Effects of an energy and micronutrient supplement on iron deficiency anemia, physical activity and motor and mental development in undernourished children in Indonesia Effects of iron supplementation and anthelmintic treatment on motor and language development of preschool children in Zanzibar: double blind, placebo controlled study Reversal of developmental delays in iron-deficient anaemic infants treated with iron Randomized Trial of Early Versus Late Enteral Iron Supplementation in Infants With a Birth Weight of Less Than 1301 Grams: Neurocognitive Development at 5.3 Years' Corrected Age Efficacy of iron supplementation on fatigue and physical capacity in non-anaemic iron-deficient adults: a systematic review of randomised controlled trials Iron Supplementation in Pregnancy or Infancy and Motor Development: A Randomized Controlled Trial Effects of an energy and micronutrient supplement on mental development and behavior under natural conditions in undernourished children in Indonesia A developmental view of the effects of an energy and micronutrient supplement in undernourished children in Indonesia Iron fortified follow on formula from 9 to 18 months improves iron status but not development or growth: a randomised trial Prenatal micronutrient supplementation and intellectual and motor function in early school-aged children in Nepal. Predictors and pathways of language and motor development in four prospective cohorts of young children in Ghana, Malawi, and Burkina Faso Effects of an energy and micronutrient supplement on motor development and motor activity in undernourished children in Indonesia A cluster-randomized, controlled trial of nutritional supplementation and promotion of responsive parenting in Madagascar: the MAHAY study design and rationale 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 Infancy: mental and motor development. Effect of Iron Deficiency Anemia in Pregnancy on Child Mental Development in Rural China The effect of iron deficiency and mental stimulation on Indonesian children's cognitive performance and development. Maternal Multiple Micronutrient Supplements and Child Cognition: A Randomized Trial in Indonesia The effectiveness of methylphenidate in the management of Attention Deficit Hyperactivity Disorder (ADHD) in people with intellectual disabilities: A systematic review. Preschool micronutrient supplementation effects on intellectual and motor function in school-aged Nepalese children. Cluster Randomised Trials in Cochrane Reviews: Evaluation of Methodological and Reporting Practice Iron and zinc supplementation promote motor development and exploratory behavior among Bangladeshi infants. Developmental effects of micronutrient supplementation and malaria in Zanzibari children.
Objectives : This paper reports the effects of an energy and micronutrient supplementation on mental and motor development , activity and behavior under natural conditions of children classified as iron deficient anemic and iron replete . Design : Children were r and omly assigned to two different nutritional supplements : ( 1 ) 12 mg iron+either 1171 or 209 kJ ; ( 2 ) 104 kJ+0 iron . Treatment lasted for 6 months . Setting : The sites were six tea plantations in Pangalengan , West Java . Subjects : Eighteen anemic subjects ( hemoglobin<110 g/L ; transferrin saturation (TS)<16 % ) and 18 matched ( sex and age ) controls ( hemoglobin>110 g/L ; TS>16 % ) were selected from a pool of children with the following characteristics : no chronic disease ; length-for-age ≤−1 st and ard deviation ( s.d . ) and weight-for-length between −1 and −2 s.d . of the median of the reference of the World Health Organization . Methods : Hemoglobin , ferritin , transferrin saturation and erythrocyte protoporphyrin were evaluated before and 6 months after treatment . The following psychological measurements were obtained at baseline and 2 , 4 and 6 months later . Mental and motor development was evaluated with the Bayley Scale . Motor activity was measured by 4 h continuous observations at home and at day care centers . The interactions between the child and its social and physical environment were also evaluated during 4 h of observations . Results : Anemic children  showed faster motor development and greater physical activity than the control children did . None of the other tests showed inter-group differences . Sponsorship : Nestlé Foundation . European journal of Clinical Nutrition ( 2000 ) 54 , Suppl 2 , Abstract Objective : To measure the effects of iron supplementation and anthelmintic treatment on iron status , anaemia , growth , morbidity , and development of children aged 6–59 months . Design : Double blind , placebo controlled r and omised factorial trial of iron supplementation and anthelmintic treatment . Setting : Community in Pemba Isl and , Zanzibar . Participants : 614 preschool children aged 6–59 months . Main outcome measures : Development of language and motor skills assessed by parental interview before and after treatment in age appropriate subgroups . Results : Before intervention , anaemia was prevalent and severe , and geohelminth infections were prevalent and light — Plasmodium falciparum infection was nearly universal . Iron supplementation significantly improved iron status , but not haemoglobin status . Iron supplementation improved language development by 0.8 ( 95 % confidence interval 0.2 to 1.4 ) points on the 20 point scale . Iron supplementation also improved motor development , but this effect was modified by baseline haemoglobin concentrations ( P=0.015 for interaction term ) and was apparent only in children with baseline haemoglobin concentrations < 90 g/l . In children with a baseline haemoglobin concentration of 68 g/l ( one st and ard deviation below the mean value ) , iron treatment increased scores by 1.1 ( 0.1 to 2.1 ) points on the 18 point motor scale . Mebendazole significantly reduced the number and severity of infections caused by Ascaris lumbricoides and Trichuris trichiura , but not by hookworms . Mebendazole  increased development scores by 0.4 ( −0.3 to 1.1 ) points on the motor scale and 0.3 ( −0.3 to 0.9 ) points on the language scale . Conclusions : Iron supplementation improved motor and language development of preschool children in rural Africa . The effects of iron on motor development were limited to children with more severe anaemia ( baseline haemoglobin concentration < 90 g/l ) . Mebendazole had a positive effect on motor and language development , but this was not statistically significant . What is already known on this topic Iron is needed for development and functioning of the human brain Anaemic children show developmental delays , but it is not yet clear whether iron deficiency causes these deficits or whether iron supplementation can reverse them Helminth infections in schoolchildren are associated with cognitive deficits , but few studies have been made of helminth infection and early child development What this study adds Low doses of oral iron supplementation given daily improved language development in children aged 1–4 years in Zanzibar Iron supplementation improved motor development , but only in children with initial haemoglobin concentrations below 90 g/l The effects of routine anthelmintic treatment on motor and language milestones were positive , but non-significant , with our sample Iron-deficient anaemic infants perform worse in tests of mental and motor development than do iron-sufficient infants of a comparable age . A r and omised , double-blind trial was done to monitor the effects of iron supplementation on performance in the Bayley scales of mental and motor development among 12 - 18-month-old infants in Indonesia . Iron-deficient anaemic infants ( n = 50 ) were assigned r and omly to receive dietary ferrous sulphate or placebo for 4 month . Similar treatment r and omisation was done among nonanaemic iron-deficient ( n = 29 ) and iron-sufficient ( n = 47 ) infants . Before intervention , the mean mental and motor scores of the iron-deficient anaemic infants were significantly ( p < 0.01 ) lower than those of the nonanaemic iron-deficient and iron-sufficient classes . After intervention , developmental delays were reversed among iron-deficient anaemic infants who had received iron but they remained the same among placebo-treated iron-deficient anaemic infants . Neither ferrous sulphate nor placebo had significant effects on the scores of the other two iron-status classes . The poor performance of 12 - 18-month-old iron-deficient anaemic infants in the Bayley scales of mental and motor development can be improved to the level of performance of iron-sufficient infants by treatment with ferrous sulphate BACKGROUND . Iron deficiency in early childhood may impair neurodevelopment . In a masked , r and omized , controlled trial of early versus late enteral iron supplementation in preterm infants with birth weights of < 1301 g , early iron supplementation reduced the incidence of iron deficiency and the number of blood transfusions . OBJECTIVE . We sought to examine whether early enteral iron supplementation improves neurocognitive and motor development in these infants . METHODS . Children who participated in the above mentioned trial were evaluated by applying the Kaufmann Assessment Battery for Children and the Gross Motor Function Classification Scale at the age of school entry . RESULTS . Of the 204 infants initially r and omized , 10 died and 30 were lost to follow-up . A total of 164 ( 85 % of the survivors ) were evaluated at a median corrected age of 5.3 years . In this population ( n = 164 ) , the mean ( ±SD ) mental processing composite in the early iron group was 92 ( ±17 ) versus 89 ( ±16 ) in the late iron group . An abnormal neurologic examination was found in 17 of 90 versus 26 of 74 , and a Gross Motor Function Classification Scale score of > 1 was found in 2 of 90 versus 5 of 74 , respectively . Fifty-nine of 90 children in the early iron group were without disability , compared with 40 of 74 in the late iron group . Severe disability was found in 5 of 90 versus 6 of 74 children and 67 of 90 versus 49 of 74 qualified for regular schooling , respectively . CONCLUSIONS . Early enteral iron supplementation showed a trend toward a beneficial effect on long-term neurocognitive and psychomotor development and showed no evidence for any adverse effect . Because the initial study was not design ed to evaluate effects on neurocognitive development , the power was insufficient to detect small but potentially clinical ly relevant improvements . Additional studies are required to confirm the trend towards a better outcome observed in the early iron group Objective Iron supplementation in iron-deficiency anaemia is st and ard practice , but the benefits of iron supplementation in iron-deficient non-anaemic ( IDNA ) individuals remains controversial . Our objective is to identify the effects of iron therapy on fatigue and physical capacity in IDNA adults . Design Systematic review and meta- analysis of r and omised controlled trials ( RCTs ) . Setting Primary care . Participants Adults ( ≥18 years ) who were iron deficient but non-anaemic . Interventions Oral , intramuscular or intravenous iron supplementation ; all therapy doses , frequencies and duration s were included . Comparators Placebo or active therapy . Results We identified RCTs in Medline , Embase , Cochrane Central Register of Controlled Trials , Cumulative Index of Nursing and Allied Health , SportD iscus and CAB Abstract s from inception to 31 October 2016 . We search ed the WHO ’s International Clinical Trials Registry Platform for relevant ongoing trials and performed forward search es of included trials and relevant review s in Web of Science . We assessed internal validity of included trials using the Cochrane Risk of Bias tool and the external validity using the Grading of Recommendations Assessment , Development and Evaluation methodology . From 11 580 citations , we included 18 unique trials and 2 companion papers enrolling 1170 patients . Using a Mantel-Haenszel r and om-effects model , iron supplementation was associated with reduced self-reported fatigue ( st and ardised mean difference ( SMD ) −0.38 ; 95 % CI −0.52 to −0.23 ; I2 0 % ; 4 trials ; 714 participants ) but was not associated with differences in objective measures of physical capacity , including maximal oxygen consumption ( SMD 0.11 ; 95 % CI −0.15 to 0.37 ; I2 0 % ; 9 trials ; 235 participants ) and timed methods of exercise testing  . Iron supplementation significantly increased serum haemoglobin concentration ( MD 4.01 g/L ; 95 % CI 1.22 to 6.81 ; I2 48 % ; 12 trials ; 298 participants ) and serum ferritin ( MD 9.23 µmol/L ; 95 % CI 6.48 to 11.97 ; I2 58 % ; 14 trials ; 616 participants ) . Conclusion In IDNA adults , iron supplementation is associated with reduced subjective measures of fatigue but not with objective improvements in physical capacity . Given the global prevalence of both iron deficiency and fatigue , patients and practitioners could consider consumption of iron-rich foods or iron supplementation to improve symptoms of fatigue in the absence of documented anaemia . PROSPERO registration number CRD42014007085 BACKGROUND AND OBJECTIVE : Insufficient iron levels for optimal fetal and infant development is a concern during pregnancy and infancy . The goal of this study was to assess the effects of iron supplementation in pregnancy and /or infancy on motor development at 9 months . METHODS : The study was a r and omized controlled trial ( RCT ) of infancy iron supplementation linked to an RCT of pregnancy iron supplementation  , conducted in Hebei , China . A total of 1482 infants were r and omly assigned to receive placebo ( n = 730 ) or supplemental iron ( n = 752 ) from 6 weeks to 9 months . Gross motor development ( assessed by using the Peabody Developmental Motor Scale , Second Edition , instrument ) was the primary outcome . Neurologic integrity and motor quality were secondary outcomes . RESULTS : Motor outcome was available for 1196 infants , divided into 4 supplementation period groups : ( 1 ) placebo in pregnancy/placebo in infancy ( n = 288 ) ; ( 2 ) placebo in pregnancy/iron in infancy ( n = 305 ) ; ( 3 ) iron in pregnancy/placebo in infancy ( n = 298 ) ; and ( 4 ) iron in pregnancy/iron in infancy ( n = 305 ) . Using the Peabody Developmental Motor Scale , instrument , iron supplementation in infancy but not pregnancy improved gross motor scores : overall , P < .001 ; reflexes , P = .03 ; stationary , P < .001 ; and locomotion , P < .001 . Iron supplementation in infancy improved motor scores by 0.3 SD compared with no supplementation or supplementation during pregnancy alone . Effects of iron supplementation in infancy alone were similar to effects with iron in both pregnancy and infancy . CONCLUSIONS : The RCT design supports the causal inference that iron supplementation in infancy , with or without iron supplementation in pregnancy , improved gross motor test scores at 9 months Objectives : This paper reports the effects of an energy and micronutrient supplement on mental development and on the social – cognitive and emotionally regulatory behaviors of nutritionally at risk infants and toddlers in Pangalengan , Indonesia . Design : Two cohorts of children were r and omly assigned to three treatments : E=1171 kJ+12 mg iron ; M=12 mg iron+209 kJ ; S=104 kJoule . Supplementation was given for 12 months . Setting : The sites were six tea plantations in Pangalengan , West Java . Subjects : A 12-month-old ( N=53 ) and an 18-month-old ( N=83 ) cohort were recruited from day-care-centers . Twenty children who received S belonged to the 12- and 18-month-old cohort . Inclusion criteria were : no chronic disease ; length-for-age ≤−1 st and ard deviation ( s.d . ) and weight-for-length between −1 and −2 s.d . of the median of the reference of the World Health Organization . Methods : Evaluations of intake were made at baseline and every 2 months thereafter . Motor development was assessed with the Bayley Scale and with a custom-made scale to assess gross motor development leading to bipedal locomotion . Four hours of continuous observations were made of the child ’s interaction with the social and physical environment . Results : In the 12-month-old cohort , as compared with the M and S groups , the children who received the E supplement walked at an earlier age , had higher scores in the Bayley Scale and showed more mature social – cognitive and emotional regulatory behaviors . Similar intergroup differences were observed in the 18-month-old cohort in social cognition and regulation of emotions . Sponsorship : Nestlé Foundation . European Journal of Clinical Nutrition ( 2000 ) 54 , Suppl 2 , Objectives : This paper presents the results of a structural equation model testing whether the longitudinal data of the Pangalengan subjects fit the theoretical model regarding the intellectual delay of undernourished children . Design : Two cohorts of children were r and omly assigned to three treatments : E=1171 kJ+12 mg iron ; M=12 mg iron+209 kJ ; S=104 kJ. Supplementation was given for 6 months . Setting : The sites were six tea plantations in Indonesia . Subjects : A 12-month-old ( n=53 ) and an 18-month-old ( n=83 ) cohort were recruited from day-care-centers . Inclusion criteria were : no chronic disease ; length-for-age=<1 st and ard deviation ( s.d . ) and weight-for-length between −1 and −2 s.d . of the median of the reference of the World Health Organization . Methods : Twenty-four-hour dietary intakes were assessed using the weighted individual inventory technique . Body weight and length were obtained using st and ard procedures ; motor development was assessed with the Bayley Scale and with a custom made scale for motor development leading to bipedal locomotion . Four-hour observations were made of the child ’s interactions with the environment . Carrying a child in the arms and exploratory behavior were used as indicators of caregiving and exploration . All measurements were obtained every 2 months . Results : The original model did not fit the data . The model was then modified with the inclusion of two new pathways : from activity and from motor development to mental development . Following these adjustments the model fit the data for each cohort and for both cohorts combined . Sponsorship : Nestlé Foundation . European Journal of Clinical Nutrition ( 2000 ) 54 , Suppl 2 , AIMS Iron deficiency anaemia is associated , in observational studies , with developmental disadvantage . This study tested the hypothesis that feeding iron supplemented formula from 9 to 18 months of age would improve developmental performance . SUBJECTS AND METHODS 493 healthy children aged 9 months being fed pasteurised cows ’ milk were recruited from three UK centres . They were r and omised to : cows ’ milk as before , formula containing 0.9 mg/litre iron , or formula containing 1.2 mg/litre iron , until 18 months of age . Bayley mental and psychomotor developmental indices were measured at 18 months , as were growth and haematological indices . RESULTS Children fed iron fortified formula had higher plasma ferritin concentrations , but there were no significant intergroup differences in development or growth . CONCLUSIONS There are no developmental or growth advantages in children given iron supplemented formula , but a benefit for a minority who were anaemic , or the possibility that a benefit may emerge at a later age , can not be excluded 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 Background Previous review s have identified 44 risk factors for poor early child development ( ECD ) in low‐ and middle‐income countries . Further underst and ing of their relative influence and pathways is needed to inform the design of interventions targeting ECD . Methods We conducted path analyses of factors associated with 18‐month language and motor development in four prospect i ve cohorts of children who participated in trials conducted as part of the International Lipid‐Based Nutrient Supplements ( iLiNS ) Project in Ghana ( n = 1,023 ) , Malawi ( n = 675 and 1,385 ) , and Burkina Faso ( n = 1,122 ) . In two cohorts , women were enrolled during pregnancy . In two cohorts , infants were enrolled at 6 or 9 months . In multiple linear regression and structural equation models ( SEM ) , we examined 22 out of 44 factors identified in previous review s , plus 12 additional factors expected to be associated with ECD . Results Out of 42 indicators of the 34 factors examined , 6 were associated with 18‐month language and /or motor development in 3 or 4 cohorts : child linear and ponderal growth , variety of play material s , activities with caregivers , dietary diversity , and child hemoglobin/iron status . Factors that were not associated with child development were indicators of maternal Hb/iron status , maternal illness and inflammation during pregnancy , maternal perceived stress and depression , exclusive breastfeeding during 6 months postpartum , and child diarrhea , fever , malaria , and acute respiratory infections . Associations between socioeconomic status and language development were consistently mediated to a greater extent by caregiving practice s than by maternal or child biomedical conditions , while this pattern for motor development was not consistent across cohorts . Conclusions Key elements of interventions to ensure quality ECD are likely to be promotion of caregiver activities with children , a variety of play material s , and a diverse diet , and prevention of faltering in linear and ponderal growth and improvement in child hemoglobin/iron status Objectives : This paper reports the effects of an energy and micronutrient supplement on the motor development , motor milestones and motor activity of nutritionally at risk infants and toddlers in Pangalengan , Indonesia . Design : Two cohorts of children were r and omly assigned to three treatments E=1171 kJ+12 mg iron ; M=209 kJ+12 mg iron ; S=104 kJ. Supplementation was given for 12 months . Setting : The sites were six tea plantations in Pangalengan , West Java . Subjects : A 12-month-old ( n=53 ) and an 18-month-old ( n=83 ) cohort were recruited from day-care-centers . Twenty children that received S belonged to the 12- and 18-month-old cohorts . Inclusion criteria were : no chronic disease ; length-for-age≤−1 st and ard deviation ( s.d . ) and weight-for-length between −1 and −2 s.d . of the median of the reference of the World Health Organization . Methods : Evaluations of intake were made at baseline and every 2 months thereafter . Motor development was assessed with the Bayley Scale and with a custom-made scale to assess gross motor development leading to bipedal locomotion . Motor activity was assessed through 4 h continuous observations of the child ’s interaction with the social and physical environment . Results : In the 12-month-old cohort , as compared to the M and S groups the children that received the E supplement walked at an earlier age , had higher scores in the Bayley Scale and were motorically more active . Similar intergroup differences were observed in the 18-month-old cohort in the total motor activity score . Sponsorship : Nestlé Foundation . European Journal of Clinical Nutrition ( 2000 ) 54 , Suppl 2 , Background Over half of the world ’s children suffer from poor nutrition , and as a consequence they experience delays in physical and mental health , and cognitive development . There is little data evaluating the effects of delivery of lipid-based , nutrition supplementation on growth and development during pregnancy and early childhood within the context of a scaled-up program . Furthermore , there is limited evidence on effects of scaled-up , home-visiting programs that focus on the promotion of child development within the context of an existing , national nutrition program . Methods / Design The MAHAY ( " smart " in Malagasy ) study uses a multi-arm r and omized-controlled trial ( RCT ) to test the effects and cost-effectiveness of combined interventions to address chronic malnutrition and poor child development . The arms of the trial are : ( T0 ) existing program with monthly growth monitoring and nutritional/hygiene education ; ( T1 ) is T0 + home visits for intensive nutrition counseling within a behavior change framework ; ( T2 ) is T1 + lipid-based supplementation ( LNS ) for children 6–18 months old ; ( T3 ) is T2 + LNS supplementation of pregnant/lactating women ; and ( T4 ) is T1 + intensive home visiting program to support child development . There are anticipated to be n = 25 communities in each arm ( n = 1250 pregnant women , n = 1250 children 0–6 months old , and n = 1250 children 6–18 months old ) . Primary outcomes include growth ( length/height-for-age z-scores ) and child development ( mental , motor and social development ) . Secondary outcomes include care-giver reported child morbidity , household food security and diet diversity , micro-nutrient status , maternal knowledge of child care and feeding practice s , and home stimulation practice s. We will estimate unadjusted and adjusted intention-to-treat effects . Study protocol s have been review ed and approved by the Malagasy Ethics Committee at the Ministry of Health in Madagascar and by the institutional review board at the University of California , Davis . This study is funded by the Strategic Impact Evaluation Fund ( SIEF ) , the World Bank Innovation Grant , the Early Learning Partnership Grant , the Japan Scaling-up for Nutrition Trustfund , and Gr and Challenges Canada . The implementation of the study is financed by Madagascar 's National Nutrition Office . Trial registration Current Controlled Trials IS RCT N14393738 . Registered June 23 , 2015 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 In a prospect i ve cohort study of 196 infants from birth to age 15 mo , the relationship of iron status to psychomotor development , the effect of a short-term trial of oral iron or placebo , and the effect of longer-term oral iron therapy was assessed . Development was assessed with the Bayley Scale of Infant Development in anemic , nonanemic , iron-deficient , and control children . Anemic infants had significantly lower indices than did control or nonanemic , iron-deficient infants . Control infants and nonanemic , iron-deficient infants performed comparably . No difference between the effect of oral administration of iron or placebo was noted after 10 d or 3 mo of iron therapy . A hemoglobin concentration of less than 105 g/L and anemia duration greater than 3 mo were correlated with significantly lower motor and mental scores , suggesting that when iron deficiency progresses to anemia , adverse influences in the performance of developmental tests appear and persist , despite iron therapy OBJECTIVE : To determine the impact of iron deficiency anemia ( IDA ) in pregnancy on young child development . METHODS : A 2-year follow-up of 850 children born to women who participated in a double-blind cluster r and omized controlled trial of prenatal micronutrient supplementation in western rural China . These women were r and omly assigned to receive either daily folic acid , iron/folic acid ( 60 mg iron ) , or multiple micronutrients ( with 30 mg iron ) during pregnancy . Children were categorized into the prenatal-IDA and prenatal – non-IDA groups based on the mother ’s hemoglobin in the third trimester . Each group contained 3 subgroups based on mother ’s treatment : folic acid , iron/folic acid , and multiple micronutrients .  Bayley scales of infant development were administered to the children to assess their development at 3 , 6 , 12 , 18 , and 24 months of age . RESULTS : Compared with the prenatal – non-IDA group , the prenatal-IDA group showed a significantly lower mental development index at 12 , 18 , and 24 months of age . The adjusted mean difference was 5.8 ( 95 % confidence interval [ CI ] , 1.1–10.5 ) , 5.1 ( 95 % CI , 1.2–9.0 ) , and 5.3 ( 95 % CI , 0.9–9.7 ) , respectively . Further analysis showed that the mental development indexes in the prenatal-IDA group and prenatal – non-IDA group were similar with supplementation of iron/folic acid but were significantly lower in the prenatal-IDA group with supplementation of folic acid or multiple micronutrients . CONCLUSIONS : Prenatal IDA in the third trimester is associated with mental development of the child . However , prenatal supplementation with sufficient iron protects child development even when the woman ’s IDA was not properly corrected in pregnancy Three studies conducted in Indonesia will be described . Soewondo ( 12 ) investigated the relation of iron deficiency and cognitive function and impact of iron supplementation on verbal intelligence , attention and concept learning among iron deficient children without anemia and iron deficient anemic children . Half of 176 children , aged 3 - 6 years , received elemental Fe for 8 weeks and the other half received  placebo . There were significant changes from pre to post intervention evaluations in ferritin , transferrin saturation , free erythrocyte protoporphyrin , and hemoglobin in the iron deficient anemic children . Pre and post treatment psychological test data showed that iron deficiency anemia produced alterations in cognitive processes related to visual attention and concept acquisition . These alterations can be reversed with iron treatment . Idjradinata ( 4 ) assessed the impact of iron supplementation on iron deficient infant 's mental and psychomotor development . Hundred twenty six subjects aged 12 to 18 month were r and omly assigned to either iron treatment or placebo intervention . After 4 months of iron supplementation , the hemoglobin , ferritin and transferrin saturation changed significantly in the iron deficient infants . A developmental delay was observed in the iron deficient anemic infants before intervention and the conditions were reversed after 4 months of iron treatment . Soemiarti ( 8) examined the effectiveness of a  training course  given to mothers of children aged 12 to 24 month on the rearing environment and consequently to the child 's development .  The subjects were 69 mothers of 20 - 35 years old . The training lasted for 21 days by giving mothers training using the program " Ibu Maju Anak Bermutu " . The rearing environment improved , also the child 's mental and psychomotor development 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 The effectiveness of psychostimulants , primarily methylpheni date ( MPH ) , in the treatment of Attention Deficit Hyperactivity Disorder ( ADHD ) in the general population of typically growing children and adolescents is well established through many R and omised Controlled Trials ( RCTs ) . AIMS AND METHODS We carried out a systematic review of all the RCTs in people with intellectual disabilities ( ID ) that assessed effectiveness of MPH on the core ADHD symptoms . OUTCOMES AND RESULTS We included 15 papers from 13 studies that were all on children and adolescents with ID ( 315 participants were on MPH and placebo respectively ) , 12 of which used a cross over design , and one used a parallel design . On average around 40 - 50 % responded to MPH in the ID group whereas around 70 - 80 % response rate is reported among the non-ID children . Because of the heterogeneity of the outcome data it was not possible to carry out a meta- analysis . Significant adverse events included sleep difficulties and poor appetite along with weight loss and also irritability , social withdrawal and increased motor activities including tic . CONCLUSIONS AND IMPLEMENTATION On the basis of the poor quality evidence that is available , it seems that MPH may be effective in some but not all children and adolescents with ID and ADHD OBJECTIVE To examine intellectual and motor functioning of children who received micronutrient supplementation from 12 to 35 months of age . DESIGN Cohort follow-up of children 7 to 9 years of age who participated in a 2 × 2 factorial , placebo-controlled , r and omized trial from October 2001 through January 2006 . SETTING Rural Nepal . PARTICIPANTS A total of 734 children 12 to 35 months of age at supplementation and 7 to 9 years of age at testing . INTERVENTIONS Children received iron plus folic acid ( 12.5 mg of iron and 50 μg of folic acid ) ; zinc ( 10 mg ) ; iron plus folic acid and zinc ; or placebo . MAIN OUTCOME MEASURES Intellectual , motor , and executive function . RESULTS In both the unadjusted and adjusted analyses , iron plus folic acid supplementation had no effect overall or on any individual outcome measures being tested . In the unadjusted analysis , zinc supplementation had an overall effect , although none of the individual test score differences were significant . In the adjusted analysis , the overall difference was not significant . CONCLUSION In rural Nepal , we found that iron plus folic acid or zinc supplementation during the preschool years had no effect on aspects of intellectual , executive , and motor function at 7 to 9 years of age , suggesting no long-term developmental benefit of iron or zinc supplementation during 12 to 35 months of age Objective Systematic review s can include cluster-r and omised controlled trials ( C- RCTs ) , which require different analysis compared with st and ard individual-r and omised controlled trials . However , it is not known whether review authors follow the method ological and reporting guidance when including these trials . The aim of this study was to assess the method ological and reporting practice of Cochrane review s that included C- RCTs against criteria developed from existing guidance . Methods Criteria were developed , based on method ological literature and personal experience supervising review production and quality . Criteria were grouped into four themes : identifying , reporting , assessing risk of bias , and analysing C- RCTs . The Cochrane Data base of Systematic Review s was search ed ( 2nd December 2013 ) , and the 50 most recent review s that included C- RCTs were retrieved . Each review was then assessed using the criteria . Results The 50 review s we identified were published by 26 Cochrane Review Groups between June 2013 and November 2013 . For identifying C- RCTs , only 56 % identified that C- RCTs were eligible for inclusion in the review in the eligibility criteria . For reporting C- RCTs , only eight ( 24 % ) of the 33 review s reported the method of cluster adjustment for their included C- RCTs . For assessing risk of bias , only one review assessed all five C- RCT -specific risk-of-bias criteria . For analysing C- RCTs , of the 27 review s that presented unadjusted data , only nine ( 33 % ) provided a warning that confidence intervals may be artificially narrow . Of the 34 review s that reported data from unadjusted C- RCTs , only 13 ( 38 % ) excluded the unadjusted results from the meta-analyses . Conclusions The method ological and reporting practice s in Cochrane review s incorporating C- RCTs could be greatly improved , particularly with regard to analyses . Criteria developed as part of the current study could be used by review authors or editors to identify errors and improve the quality of published systematic review s incorporating C- RCTs BACKGROUND Iron and zinc deficiency are prevalent during infancy in low-income countries . OBJECTIVES The objectives were to examine whether a weekly supplement of iron , zinc , iron+zinc , or a micronutrient mix ( MM ) of 16 vitamins and minerals would alter infant development and behavior . DESIGN The participants were 221 infants from rural Bangladesh at risk of micronutrient deficiencies .  Development and behavior were evaluated at 6 and 12 mo of age by using the Bayley Scales of Infant Development II and the Home Observation Measurement of Environment ( HOME ) scale . In this double-blind trial , the infants were r and omly assigned to 1 of 5 treatment conditions : iron ( 20 mg ) , zinc ( 20 mg ) , iron+zinc , MM ( 16 vitamins and minerals , including iron and zinc ) , or riboflavin weekly from 6 to 12 mo . Multivariate analyses were conducted to examine the change in development and behavior for each supplementation group , with control for maternal education , HOME score , months breastfed , anemia , growth at 6 mo , and change in growth from 6 to 12 mo . RESULTS Iron and zinc administered together and with other micronutrients had a beneficial effect on infant motor development .  Iron and zinc administered individually and in combination had a beneficial effect on orientation-engagement . Two-thirds of the infants were mildly anemic , no treatment effects on hemoglobin concentration were observed , and hemoglobin was not associated with measures of development or behavior . CONCLUSION The beneficial effects of weekly iron and zinc supplementation on motor development and orientation-engagement suggest that infants benefit from these minerals when administered together BACKGROUND Children 's development is affected by the interplay of internal and external factors and changes in one factor can precipitate changes in multiple developmental domains . AIMS The aim of this study was to test a theoretical model of children 's development using structural equation modeling . STUDY DESIGN This was design ed as a sub study of a r and omized , placebo-controlled , 2 × 2 factorial trial of the effects of daily supplementation with iron ( 12.5 mg ) + folic acid ( 50 μg ) ( FeFA ) with or without zinc ( 10 mg ) ( Zn ) on child mortality . SUBJECTS Zanzibari children aged 5 - 9 mo ( n = 106 ) and 10 - 14 mo ( n = 141 ) at baseline were included in this sub study . OUTCOME MEASURES Longitudinal data on children 's hemoglobin , growth , malaria infection , motor development , motor activity , and language development and caregiver behavior were used to test the fit of the theoretical model for two age groups and to examine the direct and indirect relationships among the variables in the model . RESULTS The theoretical models were a good fit to the data for both age groups and revealed that FeFA with or without Zn had positive effects on motor development . FeFA alone had negative effects on language development in both age groups and Zn alone had negative effects on language development in children aged 10 - 14 mo . The incidence of malaria had negative effects on the majority of health and development outcomes in children aged 5 - 9 mo , and on motor development and hemoglobin in children aged 10 - 14 mo . CONCLUSIONS These findings illustrate how nutrition and health factors can affect different domains of development and how these changes can precipitate changes in other domains . More work is needed to better underst and the multiple impacts of internal and external factors on children 's development and how changes in developmental domains interact with each other over time to determine children 's overall developmental trajectory . The r and omized , placebo-controlled study was registered as an International St and ard R and omized Controlled Trial , number IS RCT N59549825
Iron supplementation improves mental development score modestly .
This effect is particularly apparent for intelligence tests above 7 years of age and in initially anaemic or iron-deficient anaemic subjects .
There is no convincing evidence that iron treatment has an effect on mental development in children below 27 months of age or on motor development
OBJECTIVE To evaluate the effect of iron supplementation on  mental and motor development in children through a systematic review of r and omised controlled trials ( RCTs ) .