Associations of linear growth and relative weight gain during early life with adult health and human capital in countries of low and middle income: findings from five birth cohort studies Effects of maternal multiple micronutrient supplementation on fetal growth: a double-blind randomized controlled trial in rural Burkina Faso. Multimicronutrient supplementation for undernourished pregnant women and the birth size of their offspring: a double-blind, randomized, placebo-controlled trial. A Comparative Evaluation of Multiple Micronutrient and Iron–Folic Acid Supplementation during Pregnancy in Pakistan: Impact on Pregnancy Outcomes Effects of antenatal multiple micronutrient supplementation on birthweight and gestational duration in Nepal: double-blind, randomised controlled trial Timing of initiation, patterns of breastfeeding, and infant survival: prospective analysis of pooled data from three randomised trials. Effects of prenatal multimicronutrient supplements on birth weight and perinatal mortality: a randomised, controlled trial in Guinea-Bissau 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 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
Summary Background Fast weight gain and linear growth in children in low-income and middle-income countries are associated with enhanced survival and improved cognitive development , but might increase risk of obesity and related adult cardiometabolic diseases . We investigated how linear growth and relative weight gain during infancy and childhood are related to health and human capital outcomes in young adults . Methods We used data from five prospect i ve birth cohort studies from Brazil , Guatemala , India , the Philippines , and South Africa . We investigated  body-mass index , systolic and diastolic blood pressure , plasma glucose concentration , height , years of attained schooling , and related categorical indicators of adverse outcomes in young adults . With linear and logistic regression models , we assessed how these outcomes relate to birthweight and to statistically independent measures representing linear growth and weight gain independent of linear growth ( relative weight gain ) in three age periods : 0–2 years , 2 years to mid-childhood , and mid-childhood to adulthood . Findings We obtained data for 8362 participants who had at least one adult outcome of interest . A higher birthweight was consistently associated with an adult body-mass index of greater than 25 kg/m2 ( odds ratio 1·28 , 95 % CI 1·21–1·35 ) and a reduced likelihood of short adult stature ( 0·49 , 0·44–0·54 ) and of not completing secondary school ( 0·82 , 0·78–0·87 ) . Faster linear growth was strongly associated with a reduced risk of short adult stature ( age 2 years : 0·23 , 0·20–0·52 ; mid-childhood : 0·39 , 0·36–0·43 ) and of not completing secondary school ( age 2 years : 0·74 , 0·67–0·78 ; mid-childhood : 0·87 , 0·83–0·92 ) , but did raise the likelihood of overweight ( age 2 years : 1·24 , 1·17–1·31 ; mid-childhood : 1·12 , 1·06–1·18 ) and elevated blood pressure ( age 2 years : 1·12 , 1·06–1·19 ; mid-childhood : 1·07 , 1·01–1·13 ) . Faster relative weight gain was associated with an increased risk of adult overweight ( age 2 years : 1·51 , 1·43–1·60 ; mid-childhood : 1·76 , 1·69–1·91 ) and elevated blood pressure ( age 2 years : 1·07 , 1·01–1·13 ; mid-childhood : 1·22 , 1·15–1·30 ) . Linear growth and relative weight gain were not associated with dysglycaemia , but a higher birthweight was associated with decreased risk of the disorder ( 0·89 , 0·81–0·98 ) . Interpretation Interventions in countries of low and middle income to increase birthweight and linear growth during the first 2 years of life are likely to result in substantial gains in height and schooling and give some protection from adult chronic disease risk factors , with few adverse trade-offs . Funding Wellcome Trust and Bill & Melinda Gates Foundation 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 OBJECTIVE 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 .  DESIGN R and omized , double-blind , placebo-controlled trial . SETTING Tertiary care hospital . PARTICIPANTS 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 . MAIN OUTCOME MEASURES Birth weight , length , midarm circumference , incidence of low birth weight , and early neonatal morbidity . RESULTS 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 ) . CONCLUSION 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 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 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 Although the benefits of exclusive breastfeeding for child health and survival , particularly in the post-neonatal period , are established , the independent beneficial effect of early breastfeeding initiation remains unclear . We studied the association between timing of breastfeeding initiation and  post-enrolment neonatal and post-neonatal mortality up to 6 months of age , as well as the associations between breastfeeding pattern and mortality . METHODS We examined associations between timing of breastfeeding initiation , post-enrolment neonatal mortality ( enrolment 28 days ) , and post-neonatal mortality up to 6 months of age ( 29 - 180 days ) in a large cohort from three neonatal vitamin A trials in Ghana , India , and Tanzania . Newborn babies were eligible for these trials if their mother reported that they were likely to stay in the study area for the next 6 months , they could feed orally , were aged less than 3 days , and the primary caregiver gave informed consent . We excluded infants who initiated breastfeeding after 96 h , did not initiate , or had missing initiation status . We pooled the data from both r and omised groups of the three trials and then categorised time of breastfeeding initiation as : at ≤1 h , 2 - 23 h , and 24 - 96 h. We defined breastfeeding patterns as exclusive , predominant , or partial breastfeeding at 4 days , 1 month , and 3 months of age . We estimated relative risks using log binomial regression and Poisson regression with robust variances . Multivariate models controlled for site and potential confounders . FINDINGS Of 99 938 enrolled infants , 99 632 babies initiated breastfeeding by 96 h of age and were included in our prospect i ve cohort . 56 981 ( 57·2 % ) initiated breastfeeding at ≤1 h , 38 043 ( 38·2 % ) at 2 - 23 h , and 4608 ( 4·6 % ) at 24 - 96 h. Compared with infants initiating breastfeeding within the first hour of life , neonatal mortality between enrolment and 28 days was higher in infants initiating at 2 - 23 h ( adjusted relative risk 1·41 [ 95 % CI 1·24 - 1·62 ] , p<0·0001 ) , and in those initiating at 24 - 96 h ( 1·79 [ 1·39 - 2·30 ] , p<0·0001 ) . These associations were similar when deaths in the first 4 days of life were excluded ( 1·32 [ 1·10 - 1·58 ] , p=0·003 , for breastfeeding initiation at 2 - 23 h , and 1·90 [ 1·38 - 2·62 ] , p=0·0001 , for initiation at 24 - 96 h ) . When data were stratified by exclusive breastfeeding status at 4 days of age ( p value for interaction=0·690 ) , these associations were also similar in magnitude but with wider confidence intervals for initiation at 2 - 23 h ( 1·41 [ 1·12 - 1·77 ] , p=0·003 ) and for initiation at 24 - 96 h ( 1·51 [ 0·63 - 3·65 ] , p=0·357 ) . Exclusive breastfeeding was also associated with the lower mortality during the first 6 months of life ( 1 - 3 months mortality : exclusive vs partial breastfeeding at 1 month 1·83 [ 1·45 - 2·32 ] , p<0·0001 , and exclusive breastfeeding vs no breastfeeding at 1 month 10·88 [ 8·27 - 14·31 ] , p<0·0001 ) . INTERPRETATION Our findings suggest that early initiation of breastfeeding reduces neonatal and early infant mortality both through increasing rates of exclusive breastfeeding and by additional mechanisms . Both practice s should be promoted by public health programmes and should be used in models to estimate lives saved . FUNDING Bill & Melinda Gates Foundation through a grant to the WHO 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 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 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
Background : Negative birth outcomes [ small-for-gestational age ( SGA ) and preterm birth ( PTB ) ] are common in low- and middle-income countries and have important subsequent health and developmental impacts on children .
There are numerous nutritional and non-nutritional interventions that can decrease the risk of negative birth outcomes and reduce subsequent risk of mortality and growth faltering .
Objective : The objective of this article was to review the current evidence for the impact of nutritional interventions in pregnancy [ calcium supplementation , iron and folic acid supplementation , multiple micronutrient ( MMN ) supplementation , and balanced energy supplementation ( BES ) ] and risk factors ( maternal anemia ) on birth outcomes , with the specific goal of determining which intervention- outcome linkages should be included in the Lives Saved Tool ( LiST ) software .