Folic Acid Supplement Intake Research Articles

Folic acid intake and folate status and colorectal cancer risk: A systematic review and meta-analysis

To evaluate the controversies among the studies assessing the association between folic acid intake or folate status and colorectal cancer risk. PubMed, Cochrane library and references of related articles were searched from January 2000 to September 2016. Studies on folic acid intake or folate status and colorectal cancer or adenoma risk were included. Full text review was conducted for potentially eligible studies. Quality assessment was performed. Random-effects meta-analysis was used to estimate risk ratio and 95% Confidence Intervals. Analysis was conducted by Comprehensive Meta-Analysis software. Folic acid supplement intake showed no significant effect on colorectal cancer risk in meta-analysis of randomized controlled trials, RR: 1.07(95% CI: 0.86-1.43). The effect on risk was not significant in cohort studies either; RR=0.96(95% CI: 0.76-1.21). However, there was significant reduced colorectal cancer risk in total folate intake in cohort studies; 0.71 (95% CI: 0.59-0.86). Odds Ratio was also significantly reduced in case control studies; 0.77 (95% CI: 0.62-0.95). Nevertheless once folate status was measured as Red Blood Cell folate content, no significant effect on colorectal cancer risk was observed; 1.05 (95% CI: 0.85-1.30). The differences in bioavailability and metabolism of synthetic folic acid and natural dietary folate as well as variation in the baseline characteristics of subjects and various methods of folate status assessment might be the main reasons for these controversies. Findings of present study highlightthe importance of individualized folic acid supplement intake given the fact that the beneficiary effects of long term folic acid supplementation is not confirmed.

Maternal use of folic acid supplements and infant risk of neural tube defects in Norway 1999-2013.

Like most European countries, Norway has refrained from mandatory food fortification with folic acid to reduce the number of neural tube defects. We explored the role of folic acid and multivitamin supplements in the prevention of neural tube defects among newborn infants. We used data from the Medical Birth Registry of Norway, 1999-2013. A total of 528,220 women had 880,568 pregnancies resulting in 896,674 live- and stillborn infants, of whom 270 had neural tube defects. Relative risks were estimated with log-binomial regression. From 1999 to 2013, intake of folic acid supplements increased from 4.8% to 27.4%. Vitamin supplement use was more frequent in older, married or cohabiting women and those with lower parity, as well as women who did not smoke during pregnancy. The overall adjusted relative risk of infant neural tube defects associated with maternal vitamin intake before pregnancy relative to no intake was 0.76 (95% confidence interval: 0.53-1.10). When we divided our study period in two (1999-2005 and 2006-2013), we found a significantly reduced risk of neural tube defects overall by vitamin use in the second time period, but not in the first: adjusted relative risk 0.54 (95% confidence interval: 0.31-0.91) and 1.02 (95% confidence interval: 0.63-1.65), respectively. OVER THE FULL STUDY PERIOD, WE FOUND NO STATISTICALLY SIGNIFICANT ASSOCIATION BETWEEN VITAMIN USE AND NEURAL TUBE DEFECTS OVERALL HOWEVER, VITAMIN USE WAS ASSOCIATED WITH A SIGNIFICANTLY LOWER RISK OF NEURAL TUBE DEFECTS IN THE SECOND HALF OF THE STUDY PERIOD, 2006-2013.

Multivitamin, calcium and folic acid supplements and the risk of colorectal cancer in Lynch syndrome.

People with a DNA mismatch repair (MMR) gene mutation have a substantially elevated risk of colorectal cancer (CRC) but the modifiers of this risk are not well established. We investigated the association between dietary supplement intake and CRC risk for carriers. This study included 1966 (56% female) carriers of an MMR gene mutation (719 MLH1, 931 MSH2, 211 MSH6 and 105 PMS2) who were recruited from the USA, Canada, Australia and New Zealand into the Colon Cancer Family Registry between 1997 and 2012. Information on lifestyle factors including supplement intake was collected at the time of recruitment. Using Cox proportional hazards regression weighted to correct for ascertainment bias, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between self-reported multivitamin, calcium and folic acid supplement intake and CRC risk. Of 744 carriers with CRC, 18%, 6% and 5% reported intake of multivitamin, calcium and folic acid supplements for at least 1 month, respectively, compared with 27%, 11% and 10% of 1222 carriers without CRC. After adjusting for identified confounding variables, a decreased CRC risk was associated with multivitam inintake for at least 3 years (HR 0.47, 95% CI 0.32-0.69) and calcium intake for at least 3 years(HR 0.42, 95% CI 0.23-0.74), compared with never users. There was no evidence of an association between folic acid supplement intake and CRC risk (P = 0.82). Intake of multivitamin and calcium supplements might be associated with a decreased risk of CRC for MMR gene mutation carriers.

Folic acid and diseases - supplement it or not?

folic acid is a water soluble vitamin, which is synthetically-produced and found in fortified foods and supplements. Folate is found naturally in plants, such as the dark green leafy vegetables. Folate is not synthesized de novo by humans, therefore the daily requirements are met from the dietary intake of folic acid supplements or food rich in this vitamin. Folate deficiency could lead to numerous common health problems. Hyperhomocysteinemia and the possibility of malignancy developments are the long term consequences of this deficit albeit contradictory findings on these claims. the articles included in this review focused on recent updated evidence-based reports and meta-analyses on the associations of the serum folate/folic acid and the various diseases found globally. the benefit of folic acid supplementation in the pre-conception period for the prevention of neural tube defects (NTDs) was well established and it was suggested that counseling sessions should be given to women with previous pregnancies affected by NTDs. However, supplementation of folic acid and its medicinal effects in the treatment of other diseases were contradictory and unclear. more detailed investigations into the health benefits of folic acid are needed before it could be recommended for supplementation, treatment or prevention of some of the diseases discussed in this review.

Pre-conceptional intake of folic acid supplements is inversely associated with risk of preterm birth and small-for-gestational-age birth: a prospective cohort study.

Associations of folic acid supplementation with risk of preterm birth (PTB) and small-for-gestational-age (SGA) birth were unclear for the Chinese populations. The aim of the present study was to investigate the associations in a large Chinese prospective cohort study: the Jiaxing Birth Cohort. In the Jiaxing Birth Cohort, 240 954 pregnant women visited local clinics or hospitals within their first trimester in Southeast China during 1999-2012. Information on anthropometric parameters, folic acid supplementation and other maternal characteristics were collected by in-person interviews during their first visit. Pregnancy outcomes were recorded during the follow-up of these participants. Multinomial logistic regression was used to examine the association of folic acid supplementation with pregnancy outcomes. The prevalence of folic acid supplementation was 24·9% in the cohort. The prevalence of PTB and SGA birth was 3·48 and 9·2%, respectively. Pre-conceptional folic acid supplementation was associated with 8% lower risk of PTB (relative risk (RR) 0·92; 95% CI 0·85, 1·00; P=0·04) and 19% lower risk of SGA birth (RR 0·81; 95% CI 0·70, 0·95; P=0·008), compared with non-users. Higher frequency of pre-conceptional folic acid use was associated with lower risk of PTB (P trend=0·032) and SGA birth (P trend=0·046). No significant association between post-conceptional initiation of folic acid supplementation and either outcome was observed. In conclusion, the present study suggests an association between pre-conceptional, but not post-conceptional, folic acid supplementation and lower risk of PTB and SGA birth in the Jiaxing Birth Cohort. Further research in other cohorts of large sample size is needed to replicate these findings.

Supplemental folic acid in pregnancy and maternal cancer risk

BackgroundThere is evidence that increased intake of folate protects against the development of several types of cancer. Some studies have, however, raised concern about the safety of folate in relation to cancer risk. Here we examined the risk of maternal cancer after intake of supplemental folic acid in pregnancy. MethodsThis is a population-based cohort study comprising 429,004 women with data from the Medical Birth Registry of Norway, the Cancer Registry of Norway, and other national registries from 1999 to 2010. Altogether 3781 cancer cases were identified during follow-up (average 7 years). Cox proportional hazards regression models were used to estimate hazard ratios of maternal cancer according to folic acid use prior to and during one or two or more pregnancies as compared to no supplement use. ResultsFolic acid supplementation use had no overall effect on cancer risk in women using folic acid supplementation in one (HR 1.08; 95% CI 1.00–1.18) or two or more pregnancies (HR 1.06; 95% CI 0.91–1.22) (ptrend=0.12). Analyses of 13 cancer types revealed no associations between folic acid and cancer. ConclusionFolic acid supplementation before and during pregnancy had no overall effect on maternal cancer risk. ImpactFolic acid substitution before and/or during pregnancy does not increase the short-term overall maternal cancer risk.

Periconceptional Folic Acid Supplementation and Infant Risk of Congenital Heart Defects inNorway 1999–2009

The birth prevalence of congenital heart defects (CHDs) has decreased in Canada and Europe. Recommended intake of folic acid in pregnancy is a suggestive risk-reducing factor for CHDs. We investigated the association between periconceptional intake of folic acid supplements and infant risk of CHDs. Information on maternal intake of folic acid supplements before and during pregnancy in the Medical Birth Registry of Norway 1999-2009 was updated with information on CHD diagnoses from national health registers and the Cardiovascular Diseases in Norway Project. The association between folic acid intake and infant risk of CHD was estimated as relative risk (RR) with binomial log linear regression. Among 517 784 non-chromosomal singleton births, 6200 children were identified with CHD and 1153 with severe CHD. For all births, 18.4% of the mothers initiated folic acid supplements before pregnancy and 31.6% during pregnancy. The adjusted RR for severe CHD was 0.99 [95% confidence interval [CI] 0.86, 1.13] comparing periconceptional intake of folic acid with no intake. Specifically, RR for conotruncal defects was 0.99 [95% CI 0.80, 1.22], atrioventricular septal defects 1.19 [95% CI 0.78, 1.81], left ventricular outflow tract obstructions 1.02 [95% CI 0.78, 1.32], and right ventricular outflow tract obstructions 0.97 [95% CI 0.72, 1.29]. Birth prevalence of septal defects was higher in the group exposed to folic acid supplements with RR 1.19 [95% CI 1.10, 1.30]. Periconceptional folic acid supplement use showed no association with severe CHDs in the newborn. An unexpected association with an increased risk of septal defects warrants further investigation.

Folic acid supplementation, dietary folate intake and risk of preterm birth in China.

Folic acid supplementation has been suggested to reduce the risk of preterm birth. However, results from previous epidemiologic studies have been inconclusive. We investigated the hypothesis that folic acid supplementation and dietary folate intake during pre- and post-conception reduces the risk of preterm birth. We analyzed data from a birth cohort study conducted between 2010 and 2012 in Lanzhou, China, including 10,179 pregnant women with live singleton births. Compared to non-users, folic acid supplement users with >12-week duration had a reduced risk of preterm birth (OR 0.67, 95% CI 0.55-0.83) with a significant dose-response relationship (P for trend=0.01). A similar pattern was observed for spontaneous preterm birth. Stronger associations were seen for ever use of folic acid supplement and very preterm birth (OR 0.50, 95% CI 0.36-0.69) and spontaneous very preterm birth (OR 0.42, 95% CI 0.29-0.63). Dietary folate intake during preconception and pregnancy were also associated with reduced risk of preterm birth (OR 0.68, 95% CI 0.56-0.83, OR 0.57, 95% CI 0.47-0.70 for the highest quartiles, respectively), particularly for spontaneous very preterm (OR 0.41, 95% CI 0.24-0.72, OR 0.26, 95% CI 0.15-0.47 for the highest quartiles, respectively). There were also decreased risks of preterm birth observed per 10-µg increase in dietary folate intake, and similar associations were found after stratification by folic acid supplementation status. Our results suggest that folic acid supplementation and higher dietary folate intake during preconception and pregnancy reduces the risk of preterm birth, and the protective effect varies by preterm subtypes.

Prevalence and correlates of high red blood cell folate concentrations in the Canadian population using 3 proposed cut-offs.

A distinct shift towards higher folate concentrations has emerged in Canada. These higher concentrations have known benefits, including prevention of neural tube defects, but concerns have been raised regarding potential associations with adverse health outcomes. The aim of this research was to propose cut-offs for high red blood cell (RBC) folate concentrations and identify their correlates. RBC folate was measured in a nationally representative cross-sectional sample of Canadians (N = 5248) aged 6 to 79 years. RBC folate concentrations were adjusted from the IMMULITE 2000 immunoassay to a microbiologic assay. The population was characterized at 3 RBC folate cut-offs: 1450 nmol/L, 1800 nmol/L, and 2150 nmol/L. We used t tests to examine differences by age, sex, income, and body mass index (BMI) at each cut-off and logistic regression to explore associations with folic acid supplement intake. The prevalence of high RBC folate was 16%, 6%, and 2% at thresholds of 1450 nmol/L, 1800 nmol/L, and 2150 nmol/L, respectively. Females, those aged 60 to 79 years, and overweight or obese participants had the greatest prevalence of having high RBC folate at each cut-off. Folic acid supplement users were more likely than non-users to have high RBC folate concentrations. Older age, higher BMI, and folic acid supplement use were identified as correlates of high folate status. A high RBC folate concentration cut-off will advance the field towards consistent measurement and reporting of high folate status. This may facilitate future investigation of associations between RBC folate concentrations at the upper end of the distribution and health outcomes.

Family structure and use of prenatal care.

This cross-sectional study intended to assess the use of prenatal care according to the family structure in a population with free universal access to prenatal care. In 2005-2006, the Portuguese birth cohort was assembled by the recruitment of puerperae at public maternity wards in Porto, Portugal. In the current analysis, 7,211 were included. Data on socio-demographic characteristics, obstetric history, and prenatal care were self-reported. Single mothers were considered as those whose household composition did not include a partner at delivery. Approximately 6% of the puerperae were single mothers. These women were more likely to have an unplanned pregnancy (OR = 6.30; 95%CI: 4.94-8.04), an inadequate prenatal care (OR = 2.30; 95%CI: 1.32-4.02), and to miss the ultrasound and the intake of folic acid supplements during the first trimester of pregnancy (OR = 1.71; 95%CI: 1.30-2.27; and OR = 1.67; 95%CI: 1.32-2.13, respectively). The adequacy and use of prenatal care was less frequent in single mothers. Educational interventions should reinforce the use and early initiation of prenatal care.

Arsenic is associated with reduced effect of folic acid in myelomeningocele prevention: a case control study in Bangladesh.

BackgroundArsenic induces neural tube defects in several animal models, but its potential to cause neural tube defects in humans is unknown. Our objective was to investigate the associations between maternal arsenic exposure, periconceptional folic acid supplementation, and risk of posterior neural tube defect (myelomeningocele) among a highly exposed population in rural Bangladesh.MethodsWe performed a case–control study that recruited physician-confirmed cases from community health clinics served by Dhaka Community Hospital in Bangladesh, as well as local health facilities that treat children with myelomeningocele. Controls were selected from pregnancy registries in the same areas. Maternal arsenic exposure was estimated from drinking water samples taken from wells used during the first trimester of pregnancy. Periconceptional folic acid use was ascertained by self-report, and maternal folate status was further assessed by plasma folate levels measured at the time of the study visit.ResultsFifty-seven cases of myelomeningocele were identified along with 55 controls. A significant interaction was observed between drinking water inorganic arsenic and periconceptional folic acid use. As drinking water inorganic arsenic concentrations increased from 1 to 25 μg/L, the estimated protective effect of folic acid use declined (OR 0.22 to 1.03), and was not protective at higher concentrations of arsenic. No main effect of arsenic exposure on myelomeningocele risk was identified.ConclusionsOur study found a significant interaction between drinking water inorganic arsenic concentration from wells used during the first trimester of pregnancy and reported intake of periconceptional folic acid supplements. Results suggest that environmental arsenic exposure reduces the effectiveness of folic acid supplementation in preventing myelomeningocele.

The effects of folic acid on global DNA methylation and colonosphere formation in colon cancer cell lines

Folate and its synthetic form, folic acid (FA), are essential vitamins for the regeneration of S-adenosyl methionine molecules, thereby maintaining adequate cellular methylation. The deregulation of DNA methylation is a contributing factor to carcinogenesis, as alterations in genetic methylation may contribute to stem cell reprogramming and dedifferentiation processes that lead to a cancer stem cell (CSC) phenotype. Here, we investigate the potential effects of FA exposure on DNA methylation and colonosphere formation in cultured human colorectal cancer (CRC) cell lines. We show for the first time that HCT116, LS174T, and SW480 cells grown without adequate FA demonstrate significantly impaired colonosphere forming ability with limited changes in CD133, CD166, and EpCAM surface expression. These differences were accompanied by concomitant changes to DNA methyltransferase (DNMT) enzyme expression and DNA methylation levels, which varied depending on cell line. Taken together, these results demonstrate an interaction between FA metabolism and CSC phenotype in vitro and help elucidate a connection between supplemental FA intake and CRC development.

Folic acid supplementation and dietary folate intake, and risk of preeclampsia.

Folic acid supplementation has been suggested to reduce the risk of preeclampsia. However, results from few epidemiologic studies have been inconclusive. We investigated the hypothesis that folic acid supplementation and dietary folate intake before conception and during pregnancy reduce the risk of preeclampsia. A birth cohort study was conducted in 2010-2012 at the Gansu Provincial Maternity & Child Care Hospital in Lanzhou, China. A total of 10,041 pregnant women without chronic hypertension or gestational hypertension were enrolled. Compared with nonusers, folic acid supplement users had a reduced risk of preeclampsia (OR=0.61, 95% CI: 0.43-0.87). A significant dose-response of duration of use was observed among women who used folic acid supplemention during pregnancy only (P-trend=0.007). The reduced risk associated with folic acid supplement was similar for mild or severe preeclampsia and for early- or late-onset preeclampsia, although the statistical significant associations were only observed for mild (OR=0.50, 95% CI: 0.30-0.81) and late-onset (OR=0.60, 95% CI: 0.42-0.86) preeclampsia. The reduced risk associated with dietary folate intake during pregnancy was only seen for severe preeclampsia (OR=0.52, 95% CI: 0.31-0.87, for the highest quartile of dietary folate intake compared with the lowest). Our study results suggest that folic acid supplementation and higher dietary folate intake during pregnancy reduce the risk of preeclampsia. Future studies are needed to confirm the associations.

Nausea and vomiting in early pregnancy and the risk of neural tube defects: a case-control study.

There has been considerable professional debate on the association between nausea and vomiting in early pregnancy (NVP) and neural tube defects (NTDs) risk. This study explored the association between NVP and NTDs risk, and the effect of folic acid supplements on the association. A 1:1 matched case-control study was conducted and conditional logistic regression model was used to analyze the associations. The result showed the odds ratio (OR) of severe NVP for NTDs was 2.403 (95%CI 1.437,4.017; P<0.001) and that of moderate NVP was 1.469 (95%CI 1.063,2.031; P = 0.020) compared with light NVP when adjusted by the potential confounders. Stratified by intake of folic acid supplements, the ORs for severe and moderate NVP turned to 2.147 (95%CI 1.140, 4.043; P = 0.018) and 2.055 (95%CI 1.320, 3.199; P = 0.001) in the stratum of non-intake of folic acid supplements while ORs reduced to 1.851 (95%CI 0.729, 4.699; P = 0.195) and 1.003 (95%CI 0.594, 1.694; P = 0.992) in the stratum of intake of folic acid supplements, respectively. We conclude that severe/moderate NVP has an association with the risk of NTDs, which was not found in the group with intake of folic acid supplements. Folic acid supplements should be recommended to use for the prevention of NTDs.

Derivation and Validation of Homocysteine Score in U.S. Men and Women1–3

One-carbon metabolism, which is crucial in DNA synthesis and genomic stability, is an interrelated network of biochemical reactions involved in several dietary and lifestyle factors. The development of the homocysteine score using these factors may be useful to reflect the status of one-carbon metabolism in large epidemiologic studies without biologic samples to measure homocysteine directly. The aim of this study was to develop an homocysteine score that reflects one-carbon metabolism better than individual dietary or lifestyle factors. We divided 2023 participants with measured plasma total homocysteine data in the Nurses' Health Study and the Health Professionals Follow-Up Study into training (n = 1619) and testing (n = 404) subsets. Using multivariable linear regression, we selected lifestyle determinants of plasma homocysteine in the training set and derived the homocysteine score weighted by the β coefficient for each predictor. The validation of the homocysteine score was assessed using the plasma homocysteine in the independent samples of the training set. In the training set, smoking, multivitamin use, and caffeine, alcohol, and dietary and supplemental folate intake were significant independent determinants of plasma homocysteine in multivariable linear regression (P ≤ 0.01) and were included in the derivation of the homocysteine score. The Pearson correlation of the homocysteine score with plasma homocysteine was 0.30 in the testing subset (P < 0.001). The homocysteine score was positively associated with the plasma homocysteine concentration in the testing subset and in an independent population of women; the mean difference of plasma homocysteine concentration between the extreme quintiles of homocysteine score ranged from 0.83 μmol/L to 1.52 μmol/L. Population misclassification either from the lowest quintile of plasma homocysteine into the highest quintile of the homocysteine score or from the highest quintile of plasma homocysteine into the lowest quintile of the homocysteine score was ≤12%. These data indicate that the homocysteine score may be used with relatively inexpensive and simple questionnaires to rank an individual's one-carbon metabolism status when homocysteine data are not available.

Folic acid supplements during pregnancy and child psychomotor development after the first year of life.

Folate intake during pregnancy has been associated with improved neuropsychological development in children, although the effects of high dosages of folic acid (FA) supplements are unclear. To examine the association between the use of high dosages of FA supplements during pregnancy and child neuropsychological development after the first year of life. The multicenter prospective mother-child cohort Infancia y Medio Ambiente (INMA) Project recruited pregnant women from 4 areas of Spain (Asturias, Sabadell, Gipuzkoa, and Valencia) between November 2003 and January 2008. Pregnant women completed an interviewer-administered questionnaire on the usual dietary folate intake and FA supplements at 10 to 13 weeks and 28 to 32 weeks of gestation. The main analyses were based on a sample of 2213 children with complete information on neuropsychological development and FA supplement intake during pregnancy. Multiple linear and logistic regression analyses were used to explore the effects of FA supplements on child neuropsychological development. Neuropsychological development was assessed using the Bayley Scales of Infant Development. We calculated mental scale and psychomotor scale scores. One SD below the mean established a delay in neurodevelopment (score <85). A high proportion of women (57.3%) did not reach the recommended dosages of FA supplements (400 μg/d), but 25.2% women took more than 1000 μg/d of FA supplements (3.5% consuming >5000 μg/d). In multivariate analysis, we observed that children whose mothers used FA supplement dosages higher than 5000 μg/d during pregnancy had a statistically significantly lower mean psychomotor scale score (difference, -4.35 points; 95% CI, -8.34 to -0.36) than children whose mothers used a recommended dosage of FA supplements (400-1000 μg/d). An increased risk of delayed psychomotor development (psychomotor scale score <85) was also evident among children whose mothers took FA supplement dosages higher than 5000 μg/d, although the association was not statistically significant (odds ratio = 1.59; 95% CI, 0.82-3.08). To our knowledge, this is the first time a detrimental effect of high dosages of FA supplements during pregnancy on psychomotor development after the first year of life has been shown. Further research from longitudinal studies is warranted to confirm these results.

Folic acid supplementation, dietary folate intake during pregnancy and risk for spontaneous preterm delivery: a prospective observational cohort study.

BackgroundHealth authorities in numerous countries recommend periconceptional folic acid supplementation to prevent neural tube defects. The objective of this study was to examine the association of dietary folate intake and folic acid supplementation during different periods of pregnancy with the risk of spontaneous preterm delivery (PTD).MethodsThe Norwegian Mother and Child Cohort Study is a population-based prospective cohort study. A total of 66,014 women with singleton pregnancies resulting in live births in 2002–2009 were included. Folic acid supplementation was self-reported from 26 weeks before pregnancy until pregnancy week 24. At gestational week 22, the women completed a food frequency questionnaire, which allowed the calculation of their average total folate intake from foods and supplements for the first 4–5 months of pregnancy. Spontaneous PTD was defined as the spontaneous onset of delivery between weeks 22+0 and 36+6 (n = 1,755).ResultsThe median total folate intake was 313 μg/d (interquartile range IQR 167–558) in the overall population and 530 μg/d (IQR 355–636) in the supplement users. Eighty-five percent reported any folic acid supplementation from <8 weeks before to 24 weeks after conception while only 44% initiated folic acid supplementation before pregnancy. Cox regression analysis showed that the amount of dietary folate intake (hazard ratio HR 1.00; confidence interval 95% CI 0.61-1.65) and supplemental folate intake (HR 1.00; CI 1.00-1.00) was not significantly associated with the risk of PTD. The initiation of folic acid supplementation more than 8 weeks before conception was associated with an increased risk for spontaneous PTD (HR 1.18; CI 1.05-1.32) compared to no folic acid supplementation preconception. There was no significant association with PTD when supplementation was initiated within 8 weeks preconception (HR 0.99; CI 0.87-1.13). All analyses were adjusted for maternal characteristics and socioeconomic, health and dietary variables.ConclusionsOur findings do not support a protective effect of dietary folate intake or folic acid supplementation on spontaneous PTD. Preconceptional folic acid supplementation starting more than 8 weeks before conception was associated with an increased risk of spontaneous PTD. These results require further investigation before discussing an expansion of folic acid supplementation guidelines.Electronic supplementary materialThe online version of this article (doi:10.1186/s12884-014-0375-1) contains supplementary material, which is available to authorized users.

Validation of Bone Metastases Coding in an Oncology Electronic Medical Records Database and a Commercial Claims Database

s / Annals of Epidemiology 24 (2014) 682e702 684 Methods: Using SEER 18 cancer incidence rates and county-level %rurality, Two-way ANCOVA was performed on data stratified at the State and Rural Urban Continuum Code (RUCC) levels and adjusted for obesity, smoking, alcohol use, inactivity, and race. Results: RUCC and %rurality were positively correlated (0.63; p 50 mg/mL, receipt of scintigraphy, or receipt of hospital-administered antiresportive therapy. Chart review was conducted by a research nurse blinded to patient metastasis status. Results: Of 212 patients, 113 (53%) had evidence of metastases according to the algorithms and 43 (20%) had metastases according to chart review. The positive predictive value (PPV) of all algorithms was low. The highest performing algorithm to detect any metastases was a PSA value >50 mg/mL and receipt of scintigraphy, in the absence of antiresportive therapy, with a PPV of 28% (95% CI 14%-47%). Conclusion: In their present form, algorithms based on PSA, antiresorptive treatment, or scintigraphy were not suitable for identification of additional cases of metastases. Further investigation of alternate components, cutoffs, or timing is needed. Additionally chart reviews may not represent a “gold standard” for validation of metastases, a condition that can be asymptomatic and therefore prone to under or delayed registration. P08. Prostate-Specific Antigen Testing and Shared Decision Making for Prostate Cancer Screening Jun Li MD, PhD, Zahava Berkowitz, Thomas Richards, Ingrid Hall. CDC Purposes: To describe the prevalence of prostate specific antigen (PSA) testing from 2001-2010 and assess associations between shared decisionmaking (SDM) on PSA testing. Methods: We estimated prevalence of PSA testing using data from the 2000, 2003, 2005, 2008, and 2010 National Health Interview Surveys. Changes in the prevalence by age group, race/ethnicity, and year were assessed with logistic regression models and general linear contrasts of the predicted margins. Bivariate analyses were conducted to assess associations between demographic and health-related characteristics and PSA testing. Results: Men aged 75years had a small but significant decrease in PSA testing from 2008 to 2010 (50.8% vs. 43.9%, P < 0.05). However, in 2010, they continued to have a significantly higher prevalence of PSA testing (43.9%) than men aged 50-74 (38.4%), and men aged 40-49 (9.7%). Menwho had prescreening discussions about the advantages and disadvantages of PSA testing (54.9%) and about disadvantages alone (44.1%) were more likely to receive PSA testing than men who had no discussion (17.7%), respectively (both P <0.05). Conclusions: Men aged 75 years continued to receive more PSA testing than youngermen. Pre-screening discussionswere positively associatedwith PSA testing. Additional research is needed on how SDM is being conducted in clinical practice and the role played by patient’s values and preferences in decisions about PSA testing. P09. Supplemental Folic Acid in Pregnancy and Maternal Cancer Risk Jan Helge Seglem Mortensen MD, Nina Oyen Professor, PhD, Tatiana Fomina PhD, Mads Melby Professor, MD, DMSc, Stein Emil Vollset Professor, DrPH, Tone Bjorge Professor, PhD, MD. University of Bergen Background: The World Health Organization has recommended women planning pregnancy to consume a daily dose of folic acid to reduce offspring risk of neural tube defects and possibly other congenital malformations. However, there are concerns that folic acid supplementation may have a carcinogenic effect. Purpose: The present population-based study examined the later risk of maternal cancer after intake of supplemental folic acid in pregnancy. Methods: Among 430,000womenwith one ormore childbirths in the period 1999-2010, 3,800 women developed cancer. Data was retrieved from national health registries in Norway. Cox proportional hazards regression models were used to estimate hazard ratios for maternal cancer according to folic acid use prior to and during one or more pregnancies as compared to no supplement use. Results: Folic acid had no overall effect on cancer risk in women using folic acid supplementation. In exploratory sub-group analyses, two cancer types showed a positive association with folic acid intake in pregnancy, colorectal cancer (two times higher risk) in women using folic acid in two or more pregnancies, and lung cancer (three times higher risk) in non-smoking women who used folic acid in one or more pregnancies. Conclusion: Folic acid substitution before and during pregnancy had no effect on overall cancer risk. However, exploratory sub-group analyses suggested that pregnancy related folic acid use increased the risk of some cancer types. Acknowledgments: This study was supported by the Norwegian Cancer Society, and the Regional Health Authorities Western Norway.

Maternal prepregnancy folate intake and risk of spontaneous abortion and stillbirth.

To evaluate prospectively the relationship between prepregnancy folate intake and risk of spontaneous abortion and stillbirth. Women in the Nurses' Health Study II who self-reported a pregnancy between 1992 and 2009 were included in this analysis. Dietary folate and supplement use was assessed every 4 years, starting in 1991, by a food frequency questionnaire. Pregnancies were self-reported with case pregnancies lost spontaneously (spontaneous abortion less than 20 weeks of gestation and stillbirth 20+ weeks of gestation) and comparison pregnancies ending in ectopic pregnancy, induced abortion, or live birth. Among the 11,072 women, 15,950 pregnancies were reported of which 2,756 (17.3%) ended in spontaneous abortion and 120 (0.8%) ended in stillbirth. Compared with women in the lowest quintile of prepregnancy folate intake (less than 285 micrograms/d), those in the highest quintile (greater than 851 micrograms/d) had a relative risk of spontaneous abortion of 0.91 (95% confidence interval [CI] 0.82-1.02) after multivariable adjustment (P trend=.04). This association was primarily attributable to intake of folate from supplements. Compared with women without supplemental folate intake (0 micrograms/d), those in the highest category (greater than 730 micrograms/d) had a relative risk of spontaneous abortion of 0.80 (95% CI 0.71-0.90) after multivariable adjustment (P trend <.001). The association of prepregnancy supplemental folate with risk of spontaneous abortion was consistent across gestational period of loss. A similar inverse trend was observed with the risk of stillbirth, which fell short of conventional significance (P trend=.06). Higher intake of folate from supplements was associated with reduced risk of spontaneous abortion. Women at risk of pregnancy should use supplemental folate for neural tube defect prevention and because it may decrease the risk of spontaneous abortion. : II.

A Prospective Study of Folate, Vitamin B6, and Vitamin B12Intake in Relation to Exfoliation Glaucoma or Suspected Exfoliation Glaucoma

Effective strategies for primary prevention are lacking for exfoliation glaucoma (EG), which is the most common type of secondary glaucoma. To examine the association between B vitamin intake and EG or suspected EG (EG/SEG) risk. National prospective cohort study using more than 20 years of follow-up data from the Nurses' Health Study (all female registered nurses) and the Health Professionals Follow-up Study (all male health professionals) from June 1, 1980, to May 31, 2010 (Nurses' Health Study) and January 1, 1986, to December 31, 2010 (Health Professionals Follow-up Study). We included a subset of 78,980 Nurses' Health Study women and 41,221 Health Professionals Follow-up Study men who were 40 years or older, free of glaucoma, had completed diet questionnaires, and reported eye examinations (follow-up rate, >85%). Cumulatively updated intake of B vitamins (folate, vitamin B6, and vitamin B12) as ascertained by repeated administration of validated questionnaires. Incident cases of EG/SEG, totaling 399 (329 women and 70 men), were first identified with the questionnaires and were subsequently confirmed with medical records. Multivariable relative risks for EG/SEG were calculated in each cohort and then pooled with meta-analysis. Vitamin B₆ and vitamin B₁₂ intake was not associated with EG/SEG risk in pooled analyses (P = .52 and P = .99 for linear trend, respectively). However, a suggestive trend of a reduced risk was observed with higher intake of folate: compared with the lowest quintile of cumulatively averaged updated total folate intake, the multivariable relative risk for EG/SEG for the highest quintile (≥654 μg/d) was 0.75 (95% CI, 0.54-1.04; P = .02 for linear trend). These results were not materially altered after adjustment for vitamin B₆ and vitamin B₁₂ intake. An association was observed for supplemental folate intake but not for dietary folate only (P = .03 and P = .64 for linear trend, respectively). Greater frequency of multivitamin use showed a modest suggestive inverse association (current multivitamin use of ≥6 times per week vs nonuse multivariable relative risk, 0.84; 95% CI, 0.64-1.11; P = .06 for linear trend). Higher total folate intake was associated with a suggestive lower risk for EG/SEG, supporting a possible causal role of homocysteine in EG/SEG.