Impact of prenatal multiple micronutrients on survival and growth during infancy: a randomized controlled trial. Effect of multimicronutrient supplementation on gestational length and birth size: a randomized, placebo-controlled, double-blind effectiveness trial in Zimbabwe. Effects of maternal micronutrient supplementation on fetal loss and infant mortality: a cluster-randomized trial in Nepal. 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. Effects of maternal multiple micronutrient supplementation on fetal growth: a double-blind randomized controlled trial in rural Burkina Faso. Effects of prenatal food and micronutrient supplementation on infant development: a randomized trial from the Maternal and Infant Nutrition Interventions, Matlab (MINIMat) study. A Comparative Evaluation of Multiple Micronutrient and Iron–Folic Acid Supplementation during Pregnancy in Pakistan: Impact on Pregnancy Outcomes Effects of prenatal micronutrient and early food supplementation on maternal hemoglobin, birth weight, and infant mortality among children in Bangladesh: the MINIMat randomized trial. Maternal Multiple Micronutrient Supplements and Child Cognition: A Randomized Trial in Indonesia Effects of antenatal multiple micronutrient supplementation on birthweight and gestational duration in Nepal: double-blind, randomised controlled trial Effects of prenatal food and micronutrient supplementation on child growth from birth to 54 months of age: a randomized trial in Bangladesh Effects of antenatal multiple micronutrient supplementation on children's weight and size at 2 years of age in Nepal: follow-up of a double-blind randomised controlled trial Effects of antenatal multiple micronutrient supplementation on lung function in mid-childhood: follow-up of a double-blind randomised controlled trial in Nepal Prenatal micronutrient supplementation and intellectual and motor function in early school-aged children in Nepal. Combined Food and Micronutrient Supplements during Pregnancy Have Limited Impact on Child Blood Pressure and Kidney Function in Rural Bangladesh1234 Antenatal and postnatal iron supplementation and childhood mortality in rural Nepal: a prospective follow-up in a randomized, controlled community trial. Effects of prenatal multimicronutrient supplements on birth weight and perinatal mortality: a randomised, controlled trial in Guinea-Bissau No effect of maternal micronutrient supplementation on early childhood growth in rural western China: 30 month follow-up evaluation of a double blind, cluster randomized controlled trial Effect of antenatal multiple micronutrient supplementation on anthropometry and blood pressure in mid-childhood in Nepal: follow-up of a double-blind 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 Antenatal supplementation with folic acid + iron + zinc improves linear growth and reduces peripheral adiposity in school-age children in rural Nepal. Effects of Maternal Multimicronutrient Supplementation on the Mental Development of Infants in Rural Western China: Follow-up Evaluation of a Double-Blind, Randomized, Controlled Trial Early invitation to food and/or multiple micronutrient supplementation in pregnancy does not affect body composition in offspring at 54 months: follow-up of the MINIMat randomised trial, Bangladesh. Vitamins and perinatal outcomes among HIV-negative women in Tanzania. Multiple micronutrient supplementation during early childhood increases child size at 2 y of age only among high compliers. Preventing low Birthweight through Maternal Multiple Micronutrient Supplementation: A Cluster-Randomized, Controlled Trial in Indramayu, West Java Effects of alternative maternal micronutrient supplements on low birth weight in rural Nepal: double blind randomised community trial Periconceptional maternal micronutrient supplementation is associated with widespread gender related changes in the epigenome: a study of a unique resource in the Gambia. Effect of maternal multiple micronutrient supplementation on fetal loss and infant death in Indonesia: a double-blind cluster-randomised trial. Effect of maternal multiple micronutrient vs iron-folic acid supplementation on infant mortality and adverse birth outcomes in rural Bangladesh: the JiVitA-3 randomized trial.
BACKGROUND Although prenatal multiple micronutrients can improve fetal growth , their benefit on postnatal health remains uncertain . OBJECTIVE We assessed the effect of the UNICEF/WHO/United Nations University multiple micronutrient supplement for  pregnant and lactating women  ( UNIMMAP ) compared with the usual iron and folic acid supplement ( IFA ) on survival , growth , and morbidity during infancy . DESIGN In a double-blind , r and omized trial , we followed 1294 singleton newborns whose mothers had prenatally received either the UNIMMAP or IFA .  We assessed monthly anthropometric measures and health variables up to age 12 mo . Children were assessed again at a mean age of 30 mo . Mixed-effects models accounted for repeated measurements . RESULTS The UNIMMAP result ed in a 27 % ( HR : 0.73 ; 95 % CI : 0.60 , 0.87 ; P = 0.002 ) reduction in the rate of stunting in 15,261 infant-months with a higher length-for-age z score of 0.13 ( 95 % CI : 0.02 , 0.24 ; P = 0.02 ) over the whole observation period . However , by age 30 mo , this difference was not observed . An effect of the UNIMMAP on weight-for-length ( P-interaction = 0.004 ) and head circumference-for-age ( P-interaction = 0.03 ) became apparent by the end of the first year of life . By the age of 30 mo , children from the UNIMMAP group had a higher weight-for-height z score of 0.20 ( 95 % CI : 0.06 , 0.34 ; P = 0.004 ) . No difference in mortality or morbidity was identified in groups , except a 14 % reduction in reported episodes of fever ( 95 % CI : 1 % , 28 % ; P = 0.04 ) . CONCLUSIONS Improved linear fetal growth with continuation into early life and enhanced postnatal growth were 2 mechanisms that mediated the effect of the prenatal UNIMMAP on infant nutritional status . Additional follow-up to assess long-term effects is warranted BACKGROUND Multiple micronutrient deficiencies may contribute to low birth weight , which is a major global determinant of mortality . OBJECTIVE We assessed the effect of prenatal multimicronutrient supplementation on gestational length and birth size . DESIGN We conducted a r and omized , placebo-controlled , double-blind effectiveness trial among antenatal care attendees in Harare , Zimbabwe . Pregnant women ( 22 - 35 wk of gestation ) were r and omly allocated to receive a multimicronutrient or placebo supplement daily until delivery . Supplementation with iron and folic acid was part of antenatal care . RESULTS 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 ) . CONCLUSION Antenatal multimicronutrient supplementation may be one strategy to increase birth size BACKGROUND We previously reported that maternal micronutrient supplementation in rural Nepal decreased low birth weight by approximately 15 % . OBJECTIVE We examined the effect of daily maternal micronutrient supplementation on  fetal loss and infant mortality .  DESIGN The study was a double-blind , cluster-r and omized , 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 . RESULTS 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 ) . CONCLUSIONS 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 BACKGROUND Little is known about the benefits of prenatal multivitamin and mineral supplements in reducing  low birth weight .  OBJECTIVE We conducted a r and omized , 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 . DESIGN 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 . RESULTS 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 . CONCLUSION These findings suggest that MM supplementation during pregnancy does not lead to greater infant birth size than does iron-only supplementation BACKGROUND Intrauterine growth retardation is a major predictor of child health in developing countries . OBJECTIVE 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 . DESIGN An intention-to-treat , double-blind , r and omized controlled trial including 1426 pregnancies was carried out in rural Burkina Faso . Tablet intake was directly observed . RESULTS 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 ) . CONCLUSIONS Maternal UNIMMAP modestly but significantly increased fetal growth . The result ing 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 clinical trials.gov as NCT00642408 BACKGROUND Few data exist for the effects of multiple micronutrient ( MM ) or food supplementation to undernourished pregnant women on their offsprings ' development . OBJECTIVE We aim ed 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 . DESIGN A large , r and omized , controlled trial of pregnancy supplementation was conducted in Bangladesh . A sub sample 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 . RESULTS 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 ) . CONCLUSIONS 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 implication Background 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 . Objective 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-r and omized design . Methods We r and omly assigned 2,378 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 . Results 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 1,000 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 sub clinical 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 . Conclusions 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 setting CONTEXT Nutritional insult in fetal life and small size at birth are common in low-income countries and are associated with serious health consequences . OBJECTIVES To test the hypothesis that prenatal multiple micronutrient supplementation ( MMS ) and an early invitation to food supplementation would increase maternal hemoglobin level and birth weight and decrease infant mortality , and to assess whether a combination of these interventions would further enhance these outcomes . DESIGN , SETTING , AND PARTICIPANTS A r and omized trial with a factorial design in Matlab , Bangladesh , of 4436 pregnant women , recruited between November 11 , 2001 , and October 30 , 2003 , with follow-up until June 23 , 2009 . INTERVENTIONS Participants were r and omized into 6 groups ;  a double-masked supplementation with capsules of 30 mg of iron and 400 μg of folic acid , 60 mg of iron and 400 μg of folic acid , or MMS containing a daily allowance of 15 micronutrients , including 30 mg of iron and 400 μg of folic acid , was combined with food supplementation ( 608 kcal 6 days per week ) r and omized to either early invitation ( 9 weeks ' gestation ) or usual invitation ( 20 weeks ' gestation ) . MAIN OUTCOME MEASURES Maternal hemoglobin level at 30 weeks ' gestation , birth weight , and infant mortality . Under 5-year mortality was also assessed . RESULTS Adjusted maternal hemoglobin level at 30 weeks ' gestation was 115.0 g/L ( 95 % CI , 114.4 - 115.5 g/L ) , with no significant differences among micronutrient groups . Mean maternal hemoglobin level was lower in the early vs usual invitation groups ( 114.5 vs 115.4 g/L ; difference , -0.9 g/L ; 95 % CI , -1.7 to -0.1 ; P = .04 ) . There were 3625 live births out of 4436 pregnancies . Mean birth weight among 3267 singletons was 2694 g ( 95 % CI , 2680 - 2708 g ) , with no significant differences among groups . The early invitation with MMS group had an infant mortality rate of 16.8 per 1000 live births vs 44.1 per 1000 live births for usual invitation with 60 mg of iron and 400 μg of folic acid ( hazard ratio [ HR ] , 0.38 ; 95 % CI , 0.18 - 0.78 ) . Early invitation with MMS group had an under 5-year mortality rate of 18 per 1000 live births ( 54 per 1000 live births for usual invitation with 60 mg of iron and 400 μg of folic acid ; HR , 0.34 ; 95 % CI , 0.18 - 0.65 ) . Usual invitation with MMS group had the highest incidence of spontaneous abortions and the highest infant mortality rate . CONCLUSION Among pregnant women in poor communities in Bangladesh , treatment with multiple micronutrients , including iron and folic acid combined with early food supplementation , vs a st and ard program that included treatment with iron and folic acid and usual food supplementation , result ed in decreased childhood mortality . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N16581394 OBJECTIVES : We investigated the relative benefit of maternal multiple micronutrient ( MMN ) supplementation during pregnancy and until 3 months postpartum compared with iron/folic acid supplementation on child development at preschool age ( 42 months ) . METHODS : We assessed 487 children of mothers who participated in the Supplementation with Multiple Micronutrients Intervention Trial , a cluster-r and omized trial in Indonesia , on tests adapted and vali date d in the local context measuring motor , language , visual attention/spatial , executive , and socioemotional abilities . Analysis was according to intention to treat . RESULTS : In children of undernourished mothers ( mid-upper arm circumference < 23.5 cm ) , a significant benefit of MMNs was observed on motor ability ( B = 0.39 [ 95 % confidence interval ( CI ) : 0.08–0.70 ] ; P = .015 ) and visual attention/spatial ability ( B = 0.37 [ 95 % CI : 0.11–0.62 ] ; P = .004 ) . In children of anemic mothers ( hemoglobin concentration < 110 g/L ) , a significant benefit of MMNs on visual attention/spatial ability ( B = 0.24 [ 95 % CI : 0.02–0.46 ] ; P = .030 ) was also observed . No robust effects of maternal MMN supplementation were found in any developmental domain over all children . CONCLUSIONS : When pregnant women are undernourished or anemic , provision of MMN supplements can improve the motor and cognitive abilities of their children up to 3.5 years later , particularly for both motor function and visual attention/spatial ability . Maternal MMN but not iron/folic acid supplementation protected children from the detrimental effects of maternal undernutrition on child motor and cognitive development BACKGROUND 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 . METHODS We did a double-blind , r and omised 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 r and omly 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 St and ard R and omised Controlled Trial , number IS RCT N88625934 . FINDINGS 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 ) . INTERPRETATION 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 st and ard 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 Background There is a lack of information on the optimal timing of food supplementation to malnourished pregnant women and possible combined effects of food and multiple micronutrient supplementations ( MMS ) on their offspring 's growth . We evaluated the effects of prenatal food and micronutrient interventions on postnatal child growth . The hypothesis was that prenatal MMS and early invitation to food supplementation would increase physical growth in the offspring during 0 - 54 months and a combination of these interventions would further improve these outcomes . Methods In the large , r and omized MINIMat trial ( Maternal and Infant Nutrition Interventions in Matlab ) , Bangladesh , 4436 pregnant women were enrolled between November 2001 and October 2003 and their children were followed until March 2009 . Participants were r and omized into six groups comprising 30 mg Fe and 400 μg folic acid ( Fe30F ) , 60 mg Fe and 400 μg folic acid ( Fe60F ) or MMS combined with either an early ( immediately after identification of pregnancy ) or a later usual ( at the time of their choosing , i.e. , usual care in this community ) program invitation to food supplementation .  The anthropometry of 3267 children was followed from birth to 54 months , and 2735 children were available for analysis at 54 months . Results There were no differences in characteristics of mothers and households among the different intervention groups . The average birth weight was 2694 g and birth length was 47.7 cm , with no difference among intervention groups . Early invitation to food supplementation ( in comparison with usual invitation ) reduced the proportion of stunting from early infancy up to 54 months for boys ( p = 0.01 ) , but not for girls ( p = 0.31 ) . MMS result ed in more stunting than st and ard Fe60F ( p = 0.02 ) . There was no interaction between the food and micronutrient supplementation on the growth outcome . Conclusions Early food supplementation in pregnancy reduced the occurrence of stunting during 0 - 54 months in boys , but not in girls , and prenatal MMS  increased the proportion of stunting in boys . These effects on postnatal growth suggest programming effects in early fetal life . Trial registration numberIS RCT N : IS RCT Summary Background The negative effects of low birthweight on the later health of children in developing countries have been well studied . However , undertaking programmes to address this issue can be difficult since there is no simple correlation between increasing birthweight and improving child health . In 2005 , we published results of a r and omised controlled trial in Nepal , in which 1200 women received either iron and folic acid or a supplement that provided the recommended daily allowance of 15 vitamins and minerals , over the second and third trimesters of pregnancy . Here , we report on 2–3 years ' follow-up of children born during the trial . Methods We visited children at home and obtained data for the primary outcomes of weight and height , for childhood illnesses , and maternal blood haemoglobin . The study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N88625934 . Findings Between December , 2005 , and December , 2006 , we assessed 917 children ( 455 controls , 462 intervention ) at a mean age of 2·5 years . Mean birthweight had been 77 g ( 95 % CI 24–130 ) greater in the micronutrient group than in controls . At 2·5 years old , controls weighed a mean of 10·7 kg ( SD 1·38 ) , and those in the intervention group 10·9 kg ( SD 1·54 ) . Children of women who had  taken multiple micronutrient supplements  during pregnancy were a mean 204 g ( 95 % CI 27–381 ) heavier than controls . They also had greater measurements than controls in the circumference of the head ( 2·4 mm [ 95 % CI 0·6–4·3 ] ) , chest ( 3·2 mm [ 0·4–6·0 ] ) , and mid-upper arm ( 2·4 mm [ 1·1–3·7 ] ) , and in triceps skinfold thickness ( 2·0 mm [ 0·0–0·4 ] ) . Systolic blood pressure was slightly lower in the intervention group ( 2·5 mm Hg [ 0·5–4·6 ] ) . Interpretation In a poor population , the effects of  maternal multiple micronutrient supplementation  on the fetus persisted into childhood , with increases in both weight and body size . These increases were small , however , since those exposed to micronutrients had an average of 2 % higher weight than controls . The public-health implication s of changes in weight and blood pressure need to be clarified through further follow-up A r and omised trial of prenatal multiple micronutrient supplementation in Nepalese women increased birthweight and weight at 2 years of age in offspring , compared to those born to mothers who only received iron and folic acid supplements . Further follow-up of this cohort provided an opportunity to investigate the effect of antenatal multiple micronutrients on subsequent lung function by measuring spirometry at 7–9 years of age in children born during the trial . 841 children ( 80 % of the cohort ) were seen at mean±sd 8.5±0.4 years . Technically successful spirometry results were obtained in 793 ( 94.3 % ) children , 50 % of whom had been r and omised to micronutrient supplementation .  Background characteristics , including anthropometry , were similar in the two allocation groups . Lung function was also similar , mean ( 95 % CI ) difference in z-scores ( supplementation minus control ) was −0.08 ( −0.19–0.04 ) , −0.05 ( −0.17–0.06 ) and −0.04 ( −0.15–0.07 ) for forced expiratory volume in 1 s ( FEV1 ) , forced vital capacity and FEV1/FVC , respectively . Compared with healthy white children , FEV1 and FVC in the “ healthy ” Nepalese children were ∼1 ( ∼13 % ) z-score lower , with no difference in FEV1/FVC . We conclude that , compared with routine iron and folic acid , multiple micronutrient supplementation during pregnancy has no effect on spirometric lung function in Nepalese children at 8.5 years of age . Prenatal multiple micronutrient supplements do not improve spirometric lung function at 8 years in Nepalese children CONTEXT Iron and zinc are important for the development of both intellectual and motor skills . Few studies have examined whether iron and zinc supplementation during gestation , a critical period of central nervous system development , affects children 's later functioning . OBJECTIVE To examine intellectual and motor functioning of children whose mothers received micronutrient supplementation during pregnancy . DESIGN , SETTING , AND PARTICIPANTS Cohort follow-up of 676 children aged 7 to 9 years in June 2007-April 2009 who had been born to women in 4 of 5 groups of a community-based , double-blind , r and omized controlled trial of prenatal micronutrient supplementation between 1999 and 2001 in rural Nepal . Study children were also in the placebo group of a subsequent preschool iron and zinc supplementation trial . INTERVENTIONS Women whose children were followed up had been r and omly assigned to receive daily iron/folic acid , iron/folic acid/zinc , or multiple micronutrients containing these plus 11 other micronutrients , all with vitamin A , vs a control group of vitamin A alone from early pregnancy through 3 months postpartum . These children did not receive additional micronutrient supplementation other than biannual vitamin A supplementation . MAIN OUTCOME MEASURES Children 's intellectual functioning , assessed using the Universal Nonverbal Intelligence Test ( UNIT ) ; tests of executive function , including go/no-go , the Stroop test , and backward digit span ; and motor function , assessed using the Movement Assessment Battery for Children ( MABC ) and finger-tapping test . RESULTS The difference across outcomes was significant ( Bonferroni-adjusted P < .001 ) for iron/folic acid vs control but not for other supplement groups . The mean UNIT T score in the iron/folic acid group was 51.7 ( SD , 8.5 ) and in the control group was 48.2 ( SD , 10.2 ) , with an adjusted mean difference of 2.38 ( 95 % confidence interval [ CI ] , 0.06 - 4.70 ; P = .04 ) . Differences were not significant between the control group and either the iron/folic acid/zinc ( 0.73 ; 95 % CI , -0.95 to 2.42 ) or multiple micronutrient ( 1.00 ; 95 % CI , -0.55 to 2.56 ) groups . In tests of executive function , scores were better in the iron/folic acid group relative to the control group for the Stroop test ( adjusted mean difference in proportion who failed , -0.14 ; 95 % CI , -0.23 to -0.04 ) and backward digit span ( adjusted mean difference , 0.36 ; 95 % CI , 0.01 - 0.71 ) but not for the go/no-go test . The MABC score was lower ( better ) in the iron/folic acid group compared with the control group but not after adjustment for confounders ( mean difference , -1.47 ; 95 % CI , -3.06 to 0.12 ; P = .07 ) . Finger-tapping test scores were higher ( mean difference , 2.05 ; 95 % CI , 0.87 - 3.24 ; P = .001 ) in the iron/folic acid group . CONCLUSION Aspects of intellectual functioning including working memory , inhibitory control , and fine motor functioning among offspring were positively associated with prenatal iron/folic acid supplementation in an area where iron deficiency is prevalent . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00115271 Observational evidence suggests nutritional exposures during in utero development may have long-lasting consequences for health ; data from interventions are scarce . Here , we present a trial follow-up study to assess the association between prenatal food and micronutrient supplementation and  childhood blood pressure and kidney function .  During the MINIMat Trial in rural Bangladesh , women were r and omly assigned early in pregnancy to receive an early or later invitation to attend a food supplementation program and additionally to receive either iron and folate or multiple micronutrient tablets daily .  The 3267 singleton birth individuals with measured anthropometry born during the trial were eligible for a follow-up study at 4.5 y old . A total of 77 % of eligible individuals were recruited and blood pressure , kidney size by ultrasound , and glomerular filtration rate ( GFR ; calculated from plasma cystatin c ) were assessed . In adjusted analysis , early invitation to food supplementation was associated with a 0.72-mm Hg [ ( 95 % CI : 0.16 , 1.28 ) ; P = 0.01 ] lower childhood diastolic blood pressure and maternal MMS  supplementation was associated with a marginally higher [ 0.87 mm Hg ( 95 % CI : 0.18 , 1.56 ) ; P = 0.01 ] childhood diastolic blood pressure . There was also some evidence that a supplement higher in iron was associated with a higher offspring GFR . No other effects of the food or micronutrient interventions were observed and there was no interaction between the interventions on the outcomes studied . These marginal associations and small effect sizes suggest limited public health importance in early childhood The long-term benefits of antenatal iron supplementation in child survival are not known . In 1999 - 2001 , 4,926 pregnant women in rural Nepal participated in a cluster-r and omized , double-masked , controlled trial involving 4 alternative combinations of micronutrient supplements , each containing vitamin A. The authors examined the impact on birth weight and early infant mortality in comparison with controls , who received vitamin A only . They followed the surviving offspring of these women at approximately age 7 years to study effects of in utero supplementation on survival . Of 4,130 livebirths , 209 infants died in the first 3 months and 8 were lost to follow-up . Of those remaining , 3,761 were followed , 150 died between ages 3 months and 7 years , and 152 were lost to follow-up . Mortality rates per 1,000 child-years from birth to age 7 years differed by maternal supplementation group , as follows : folic acid , 13.4 ; folic acid-iron , 10.3 ; folic acid-iron-zinc , 12.0 ; multiple micronutrients ; 14.0 ; and controls , 15.2 . Hazard ratios were 0.90 ( 95 % confidence interval ( CI ) : 0.65 , 1.22 ) , 0.69 ( 95 % CI : 0.49 , 0.99 ) , 0.80 ( 95 % CI : 0.58 , 1.11 ) , and 0.93 ( 95 % CI : 0.66 , 1.31 ) , respectively , in the 4 supplementation groups . Maternal iron-folic acid supplementation  reduced mortality among these children by 31 % between birth and age 7 years . These results provide additional motivation for strengthening antenatal iron-folic acid programs Objectives : To assess the effects of daily prenatal multimicronutrient supplementation on  birth weight ( BW ) and perinatal mortality . Design : R and omised , controlled , double masked trial . Setting : Urban Guinea-Bissau , West Africa . Subjects : 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 . Interventions : Identical-looking supplements containing one ( MN-1 ) or two ( MN-2 ) Recommended Dietary Allowances ( RDA ) of 15 micronutrients , or iron and folic acid ( control ) . Results : 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 . Conclusions : 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 Background / Objectives : Little is known about the long-term effects of maternal multi-micronutrient supplementation on the growth of children during early childhood . In this follow-up study , the effects of maternal supplementation with multi-micronutrients in pregnancy on postnatal child growth are examined . Subjects/ Methods : A longitudinal follow-up of a subset of newborns ( n=1388 ) whose mothers were r and omly assigned to receive the supplements of folic acid , iron – folic acid or multi-micronutrients daily during pregnancy in the original trial was conducted . Children ’s weight and length were measured and assessed during monthly home visits from birth to 30 months of age . Results : The pooled prevalence rate of stunting over different time points during the first 30 months was 13.5 , 14.9 and 12.1 % for the folic acid group , iron – folic acid group and multi-micronutrient group , respectively . However , there were no significant differences in the pooled odds of stunting in children between the multi-micronutrient group and the folic acid ( odds ratio ( OR ) 0.97 , 95 % confidence interval ( CI ) : 0.74–1.26 ) , and between the multi-micronutrient group and the iron – folic acid group ( OR 0.82 , 95 % CI : 0.63–1.07 ) . Similar results for the three groups were found for the occurrences of underweight and wasting in children . Furthermore , no significant differences were observed in length , weight , length-for-age , weight-for-age and weight-for-length Z-scores among the three treatment groups . Conclusions : Currently , available evidence is insufficient to support a greater advantage of the effect of maternal multi-micronutrient supplementation on child growth over iron – folic acid or folic acid only supplementation during the first 30 months Summary Background In 2002–04 , we did a r and omised controlled trial in southern Nepal , and reported that children born to mothers taking multiple micronutrient supplements during pregnancy had a mean birthweight 77 g greater than children born to mothers  taking iron and folic acid supplements . Children born to mothers in the study group were a mean 204 g heavier at 2·5 years of age and their systolic blood pressure was a mean 2·5 mm Hg lower than children born to mothers in the control group . We aim ed to follow up the same children to mid-childhood ( age 8·5 years ) to investigate whether these differences would be sustained . Methods For this follow-up study , we identified children from the original trial and measured anthropometry , body composition with bioelectrical impedance ( with population -specific isotope calibration ) , blood pressure , and renal dimensions by ultrasound . We documented socioeconomic status , household food security , and air pollution . Main outcomes of the follow-up at 8 years were Z scores for weight-for-age , height-for-age , and body-mass index ( BMI ) -for-age according to WHO Child Growth St and ards for children aged 5–19 years , and blood pressure . This study is registered with the International St and ard R and omised Controlled Trial register , number IS RCT N88625934 . Findings Between Sept 21 , 2011 , and Dec 7 , 2012 , we assessed 841 children ( 422 in the control group and 419 in the intervention group ) . Unadjusted differences ( intervention minus control ) in Z scores were 0·05 for weight-for-age ( 95 % CI −0·09 to 0·19 ) , 0·02 in height-for-age ( −0·10 to 0·15 ) , and 0·04 in BMI -for-age ( −0·09 to 0·18 ) . We recorded no difference in blood pressure . Adjusted differences were similar for all outcomes . Interpretation We recorded no differences in phenotype between children born to mothers who received antenatal multiple micronutrient or iron and folate supplements at age 8·5 years . Our findings did not extend to physiological differences or potential longer-term effects . Funding The Wellcome Trust Background 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 . Objectives 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 . Methods Pregnant women from 78 villages in Niger were included in a cluster-r and omized , 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 . Results 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 . Conclusions 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 BACKGROUND We previously reported that a r and omized controlled trial of antenatal micronutrient supplements in rural Nepal decreased the risk of low birth weight by approximately 15 % . OBJECTIVE The objective was to examine the effects of micronutrient supplementation on growth and body composition in children of supplemented mothers through school age . DESIGN Mothers received 1 of 5 micronutrient supplements daily : folic acid , folic acid + iron , folic acid + iron + zinc , multiple micronutrients , or a control . All of the supplements contained vitamin A.  Children born during this trial were revisited at age 6 - 8 y to measure height , weight , midupper arm circumference , waist circumference , and triceps and subscapular skinfold thicknesses . Arm fat and muscle area were estimated by using st and ard formulas , and height-for-age , weight-for-age , and body mass index-for-age z scores were calculated by using the World Health Organization growth st and ard . RESULTS Of the 3771 surviving children , 3324 were revisited and consented to anthropometric measurements . Maternal supplementation with folic acid + iron + zinc result ed in an increase in mean height ( 0.64 cm ; 95 % CI : 0.04 , 1.25 ) and a reduction in mean triceps skinfold thickness ( -0.25 mm ; 95 % CI : -0.44 , -0.06 ) , subscapular skinfold thickness ( -0.20 mm ; 95 % CI : -0.33 , -0.06 ) , and arm fat area ( -0.18 cm(2 ) ; -0.34 , -0.01 ) . No significant differences were found between groups in mean weight or body mass index-for-age z scores , waist circumference , or arm muscle area . Other micronutrient combinations including a multiple micronutrient formulation failed to show a growth benefit . CONCLUSION Antenatal supplementation with zinc may benefit child growth , particularly in areas where a deficiency of this nutrient is common OBJECTIVE . We investigated the benefits of maternal multimicronutrient supplementation during gestation on the mental and psychomotor development  of infants . METHODS . In a double-blind , r and omized , controlled trial , pregnant women ( N = 5828 ) in 2 rural counties in western China were assigned r and omly to receive multimicronutrient ( 5 minerals and 10 vitamins at levels approximating the recommended daily allowance ) , folic acid plus iron , or folic acid supplementation daily from ∼14 weeks of gestation until delivery . We assessed a subset of the newborns ( N = 1305 ) from the 3 supplementation groups by measuring their mental and psychomotor development with the Bayley Scales of Infant Development , at 3 , 6 , and 12 months of age . Multilevel analyses were used to compare the mental development and psychomotor development raw scores at 3 , 6 , and 12 months . RESULTS . Multimicronutrient supplementation was associated with mean increases in mental development raw scores for infants at 1 year of age of 1.00 and 1.22 points , compared with folic acid only and folic acid plus iron supplementation , respectively . However , supplementation did not increase significantly the psychomotor development raw scores up to 1 year of age . CONCLUSION . Compared with iron and folic acid supplementation , the administration of multimicronutrients to pregnant women  improved the mental development of their children at 1 year of age Growth patterns in early life are associated with later health . The effect of nutrition during in utero development on later body composition is unclear . We evaluated whether prenatal early invitation to food and /or multiple micronutrient supplementation ( MMS ) in pregnancy has an effect on offspring body composition at 54 months of age . In Maternal and Infant Nutrition Interventions in Matlab trial ( IS RCT N16581394 ) in Bangladesh , 4436 pregnant women were r and omised into six equally sized groups : double-masked supplementation with capsules of either 30 mg Fe and 400 μg folic acid , or 60 mg Fe and 400 μg folic acid , or MMS ( 15 micronutrients ) , was combined with a r and omised early invitation ( around 9 weeks ) or a usual invitation ( around 20 weeks ) to start food supplementation ( 608 kcal 6 days per week ) . At 54 months , the body composition of the offspring was assessed by leg-to-leg bioelectrical impedance analysis . Of the 3267 live singletons with birth anthropometry , 2290 children were measured at 54 months , representing 70 % of the live births . There was no interaction between the food and micronutrient supplementation on body composition outcomes . There were no significant differences in a range of anthropometric and body composition measurements , including weight , height , mid-upper arm circumference , head circumference , skinfold thickness , and fat mass and fat-free mass between the different prenatal food and micronutrient groups using an intention-to-treat analysis . This analysis shows that early invitation to food supplementation and MMS provided to rural Bangladeshi women during pregnancy did not affect offspring body composition at 54 months of age BACKGROUND 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 . METHODS In a double-blind trial in Dar es Salaam , Tanzania , we r and omly 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 . RESULTS 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 ) . CONCLUSIONS 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 . ( Clinical Trials.gov number , NCT00197548 [ Clinical Trials.gov ] . ) BACKGROUND Micronutrient deficiencies are common , even in middle-income countries . OBJECTIVE The objectives were to determine whether multiple micronutrient ( MM ) supplementation from 3 to 24 mo of age improves growth and whether the effect is modified by MM supplementation during pregnancy . DESIGN We conducted a r and omized , double-blind , controlled trial in central Mexico . Singleton live births ( n = 650 ) from a prenatal MM trial were r and omly assigned to receive either MM supplements ( 1 - 1.5 times the Recommended Dietary Allowance of vitamins A , B-6 , B-12 , and C ; folic acid ; iron ; zinc ; and other nutrients ) or supplements containing similar amounts of iron and vitamin A ( Fe-A ) within the maternal supplementation groups ( MM and iron only ) 6 d/wk from 3 to 24 mo of age . Anthropometric measurements were obtained at 3 and 24 mo of age . RESULTS There was no effect of supplement group on child growth in intention-to-treat analyses . However , infants who consumed MM supplements regularly ( greater than the median compliance of 79 % ) were 0.8 ( 95 % CI : -0.4 , 1.9 ) and 1.6 ( 95 % CI : 0.4 , 2.8 ) cm taller at 24 mo in the maternal MM and iron-only groups , respectively , than were those in the Fe-A group ; these differences were 0.2 ( 95 % CI : -1.0 , 1.4 ) and -0.5 ( 95 % CI : -1.7 , 0.7 ) cm among those with compliance below the median . Mean body mass index ( in kg/m(2 ) ) was significantly higher in those exposed to iron only in utero and Fe-A during childhood ( 16.2 ) than in the other groups ( 15.8 ) . CONCLUSIONS MM supplements increased the length of children who consumed them regularly from 3 to 24 mo . Strategies that promote compliance through effective delivery of micronutrient interventions are needed Background 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 . Objective 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 . Methods We carried out a cluster-r and omized , 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 . Results 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 . Conclusions 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 Abstract Objective : To assess the impact on birth size and risk of low birth weight of alternative combinations of micronutrients given to pregnant women . Design : Double blind cluster r and omised controlled trial . Setting : Rural community in south eastern Nepal . Participants : 4926 pregnant women and 4130 live born infants . Interventions : 426 communities were r and omised 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 ) . Main outcome measures : Birth weight , length , and head and chest circumference assessed within 72 hours of birth . Low birth weight was defined < 2500 g. Results : 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 . Conclusions : 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 . What is already known on this topic Deficiencies in micronutrients are common in women in developing countries and have been associated with low birth weight and preterm delivery What this study adds In rural Nepal maternal supplementation with folic acid-iron reduced the incidence of low birth weight by 16 % A multiple micronutrient supplement of 14 micronutrients , including folic acid , iron , and zinc , reduced low birth weight by 14 % , thus conferring no advantage over folic In addition to the genetic constitution inherited by an organism , the developmental trajectory and result ing mature phenotype are also determined by mechanisms acting during critical windows in early life that influence and establish stable patterns of gene expression . This is the crux of the developmental origins of health and disease hypothesis that suggests undernutrition during gestation and infancy predisposes to ill health in later life . The hypothesis that periconceptional maternal micronutrient supplementation might affect fetal genome-wide methylation within gene promoters was explored in cord blood sample s from offspring of Gambian women enrolled into a unique r and omized , double blind controlled trial . Significant changes in the epigenome in cord blood DNA sample s were further explored in a subset of offspring at 9 months . Gender-specific changes related to  periconceptional nutritional supplementation  were identified in cord blood DNA sample s , some of which showed persistent changes in infant blood DNA sample s. Significant effects of  periconceptional micronutrient supplementation  were also observed in postnatal sample s which were not evident in cord blood . In this Gambian population , the increased death rate of individuals born in nutritionally poor seasons has been related to infection and it is of interest that we identified differential methylation at genes associated with defence against infection and immune response . Although the sample size was relatively small , these pilot data suggest that periconceptional nutrition in humans is an important determinant of newborn whole genome methylation patterns but may also influence postnatal developmental patterns of gene promoter methylation linking early with disease risk BACKGROUND 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 . METHODS In a double-blind cluster-r and omised trial in Lombok , Indonesia , we r and omly 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 St and ard R and omised Controlled Trial , number IS RCT N34151616 . FINDINGS 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 . INTERPRETATION 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 IMPORTANCE Maternal micronutrient deficiencies may adversely affect fetal and infant health , yet there is insufficient evidence of effects on these outcomes to guide antenatal micronutrient supplementation in South Asia . OBJECTIVE To assess effects of antenatal multiple micronutrient vs iron-folic acid supplementation on 6-month  infant mortality and adverse birth outcomes . DESIGN , SETTING , AND PARTICIPANTS Cluster r and omized , double-masked trial in Bangladesh , with pregnancy surveillance starting December 4 , 2007 , and recruitment on January 11 , 2008 . Six-month infant follow-up ended August 30 , 2012 . Surveillance included 127,282 women ; 44,567 became pregnant and were included in the analysis and delivered 28,516 live-born infants . Median gestation at enrollment was 9 weeks ( interquartile range , 7 - 12 ) . INTERVENTIONS Women were provided supplements containing 15 micronutrients or iron-folic acid alone , taken daily from early pregnancy to 12 weeks postpartum . MAIN OUTCOMES AND MEASURES The primary outcome was all-cause infant mortality through 6 months ( 180 days ) . Prespecified secondary outcomes in this analysis included stillbirth , preterm birth ( < 37 weeks ) , and low birth weight ( < 2500 g ) . To maintain overall significance of α = .05 , a Bonferroni-corrected α = .01 was calculated to evaluate statistical significance of primary and 4 secondary risk outcomes ( .05/5 ) . RESULTS Among the 22,405 pregnancies in the multiple micronutrient group and the 22,162 pregnancies in the iron-folic acid group , there were 14,374 and 14,142 live-born infants , respectively , included in the analysis . At 6 months , multiple micronutrients did not significantly reduce infant mortality ; there were 764 deaths ( 54.0 per 1000 live births ) in the iron-folic acid group and 741 deaths ( 51.6 per 1000 live births ) in the multiple micronutrient group ( relative risk [ RR ] , 0.95 ; 95 % CI , 0.86 - 1.06 ) . Multiple micronutrient supplementation result ed in a non-statistically significant reduction in stillbirths ( 43.1 vs 48.2 per 1000 births ; RR , 0.89 ; 95 % CI , 0.81 - 0.99 ; P = .02 ) and significant reductions in preterm births ( 18.6 vs 21.8 per 100 live births ; RR , 0.85 ; 95 % CI , 0.80 - 0.91 ; P < .001 ) and low birth weight ( 40.2 vs 45.7 per 100 live births ; RR , 0.88 ; 95 % CI , 0.85 - 0.91 ; P < .001 ) . CONCLUSIONS AND RELEVANCE In Bangladesh , antenatal multiple micronutrient compared with iron-folic acid supplementation did not reduce all-cause infant mortality to age 6 months but result ed in a non-statistically significant reduction in stillbirths and significant reductions in preterm births and low birth weight . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00860470
Background Multiple micronutrient supplementation for pregnant women reduces low birth weight and has been recommended in low- and middle-income countries ( LMICs ) to improve child survival , growth and health .
We aim ed to review the evidence from long-term follow-up studies of multiple micronutrient supplementation beginning in the later first or second trimester .