during pregnancy with L-arginine and antioxidant vitamins in medical food on pre-eclampsia in high risk population: randomised controlled trial. Effects of alternative maternal micronutrient supplements on low birth weight in rural Nepal: double blind randomised community trial. Lower rate of preeclampsia after antioxidant supplementation in pregnant women with low antioxidant status. 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. Effect of maternal multiple micronutrient supplementation on fetal loss and infant death in Indonesia: a double-blind cluster-randomised 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 prenatal food and micronutrient supplementation on infant development: a randomized trial from the Maternal and Infant Nutrition Interventions, Matlab (MINIMat) study. Effects of prenatal multimicronutrient supplements on birth weight and perinatal mortality: a randomised, controlled trial in Guinea-Bissau. Multimicronutrient supplementation for undernourished pregnant women and the birth size of their offspring: a double-blind, randomized, placebo-controlled trial. Effects of maternal multiple micronutrient supplementation on fetal growth: a double-blind randomized controlled trial in rural Burkina Faso. 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. Fortified mineral water improves folate status and decreases plasma homocysteine concentration in pregnant women. Effects of antenatal multiple micronutrient supplementation on birthweight and gestational duration in Nepal: double-blind, randomised controlled trial.
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. Multiple micronutrient deficiencies may contribute to low birth weight, which is a major global determinant of mortality.
                We assessed the effect of prenatal multimicronutrient supplementation on gestational length and birth size.
                We conducted a randomized, placebo-controlled, double-blind effectiveness trial among antenatal care attendees in Harare, Zimbabwe. Pregnant women (22-35 wk of gestation) were randomly allocated to receive a multimicronutrient or placebo supplement daily until delivery. Supplementation with iron and folic acid was part of antenatal care.
                Of 1669 women, birth data were available from 1106 (66%), of whom 360 (33%) had HIV infection. The mean gestational length was 39.1 wk, and 16.6% of the women had a gestational length < 37 wk. The mean birth weight was 3030 g, and 10.5% of the infants had a birth weight < 2500 g. Multimicronutrient supplementation was associated with tendencies for increased gestational length (0.3 wk; 95% CI: -0.04, 0.6 wk; P = 0.06), birth weight (49 g; -6, 104 g; P = 0.08), and head circumference (0.2 cm; -0.02, 0.4 cm; P = 0.07) but was not associated with low birth weight (birth weight < 2500 g) (relative risk: 0.84; 0.59, 1.18; P = 0.31). The effect of multimicronutrient supplementation on birth weight was not significantly different between HIV-uninfected (26 g; -38, 91 g) and HIV-infected (101 g; -3, 205 g) subjects (interaction, P > 0.10).
                Antenatal multimicronutrient supplementation may be one strategy to increase birth size. 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. Prematurity and low birth weight are associated with high perinatal and infant mortality, especially in developing countries. Maternal micronutrient deficiencies may contribute to these adverse outcomes.
                In a double-blind trial in Dar es Salaam, Tanzania, we randomly assigned 8468 pregnant women (gestational age of fetus, 12 to 27 weeks) who were negative for human immunodeficiency virus infection to receive daily multivitamins (including multiples of the recommended dietary allowance) or placebo. All the women received prenatal supplemental iron and folic acid. The primary outcomes were low birth weight (<2500 g), prematurity, and fetal death.
                The incidence of low birth weight was 7.8% among the infants in the multivitamin group and 9.4% among those in the placebo group (relative risk, 0.82; 95% confidence interval [CI], 0.70 to 0.95; P=0.01). The mean difference in birth weight between the groups was modest (67 g, P<0.001). The rates of prematurity were 16.9% in the multivitamin group and 16.7% in the placebo group (relative risk, 1.01; 95% CI, 0.91 to 1.11; P=0.87), and the rates of fetal death were 4.3% and 5.0%, respectively (relative risk, 0.87; 95% CI, 0.72 to 1.05; P=0.15). Supplementation reduced both the risk of a birth size that was small for gestational age (<10th percentile; 10.7% in the multivitamin group vs. 13.6% in the placebo group; relative risk, 0.77; 95% CI, 0.68 to 0.87; P<0.001) and the risk of maternal anemia (hemoglobin level, <11 g per deciliter; relative risk, 0.88; 95% CI, 0.80 to 0.97; P=0.01), although the difference in the mean hemoglobin levels between the groups was small (0.2 g per deciliter, P<0.001).
                Multivitamin supplementation reduced the incidence of low birth weight and small-for-gestational-age births but had no significant effects on prematurity or fetal death. Multivitamins should be considered for all pregnant women in developing countries. (ClinicalTrials.gov number, NCT00197548 [ClinicalTrials.gov].).
                Copyright 2007 Massachusetts Medical Society. To test the hypothesis that a relative deficiency in L-arginine, the substrate for synthesis of the vasodilatory gas nitric oxide, may be associated with the development of pre-eclampsia in a population at high risk.
                Randomised, blinded, placebo controlled clinical trial.
                Tertiary public hospital in Mexico City.
                Pregnant women with a history of a previous pregnancy complicated by pre-eclampsia, or pre-eclampsia in a first degree relative, and deemed to be at increased risk of recurrence of the disease were studied from week 14-32 of gestation and followed until delivery.
                Supplementation with a medical food-bars containing L-arginine plus antioxidant vitamins, antioxidant vitamins alone, or placebo-during pregnancy.
                Development of pre-eclampsia/eclampsia.
                222 women were allocated to the placebo group, 228 received L-arginine plus antioxidant vitamins, and 222 received antioxidant vitamins alone. Women had 4-8 prenatal visits while receiving the bars. The incidence of pre-eclampsia was reduced significantly (χ(2) = 19.41; P < 0.001) in women randomised to L-arginine plus antioxidant vitamins compared with placebo (absolute risk reduction 0.17 (95% confidence interval 0.12 to 0.21). Antioxidant vitamins alone showed an observed benefit, but this effect was not statistically significant compared with placebo (χ(2) = 3.76; P = 0.052; absolute risk reduction 0.07, 0.005 to 0.15). L-arginine plus antioxidant vitamins compared with antioxidant vitamins alone resulted in a significant effect (P = 0.004; absolute risk reduction 0.09, 0.05 to 0.14).
                Supplementation during pregnancy with a medical food containing L-arginine and antioxidant vitamins reduced the incidence of pre-eclampsia in a population at high risk of the condition. Antioxidant vitamins alone did not have a protective effect for prevention of pre-eclampsia. Supplementation with L-arginine plus antioxidant vitamins needs to be evaluated in a low risk population to determine the generalisability of the protective effect, and the relative contributions of L-arginine and antioxidant vitamins to the observed effects of the combined treatment need to be determined. Trial registration Clinical trials NCT00469846. 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. To investigate maternal and neonatal outcomes after antioxidant supplementation relatively early in pregnancy (8 to 12 weeks) for pregnant women with low antioxidant status.
                A randomized, double-blind, placebo-controlled trial of daily antioxidant supplementation was performed on pregnant women screening positive for low antioxidant status at 8 to 12 weeks of gestation. Low antioxidant status was defined as a superoxidedismutase (SOD) level below 1102 U/g Hb or 164 U/mL. The supplementation group received the following antioxidants daily: vitamins A (1000 IU), B6 (2.2 mg), B12 (2.2 microg), C (200 mg), and E (400 IU), folic acid (400 microg), N-acetylcysteine (200 mg), Cu (2 mg), Zn (15 mg), Mn (0.5 mg), Fe (30 mg), calcium (800 mg), and selenium (100 microg). The control group received Fe (30 mg) and folic acid (400 microg). Maternal (preeclampsia, abortion, and hypertension) and perinatal outcomes were assessed.
                In the supplementation group (29 subjects), we observed 2 cases of preeclampsia (6.8%, 1 mild and 1 severe), 1 of IUGR (birth weight 2300 g at 38 weeks), and 1 preterm delivery. In the control group (31 subjects), there were 8 abortions, 9 cases of preeclampsia (29%, 6 mild and 3 severe) with perinatal outcome: 3 preterm delivery cases and 1 IUGR (birth weight 2030 g at 39 weeks). Preeclampsia was significantly less frequent in the supplementation group when compared to the control group (2 vs. 9 cases, p = 0.043, OR = 0.18 [95% CI: 0.03, 0.92]). Finally we focused on the prediction of preeclampsia at 8 to 12 weeks. Combined sensitivity of markers of antioxidant status (SOD slutathione peroxidase, [GPx], and total anti-oxidant status [TAS]) was 33% (false-positive rate of 4.5%).
                Antioxidant supplementation was associated with better maternal and perinatal outcome in pregnant women with low antioxidant status than control supplementation with iron and folate alone. In a selected population already screened positive for low SOD, preeclampsia can be detected in 33% of asymptomatic cases in the first trimester using SOD, GPx, and TAS. It seems feasible that panels of both biochemical and molecular markers may be clinically useful in the prediction of this disease. 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. Maternal nutrient supplementation in developing countries is generally restricted to provision of iron and folic acid (IFA). Change in practice toward supplementation with multiple micronutrients (MMN) has been hindered by little evidence of the effects of MMN on fetal loss and infant death. We assessed the effect of maternal supplementation with MMN, compared with IFA, on fetal loss and infant death in the setting of routine prenatal care services.
                In a double-blind cluster-randomised trial in Lombok, Indonesia, we randomly assigned 262 midwives to distribute IFA (n=15 ,86) or MMN (n=15,804) supplements to 31 290 pregnant women through government prenatal care services that were strengthened by training and community-based advocacy. Women obtained supplements, to be taken daily, every month from enrolment to 90 days post partum. The primary outcome was early infant mortality (deaths until 90 days post partum). Secondary outcomes were neonatal mortality, fetal loss (abortions and stillbirths), and low birthweight. Analysis was by intention to treat. The study is registered as an International Standard Randomised Controlled Trial, number ISRCTN34151616.
                Infants of women consuming MMN supplements had an 18% reduction in early infant mortality compared with those of women given IFA (35.5 deaths per 1000 livebirths vs 43 per 1000; relative risk [RR] 0.82, 95% CI 0.70-0.95, p=0.010). Infants whose mothers were undernourished (mid upper arm circumference <23.5 cm) or anaemic (haemoglobin <110 g/L) at enrolment had a reduction in early infant mortality of 25% (RR 0.75, 0.62-0.90, p=0.0021) and 38% (RR 0.62, 0.49-0.78, p<0.0001), respectively. Combined fetal loss and neonatal deaths were reduced by 11% (RR 0.89, 0.81-1.00, p=0.045), with significant effects in undernourished (RR 0.85, 0.73-0.98, p=0.022) or anaemic (RR 0.71, 0.58-0.87, p=0.0010) women. A cohort of 11 101 infants weighed within 1 h of birth showed a 14% (RR 0.86, 0.73-1.01, p=0.060) decreased risk of low birthweight for those in the MMN group, with a 33% (RR 0.67, 0.51-0.89, p=0.0062) decrease for infants of women anaemic at enrolment.
                Maternal MMN supplementation, as compared with IFA, can reduce early infant mortality, especially in undernourished and anaemic women. Maternal MMN supplementation might therefore be an important part of overall strengthening of prenatal-care programmes. 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. Few data exist for the effects of multiple micronutrient (MM) or food supplementation to undernourished pregnant women on their offsprings' development.
                We aimed to compare the effects on infant development of early (8-10 wk gestation) or usual ( approximately 17 wk gestation) supplementation with food and MM, 30 mg Fe + 400 microg folate, or 60 mg Fe + 400 microg folate.
                A large, randomized, controlled trial of pregnancy supplementation was conducted in Bangladesh. A subsample of infants (n = 2853) were assessed on 2 problem-solving tests (support and cover tests), the motor index of the Bayley Scales of Infant Development, and Wolke's behavior ratings at 7 mo of age.
                There were no significant effects of any intervention in the group as a whole. However, infants of undernourished mothers [body mass index (BMI; in kg/m2) < 18.5] who received early food supplementation performed slightly but significantly (P = 0.035) better on the support test than did infants of mothers who received usual food supplementation (z score: 0.17; 95% CI: 0.01, 0.33). There were no benefits in infants of higher-BMI mothers (P = 0.024 for BMI x food interaction). Children of low-BMI mothers who received MMs had slightly better motor scores (z score: 0.28; 95% CI: 0.08, 0.48) and activity ratings (z score: 0.24; 95% CI: 0.037, 0.45) than did those who received 30 mg Fe + 400 microg folate, whereas other children did not benefit (P = 0.05 for both motor scores and BMI x micronutrients and for activity and BMI x micronutrients).
                Small benefits from early food and MM supplementation were found in infants of low-BMI but not of high-BMI mothers. However, the benefits were of doubtful functional importance, and longer follow-up is required to determine programmatic implications. To assess the effects of daily prenatal multimicronutrient supplementation on birth weight (BW) and perinatal mortality.
                Randomised, controlled, double masked trial.Setting:Urban Guinea-Bissau, West Africa.
                A total of 2100 pregnant women (22+/-7 weeks pregnant at entry) were recruited through antenatal clinics, of which 1670 (79.5%) completed the trial. BW was available for 1100 live born babies.
                Identical-looking supplements containing one (MN-1) or two (MN-2) Recommended Dietary Allowances (RDA) of 15 micronutrients, or iron and folic acid (control).
                Mean BW among 1100 live born infants was 3050+/-498 g with 11.9% being low birth weight (LBW, BW < 2500 g). Perinatal mortality was 82 per 1000 deliveries (N = 1670), and neonatal mortality 45 per 1000 live births (N = 1599). Mean BW in MN-1 (n = 360) and MN-2 (n = 374) groups were 53 [-19; 125] and 95 [24; 166] g higher than controls (n = 366). Proportion of LBW was 13.6% in control, and 12.0 and 10.1% in the MN-1 and MN-2 groups, respectively (P = 0.33). Among anaemic women (30%), MN-2 increased BW with 218 [81; 354] g compared to controls, with a decreased risk of LBW of 69 [27; 87]%. There were apparently no differences in perinatal mortality between groups.
                Prenatal micronutrient supplementation increased BW but did not reduce perinatal mortality in this study. Multimicronutrient supplementation with two RDA should be considered in future programmes to reduce the proportion of LBW. To evaluate the effect of multimicronutrient supplementation for undernourished pregnant women on the birth size of their offspring, incidence of low-birth-weight infants (<2500 g), and early neonatal morbidity.
                Randomized, double-blind, placebo-controlled trial.
                Tertiary care hospital.
                Two hundred pregnant women (of 13 465 approached) with a body mass index (calculated as weight in kilograms divided by the square of height in meters) of less than 18.5 and/or a hemoglobin level of 7 to 9 g/dL were enrolled at 24 to 32 weeks of gestation. One hundred forty-six neonates (73.0%) were available for analysis of birth size and 170 (85.0%) for analysis of morbidity in the 7 days after delivery. Intervention The micronutrient supplementation group (n = 99) received a multimicronutrient supplement containing 29 vitamins and minerals once a day, from enrollment until delivery (median duration, 58 days; interquartile range, 37-77 days; compliance, 87%). The comparison group (n = 101) received placebo for 52 (15-66) days, with 85% compliance. All subjects also received supplements of iron (given in the form of ferrous sulfate, containing 60 mg of elemental iron), 60 mg/d, and folic acid, 500 mug/d.
                Birth weight, length, midarm circumference, incidence of low birth weight, and early neonatal morbidity.
                Infants in the micronutrient group were heavier by 98 g (95% confidence interval [CI], -16 to 213 g) and measured 0.80 cm (95% CI, 0.03-1.57 cm) longer and 0.20 cm (95% CI, 0.04-0.36 cm) larger in midarm circumference compared with the placebo group. Incidence of low birth weight declined from 43.1% to 16.2% with multimicronutrient supplementation a (a 70% decrease; relative risk, 0.30; 95% CI, 0.13-0.71; P=.006), and that of early neonatal morbidity declined from 28.0% to 14.8% (a 58% decrease; relative risk, 0.42; 95% CI, 0.19-0.94; P=.04).
                Compared with iron and folic acid supplementation, the administration of multimicronutrients to undernourished pregnant women may reduce the incidence of low birth weight and early neonatal morbidity. Intrauterine growth retardation is a major predictor of child health in developing countries.
                We tested whether providing pregnant women with the UNICEF/WHO/UNU international multiple micronutrient preparation (UNIMMAP), rather than iron and folic acid alone, improved fetal growth and its correlates.
                An intention-to-treat, double-blind, randomized controlled trial including 1426 pregnancies was carried out in rural Burkina Faso. Tablet intake was directly observed.
                Pregnancy outcome was known in 96.3% of the participants. After adjustment for gestational age at delivery, both birth weight (52 g; 95% CI: 4, 100; P = 0.035) and birth length (3.6 mm; 95% CI: 0.8, 6.3; P = 0.012) were significantly higher in the UNIMMAP group. UNIMMAP had a differential effect by percentiles of birth weight and length distributions: the risk of large-for-gestational-age infants was higher in the UNIMMAP group (OR: 1.58; 95% CI: 1.04, 2.38; P = 0.03), although the risk of low birth weight remained unchanged. The effect of UNIMMAP on birth size was modified by maternal body mass index at enrollment and could be more important in multiparous women and women taking sulfadoxine-pyrimethamine. Unexpectedly, the risk of perinatal death was marginally significantly increased in the UNIMMAP group (OR: 1.78; 95% CI: 0.95, 3.32; P = 0.07), and this seemed to affect mainly primiparous women (OR: 3.44; 95% CI: 1.1, 10.7; P for interaction = 0.11).
                Maternal UNIMMAP modestly but significantly increased fetal growth. The resulting benefit on infant growth and survival needs to be assessed. The possible lack of benefit and potential harm in primiparous women should be further investigated. This trial was registered at clinicaltrials.gov as NCT00642408. 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. There is no mandatory folic acid fortification of food in Finland. We investigated the effects of mineral water fortified with folic acid, vitamins B6, B12, D and calcium on serum and erythrocyte folate concentrations, serum vitamin B12 and plasma homocysteine concentrations in pregnancy.
                A randomized, controlled, double-blind, parallel-group intervention study.
                Seventy-four pregnant women were recruited from two health care units. The study began at the eleventh week with a two-week run-in period, followed by an eight-week intervention period. The diet was monitored by food records. During the intervention, subjects consumed 1000 mL/day fortified or normal mineral water. The pregnancies were monitored carefully.
                The folate intake was 255 microg/day in the study group and 274 microg/day in the controls. Serum folate concentrations increased in the study group by 10.3 nmol/L and decreased in the controls by 2.7 nmol/L (P<0.05) during the study. The erythrocyte folate concentrations increased in the study group by 360.9 nmol/L and in the controls by 195.6 nmol/L (P=0.004) and serum homocysteine concentrations fell by 1.1 micromol/L and by 0.3 micromol/L, respectively (P<0.05).
                Finnish pregnant women have low dietary folate intake. Fortified mineral water improved folate status and reduced plasma homocysteine concentrations in the pregnant subjects. Neonatal mortality is the biggest contributor to global mortality of children younger than 5 years, and low birthweight is a crucial underlying factor. We tested the hypotheses that antenatal multiple micronutrient supplementation would increase infant birthweight and gestational duration.
                We did a double-blind, randomised controlled trial in Dhanusha district, Nepal. Women attending for antenatal care with singleton pregnancies at up to 20 weeks' gestation were invited to participate. Participants were randomly allocated either routine iron and folic acid supplements (control; n=600) or a multiple micronutrient supplement providing a recommended daily allowance of 15 vitamins and minerals (intervention; n=600). Supplementation began at a minimum of 12 weeks' gestation and continued until delivery. Primary outcome measures were birthweight and gestational duration. Analysis was by intention to treat. The study is registered as an International Standard Randomised Controlled Trial, number ISRCTN88625934.
                Birthweight was available for 523/600 infants in the control group and 529/600 in the intervention group. Mean birthweight was 2733 g (SD 422) in the control group and 2810 g (453) in the intervention group, representing a mean difference of 77 g (95% CI 24-130; p=0.004) and a relative fall in the proportion of low birthweight by 25%. No difference was recorded in the duration of gestation (0.2 weeks [-0.1 to 0.4]; p=0.12), infant length (0.3 cm [-0.1 to 0.6]; p=0.16), or head circumference (0.2 cm [-0.1 to 0.4]; p=0.18).
                In a poor community in Nepal, consumption of a daily supplement containing a recommended daily allowance of 15 micronutrients in the second and third trimesters of pregnancy was associated with increased birthweight when compared with a standard iron and folic acid preparation. The effects on perinatal morbidity and mortality need further comparisons between studies. Published online March 3, 2005 http://image.thelancet.com/extras/04art11045web.pdf.
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.