Effect of Iron Deficiency Anemia in Pregnancy on Child Mental Development in Rural China Infant motor development in rural Vietnam and intrauterine exposures to anaemia, iron deficiency and common mental disorders: a prospective community-based study Effect of iron supplementation during pregnancy on the intelligence quotient and behavior of children at 4 y of age: long-term follow-up of a randomized controlled trial. Efficacy and tolerability of low-dose iron supplements during pregnancy: a randomized controlled trial. Effects of prenatal food and micronutrient supplementation on infant development: a randomized trial from the Maternal and Infant Nutrition Interventions, Matlab (MINIMat) study. Mental and psychomotor development in Indonesian infants of mothers supplemented with vitamin A in addition to iron during pregnancy. The Effect of Intermittent Antenatal Iron Supplementation on Maternal and Infant Outcomes in Rural Viet Nam: A Cluster Randomised Trial Maternal Multiple Micronutrient Supplements and Child Cognition: A Randomized Trial in Indonesia Prenatal Hemoglobin Levels and Early Cognitive and Motor Functions of One-Year-Old Children Effect of iron supplementation during pregnancy on the behaviour of children at early school age: long-term follow-up of a randomised controlled trial. Prenatal micronutrient supplementation and intellectual and motor function in early school-aged children in Nepal. Iron Supplementation in Pregnancy or Infancy and Motor Development: A Randomized Controlled Trial 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 Effects of alternative maternal micronutrient supplements on low birth weight in rural Nepal: double blind randomised community trial
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 Background Antenatal anaemia , iron deficiency and common mental disorders ( CMD ) are prevalent in low- and middle-income countries . The aim of this study was to examine the direct and indirect effects of antenatal exposures to these risks and infant motor development . Methods A cohort of women who were pregnant with a single foetus and between 12 and 20 weeks pregnant in 50 r and omly-selected rural communes in Ha Nam province was recruited . Participants provided data twice during pregnancy ( early and late gestation ) and twice after giving birth ( 8 weeks and 6 months postpartum ) . The Edinburgh Postnatal Depression Scale was used at all four data collection waves to detect CMD ( score ≥ 4 ) . Maternal anaemia ( Hb < 11 g/dL ) and iron deficiency ( ferritin < 15 ng/mL ) were evaluated at early and late gestation . Infants ’ motor development was assessed by the Bayley of Infant and Toddler Development Motor Scales ( BSID-M ) at the age of six months . Direct and indirect effects of the exposures on the outcome were examined with Path analysis . Results In total , 497 of 523 ( 97 % ) eligible pregnant women were recruited and 418 mother-infant pairs provided complete data and were included in the analyses . The prevalence of anaemia was 21.5 % in early pregnancy and 24.4 % in late pregnancy . There was 4.1 % iron deficiency at early pregnancy and 48.2 % at late pregnancy . Clinical ly significant symptoms of CMD were apparent among 40 % women in early pregnancy and 28 % in late pregnancy . There were direct adverse effects on infant BSID-M scores at 6 months of age due to antenatal anaemia in late pregnancy ( an estimated mean reduction of 2.61 points , 95 % Confidence Interval , CI , 0.57 to 4.65 ) and CMD in early pregnancy ( 7.13 points , 95 % CI 3.13 to 11.13 ) . Iron deficiency and anaemia in early pregnancy were indirectly related to the outcome via anaemia during late pregnancy . Conclusions Antenatal anaemia , iron deficiency , and CMD have a negative impact on subsequent infant motor development . These findings highlight the need to improve the quality of antenatal care when developing interventions for pregnant women that aim to optimise early childhood development in low- and middle-income countries BACKGROUND Iron supplements are often prescribed during pregnancy despite the lack of intervention trials that have assessed the effects of supplementation in pregnancy on childhood development . OBJECTIVE The objective was to determine whether iron supplementation during pregnancy influences  childhood intelligence quotient ( IQ )  in an industrialized country . DESIGN Pregnant women ( n = 430 ) were r and omly allocated to receive iron ( 20 mg/d ) or placebo from 20 wk gestation until delivery , and the women and their children were followed up over the long term ( 4 y ) . Seventy percent of these families participated in the follow-up . The proportion of women with iron deficiency anemia at the end of pregnancy was 1 % ( 2 of 146 ) in the iron group and 11 % ( 15 of 141 ) in the placebo group . The primary outcome was the IQ of the children at 4 y of age , as assessed by the Stanford-Binet Intelligence Scale . Secondary outcomes included child behavior and the general health of the mothers . RESULTS The mean IQ was not significantly different ( P = 0.980 ) between the children of the iron-supplemented mothers ( 109 + /- 11 ; n = 153 ) and the children of the mothers in the placebo group ( 109 + /- 11 ; n = 149 ) . However , the percentage of children with an abnormal behavior score was higher in the iron group ( 24 of 151 , or 16 % ) than in the placebo group ( 12 of 149 , or 8 % ) ; the relative risk was 1.97 ( 95 % CI : 1.03 , 3.80 ; P = 0.037 ) . There was no significant difference in the health of the mothers between groups , as assessed by the SF-36 Health Survey . CONCLUSIONS Prenatal iron supplementation that reduces the incidence of iron deficiency anemia from 11 % to 1 % has no effect on the IQ of the offspring at 4 y of age BACKGROUND Iron deficiency anemia ( IDA ) is common in pregnant women , but previous trials aim ed at preventing IDA used high-dose iron supplements that are known to cause gastrointestinal side effects . OBJECTIVE The objective was to assess the effect on  maternal IDA and iron deficiency ( ID , without anemia ) of supplementing pregnant women with a low dosage ( 20 mg/d ) of iron . Effects on iron status were assessed at the time of delivery and at 6 mo postpartum . Gastrointestinal side effects were assessed at 24 and 36 wk of gestation . DESIGN This was a r and omized , double-blind , placebo-controlled trial of a 20-mg daily iron supplement ( ferrous sulfate ) given from 20 wk of gestation until delivery . RESULTS A total of 430 women were enrolled , and 386 ( 89.7 % ) completed the follow-up to 6 mo postpartum . At delivery , fewer women from the iron-supplemented group than from the placebo group had IDA [ 6/198 , or 3 % , compared with 20/185 , or 11 % ; relative risk ( RR ) : 0.28 ; 95 % CI : 0.12 , 0.68 ; P < 0.005 ] , and fewer women from the iron-supplemented group had ID ( 65/186 , or 35 % , compared with 102/176 , or 58 % ; RR : 0.60 ; 95 % CI : 0.48 , 0.76 ; P < 0.001 ) . There was no significant difference in gastrointestinal side effects between groups . At 6 mo postpartum , fewer women from the iron-supplemented group had ID ( 31/190 , or 16 % , compared with 51/177 , or 29 % ; RR : 0.57 ; 95 % CI : 0.38 , 0.84 ; P < 0.005 ) . The rate of IDA between the groups did not differ significantly at 6 mo postpartum . CONCLUSION Supplementing the diet of women with 20 mg Fe/d from week 20 of pregnancy until delivery is an effective strategy for preventing IDA and ID without side effects 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 Maternal nutrition is important for fetal development , but its impact on the functional outcome of infants is still unclear . The present study investigated the effects of vitamin A and Fe supplementation during gestation on  infant mental and psychomotor development . Mothers of infants from five villages in Indonesia were r and omly assigned to supervised , double-blind supplementation once per week from approximately 18 weeks of pregnancy until delivery . Supplementation comprised 120 mg Fe+500 microg folic acid with ( n 94 ) or without ( n 94 ) 4800 microg retinol in the form of retinyl acetate .  Mothers of infants who participated in the national Fe+folic acid supplementation programme , but whose intake of supplements was not supervised , were recruited from four other villages ( n 88 ) . The mental and psychomotor development of infants was assessed , either at 6 or 12 months of age , using the Bayley Scales of Infant Development ( BSID ) . We found no impact of vitamin A supplementation on mental or psychomotor development of infants . In addition , infants whose mothers had received weekly Fe supplementation had similar mental and psychomotor indices as those whose mothers had participated in the governmental Fe supplementation programme . The study population was moderately Fe and vitamin A deficient . The size of the treatment groups was large enough to detect a mean difference of 10 points on the BSID , which is less than 1 sd ( 15 points ) of the average performance of an infant on the BSID . In conclusion , the present study did not find an impact of weekly supplementation of 4800 RE vitamin A in addition to Fe during gestation on functional development  of Indonesian infants . However , smaller improvements in development may be seen if studied in a larger and /or more deficient population Beverley-Anne Biggs and colleagues conduct a community-based cluster r and omized trial in rural Viet Nam to compare the effect of antenatal iron-folic acid supplementation taken daily or twice weekly on  maternal and infant outcomes . Please see later in the article for the Editors ' 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 OBJECTIVE : To explore the relationship between prenatal hemoglobin ( Hb ) concentration and infant cognitive and motor functions . METHODS : Our prospect i ve cohort study included 1-year-old children born to women enrolled at their first antenatal care ( ANC ) visit in Allada , Benin , before 29 weeks of pregnancy , within a trial comparing the efficacy of sulfadoxine-pyrimethamine and mefloquine . Hb concentrations of pregnant women were determined from venous blood sample s collected at first and second ANC visits of at least 1-month interval and at delivery . Women were prescribed oral iron , folic acid , and anthelminthics after the first ANC visit . A total of 636 children ( 76.8 % of eligible children ) were assessed by trained research nurses for cognitive and motor functions by using the Mullen Scales of Early Learning . RESULTS : Prevalence of anemia ( Hb < 110 g/L ) decreased from 67.0 % at first ANC visit ( mean gestational age [ SD ] , 22.1 [ 4.0 ] weeks ) to 38.4 % at delivery . Mean ( SD ) Hb concentrations increased from 103.7 ( 12.3 ) at first ANC visit to 112.4 ( 14.1 ) at delivery . We observed a significant negative quadratic relationship between infant gross motor ( GM ) function and Hb concentration at first and second ANC visits . Thus , infant GM scores increased sharply with increasing maternal Hb concentration until 90 g/L where increasing GM was mild , and began to decline after 110 g/L. CONCLUSIONS : There appears to be an Hb concentration range that may be optimal for GM function of 1-year-old children . This may reflect the importance of physiologic hemodilution , which occurs after the second trimester until 34 weeks of gestation Although routine Fe supplementation in pregnancy is a common practice , its clinical benefits or risks are uncertain . Children born to mothers in the Fe group in a trial of Fe supplementation in pregnancy have been found to have a significantly higher risk of abnormal behaviour at 4 years of age than those born to mothers in the placebo group . The objective of the present study therefore was to determine whether Fe supplementation in pregnancy influences child behaviour at early school age . The study was a follow-up of children at 6 - 8 years of age after women ( n 430 ) were r and omly allocated to receive a daily Fe supplement ( 20 mg ) or placebo from 20 weeks gestation until delivery . The supplement reduced the incidence of Fe-deficiency anaemia at delivery from 9 % to 1 % . Child behaviour and temperament were assessed using the Strengths and Difficulties Question naire and the Short Temperament Scale for Children . Of the children , 264 ( 61 % ) participated in the follow-up . Mean behaviour and temperament scores and the proportion of parent-rated and teacher-rated abnormal total difficulties scores did not differ between the Fe and placebo groups . However , the incidence of children with an abnormal teacher-rated peer problems subscale score was higher in the Fe group ( eleven of 112 subjects ; 8 % ) than in the placebo group ( three of 113 subjects ; 2 % ) ; the relative risk was 3.70 ( 95 % CI 1.06 , 12.91 ; P = 0.026 ) . We conclude that prenatal Fe supplementation had no consistent effect on child behaviour at early school age in this study population . Further investigation regarding the long-term effects of this common practice is warranted 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 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 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 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 Although antenatal iron supplementation is beneficial to mothers , its impact on the neurodevelopment of offspring is controversial .
A systematic review and meta- analysis was undertaken to assess whether routine maternal antenatal iron supplementation confers later neurodevelopmental benefit  to offspring .