Prenatal folic acid supplements reduce the risk of neural tube defects in children, but it has not been determined whether they protect against other neurodevelopmental disorders.
To examine the association between maternal use of prenatal folic acid supplements and subsequent risk of autism spectrum disorders (ASDs) (autistic disorder, Asperger syndrome, pervasive developmental disorder-not otherwise specified [PDD-NOS]) in children.
The study sample of 85,176 children was derived from the population-based, prospective Norwegian Mother and Child Cohort Study (MoBa). The children were born in 2002-2008; by the end of follow-up on March 31, 2012, the age range was 3.3 through 10.2 years (mean, 6.4 years). The exposure of primary interest was use of folic acid from 4 weeks before to 8 weeks after the start of pregnancy, defined as the first day of the last menstrual period before conception. Relative risks of ASDs were estimated by odds ratios (ORs) with 95% CIs in a logistic regression analysis. Analyses were adjusted for maternal education level, year of birth, and parity.
Specialist-confirmed diagnosis of ASDs.
At the end of follow-up, 270 children in the study sample had been diagnosed with ASDs: 114 with autistic disorder, 56 with Asperger syndrome, and 100 with PDD-NOS. In children whose mothers took folic acid, 0.10% (64/61,042) had autistic disorder, compared with 0.21% (50/24,134) in those unexposed to folic acid. The adjusted OR for autistic disorder in children of folic acid users was 0.61 (95% CI, 0.41-0.90). No association was found with Asperger syndrome or PDD-NOS, but power was limited. Similar analyses for prenatal fish oil supplements showed no such association with autistic disorder, even though fish oil use was associated with the same maternal characteristics as folic acid use.
Use of prenatal folic acid supplements around the time of conception was associated with a lower risk of autistic disorder in the MoBa cohort. Although these findings cannot establish causality, they do support prenatal folic acid supplementation.
The incidence of neural tube defects (NTDs) is declining worldwide due to the implementation of folic acid supplementation programs. Such a program was implemented over 1996-97 in Newfoundland and Labrador, Canada. The geographical distribution of birth incidence was studied prior to and after the implementation of the program to identify regions of residual high incidence. Excess residual cases may potentially be due to genetic causes or incomplete supplementation program implementation.
Maternal place of residence for all provincial live birth and stillbirth notifications, provincial maternal-fetal medicine referrals, provincial rehabilitation referrals, and all provincial hospitals with NTDs or terminations for NTDs was obtained from 1975 to 2002 for near complete case ascertainment. Bayesian small area analysis was separately performed on cases from 1975-1996 and 1997-2002. The two time periods were compared.
Birth incidence of NTDs was noted to decline after 1996, from 5.54/1000 live births to 1.08/1000 live births. 592 cases were found from 1975-1996 and 34 cases from 1997-2002. Relative risk of birth incidence was 0.93-1.18 (95% CI) for 1975-1996 and 0.97-1.02 for 1997-2002 after Bayesian smoothing. One region had an excess of residual cases greater than 34%.
The implications of this observation to the management of the public health initiative imply that overall response to the decrease in cases tends to be uniform across the province, with potentially one area of interest where extra efforts may be devoted.
Methylenetetrahydrofolate dehydrogenase (MTHFD1) catalyzes three sequential reactions that metabolize derivatives of tetrahydrofolate (THF) in folate-dependent one-carbon metabolism. Impaired MTHFD1 flux has been linked to disturbed lipid metabolism and oxidative stress. However, limited information is available on its relation to the development of atherothrombotic cardiovascular disease.
We explored the association between a MTHFD1 polymorphism (rs1076991 C?>?T) and acute myocardial infarction (AMI), and potential effect modifications by folic acid/B12 and/or vitamin B6 treatment in suspected stable angina pectoris patients (n?=?2381) participating in the randomized Western Norway B Vitamin Intervention Trial (WENBIT). During the median follow-up of 4.9 years 204 participants (8.6%) suffered an AMI. After adjusting for established CVD risk factors, the MTHFD1 polymorphism was significantly associated with AMI (HR: 1.49; 95% CI, 1.23-1.81). A similar association was observed among patients allocated to treatment with vitamin B6 alone (HR: 1.53; 95% CI, 1.01-2.31), and an even stronger relationship was seen in patients treated with both vitamin B6 and folic acid/B12 (HR: 2.35; 95% CI, 1.55-3.57). However, no risk association between the MTHFD1 polymorphism and AMI was seen in patients treated with placebo (HR: 1.29; 95% CI, 0.86-1.93) or folic acid/B12 (1.17; 95% CI, 0.83-1.65).
A common and functional MTHFD1 polymorphism is associated with increased risk of AMI, although the risk seems to be dependent on specific B vitamin treatment. Further studies are warranted to elucidate the possible mechanisms, also in order to explore potential effect modifications by nutritional factors.
Common strategies to decide whether a variable is a confounder that should be adjusted for in the analysis rely mostly on statistical criteria. The authors present findings from the Slone Epidemiology Unit Birth Defects Study, 1992-1997, a case-control study on folic acid supplementation and risk of neural tube defects. When statistical strategies for confounding evaluation are used, the adjusted odds ratio is 0.80 (95% confidence interval: 0.62, 1.21). However, the consideration of a priori causal knowledge suggests that the crude odds ratio of 0.65 (95% confidence interval: 0.46, 0.94) should be used because the adjusted odds ratio is invalid. Causal diagrams are used to encode qualitative a priori subject matter knowledge.
Fortification of grain products with folic acid has been shown to significantly reduce the occurrence of neural tube defects (NTDs) in Canada and elsewhere. However, the impact on non-NTD anomalies has not been well studied.
Using the Alberta Congenital Anomalies Surveillance System (ACASS), we examined changes in occurrence of select congenital anomalies where folic acid supplementation with multivitamins had previously been suggested to have an effect. Anomalies documented in the ACASS 1992-1996 (pre-fortification) were compared to 1999-2003 (post-fortification).
A significant decrease in spina bifida (OR 0.51, 95% CI 0.36-0.73) and ostium secundum atrial septal defects (OR 0.80, 95% CI 0.69-0.93) was evident, but there was a significant increase in obstructive defects of the renal pelvisand ureter (OR 1.45, 95% CI 1.24-1.70), abdominal wall defects (OR 1.40, 95% CI 1.04-1.88) and pyloric stenosis (OR 1.49, 95% CI 1.18-1.89).
Consistent with other studies, a 50% reduction in spina bifida was associated with the post-fortification time period. Supporting the possibility that folic acid fortification may play a role in preventing other birth defects, a 20% reduction in atrial septal defects was also associated. The increase in abdominal wall defects, most notably gastroschisis, is likely related to pre-existing increasing trends documented in several regions around the world. The increase in pyloric stenosis and obstructive urinary tract defects was not expected and any causal relationship with folic acid fortification remains unclear. Similar studies by other birth defects surveillance systems in Canada and elsewhere are needed to confirm these trends.
In 2007, the Society of Obstetricians and Gynaecologists of Canada (SOGC) introduced new guidelines on periconceptional folic acid supplementation.
To evaluate the concordance between the SOGC guidelines and actual vitamin/folic acid supplementation, and to identify maternal determinants of concordant folic acid use.MethodsFrom May to July 2010, pregnant women attending the outpatient clinic at CHU Ste-Justine in Montreal were surveyed to assess use of folic acid. Data on socio-demographic factors, lifestyles, family and personal medical history, and periconceptional folic acid supplementation were collected using a self-administrated questionnaire. Concordance between maternal reported intake of folic acid and SOGC guidelines was estimated accounting for pregnancy history, comorbidities, and lifestyles.
A total of 361 eligible women gave informed consent; of these, 97 (27%) had periconceptional folic acid supplementation intake that was concordant with guidelines. Women with no personal history of neural tube defects (NTDs) were the most concordant with guidelines (36%), followed by women with a previous child with NTD (26%), and women with health risk factors for NTDs (18%). Women who smoked and drank alcohol had the lowest concordance with guidelines (4%). Women with planned pregnancies and higher income were more likely to be concordant with guidelines; whereas, smokers, alcohol and recreational drug user and women with health risk for NTDs were less likely to be concordant.
Concordance with clinical guidelines was low, even for women with a history of NTDs. Our findings highlight the need for public health programs to inform women to consume folic acid every day before and during pregnancy.
Classical risk factors of development of cardiovascular diseases does not allow to detect all persons needing active prevention. Because of this reason great attention is given to novel biomarkers one of which is homocysteine. Most widely-spread causes of elevation of homocysteine level are such factors as deficit of folic acid and B6 and B12 vitamins, as well as genetic peculiarities. Main damaging effect of homocysteine is activation of atherothrombosis. Therapy with folic acid causes significant lowering of homocysteine level. Effect of therapy with vitamins on the risk of development of cardiovascular diseases has been assessed both in observational epidemiological studies and large prospective randomized trials. Their results are controversial. The present review is devoted to the analysis of these trials.
OMNI Research Group, Department of Obstetrics and Gynecology, Faculty of Medicine, Ottawa Hospital, University of Ottawa, 501 Smyth Road, Ottawa, ON, Canada K1H 8L6 ; Clinical Epidemiology Program, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, ON, Canada K1H 8L6 ; Department of Epidemiology, Biostatistics and Occupational Health and Department of Pediatrics, McGill University Faculty of Medicine, 3175 Cote Ste. Catherine, Montreal, QC, Canada H3T 1C5 ; Department of Epidemiology and Community Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, Canada.
Preeclampsia (PE) is hypertension with proteinuria that develops during pregnancy and affects at least 5% of pregnancies. The Effect of Folic Acid Supplementation in Pregnancy on Preeclampsia: the Folic Acid Clinical Trial (FACT) aims to recruit 3,656 high risk women to evaluate a new prevention strategy for PE: supplementation of folic acid throughout pregnancy. Pregnant women with increased risk of developing PE presenting to a trial participating center between 8(0/7) and 16(6/7) weeks of gestation are randomized in a 1?:?1 ratio to folic acid 4.0 mg or placebo after written consent is obtained. Intent-to-treat population will be analyzed. The FACT study was funded by the Canadian Institutes of Health Research in 2009, and regulatory approval from Health Canada was obtained in 2010. A web-based randomization system and electronic data collection system provide the platform for participating centers to randomize their eligible participants and enter data in real time. To date we have twenty participating Canadian centers, of which eighteen are actively recruiting, and seven participating Australian centers, of which two are actively recruiting. Recruitment in Argentina, UK, Netherlands, Brazil, West Indies, and United States is expected to begin by the second or third quarter of 2013. This trial is registered with NCT01355159.
Cites: BMJ. 2001 Nov 24;323(7323):1213-711719411
Cites: Placenta. 2002 May;23(5):359-7212061851
Cites: Am J Epidemiol. 2002 Nov 1;156(9):806-1212396998
Total plasma homocysteine (tHcy) is an independent risk factor for coronary artery disease, and tHcy is lowered by B vitamins. To assess the effect of homocysteine-lowering B-vitamin treatment on angiographic progression of coronary artery disease, this substudy of the Western Norway B Vitamin Intervention Trial (WENBIT) included patients who had undergone percutaneous coronary intervention. The patients were randomized to daily oral treatment with folic acid, vitamin B(12), and vitamin B(6) or placebo in a 2 x 2 factorial design. The coronary angiograms obtained at baseline and follow-up were evaluated. The primary angiographic end points were the changes in minimum lumen diameter and diameter stenosis. A total of 348 subjects (288 men) with a mean +/- SD age of 60 +/- 10.2 years were followed up for a median of 10.5 months (twenty-fifth, seventy-fifth percentile 9.2, 11.8). The baseline median plasma tHcy level was 10.0 mumol/L (twenty-fifth, seventy-fifth percentile 8.1, 11.0), and treatment with folic acid/vitamin B(12) lowered the tHcy levels by 22%. At follow-up, we found 309 lesions with a significant decrease from baseline in the minimum lumen diameter of a mean of -0.16 +/- 0.4 mm and an increase in the diameter stenosis of 4.4 +/- 0.7%. Treatment with folic acid/vitamin B(12) or vitamin B(6) was not associated with a change in diameter stenosis or minimum lumen diameter. In a post hoc analysis, folic acid/vitamin B(12) treatment was significantly associated with rapid progression (odds ratio 1.84, 95% confidence interval 1.07 to 3.18). In conclusion, vitamin B treatment showed no beneficial effect on the angiographic progression of coronary artery disease, and the post hoc analyses suggested that folic acid/vitamin B(12) treatment might promote more rapid progression.
Peri-conceptional use of folic acid supplements is recommended to prevent neural tube defects. Correct supplement use seems to be less common among ethnic minorities. We examined ethnic differences in folic acid supplement use before and during pregnancy and possible effect modification by education or planning of pregnancy.
The participants were 811 healthy pregnant women from a population-based cohort study in Oslo, Norway in 2008-2010. Ethnicity was categorized to five groups (European, Middle Eastern, South Asian, East Asian, African). Data on folic acid supplement use were obtained from hospital records and remaining data by a questionnaire. Logistic regression analyses were adjusted for age, parity, planning of pregnancy, education and Norwegian language skills.
Before pregnancy, 30.1% of European women and 7.1 to 13.6% of women in the other ethnic groups used folic acid supplements (p?