Effect of time of initiation and dose of prenatal iron and folic acid supplementation on iron and folate nutriture of Korean women during pregnancy. Colorectal Adenomas in a Randomized Folate Trial: The Role of Baseline Dietary and Circulating Folate Levels Kinetics of folate turnover in pregnant women (second trimester) and nonpregnant controls during folic acid supplementation: stable-isotopic labeling of plasma folate, urinary folate and folate catabolites shows subtle effects of pregnancy on turnover of folate pools. Antenatal supplementation with micronutrients and biochemical indicators of status and subclinical infection in rural Nepal. Folic acid supplementation in early pregnancy and asthma in children aged 6 years. Maternal dietary folate, folic acid and vitamin D intakes during pregnancy and lactation and the risk of cows' milk allergy in the offspring. Effect of folic acid supplementation on small-for-gestational-age infants born at term Low-Dose folic acid supplementation decreases plasma homocysteine concentrations: a randomised trial. Folate intakes and awareness of folate to prevent neural tube defects: a survey of women living in Vancouver, Canada. Dietary and serum folate: their influence on the outcome of pregnancy.
BACKGROUND In Korea , it is customary to prescribe iron and folic acid supplements to pregnant women after the 20th wk of gestation ; however , little evidence exists to support this practice . OBJECTIVE The objective was to determine the effects of time of initiation and dose of prenatal iron and folic acid supplementation on the iron and folate nutriture of Korean women during pregnancy . DESIGN A total of 131 pregnant women were placed into 1 of 5 experimental groups , either the control group or 1 of 4 supplemented groups . The supplemented groups varied by time of initiation , which was either during the first trimester or at week 20 of gestation , and by dose of iron and folic acid supplements provided , which consisted of either 30 mg Fe plus 175 microg folic acid or 60 mg Fe plus 350 microg folic acid . All supplemented groups continued supplementation until delivery . RESULTS Improvements in iron and folate nutriture were highly dependent on when the supplement program was initiated , but both supplement doses were equally effective . In contrast , the influence of folic acid supplementation on maternal folate status was not as pronounced as was the influence of iron supplementation on iron status . CONCLUSION In pregnant Korean women , initiating iron and folic acid supplementation earlier during pregnancy may prevent the deterioration of iron and folate nutriture more than does increasing supplement doses in later stages of pregnancy The Aspirin/Folate Polyp Prevention Study is a r and omized , placebo-controlled trial of aspirin use and folic acid supplementation and incidence of colorectal adenomas in individuals with a history of these lesions . The trial showed that folic acid supplementation does not prevent the occurrence of new adenomas and may increase risk . We extend these results by investigating whether the effect of folic acid treatment differed by baseline dietary and circulating folate levels . Diet and supplement use were ascertained at baseline through a food-frequency question naire ; a blood sample was used to determine plasma and RBC folate levels . Individuals were followed for 3 years ( first follow-up ) and subsequently for an additional 3 to 5 years ( second follow up ) . We used generalized linear regression to estimate risk ratios and 95 % confidence limits as measures of association . There was little evidence that baseline dietary and total folate intake , and plasma and RBC folate modified the association between folic acid treatment and risk of any adenomas or advanced lesions . However , there was a protective association of the highest tertile of dietary and total intake as well as circulating folate with risk of any adenomas among those in the placebo group but no association among individuals in the folic acid group . Our findings support the idea that although moderate doses of folate may be protective compared with deficiency , at some point of sufficiency , supplementation provides no additional benefit . ( Cancer Epidemiol Biomarkers Prev 2008;17(10):2625–31 To investigate the effects of pregnancy on folate metabolism , we conducted an 84-d study in second-trimester ( gestational wk 14 - 25 ) pregnant women ( n = 6 ) and nonpregnant controls ( n = 6 ) with stable-isotopic tracer methods . All subjects were fed a diet containing approximately 272 nmol/d ( 120 microg/d ) folate from food , along with supplemental folic acid that contained 15 % [ 3',5'-(2)H(2 ) ] folic acid ( [(2)H(2)]folic acid ) during d 1 - -41 and that was unlabeled during d 42 - -84 to yield a constant total folate intake of 1.02 or 1.93 micromol/d ( 450 or 850 microg/d ) . Isotopic enrichment of plasma folate , urinary folate and the urinary folate catabolites para-aminobenzoylglutamate ( pABG ) and para-acetamidobenzoylglutamate ( ApABG ) was determined at intervals throughout the study . The labeling of pABG and ApABG reflected that of tissue folate pools from which the catabolites originate . After the intake of labeled folic acid was terminated on d 41 , labeling of urinary folate exhibited a biphasic exponential decline with distinct fast and slow components . In contrast , during d 42 - -84 , the enrichment of urinary pABG and ApABG exhibited primarily monophasic exponential decline , and plasma folate underwent little decline of labeling during this period . Pregnant women and controls did not differ in estimates of body folate pool size and most aspects of the excretion of labeled urinary folate and catabolites , rates of decline of excretion , and areas under the curves for folate and catabolite excretion . Pregnant women , however , tended to have a slower rate of decline of pABG than ApABG and higher enrichment at d 42 of ApABG and pABG . These data support and extend our previous findings indicating that pregnancy ( gestational wk 14 - -26 ) causes subtle changes in folate metabolism but does not elicit substantial increases in the rate or extent of folate turnover at these moderately high folate intakes BACKGROUND Previously we showed that women in rural Nepal experience multiple micronutrient deficiencies in early pregnancy . OBJECTIVE This study examined the effects of daily antenatal micronutrient supplementation on changes in the biochemical status of several micronutrients during pregnancy . DESIGN In Nepal , we conducted a r and omized controlled trial in which 4 combinations of micronutrients ( folic acid , folic acid + iron , folic acid + iron + zinc , and a multiple micronutrient supplement containing folic acid , iron , zinc , and 11 other nutrients ) plus vitamin A , or vitamin A alone as a control , were given daily during pregnancy . In a sub sample of subjects ( n = 740 ) , blood was collected both before supplementation and at approximately 32 wk of gestation . RESULTS In the control group , serum concentrations of zinc , riboflavin , and vitamins B-12 and B-6 decreased , whereas those of copper and alpha-tocopherol increased , from the first to the third trimester . Concentrations of serum folate , 25-hydroxyvitamin D , and undercarboxylated prothrombin remained unchanged . Supplementation with folic acid alone or folic acid + iron decreased folate deficiency . However , the addition of zinc failed to increase serum folate , which suggests a negative inhibition ; multiple micronutrient supplementation increased serum folate .  Folic acid + iron + zinc failed to improve zinc status but reduced sub clinical infection .  Multiple micronutrient supplementation decreased the prevalence of serum riboflavin , vitamin B-6 , vitamin B-12 , folate , and vitamin D deficiencies but had no effect on infection . CONCLUSIONS In rural Nepal , antenatal supplementation with multiple micronutrients can ameliorate , to some extent , the burden of deficiency . The implication s of such biochemical improvements in the absence of functional and health benefits remain unclear OBJECTIVE The objective of the study was to assess whether folic acid intake during the first trimester of pregnancy is related to  asthma in the offspring by the age of 6 years . STUDY DESIGN This was a prospect i ve cohort study of 1499 women who were followed up from the first trimester of pregnancy . Their children were followed up until they were 6 years old . RESULTS Fifty-one percent of the women used folic acid in the month before conception and 88 % in the third month of pregnancy . The adjusted odds ratio for asthma per 100 μm increase in the average daily intake of folic acid was 0.98 ( 95 % confidence interval , 0.93 - 1.04 ) . For categories of daily folate intake , there was no evidence of associations with childhood asthma or evidence of any dose response relation for any time period ( all P(trend ) > .05 ) . CONCLUSION Our results do not support any association of folic acid supplementation in pregnancy and asthma risk in offspring by age 6 years Maternal nutrient intake during pregnancy and lactation potentially influences the development of allergic diseases . Cows ' milk allergy ( CMA ) is often the first manifestation of atopic diseases , but the impact of early nutritional influences on CMA has not been explored . The associations between maternal intakes of folate , folic acid and vitamin D during pregnancy and lactation were addressed in a prospect i ve , population -based birth cohort within the Finnish Type 1 Diabetes Prediction and Prevention Study . Mothers of 4921 children during pregnancy and 2940 children during lactation provided information on maternal dietary intake during the 8th month of pregnancy and the 3rd month of lactation using a detailed , vali date d FFQ . Information on diagnosed CMA in the offspring was obtained from a medical registry as well as queried from the parents . The Finnish food composition data base was used to calculate nutrient intake . Logistic regression was applied for statistical analyses .  Folate intake and folic acid and vitamin D supplement  use were associated with an increased risk of CMA in the offspring , whereas vitamin D intake from foods during pregnancy was associated with a decreased risk of CMA . Thus , maternal nutrient intake during pregnancy and lactation may affect the development of CMA in offspring . Supplementation with folic acid may not be beneficial in terms of CMA development , especially in children of allergic mothers . The association between dietary supplement use and CMA risk can at least partly be explained by increased health-seeking behaviour among more educated mothers who also use more dietary supplements 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 An elevated plasma total homocysteine concentration is a risk factor for cardiovascular disease and neural tube defects . A high daily intake of supplemental folic acid is known to decrease total homocysteine concentrations . We studied the effect of low-dose folic acid administration ( 250 or 500 microg/day for 4 weeks on plasma total homocysteine concentrations and folate status . We also investigated whether total homocysteine concentrations and blood folate concentrations returned to baseline after an 8-week washout period . In this placebo-controlled study , 144 healthy women aged 18 - 40 years received 500 microg folic acid per day , 500 microg folic acid every second day ( 250 microg/day ) , or a placebo tablet with their habitual diet ( mean dietary folate intake 280 microg/day ) . Administration of 250 and 500 microg folic acid per day for four weeks significantly increased folate concentrations in plasma ( p<0.001 ) and red blood cells ( p<0.01 ) . Total homocysteine concentrations decreased significantly ( p<0.001 ) in women ( n=50 ) who took 250 microg folic acid daily [ mean ( + /- SEM ) deviation from baseline -11.4 + /-1.98 % ] and in women ( n=45 ) who took 500 microg folic acid daily ( -21.8 + /- 1.49 % ) . Eight weeks after the end of the intervention period ( week 12 ) , plasma total homocysteine concentrations in the folic acid-supplemented groups had not returned to baseline ( week 0 ) . In conclusion , doses of folic acid as low as 250 microg daily , on an average , in addition to usual dietary intakes of folate , significantly decreased plasma total homocysteine concentrations in healthy , young women . An 8-week washout period was not sufficient for blood folate and plasma total homocysteine concentrations to return to baseline OBJECTIVE To estimate folate intake and knowledge in women of childbearing age , in relation to risk of neural tube defects . SUBJECTS/ SETTING One hundred forty-eight women ( aged 18 to 45 years ) in the Vancouver area of British Columbia , Canada . DESIGN Using an interviewer-administered survey , we examined women for folate knowledge and the relation of folate knowledge to intake in a r and om sample . Contribution of folate from food , fortified grain products , and supplements was assessed by vali date d semiquantitative food frequency question naire . STATISTICAL ANALYSIS PERFORMED Descriptive statistics , t tests , Chi;(2 ) , Pearson correlation analysis . RESULTS Mean daily folate intake from food , fortified foods , and supplementation was 812+/-710 Dietary Folate Equivalents (DFE)/day . Fortification of bread and grain products contributed 104+/-68 microg synthetic folic acid (SFA)/day ( equal to 174+/-114 DFE ) , and supplements contributed 205+/-388 microg SFA/day . Although 86 % of women met the Estimated Average Requirement ( 320 DFE/day ) for folate , only 26 % met the recommendation ( 400 microg SFA/day ) for women capable of becoming pregnant . Most ( 95 % ) of the women had heard of folate , but only 25 % knew that it could prevent birth defects . One-fourth of the women had good or very good knowledge of folate-rich foods . However , folate knowledge was not related to its intake . The most common sources of folate information were magazines/newspapers , doctors , and television/radio . Lack of awareness of the importance of folate was the most common reason given for choosing not to use folic acid supplements before pregnancy . However , 78 % of the women indicated that , with knowledge of the benefits of folate , they would use supplemental folic acid daily to reduce the risk of birth defects . APPLICATIONS/ CONCLUSIONS Educational strategies are required to increase folate awareness among women and to promote the benefits of periconceptional folic acid supplementation . Targeting physicians to educate women on the importance of folate could be a potentially successful route . We examined the influence of folate intake from diet and supplements b y 28 wk of gestation and third trimester circulating concentrations of serum folate on the outcome of pregnancy in women from Camden , NJ . Mean daily folate intake by week 28 included both dietary and supplemental folate obtained prospect ively in 832 women . Circulating concentrations of serum folate as well as serum vitamin B-12 were assayed at 28 wk of gestation ( + /- 2 wk ) by radioimmunoassay . The outcomes of interest included preterm delivery ( < 37 wk ) and  infants with low birth weight ( < 2500 g ) . Mean folate intake was significantly correlated with circulating concentrations of serum folate ( r=0.17 , P<0.001 ) . Women with a low mean daily folate intake ( < /-240 microgram/d ) had an approximately twofold greater risk of preterm delivery and infant low birth weight after maternal characteristics , energy intake , and other correlated nutrients were controlled for . Lower concentrations of serum folate at week 28 were also associated with a greater risk of preterm delivery and low birth weight
In contrast , we did not find any beneficial effect of  folate supplementation on placental weight or on length of gestation .
There is a paucity of well-conducted RCTs investigating the effect of  folate supplementation on health outcomes in pregnancy .
The beneficial effect of folic acid supplementation before and shortly after conception is well recognized , whereas the effect of supplementation during the second and third trimesters is controversial and poorly documented .
Our aims were to systematic ally review r and omized controlled trials ( RCTs ) investigating the effect of folate supplementation on birth weight , placental weight and length of gestation and to assess the dose – response relationship between folate intake ( folic acid plus dietary folate ) and health outcomes .