Folic Acid Supplement Use Research Articles

Provision of Iron and Folic Acid Supplementations for Pregnant Women in Public and Private Sectors of Tabriz, Iran

Background: This study aimed to investigate different methods used to provide necessary supplementations for pregnant women and obtain reliable data about the general status of health promotion during pregnancy. Methods: This descriptive, cross-sectional study was conducted on 401 pregnant women referring to different women’s hospitals of Tabriz, including Alzahra, Taleghani, 29-Bahman, Zakariya, Shafa, and Shams from March 2011 to September 2013. Subjects were selected using simple random sampling and had prior experience of childbirth. Results: In this study, prenatal care was provided for all the pregnant women at public (55.8%) and private sectors (44.2%). Iron supplementation used by the subjects included ferrous sulfate (150 mg) + folic acid (0.5 mg) (20.2%), regular-release ferrous sulfate (325 mg) (70.4%), folic acid (0.1 mg) + ferrous sulfate (200 mg) (6.5%), and vitamin B12 (15 mg) + ferrous fumarate (350 mg)+ vitamin C (150 mg) + folic acid (1 mg) (1.6%). Supplementations were provided before (56.7%) or after (43.3%) the onset of pregnancy. In total, 40.9% of the subjects received family planning care, 44.7% of whom referred to medical centers, 34.6% referred to health houses, 12.3% consulted gynecologists, 2.8% consulted midwives and 5% received traditional care. Conclusion: According to the results of this study, general status of iron and folic acid supplementation, their provision and average use of these substances were suboptimal. However, status, provision and use of iron were significantly more efficient than folic acid.

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.

Preventable spina bifida and anencephaly in Europe.

Promotion of voluntary folic acid supplement use among women of reproductive age has been proven to be ineffective in lowering the risk of neural tube defects in Europe. Using surveillance data from all births covered by the full member countries of the European Surveillance of Congenital Anomalies (EUROCAT), we estimated the total prevalence of spina bifida and anencephaly per 10,000 births between 2000 and 2010. We also estimated additional lifetime direct medical costs among individuals with spina bifida, compared with those without, in Germany for the year 2009. During the study period, there were 7478 documented cases of spina bifida and anencephaly among the 9,161,189 births, with an estimated average combined prevalence of 8.16 per 10,000 births (95% confidence interval, 7.98 - 8.35). For the 241 spina bifida-affected live births in 2009 in Germany, the estimated additional lifetime direct medical costs compared with non-spina bifida affected births were €65.5 million. Assuming a 50% reduction in the prevalence if folic acid has been provided to all women before pregnancy, 293 spina bifida cases could have been prevented in Germany in 2009. The estimated lifetime direct medical cost saving for the live births in 2009 was €32.9 million assuming a 50% reduction, or €26.1 million assuming a 40% risk reduction. Europe has an epidemic of spina bifida and anencephaly compared with countries with mandatory folic acid fortification policy. Primary prevention through mandatory folic acid fortification would considerably reduce the number of affected pregnancies, and associated additional costs.

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.

Preconception folic acid use influences the follicle fluid proteome.

The investigation of the human follicle fluid proteome has gained much interest in the search of new markers as predictors for in vitro fertilization and intracytoplasmic sperm injection (IVF/ICSI) treatment outcome. Follicular fluid folate, as substrate of one carbon (1-C) metabolism, affects follicular metabolism and oocyte and embryo quality. From this background, we aim to identify a folate-related follicle fluid proteome that associates with IVF/ICSI treatment outcome. In a nested case-control study embedded in a periconception cohort, we performed qualitative and quantitative proteomic analyses using nanoflow LC-MS/MS and TMT labelling in 30 monofollicular fluid samples from women undergoing IVF/ICSI treatment of which 15 used and 15 did not use a folic acid supplement. The protein data are analysed using scaffold proteome Software and differential abundances are expressed as Log2-fold change. Blood samples were obtained before and after treatment for determination of biomarkers of 1-C metabolism and estradiol. We identified 227 uniquely expressed proteins in follicular fluid. In folic acid supplement users compared to nonusers, we established a lower abundance of C-reactive protein (-2.03; P = < 0.01) and higher abundances of apolipoproteins from high-density lipoprotein (HDL), most notably A-I (+1.28; P = < 0.01) and C-I (+1.11; P = 0.016). Preconception folic acid supplement use is associated with suppression of the inflammatory pathway and upregulation of the HDL pathway in human follicular fluid, being a preferential source of cholesterol for steroid hormone synthesis. Studies are needed on the tissue specificity and on the beneficial effects of embryo quality and IVF/ICSI treatment outcome of the proteome of these pathways.

Folic acid supplementation and fecundability: a Danish prospective cohort study.

Periconceptional folic acid (FA) supplementation reduces the risk of neural tube defects and has been associated with ovulatory function. However, only two studies have associated supplementation with multivitamins (MVs) that contained FA with increased pregnancy rates. We aimed to examine the association between FA supplementation (obtained either through single FA tablets or through MVs) and fecundability. A prospective cohort study of 3895 Danish women who were planning a pregnancy between 2007 and 2011. We estimated fecundability ratios (FRs) and 95% confidence intervals (CIs) in relation to FA supplementation (either through single FA tablets or MV) using a proportional probabilities regression model, with adjustment for potential socio-demographic, reproductive and lifestyle confounders. In stratified analyses, we also estimated FR with 95% CI in relation to FA supplementation for women with regular and irregular cycles, respectively, and for women with short (<27 days), medium (27-29 days) and long cycles (⩾30 days), respectively. FA supplementation was associated with increased fecundability (FR=1.15, 95% CI=1.06-1.25), compared with non-use. The adjusted FRs for FA supplement use relative to non-use were 1.35 (95% CI=1.12-1.65) and 1.11 (95% CI=1.01-1.22) for women with irregular and regular cycles, respectively, and 1.36 (95% CI=0.95-1.95), 1.10 (95% CI=0.98-1.22) and 1.24 (95% CI=1.10-1.41) for women with short (<27 days), medium (27-29 days) and long cycles (⩾30 days), respectively. FA supplementation was associated with increased fecundability, and this association appeared to be stronger among women with irregular cycles and among women with either short or long cycle length.

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.

Folic acid supplement use and menstrual cycle characteristics: a cross-sectional study of Danish pregnancy planners

PurposeTo examine the association between folic acid (FA) supplementation obtained through either single FA tablets or multivitamins (MVs) and menstrual cycle characteristics among 5386 women aged 18–40 years, enrolled in an Internet-based study of Danish women attempting pregnancy during 2007–2011. MethodsIn a cross-sectional study, we used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations of FA supplementation with menstrual cycle regularity; short (<27 days), long (30–33 days), and very long (≥34 days) cycle lengths; and duration and intensity of menstrual bleeding. ResultsCompared with nonuse, FA supplementation was associated with reduced odds of short cycle length (OR = 0.80, 95% CI: 0.68–0.94) and a trend toward increased odds of very long cycle length (OR = 1.21, 95% CI: 0.87–1.68) compared with cycle length of 27–29 days. The inverse association with short cycle length was stronger among 18- to 30-year-old women (OR = 0.68, 95% CI: 0.53–0.87), nulliparous women (OR = 0.66, 95% CI: 0.52–0.84), and women who used both FA and MVs (OR = 0.75, 95% CI: 0.60–0.95). We found no clear association between FA supplementation and cycle regularity and duration and intensity of menstrual bleeding. ConclusionsFA supplementation was inversely associated with short menstrual cycle length. This association was strongest among women aged 18–30 years, nulliparous women, and women who used both FA and MVs.

Prospective assessment of autism traits in children exposed to antiepileptic drugs during pregnancy.

The association between autism spectrum disorders (ASDs) and prenatal anticonvulsant exposure is increasingly investigated, but comprehensive, blinded assessment using a validated instrument for autism within a well-characterized prospective cohort has not been conducted. Thus, existing studies may represent an underestimate of the true risk. Herein we present a prospective cohort study in children exposed to anticonvulsants during pregnancy, with all assessments conducted by examiners who were blinded to drug-exposure status. Participants were 105 Australian children aged 6-8 years who were recruited via the Australian Pregnancy Register for Women on Antiepileptic Medication. Maternal epilepsy, pregnancy, and medical history data were obtained prospectively. Autism traits were assessed using the Childhood Autism Rating Scale (CARS). Eleven children (10.5%) had elevated CARS scores. Two were exposed to valproate monotherapy (2/26; 7.7%), two to carbamazepine monotherapy (2/34; 5.9%), and seven to valproate in polytherapy (7/15; 46.7%). Linear regression analysis showed that the mean valproate dose during pregnancy was a significant predictor of CARS scores after controlling for polytherapy, mean carbamazepine dose, folic acid use, seizures during pregnancy, tobacco and marijuana use, maternal intelligence quotient (IQ), and socioeconomic status. First trimester folic acid supplementation and marijuana use were also significant predictors of CARS scores. Using direct assessment of children in our prospective study, we found an elevated rate of autism traits across the sample. The most important determinant of association with autistic traits was higher doses of sodium valproate exposure. The use of valproate in women who may become pregnant is now generally avoided; however, there are insufficient data regarding the risk of ASD with low-dose valproate. If this risk is no greater than with other antiepileptic drugs (AED)s, it may enable women with genetic generalized epilepsy to retain optimal seizure control as well as minimize harm to their unborn child.

Maternal predictors of RBC folate levels in an urban Canadian population.

To assess factors associated with low Red Blood Cell folate (RBCf) levels in an obstetric population in a tertiary centre. Cross-sectional study. Three hundred and fifty women completed a questionnaire detailing use of folic acid supplementation, and had their RBCf levels measured. Values ≥ 906 nmol/L were considered optimal. Factors associated with optimal RBCf were assessed, individually and in a logistic regression model. Median RBCf was 1282 nmol/L. Thirty-five women (10%) had suboptimal levels. Predictors of suboptimal RBCf were non-Caucasian ethnicity, non-consumption of folic acid supplementations, and inadequate health care provider information regarding the benefits of folic acid consumption. Although, in our population, a high proportion of women achieved optimal levels of RBCf, some women remain at risk due to inadequate folate consumption. Patient and health care provider education regarding folate can still be improved, particularly in the groups identified to be at greater risk.

Obstructive heart defects associated with candidate genes, maternal obesity, and folic acid supplementation.

Right-sided and left-sided obstructive heart defects (OHDs) are subtypes of congenital heart defects, in which the heart valves, arteries, or veins are abnormally narrow or blocked. Previous studies have suggested that the development of OHDs involved a complex interplay between genetic variants and maternal factors. Using the data from 569 OHD case families and 1,644 control families enrolled in the National Birth Defects Prevention Study (NBDPS) between 1997 and 2008, we conducted an analysis to investigate the genetic effects of 877 single nucleotide polymorphisms (SNPs) in 60 candidate genes for association with the risk of OHDs, and their interactions with maternal use of folic acid supplements, and pre-pregnancy obesity. Applying log-linear models based on the hybrid design, we identified a SNP in methylenetetrahydrofolate reductase (MTHFR) gene (C677T polymorphism) with a main genetic effect on the occurrence of OHDs. In addition, multiple SNPs in betaine-homocysteine methyltransferase (BHMT and BHMT2) were also identified to be associated with the occurrence of OHDs through significant main infant genetic effects and interaction effects with maternal use of folic acid supplements. We also identified multiple SNPs in glutamate-cysteine ligase, catalytic subunit (GCLC) and DNA (cytosine-5-)-methyltransferase 3 beta (DNMT3B) that were associated with elevated risk of OHDs among obese women. Our findings suggested that the risk of OHDs was closely related to a combined effect of variations in genes in the folate, homocysteine, or glutathione/transsulfuration pathways, maternal use of folic acid supplements and pre-pregnancy obesity.

The Association Between Circulating Total Folate and Folate Vitamers With Overall Survival After Postmenopausal Breast Cancer Diagnosis

We studied the relationship between plasma total folate and folate vitamer concentrations [5-methyltetrahydrofolic acid, pteroylglutamic acid (folic acid) and tetrahydrofolic acid] with overall survival after breast cancer diagnosis. A secondary aim was to assess the relationship between folic acid supplement use with circulating total folate and folate vitamer concentrations. Participants were postmenopausal women diagnosed with breast cancer (n = 498) with an average follow-up of 6.7 yr. Plasma total folate and folate vitamers were measured by isotope-dilution LC-MS/MS in samples collected at or postdiagnosis. Cox proportional multivariate hazards models (controlled for stage, age at diagnosis, body mass index, parity, hormone replacement therapy use, treatment, alcohol use, folic acid use, and energy intake), were used to assess overall survival after breast cancer diagnosis. We found that the relative risk of dying for women with plasma total folate concentrations in the highest quartile was 59% lower (hazard ratio: 0.41, 95% confidence interval: 0.19–0.90) compared with the lowest quartile. Data on supplement use showed that women taking folic acid supplements had significantly higher circulating total folate and folate vitamer concentrations (P < 0.0001), suggesting that increased folate consumption through diet and/or supplementation may improve prognosis after breast cancer diagnosis.

The Development of a Diet Quality Score for Preschool Children and Its Validation and Determinants in the Generation R Study1–3

AbstractBackground: Although many studies have examined health effects of infant feeding, studies on diet quality shortly after the weaning and lactation period are scarce.Objectives: Our aims were to develop and evaluate a diet score that measures overall diet quality in preschool children and to examine the sociodemographic and lifestyle determinants of this score.Methods: On the basis of national and international dietary guidelines for young children, we developed a diet score containing 10 components: intake of vegetables; fruit; bread and cereals; rice, pasta, potatoes, and legumes; dairy; meat and eggs; fish; oils and fats; candy and snacks; and sugar-sweetened beverages. The total score ranged from 0 to 10 on a continuous scale and was standardized to an energy intake of 1200 kcal/d with the residual method. The score was evaluated in 3629 children participating in the Generation R Study, a population-based prospective cohort study. Food consumption was assessed with a food-frequency questionnaire (FFQ) at a median age of 13 mo.Results: The mean ± SD diet score was 4.1 ± 1.3. The food-based diet score was positively associated with intakes of many nutrients, including n–3 (ω-3) fatty acids [FAs; 0.25 SD increase (95% CI: 0.22, 0.27) per 1 point increase in the diet score], dietary fiber [0.32 (95% CI: 0.30, 0.34)], and calcium [0.13 (95% CI: 0.11, 0.16)], and was inversely associated with intakes of sugars [−0.28 (95% CI: −0.31, −0.26)] and saturated fat [−0.03 (95% CI: −0.05, −0.01)]. A higher diet score was associated with several health-conscious behaviors, such as maternal folic acid supplement use during pregnancy, no smoking during pregnancy, and children watching less television.Conclusion: We developed a novel food-based diet score for preschool children that could be applied in future studies to compare diet quality in early childhood and to investigate associations between diet in early childhood and growth, health, and development.

Periconceptional folic acid supplementation among pregnant women with epilepsy in a developing country: A retroprospective survey in China

ObjectiveThe aims of this study were to investigate the implementation of guidelines on periconceptional folic acid supplementation among pregnant women with epilepsy (WWE) in China and to identify its potential correlations with selected sociodemographic and clinical factors. MethodsA detailed investigation was conducted in China using a structured questionnaire from December 2013 to May 2014. Data on the awareness and use of folic acid supplementation, as well as sociodemographic and clinical characteristics, were collected from 153 pregnant WWE. Descriptive analysis, followed by univariate and multivariate logistic regression analyses, was applied to the data from this survey. ResultsAmong the enrolled subjects, 67.3% became pregnant after the promulgation of the relevant guidelines. Only 26.2% of them knew the exact effects of folic acid, and 73.8% had taken folic acid at some point during periconception. In addition, the folic acid intake of most of these women (67.1%) did not exceed that of the average pregnant woman. The prevalence of folic acid supplementation for pregnant WWE three months before pregnancy was only 15.5%. There has been almost no improvement in the level of additional awareness and use of folic acid supplementation for WWE since the relevant guidelines were established in China. Pregnant WWE with higher education levels, those with a planned pregnancy, or those who live in urban areas were more likely to know about and implement folic acid supplementation during periconception. Moreover, pregnant WWE with a planned pregnancy or those living in cities seemed to have a higher folic acid intake and started folic acid supplementation earlier before conception. ConclusionThe extent of awareness and use of folic acid supplementation in pregnant WWE remains low in China. More efforts are needed to promote periconceptional folic acid supplementation for WWE, especially those with low education levels and those who live in rural areas. Planned pregnancy should be encouraged for WWE.

Risk Assessment of Folic Acid in Food Supplements

Risk Assessment of Folic Acid in Food Supplements

Folate pathway gene polymorphisms, maternal folic acid use, and risk of childhood acute lymphoblastic leukemia.

Several studies suggest that maternal folic acid supplementation before or during pregnancy protects against childhood acute lymphoblastic leukemia (ALL). We investigated associations between ALL risk and folate pathway gene polymorphisms, and their modification by maternal folic acid supplements, in a population-based case-control study (2003-2007). All Australian pediatric oncology centers provided cases; controls were recruited by national random digit dialing. Data from 392 cases and 535 controls were included. Seven folate pathway gene polymorphisms (MTHFR 677C>T, MTHFR 1298A>C, MTRR 66A>G, MTR 2756 A>G, MTR 5049 C>A, CBS 844 Ins68, and CBS 2199 T>C) were genotyped in children and their parents. Information on prepregnancy maternal folic acid supplement use was collected. ORs were estimated with unconditional logistic regression adjusted for frequency-matched variables and potential confounders. Case-parent trios were also analyzed. There was some evidence of a reduced risk of ALL among children who had, or whose father had, the MTRR 66GG genotype: ORs 0.60 [95% confidence interval (CI) 0.39-0.91] and 0.64 (95% CI, 0.40-1.03), respectively. The ORs for paternal MTHFR 677CT and TT genotypes were 1.41 (95% CI, 1.02-1.93) and 1.81 (95% CI, 1.06-3.07). ORs varied little by maternal folic acid supplementation. Some folate pathway gene polymorphisms in the child or a parent may influence ALL risk. While biologically plausible, underlying mechanisms for these associations need further elucidation. Folate pathway polymorphisms may be related to risk of childhood ALL, but larger studies are needed for conclusive results.

Highlights of This Issue

Bonn and colleagues investigated the effect of physical activity after a prostate cancer diagnosis in a large cohort. Statistically significantly lower overall mortality rates were found among men engaged in walking/bicycling ≥20 min/day, performing household work ≥1 h/day, or exercising ≥1 h/week, compared to less active men. Higher levels of physical activity were associated with reduced rates of overall and prostate cancer–specific mortality, further strengthening previous results indicating beneficial effects of physical activity on survival among men with prostate cancer.Fecal immunochemical testing (FIT) is one of the primary screening tests for colorectal cancer. Clarke and colleagues performed a meta-analysis to determine if uptake of FIT screening differs between men and women. Nineteen studies met the authors' inclusion criteria. Male FIT uptake was significantly lower than female uptake and this male/female difference persisted regardless of study design, screening organization, number of samples, age range, and setting. Further investigation is required to identify the factors that influence male nonparticipation in FIT screening.Milne and colleagues investigated associations between pediatric acute lymphoblastic leukemia (ALL) risk and folate pathway gene polymorphisms and their modification by maternal folic acid supplements. Seven folate pathway gene polymorphisms were genotyped in 392 pediatric ALL cases and pre-pregnancy maternal folic acid supplement use information was collected. The authors report some folate-pathway gene polymorphisms in the child or parent may influence ALL risk. Folate pathway polymorphisms may be related to risk of childhood ALL, but larger studies are needed for conclusive results.Schmit and colleagues searched for miRNA-related polymorphisms contributing to colorectal cancer etiology using the Axiom miRNA Target Site Genotyping Array containing 237,858 markers. The study included 596 cases from the Molecular Epidemiology of Colorectal Cancer study. The authors identified twenty-three markers with P values less than 5.0E–04 and replicated a previously published locus within the 3′-untranslated region of the insulin receptor gene INSR. This study demonstrates the potential for a miRNA-targeted genome-wide association study to identify candidate susceptibility loci and prioritize them for functional characterization.

When should we prescribe high-dose folic acid to prevent congenital heart defects?

Provide a rationale for attempting prevention of congenital heart defects (CHDs). Prevention of neural-tube defects can be achieved with preconceptional use of folic acid. Extrapolating results from animal studies to human pregnancy shows that folate deficiency as well as one-time exposure to environmental factors in the first 2 to 3 weeks of human gestation can result in severe CHD. Considering that approximately 50% of pregnancies are unplanned, this period of pregnancy can be considered high risk for cardiac, as well as neural, birth defects, as the woman usually is not aware of her pregnancy and may not yet be taking precautionary actions to protect the developing embryo. In mammals, folate supplementation prevents CHD induced by alcohol, by lithium, or by elevation of the metabolite homocysteine. Optimal protection of cardiogenesis was observed to occur with folate supplementation provided on the morning after conception and at higher doses than currently available in prenatal vitamin supplementation. Clinical studies show a similar pattern with high doses of folic acid required to prevent CHD. Today, all patients with a family history of CHD should discuss the prenatal use of folate supplementation with their obstetricians prior to becoming pregnant.

A review of the impact of dietary intakes in human pregnancy on infant birthweight.

Studies assessing maternal dietary intakes and the relationship with birthweight are inconsistent, thus attempting to draw inferences on the role of maternal nutrition in determining the fetal growth trajectory is difficult. The aim of this review is to provide updated evidence from epidemiological and randomized controlled trials on the impact of dietary and supplemental intakes of omega-3 long-chain polyunsaturated fatty acids, zinc, folate, iron, calcium, and vitamin D, as well as dietary patterns, on infant birthweight. A comprehensive review of the literature was undertaken via the electronic databases Pubmed, Cochrane Library, and Medline. Included articles were those published in English, in scholarly journals, and which provided information about diet and nutrition during pregnancy and infant birthweight. There is insufficient evidence for omega-3 fatty acid supplements’ ability to reduce risk of low birthweight (LBW), and more robust evidence from studies supplementing with zinc, calcium, and/or vitamin D needs to be established. Iron supplementation appears to increase birthweight, particularly when there are increases in maternal hemoglobin concentrations in the third trimester. There is limited evidence supporting the use of folic acid supplements to reduce the risk for LBW; however, supplementation may increase birthweight by ~130 g. Consumption of whole foods such as fruit, vegetables, low-fat dairy, and lean meats throughout pregnancy appears beneficial for appropriate birthweight. Intervention studies with an understanding of optimal dietary patterns may provide promising results for both maternal and perinatal health. Outcomes from these studies will help determine what sort of dietary advice could be promoted to women during pregnancy in order to promote the best health for themselves and their baby.

The Autism Birth Cohort (ABC):a study of autism spectrum disorders in MoBa

Background: Autism spectrum disorders (ASDs) are characterized by persistent deficits in social communication and interaction and restricted, repetitive patterns of behavior, interests or activities. In most cases, the cause of ASD is likely to be a combination of genetic predisposition and environmental exposures occurring in fetal life or early infancy. Consequently, a prospective pregnancy cohort like MoBa represents an ideal platform for studies of ASDs in children.Methods: The Autism Birth Cohort (ABC) Study has identified potential ASD cases in MoBa through questionnaire- based screening, parental and professional referrals, and linkages to the Norwegian Patient Register. ASD diagnoses have been ascertained through in-person clinical assessments and medical record reviews.Current results: By the end of 2012, the ABC Study had identified 518 ASD cases in MoBa. The ASD prevalence in school-age children is 0.7-0.8%, which is in line with nationwide estimates for Norway. The most important source of ASD case identification was registry linkages, while only a minority was detected through early screening. Published findings show that screening at 18 months misses the majority of ASD cases. Analyses of risk factors for ASDs have shown that maternal use of folic acid supplements in early pregnancy may lower the child’s risk of developing ASDs and that paternal obesity appears to increase the child’s risk of ASDs.Future plans: ASD case identification will continue through annual registry linkages and subsequent reviews of medical records. Analyses of plasma samples and RNA samples will be conducted to investigate prenatal and perinatal microbial exposures, innate immune and inflammatory responses, biomarkers of autism risk, and exposures to xenobiotics. Analyses of deciduous teeth will also investigate the effect of medications and environmental toxins. Exome sequencing of DNA from ASD cases and their parents is ongoing, and will elucidate the role of de novo DNA mutations in the pathogenesis of ASDs. Future epidemiological analyses will explore the results of the 36-month screening for ASDs, the diagnostic stability and developmental trajectories in ASD children, and psychiatric and medical comorbidities in ASDs.