title: Efficacy of different strategies to treat anemia in children: a randomized clinical trial Folic acid supplementation prevents phenytoin-induced gingival overgrowth in children Effect of Leucovorin (Folinic Acid) on the Developmental Quotient of Children with Down's Syndrome (Trisomy 21) and Influence of Thyroid Status Premature infants require additional folate and vitamin B-12 to reduce the severity of the anemia of prematurity. Does Oral Folic Acid Lower Total Homocysteine Levels and Improve Endothelial Function in Children With Chronic Renal Failure? Homocysteine lowering with folic acid supplements in children: Effects on blood pressure Supplementation with antioxidants and folinic acid for children with Down’s syndrome: randomised controlled trial Effect of folic acid supplementation on small-for-gestational-age infants born at term Hyperhomocysteinemia in children treated with antiepileptic drugs is normalized by folic acid supplementation. Effects of multivitamin and folic acid supplementation in malnourished children. The effects of antimalarials and folate supplements on haematological indices and red cell folate levels in Gambian children. Folate and Vitamin B6 Rapidly Normalize Endothelial Dysfunction In Children With Type 1 Diabetes Mellitus Influence of folic acid on birthweight and growth of the erythroblastotic infant. I. Birthweight. Folate nutrition and growth in infancy. The effect of folinic acid supplementation on homocysteine concentrations in newborns Studies on the effect of folic acid supplement on folate and vitamin B12 status in children. Evaluation of Folic Acid Supplements in Children Taking Phenytoin Treatment and prevention of anemia with ferrous sulfate plus folic acid in children attending daycare centers in Goiânia, Goiás State, Brazil: a randomized controlled trial. Folic acid in low birthweight infants
abstract: Background Anemia continues to be a major public health problem among children in many regions of the world , and it is still not clear which strategy to treat it is most effective . Objective To evaluate the efficacy and children 's acceptance of several recognized strategies to treat anemia . Methods Non-breastfed children ( n = 577 ) , 6 to 43 mo of age , were screened for the trial ; 267 were anemic ( hemoglobin < 11.7 g/dL ) , and 266 of those were r and omized into 1 of 5 treatments to received daily either : an iron supplement ( IS ) , an iron+folic acid supplement ( IFS ) , a multiple micronutrient supplement ( MMS ) , a micronutrient-fortified complementary food as porridge powder ( FCF ) , or zinc+iron+ascorbic acid fortified water ( FW ) . The iron content of each daily dose was 20 , 12.5 , 10 , 10 and 6.7 mg respectively . Hemoglobin ( Hb ) , ferritin , total iron , weight and height were measured at baseline and after 4 months of treatment . Morbidity , treatment acceptability and adherence were recorded during the intervention . Results All treatments significantly increased Hb and total iron concentration ; ferritin did not change significantly . Groups MMS , IS and IFS  increased Hb ( g/dL ) [ 1.50 ( 95%CI : 1.17 , 1.83 ) , 1.48 [ ( 1.18 , 1.78 ) and 1.57 ( 1.26 , 1.88 ) , respectively ] and total iron ( ( μg/dL ) [ 0.15 ( 0.01 , 0.29 ) , 0.19 ( 0.06 , 0.31 ) and 0.12(-0.01 , 0.25 ) , respectively ] significantly more than FCF [ 0.92 ( 0.64 , 1.20 ) ] but not to FW group [ 0.14 ( 0.04 , 0.24 ) ] . The prevalence of anemia was reduced to a greater extent in the MMS and IFS groups ( 72 % and 69 % , respectively ) than in the FCF group ( 45 % ) ( p < 0.05 ) . There were no significant differences in anthropometry or in the number of episodes of diarrhea and respiratory infections among treatment groups . The supplements MMS and IS were less acceptable to children , than IFS , FCF and FW . Conclusion The three supplements IS , ISF and MMS  increased Hb more than the FCF ; the supplements that contained micronutrients ( IFS and MMS ) were more effective for reducing the prevalence of anemia . In general , fortified foods were better accepted by the study participants than supplements . Clinical Trial.gov Objective : Gingival overgrowth is an important adverse effect of phenytoin ( PHT ) therapy , occurring in about half of the patients . This study aim ed to evaluate the effect of oral folic acid supplementation ( 0.5 mg/day ) for the prevention of PHT-induced gingival overgrowth ( PIGO )  in children with epilepsy aged 6–15 years on PHT monotherapy for 6 months . Methods : This was a r and omized , double-blind , placebo-controlled trial conducted at a tertiary level hospital from May 2008 to June 2009 . Children aged 6–15 years started on PHT monotherapy within last 1 month were eligible for inclusion . Preexisting gingival overgrowth , use of other folic acid antagonists , and macrocytic anemia were exclusion criteria . Trial subjects were r and omized to receive either folic acid or placebo . The primary outcome measure was incidence of any degree of gingival overgrowth after 6 months of PHT monotherapy . The trial was registered with clinical trials.gov ( NCT00781196 ) . Results : A total of 120 children were recruited , 62 and 58 , respectively , in folic acid and placebo arms . The 2 arms were comparable at baseline . Twenty-one percent of patients in the folic acid arm developed PIGO , as compared with 88 % receiving placebo ( p < 0.001 ) . Absolute risk reduction of PIGO by folic acid was 67 % ( 95 % confidence interval 54%–80 % ) , and relative risk reduction was 0.76 . Conclusions : Oral folic acid was found to decrease the incidence of PIGO  in children on PHT monotherapy , in a statistically significant and clinical ly relevant manner . Classification of evidence : This study provides Class I evidence that folic acid supplementation , 0.5 mg/day , is associated with prevention of gingival overgrowth in children taking PHT monotherapy Background Seven genes involved in folate metabolism are located on chromosome 21 . Previous studies have shown that folate deficiency may contribute to mental retardation in Down 's syndrome ( DS ) . Methodology We investigated the effect of oral folate supplementation ( daily dose of 1.0±0.3 mg/kg ) on cognitive functions in DS children , aged from 3 to 30 months . They received 1 mg/kg leucovorin or placebo daily , for 12 months , in a single-centre , r and omised , double-blind study . Folinic acid ( leucovorin , LV ) was preferred to folic acid as its bioavailability is higher . The developmental age ( DA ) of the patients was assessed on the Brunet-Lezine scale , from baseline to the end of treatment . Results The intent-to-treat analysis ( 113 patients ) did not show a positive effect of leucovorin treatment . However , it identified important factors influencing treatment effect , such as age , sex , and concomitant treatments , including thyroid treatment in particular . A per protocol analysis was carried out on patients evaluated by the same examiner at the beginning and end of the treatment period . This analysis of 87 patients ( 43 LV-treated vs. 44 patients on placebo )  revealed a positive effect of leucovorin on developmental age ( DA ) . DA was 53.1 % the normal value with leucovorin and only 44.1 % with placebo ( p<0.05 ) . This positive effect of leucovorin was particularly strong in patients receiving concomitant thyroxin treatment ( 59.5 % vs. 41.8 % , p<0.05 ) . No adverse event related to leucovorin was observed . Conclusion These results suggest that leucovorin improves the psychomotor development of children with Down 's syndrome , at least in some subgroups of the DS population , particularly those on thyroxin treatment . Trial Registration Clinical Trials.gov , One hundred eighty-four premature infants , < 1800 g at birth and < 36 wk gestation , were entered into a study investigating the role of additional folate and vitamin B-12 supplementation of the anemia of prematurity .  All patients initially received vitamin E and iron in accordance with accepted st and ards . Patients were r and omly assigned to four groups to receive orally 0.1 mg folate/d for 4 mo , 100 micrograms vitamin B-12 intramuscularly monthly for 4 mo , both supplements , or neither . All other activities including parenteral nutrition were carried out according to established practice s , irrespective of study group . By 10 - 12 wk , infants treated with vitamin B-12 alone or combined with folate had higher hemoglobin values than the untreated ( P < 0.0005 ) or solely folate-treated ( P < 0.01 ) groups . These findings held true irrespective of wide variations in treatment and feeding practice s. The only uncontrolled hematologic nutritional factor , selenium , showed a similar pattern of decline for 10 - 12 wk in all study patients , whether or not they received additional vitamin supplements Background —Accelerated vascular disease is common in chronic renal failure ( CRF ) and accounts for significant mortality and morbidity . Elevated homocysteine levels may contribute by an effect on endothelial function . Methods and Results —We performed a double-blind placebo-controlled r and omized crossover trial of folic acid at 5 mg/m2 in 25 normotensive children 12±3 ( 7 to 17 ) years of age with CRF ( glomerular filtration rate 26.8±13.2 mL/min per 1.73 m2 ) of noninflammatory etiology . Each subject underwent two 8-week periods of folic acid and placebo separated by an 8-week washout period . The effect of folic acid  on homocysteine levels , LDL oxidation , and both endothelial-dependent and -independent vascular function were measured . After oral folic acid , serum folate levels rose from 11.7±4.25 to 635±519 & mgr;g/L ( P = 0.001 ) , red cell folate levels rose from 364±195 to 2891±2623 & mgr;g/L ( P < 0.001 ) , and total homocysteine levels fell from 10.28±4.16 to 8.62±2.32 & mgr;mol/L ( P = 0.03 ) . In addition , there was a significant improvement in flow-mediated dilatation ( FMD ) ( endothelial-dependent dilatation ) from 7.21±2.8 % to 8.47±3.01 % ( P = 0.036 ) with no change in response to glyceryl trinitrate ( endothelial-independent dilatation ) . There was no significant change in FMD or glyceryl trinitrate during the placebo phase . There was , however , no significant difference in final FMD after placebo or folic acid . Lag times for LDL oxidation were prolonged during the treatment phase ( 58.4±18.7 to 68.1±25.9 minutes , P = 0.01 ) . Conclusion —Folic acid supplementation in children with CRF  may improve endothelial function with an increased resistance of LDL to oxidation Abstract Hyperhomocysteinemia is emerging as an independent predictor of cardiovascular disease and hypertension among children . The aim of the study was to examine the effects of oral folic acid on homocysteine and blood pressure .  Folic acid supplementation has been found to reduce homocysteine levels and in some cases blood pressure .  Five hundred and twenty children participated in the study , and 26 of them were found to be hyperhomocysteinemic ; 20 of these children r and omly received 5 mg oral folic acid supplement while the other six children were the controls . Serum homocysteine ( P < 0.001 ) levels as well as systolic ( P < 0.001 ) and diastolic ( P = 0.045 ) blood pressure were statistically significantly decreased in the intervention group compared with the controls , while folic acid levels were statistically significantly increased ( P < 0.001 ) . Total serum homocysteine levels were correlated with age , serum folate , body mass index , and blood pressure . It appears that folic acid may be a safe and effective supplement to reduce homocysteine and possibly blood pressure , which consequently may prevent cardiovascular disease in children in early life Objectives To assess whether supplementation with antioxidants , folinic acid , or both improves the psychomotor and language development of children with Down ’s syndrome . Design R and omised controlled trial with two by two factorial design . Setting Children living in the Midl and s , Greater London , and the south west of Engl and . Participants 156 infants aged under 7 months with trisomy 21 . Intervention Daily oral supplementation with antioxidants ( selenium 10 μg , zinc 5 mg , vitamin A 0.9 mg , vitamin E 100 mg , and vitamin C 50 mg ) , folinic acid ( 0.1 mg ) , antioxidants and folinic acid combined , or placebo . Main outcome measures Griffiths developmental quotient and an adapted MacArthur communicative development inventory 18 months after starting supplementation ; biochemical markers in blood and urine at age 12 months . Results Children r and omised to antioxidant supplements attained similar developmental outcomes to those without antioxidants ( mean Griffiths developmental quotient 57.3 v 56.1 ; adjusted mean difference 1.2 points , 95 % confidence interval −2.2 to 4.6 ) . Comparison of children r and omised to folinic acid supplements or no folinic acid also showed no significant differences in Griffiths developmental quotient ( mean 57.6 v 55.9 ; adjusted mean difference 1.7 , −1.7 to 5.1 ) . No between group differences were seen in the mean numbers of words said or signed :  for antioxidants versus none the ratio of means was 0.85 ( 95 % confidence interval 0.6 to 1.2 ) , and for folinic acid versus none it was 1.24 ( 0.87 to 1.77 ) . No significant differences were found between any of the groups in the biochemical outcomes measured . Adjustment for potential confounders did not appreciably change the results . Conclusions This study provides no evidence to support the use of antioxidant or folinic acid supplements in children with Down ’s syndrome . Trial registration Clinical trials NCT00378456 The effect of 250 μg folic acid (FA)/day or placebo given to 21 small-for-gestational-age infants born at term was studied during the first 3 months of life . The design of the study was double blind with r and om allocation . No r and omization was performed in respect of breast-feeding or formula-feeding with a folate content of 60–70 μg/l . No significant differences were observed in haemoglobin concentration , haematocrit , weight and length between FA-supplemented and non-supplemented infants . A negative correlation was demonstrated between gestational age and erythrocyte folate ( E-folate ) concentration at 1 week . E-folate content was higher when no supplement was given in breast-fed than in formula-fed infants PURPOSE To assess the prevalence of hyperhomocysteinemia in pediatric patients treated with antiepileptic drugs ( AEDs ) and to evaluate the effect of folic acid supplementation on plasma total homocysteine ( tHcy ) concentrations in hyperhomocysteinemic patients . METHODS 123 patients from three regional hospitals participated in the study . Patients with hyperhomocysteinemia were included in a 3-month double-blind r and omized trial testing oral folic acid supplementation ( 1 mg/day ) versus placebo . RESULTS Hyperhomocysteinemia ( tHcy > 10.4 micromol/L ) was present in 19 of 123 patients . Patients with hyperhomocysteinemia were older ( 13.7 + /- 4 vs. 11.0 + /- 3.9 years ) and had significantly lower folate and cobalamin concentrations . Multidrug ( two or more ) AED treatment and duration of therapy correlated significantly with elevated total homocysteine ( tHcy ) and low folate . In contrast , polymorphisms in the methylene tetrahydrofolate reductase gene ( MTHFR 677 C-->T , 1298 A-->C , 1793 G-->A ) had no significant impact on tHcy . Nine of 19 patients with hyperhomocysteinemia were r and omized to placebo , whereas the remaining 10 patients received folic acid supplementation . Folic acid supplementation result ed in a significant increase of folate and decrease of tHcy , whereas both parameters remained unchanged in the placebo group . CONCLUSIONS Hyperhomocysteinemia is present in 15.5 % of children receiving long-term AED treatment . Multidrug treatment and long duration of therapy enhance the risk for hyperhomocysteinemia . Folic acid supplementation significantly reduces tHcy . We recommend assessment of serum folate and plasma tHcy in children receiving AEDs OBJECTIVE To study the effect of multivitamin and folic acid supplementation on serum folate level and weight gain . MATERIAL AND METHOD A prospect i ve r and omized controlled study was conducted in malnourished children at the Nutrition Clinic , Queen Sirikit National Institute of Child Health from February to June 2000 . History taking , weight-height measurement , and blood testing for complete blood count ( CBC ) and serum folate level were done . Patients were r and omly by assigned into 2 groups . The study group was supplemented daily with multivitamins ( MVD ) along with a folic acid tablet while the control group was supplemented daily with MVD only , for 6 weeks . RESULTS Twenty-nine malnourished children were enrolled in the present study . They were r and omly by assigned into 2 groups , 14 children in the study group and 15 children in the control group . There were 11 boys ( 38 % ) and 18 girls ( 62 % ) . Mean age was 36.3 months .  Anemia and low serum folate level were found in 24 per cent and 21 per cent respectively . There was no significant difference in the data of both groups , except that anemia was more common in the study group ( p = 0.018 ) . After 6 weeks of supplementation , increases in weight and serum folate level were significantly higher in the study group , but there was no significant difference in weight increased between both groups . CONCLUSION Folate deficiency may be found in malnourished children . Efficacy of folic acid supplement is good . Folic acid needs to be supplemented in malnourished children Haematological indices and red cell folate levels ( RCF ) were measured during two annual surveys in a group of Gambian children aged 3 months-5 years who were participating in a trial of malaria chemoprophylaxis with Maloprim or chlorproguanil given with or without folate supplements . Chlorproguanil was given in an adult dose of 20 mg , Maloprim as one quarter or one half of the adult dose of 25 mg pyrimethamine and 100 mg dapsone . Antimalarials and folate supplements were given fortnightly . About 20 % of children had low RCF levels ( less than 100 ng/ml ) . Among children who did not receive supplementation with folate there were no significant differences in mean RCF levels between children who received Maloprim , chlorproguanil or placebo . Among children who received folate supplements , the mean RCF was significantly lower among those receiving chlorproguanil than among the controls . Mean RCF values were similar in children who received Maloprim or placebo . If chlorproguanil is used for malaria chemoprophylaxis in young children an age-related dose should be used BACKGROUND . Endothelial dysfunction , a precursor of vascular disease , begins early in type 1 diabetes mellitus and is associated with folate status . METHODS . A r and omized , double-blind , placebo-controlled study of folate ( 5 mg daily ) and vitamin B6 ( 100 mg daily ) in 124 children with type 1 diabetes determined the immediate and 8-week effects of these vitamins , alone and in combination , on endothelial function . Endothelial function , assessed as flow-mediated dilation and glyceryltrinitrate-induced dilation with  high-resolution ultrasound  of the brachial artery , was measured at baseline , at 2 and 4 hours after the first dose ( n = 35 ) , and at 4 and 8 weeks of treatment ( n = 122 ) . RESULTS . Flow-mediated dilation normalized in all treatment groups . From baseline to 8 weeks , flow-mediated dilation improved with folate from 2.6 % ± 4.3 % ( mean ± SD ) to 9.7 % ± 6.0 % , with vitamin B6 from 3.5 % ± 4.0 % to 8.3 % ± 4.2 % , and with folate/vitamin B6 from 2.8 % ± 3.5 % to 10.5 % ± 4.4 % . This improvement in flow-mediated dilation occurred within 2 hours and was maintained at 8 weeks for each treatment . Flow-mediated dilation in the placebo group , and glyceryltrinitrate-induced dilation in all groups , did not change . Increases in serum folate , red cell folate , and serum vitamin B6 levels related to increases in flow-mediated dilation . Improvement in flow-mediated dilation was independent of changes in total plasma homocyst(e)ine , glucose , hemoglobin A1c , and high-sensitivity C-reactive protein levels . Baseline red cell folate levels and baseline diastolic blood pressure were related inversely to improvement in flow-mediated dilation . Serum triglyceride and low-density lipoprotein cholesterol inversely related to baseline flow-mediated dilation . CONCLUSIONS . High-dose folate and vitamin B6  normalized endothelial dysfunction in children with type 1 diabetes . This effect was maintained over 8 weeks , with no additional benefit from combination treatment The birthweights of 100 infants with erythroblastosis were carefully matched as to sex , gestational age , and parity with the birthweights of 200 control infants born during the same period . At all gestational ages the average birthweight of the affected infants was below that of the controls , the average reduction being 227 g. The more severely affected infants tended to be at a lower centile for birthweight than were the mildly affected ones . The relationships between maternal serum folate , cord blood serum folate , and centile for birthweight among affected infants were also studied . There was a strong correlation between low maternal serum folate and the incidence of small-for- date s babies among the affected infants . There was also a strong correlation between maternal and cord blood serum folate values . There was a lack of correlation between maternal serum folate and cord blood haemoglobin . It is concluded that infants with erythroblastosis are lighter than controls and that the reason for this may be a shortage of folic acid available for fetal growth The effect of suboptimal folate nutrtion on the growing infant was studied in a population of infants fed a diet based on boiled , pasteurised cows ' milk . One group of infants received a daily supplement of 1 mg folic acid from age 2 months , while the other group received a placebo . The infants were seen at bimonthly intervals . In the supplemented group the red cell folate level had increased to twice its pretreatment value by 4 months , and remained at this high level to the end of the first year . Hb concentration and incidence of anaemia were similar in both groups . The incidence of infection in the two groups did not differ . Weights and lengths attained at 6 months , and the rate of gain from 2 to 6 months were higher in infants whose folate levels were above the median value than in those below it . In the second half of the first year the differences between the two groups were no longer evident Objective : The incidence of cerebrovascular accidents ( CVA ) occurring perinatally is relatively high and aspects of the multifactorial pathophysiology remain unclear . Elevated homocysteine concentrations have been shown to be associated with an increased risk for CVA in children and even in newborns . We studied the possible homocysteine lowering effect of folinic acid in newborns . Method : We included 37 newborns in our prospect i ve r and omized folinic acid ( given as 5-formyltetrahydrofolate ) intervention study from patients admitted to our neonatal intensive care unit ( 18 controls , 19 intervention group ) . We measured  total homocysteine ( tHcy ) and plasma folate concentrations at three time points ( baseline , 1 and 2 weeks after intervention ) . The intervention group was treated with folinic acid ( 70 μg/kg/day ) for 2 weeks . We calculated median concentrations ( 25th and 75th percentiles ) . Results : Median tHcy concentrations at the three time points did not differ from each other in the control group nor in the intervention group . We also could not observe different tHcy concentrations between both groups . Plasma folate concentrations increased in the intervention group ( mean increase 167 % ( 95 % confidence interval ( CI ) −291 , 625 ) ) compared with control group ( mean increase −12 % ( 95 % CI −132 , 108 ) ) , P for treatment effect : 0.03 . Conclusion : We could not demonstrate a homocysteine lowering effect of folinic acid administration in newborns . This indicates that one carbon metabolism in newborns differs form adults . Cobalamin might be a better strategy to lower tHcy concentrations in newborns The effect of folic acid supplement ( 15 mg folic acid per day ) for 5 weeks was studied on a group of 5 children aged 8 - 12 years who were admitted to hospital . The result was compared to a control group of 5 children who were given a placebo .  After supplementation , both serum and red cell folate levels in the experimental group significantly increased , i.e. , 15 fold ( 82.0 ng/ml ) and 4 fold ( 880 ng/ml ) , respectively . Serum UFBP decreased considerably while TFBP showed no significant alteration which result ed in the elevation of the % saturation to its maximum value . These findings indicated that the supplementary folic acid not only increased both serum and red cell folate levels and saturated nearly all serum UFBP but also elevated the % saturation markedly . There were no definite changes of serum vitamin B12 , UBBC , TBBC and TC levels of the experimental group from those of the control group . There were slightly but not significantly increased blood haemoglobin and haematocrit levels in both groups of children . This indicated that folic acid supplement had no definite effect on vitamin B12 and haematological findings in this study A double‐blind , cross‐over test of folic acid and placebo was carried out in children who had a folate deficiency due to prolonged treatment with phenytoin .  Despite large and long‐ lasting increases in blood folate levels , no associated changes were found in the frequency of fits , EEG , behaviour or gingival conditions . The trial therefore failed to reveal a relationship between the anti‐folate effects of phenytoin and its anticonvulsant action The objective of this study was to assess the prevalence of  anemia  and the therapeutic and prophylactic response to ferrous sulfate and folic acid . A double-blind , r and omized , controlled clinical trial was conducted with 196 children 6 to 24 months of age enrolled in municipal daycare centers in Goiânia , Goiás State , Brazil . The children were assigned to two treatment groups that received a daily dose ( 5 times a week ) of either 4.2mg/kg/day of ferrous sulfate + folic acid ( 50microg ) or 4.2mg/kg/day of ferrous sulfate + folic acid placebo . One of the prevention groups received 1.4mg/kg/day of ferrous sulfate + folic acid ( 50microg/day ) and the other 1.4mg/kg/day of ferrous sulfate + folic acid placebo . Supplementation lasted approximately three months . Baseline anemia prevalence was 56.1 % ( 95%CI : 48.9 - 63.1 ) . After treatment , anemia prevalence in the folic acid group ( 14 % ) was lower than in the placebo group ( 34.9 % ) ( p = 0.02 ) . After prophylaxis in the non-anemic children , the incidence of anemia did not differ between the groups , but there was an increase in hemoglobin level in the folic acid group ( p = 0.003 ) . Iron plus folic acid was effective for the treatment of anemia and improvement of hemoglobin level in non-anemic children A double-blind r and omized trial of 50 μg folic acid or placebo given from 2 weeks to 6 months to 130 infants of birthweight less than 2·5 kg has been conducted . While only 62 of the babies completed the 6-month follow-up , no significant difference was found between either group in respect of changes in weight , haemoglobin , serum folate , red cell folate , or evidence of infection . It is concluded that infants in this series were receiving adequate amounts of folic acid in their normal diet and did not require supplements
target: We conclude that both serum and erythrocyte folate values reflect folate intake ; however , serum folate reacts more rapidly to folate intake than erythrocyte folate .
  As to health outcomes , we found no evidence indicating that additional intake of folate can influence haematological parameters in non-anaemic paediatric patients .
  We were unable to find evidence of a favourable effect of folate supplementation on the growth of infants .
  However , the limited data available suggest that supplementing the diet of low-birth-weight infants with folic acid may moderate the rapid fall of serum and red cell folate in the first months of life
background: The aim of this systematic review was to collect all available r and omized controlled trials on the effect of folate supplementation on folate status and health outcomes within the paediatric age group .