Suchergebnisse

Background: Environmental justice research suggests that inequalities in the distribution of environmental exposure to chemical pollution systematically disadvantage the lower social strata of society. The effects of these inequalities on the human exposure to pollution are however to a large extend unknown. The purpose of this study is to assess social gradients in human biomonitoring results of a representative sample of Flemish adolescents. Methods: We investigate the associations between individual socioeconomic status (SES), measured by parental educational attainments, and internal body concentration of seven chemical compounds in biological samples of 1642 adolescents aged 14–15 in Flanders (Belgium): PCBs, HCB, DDE, lead, cadmium, benzene and PAHs. Social gradients in average and high exposure to these biomarkers were examined with geometric means and odds ratios (with 95% confidence intervals), using multiple regression models, controlling for covariates and confounders. Results: Depending on the (type of) pollutant, adolescents with a lower SES either have higher or lower internal concentrations. Chlorinated compounds (PCBs and pesticides HCB and DDE) are positively associated with SES (higher exposures for higher SES), while heavy metals (lead and cadmium) are negatively associated (higher exposures for lower SES). For metabolites of organic compounds (benzene and PAHs) we find no association with SES. Socially constructed factors, such as dietary and lifestyle habits, play an important role in these relations. Conclusions: Our study suggests that the association between individual SES and the internal body concentration of exposure to environmental pollutants in Flemish adolescents is more complex than can be assumed on the basis of the environmental justice hypothesis. ; Flemish Government (Department of Science, Department of Public Health and Environment, Nature and Energy Department)

Introduction: Previous studies suggested that green space is beneficial for the cognitive development in children. However, evidence in adolescents is limited. Therefore, we aim to investigate green space exposure in association with attention and behaviour in adolescents. Methods: This study includes 596 Flemish adolescents between 13 and 17 years old. Attention was assessed with Stroop Test (selective attention) and Continuous Performance Test (sustained and selective attention). Behaviour was determined based on the Strengths and Difficulties Questionnaire. Green space was estimated in several radius distances around their current residence and school based on high-resolution land cover data. Multilevel regression analyses were used adjusting for participant's age, sex, education level of the mother, and area deprivation index. Results: Surrounding green space in a 2000 m radius is associated with a faster reaction time in adolescents. An IQR (13%) increment in total green space within 2000 m of the residence and school combined, is associated with a 32.7 ms (95% CI: -58.9 to -6.5; p = 0.02) and a 7.28 ms (95% CI: -11.7 to -2.8; p = 0.001) shorter mean reaction time between the presentation of a stimulus and the response based on the Stroop Test and the Continuous Performance Test. Subdividing green space based on vegetation height, shows that green space higher than 3 m is associated with a faster reaction time of the Continuous Performance Test (-6.50 ms; 95% CI: -10.9 to -2.2; p = 0.004), while low green is not. We did not find an association between green space and behavioural development in adolescents. Conclusions: Our study shows that green space, especially trees, surrounding the residence and school combined is associated with better sustained and selected attention in adolescents. These findings indicate that the availability of green is important for adolescents that are growing up in a rapidly urbanizing world. ; Government of Flanders, Department of Environment & Spatial Development;

Abstract
Background
PFAS are persistent, bioaccumulative compounds repelling water, oil and stains which are widely used. There is mounting evidence linking exposure to a range of adverse health outcomes including renal, hepatic, immunotoxic, reproductive, endocrine disrupting and carcinogenic effects. PFAS possibly also induce neurobehavioral and developmental effects. Within Flanders Environment and Health Studies (FLEHS) internal exposure to PFAS and relevant health effects are assessed since 2008.

Results
Adolescents 14–15 y (2010–2011) living in an industrially contaminated area (without known PFAS contamination) and adults 50–65 y (2014) randomly sampled from the general Flemish population using a stratified clustered multi-stage design, were recruited. For the adolescents perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) were measured in serum, for the adults PFOS, PFOA, perfluorohexane sulfonate (PFHxS), perfluorononanoic acid (PFNA) and perfluorobutane sulfonate (PFBS). In adolescents the Neurobehavioral Evaluation System (NES3) computerized battery of tests developed to study the neurological effects of an exposure to environmental agents was applied. The adults did the Stroop test, the NES3 Continuous Performance Test and the NES3 Digit Span Test. In adolescents sleepiness, masculinity and femininity were assessed via the Epworth Sleepiness Scale and Personal Attributes Questionnaires, respectively. In adolescents PFOA was associated with significantly increased somnolence, and PFOS with a significant inverse association with boys' femininity and with girls' masculinity. In adolescents, PFAS were also associated with a marginal decrease in sustained attention (PFOS) and cognitive performance (PFOA) and a significant decrease in short-term memory (PFOS). However, in older adults PFOS was associated with a significant increase in the capacity to pay attention and PFHxS with a significant increase in sustained attention.

Conclusion
Our observations point to neurobehavioral and cognitive effects of PFAS. The neurobehavioral effects might in part result from the changes in sex hormone levels that have been reported to be associated with internal exposure to PFAS. Interestingly, whereas in relation to cognition some adverse effects were recorded for adolescents, for elderly persons our observations rather suggest possible weak positive effects with respect to cognition. Our observations might be in line with the view that PFAS have many, sometimes contrasting health effects.

Lipophilic contaminants are present in the environment and bioaccumulate in the food chain. Therefore, their intake via animal fat of various sources was assessed for three age groups of the Flemish population, participating in a large biomonitoring program of the Flemish government. In total, 1636 adolescents (14-15 years), I 186 mothers (18-44 years), and 1586 adults (50-65 years) participated in the study and completed a semi quantitative food frequency questionnaire. Individual consumption data were combined, via a so-called simple distribution approach, with recent data on polychlorinated dibenzo-p-dioxins/furans and dioxin-like polychlorinated biphenyls, measured via the chemical-activated luciferase gene expression (CALUX) bio-assay in food items available on the Flemish market. The median (95th percentile) estimated intakes of dioxin-like contaminants were 2.24 (4.61), 2.09 (4.26), and 1.74 (3.53) pg CALUX-TEQ kg(-1) bw d(-1) for, respectively adolescents, mothers and adults. These data are in the same range as those found in other European studies. The CALUX-TEQ results of respectively 59.8%, 53.7% and 36.2% of the adolescent, mother and adult population exceed the tolerable weekly intake (TWI) of 14 pg WHO-TEQ kg(-1) bw w(-1), as derived by the Scientific Committee on Food [Scientific Committee on Food, 2001. Opinion of the Scientific Committee on Food on the Risk Assessment of Dioxins and Dioxin-like PCBs in Food, CS/CNTM/DIOXIN/20 final Brussels, Belgium]. The main contributors of dioxin-like substances are fish and seafood (25-43% of the total intake), added fats (22-25% of the total intake) and dairy products (17-20% of the total intake). (c) 2007 Elsevier Ltd. All rights reserved.

Abstract
Background
The successive FLEHS campaigns assess internal exposure to pollutants and associated early biological and health effects in participants of different age groups.

Materials and methods
Mother–newborn pairs (N = 220 in 2008–2009, age 18–42 years; N = 269 in 2013–2014, age 18–44 years), 197 adolescents 14–15 years (2010–2011), 201 adults 20–40 years (2008–2009) and 205 adults 50–65 years (2014) were recruited. For the various groups of subjects different sets of PFAS were assessed. Perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA) and perfluorobutane sulfonate (PFBS) were determined in cord plasma and peripheral serum as these were the PFAS compounds for which we had access to high quality measurements and which were expected to be present in the highest concentrations. Participants filled out a questionnaire based on the European Community Respiratory Health Survey questionnaire on asthma and allergy. In these cross-sectional studies associations were assessed using stepwise multiple logistic regression, with confounders (including smoking and familial occurrence of the disease) and potential covariates selected on the basis of experience in our previous studies and a literature search. Forest plots of odds ratios summarize the associations between the various PFAS on the one hand and the different immune outcomes on the other hand.

Results
For several self-reported immune system-related diseases inverse associations with PFAS serum concentrations were observed. These inverse associations were more pronounced in mothers and adults than in adolescents. A significant inverse association was observed in adults and mothers (for mothers based on measurements on cord plasma) between PFNA, PFOS, and PFHxS and asthma (for mothers also for PFOA), in mothers between PFHxS, PFNA and PFOS and allergic rhinitis, in mothers and adults between PFHxS and PFOS and some forms of allergy (for mothers also for PFOA), in adults between PFOA and eczema, and in adolescents between PFOS and systemic allergy.

Conclusion
Internal exposure to PFAS was associated with changes in immunological processes consistent with what has been reported in the literature. Whereas these changes were observed in many publications to be associated with adverse health effects, our findings suggest that they can also lead to inverse associations with certain immune system-related diseases.

Because of their dirt-, water- and oil-repelling properties, per- and polyfluoroalkyl substances (PFASs) are frequently used in a broad variety of consumer products. They have been detected in human samples worldwide. In Flanders, Belgium, the Flemish Environment and Health Studies (FLEHS) measured the levels of five PFAS biomarkers in four different age groups of the Flemish population and identified determinants of variability in exposure. Cord plasma or peripheric serum samples and questionnaire data were available for 220 mother-newborn pairs (2008-2009), 269 mother-newborn pairs (2013-2014), 199 adolescents (14-15 years old, 2010), 201 adults (20-40 years old, 2008-2009) and 205 adults (50-65 years old, 2014). Measured levels of perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS) and perfluorononanoic acid (PFNA) in Flanders are in the middle or low range compared to concentrations reported in other Western countries. Levels of perfluorobutanesulfonic acid (PFBS) were below the quantification limit in 98%-100% of the samples. Despite decreasing levels in time for PFOS and PFOA, 77% of the adults (2014) had serum levels exceeding HBM-I values of 5 mu/L for PFOS and 2 mu g/L for PFOA. Beside age, sex, fish consumption, parity and breastfeeding, the multiple regression models identified additionally consumption of offal and locally grown food, and use of cosmetics as possible exposures and menstruation as a possible route of elimination. Better knowledge on determinants of exposure is essential to lower PFASs exposure. ; This paper is based on research conducted within the framework of the Flemish Centre of Expertise on Environment and Health, funded by the Environment, Nature and Energy Department of the Flemish government, the Department of Public Health and the Department of Science of the Flemish government. The views expressed herein are those of the authors and are not necessarily endorsed by the Flemish government. ; Colles, A (reprint author), VITO Hlth, Boeretang 200, B-2400 Mol, Belgium. ann.colles@vito.be

Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants of public health concern. Multiple biological mechanisms have been hypothesized to contribute to PAHs-associated adverse health effects. Little is known about the impact of PAHs on endocrine stress and inflammation in adolescence. We examined 393 Flemish adolescents (14-15 years) cross-sectionally, measured urinary concentrations of hydroxylated naphthalene, fluorene, phenanthrene and pyrene metabolites, and calculated the sum of all measured metabolites. We determined hair cortisol concentration (HCC) as endocrine stress biomarker, leucocyte counts and neutrophil-lymphocyte ratio (NLR) in peripheral blood as inflammatory biomarkers, and urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) concentration as oxidative stress biomarker. Exposure-response associations were analyzed by multiple regression, adjusted for a priori selected covariates. A doubling of 1-hydroxypyrene concentration was associated with a factor of 1.13 (95% CI: 1.03, 1.24) increase in HCC and a factor of 1.07 (95% CI: 1.02, 1.13) increase in 8-oxodG. Doublings of 2- and 3-hydroxyphenanthrene concentrations were associated with a factor of 1.08 (95% CI: 1.02, 1.14) and 1.06 (95% CI: 1.00, 1.12) increase in 8-oxodG, respectively. Doubling of 2-hydroxyphenanthrene and of the sum of 2- and 3-hydroxyfluorene was associated with, respectively, a factor of 1.08 (95% CI: 1.02, 1.14) and 1.06 (95% CI: 1.01, 1.13) increase in NLR. Our results indicate the glucocorticoid pathway as a potential target for PAH exposure in adolescents and suggest oxidative stress, endocrine stress, and inflammation in adolescence as underlying mechanisms and early markers for PAH-related adverse health effects. ; Government of Flanders, Department of Environment & Spatial Development; Flemish Center of Expertise on Environment and Health

Background: Exposure to air pollution and traffic noise are associated with adverse health outcomes in adolescents. Chronic endocrine stress and systemic inflammation have been hypothesized to underlie the adverse health effects. Simultaneous assessment of inflammation and chronic endocrine stress in epidemiological studies is lacking. The aim of the study was to investigate biomarkers of chronic endocrine stress and inflammation in relation to long-term residential exposure to air pollution and traffic noise in adolescents. Methods: In Flemish adolescents (14-15 years), we determined hair cortisol concentration (HCC) as a chronic stress biomarker in 3-cm scalp-near hair sections (n = 395), and leucocyte and leucocyte subtype counts (neutrophils, monocytes, lymphocytes) as inflammatory biomarkers in peripheral blood (n = 385). Daily particulate matter (PM2.5, PM10), nitrogen dioxide (NO2) and black carbon (BC) concentrations were modelled at the residential address and averaged over 3-month and 1-year periods prior to sampling. Residential traffic noise level was estimated and classified in 5 dB intervals. Sex-specific associations between residential exposures and effect biomarkers were studied using linear regression models, adjusted for a priori selected covariates. Results: In boys, HCC increased with a factor 1.30 (95% CI: 1.10, 1.54) for an increase in 1-year mean NO2 from the 25th to 75th percentile (p75/p25), after adjustment for age, BMI, personal and neighborhood socioeconomic status. The corresponding estimate for PM10 was 1.24 (95% CI: 1.02, 1.51). Total leucocyte count in boys, adjusted for the aforementioned covariates and recent health complaints, was positively associated with PM2.5, PM10, NO2 and BC. In particular, the neutrophil count increased with a factor 1.11 (95% CI: 1.03, 1.19) for a (p75/p25)-factor increase in 1-year mean BC, corresponding estimates for PM2.5, PM10 and NO2 were 1.10 (95% CI: 1.01, 1.19), 1.10 (95% CI: 1.01, 1.20) and 1.08 (95% CI: 1.00, 1.16). Lymphocyte count increased with a factor 1.05 (95% CI: 1.01, 1.10) for a (p75/p25)-factor increase in 1-year mean NO2. Similar results were observed for 3-month mean exposures. Results were robust to adjustment for recent air pollution exposure. In girls, air pollutants were not associated with HCC or differential leucocyte count. Residential traffic noise level was not associated with HCC or leucocyte counts in boys nor girls. Conclusions: Long-term residential exposure to air pollutants was positively associated with chronic endocrine stress and inflammation in adolescent boys, not in girls. This study may contribute to a better understanding of the early pathophysiological changes that may underlie adverse health effects of air pollution exposure in adolescents. ; Government of Flanders, Department of Environment & Spatial Development; PhD fellowship at the University of Antwerp; VITO - Flemish Center of Expertise on Environment and Health

Chronic biological stress may adversely affect adolescents' physical and mental health, but insight in the personal and environmental factors that determine chronic stress is limited. We measured 3-month cumulative hair cortisol concentration (HCC) in 419 adolescents, participating in the Flemish Environment and Health Study. Adolescents' health and lifestyle characteristics, household and neighborhood socio-economic status as well as neighborhood urbanicity were assessed as potential determinants of HCC, using multiple linear regression models. We additionally explored heterogeneity of our results by sex. HCC were significantly higher in boys from densely populated neighborhoods, the association was not significant in girls. Accordingly, boys living outside cities had significantly lower HCC than boys, living in cities. HCC was significantly lower in adolescents with an optimal vitality, a measure of a positive mental health status. In adolescent girls, menarcheal status (pre-/postmenarche) was a significant determinant of HCC. Our findings are the first to suggest that residential urbanicity may have an impact on chronic biological stress in a general population of adolescent boys. ; This paper is based on research conducted within the framework of the Flemish Center of Expertise on Environment and Health (FLEHS 2016-2020), funded by the Government of Flanders, Department of Environment & Spatial Development. VV was supported by a PhD fellowship at the University of Antwerp and VITO, funded by the Flemish Center of Expertise on Environment and Health. We thank the adolescents and their families who participated in FLEHS IV. Without their effort, this study would not have been possible. We thank the field workers from the Provincial Institute of Hygiene and VITO for the sample and data collection.

Objective: Thirty years ago it was demonstrated that folic acid taken before pregnancy and in early pregnancy reduced the risk of a neural tube defect (NTD). Despite Public Health Initiatives across Europe recommending that women take 0.4 mg folic acid before becoming pregnant and during the first trimester, the prevalence of NTD pregnancies has not materially decreased in the EU since 1998, in contrast to the dramatic fall observed in the USA. This study aimed to estimate the number of NTD pregnancies that would have been prevented if flour had been fortified with folic acid in Europe from 1998 as it had been in the USA. Design and Setting: The number of NTD pregnancies from 1998 to 2017 that would have been prevented if folic acid fortification had been implemented in the 28 countries who were members of the European Union in 2019 was predicted was predicted using data on NTD prevalence from 35 EUROCAT congenital anomaly registries and literature searches for population serum folate levels and folic acid supplementation. Results: From 1998 to 2017 an estimated 95,213 NTD pregnancies occurred amongst 104 million births in the 28 countries in the EU, a prevalence of 0.92 per 1,000 births. The median serum folate level in Europe over this time period was estimated to be 14.1 μg/L. There is a lack of information about women taking folic acid supplements before becoming pregnant and during the first trimester of pregnancy, with one meta-analysis indicating that around 25% of women did so. An estimated 14,600 NTD pregnancies may have been prevented if the European countries had implemented fortification at the level adopted by the USA in 1998 and 25% of women took folic acid supplements. An estimated 19,500 NTD pregnancies would have been prevented if no women took folic acid supplements. Conclusions: This study suggests that failure to implement mandatory folic acid fortification in the 28 European countries has caused, and continues to cause, neural tube defects to occur in almost 1,000 pregnancies every year. ; info:eu-repo/semantics/publishedVersion

International audience ; Objective: Thirty years ago it was demonstrated that folic acid taken before pregnancy and in early pregnancy reduced the risk of a neural tube defect (NTD). Despite Public Health Initiatives across Europe recommending that women take 0.4 mg folic acid before becoming pregnant and during the first trimester, the prevalence of NTD pregnancies has not materially decreased in the EU since 1998, in contrast to the dramatic fall observed in the USA. This study aimed to estimate the number of NTD pregnancies that would have been prevented if flour had been fortified with folic acid in Europe from 1998 as it had been in the USA.Design and Setting: The number of NTD pregnancies from 1998 to 2017 that would have been prevented if folic acid fortification had been implemented in the 28 countries who were members of the European Union in 2019 was predicted was predicted using data on NTD prevalence from 35 EUROCAT congenital anomaly registries and literature searches for population serum folate levels and folic acid supplementation.Results: From 1998 to 2017 an estimated 95,213 NTD pregnancies occurred amongst 104 million births in the 28 countries in the EU, a prevalence of 0.92 per 1,000 births. The median serum folate level in Europe over this time period was estimated to be 14.1 mu g/L. There is a lack of information about women taking folic acid supplements before becoming pregnant and during the first trimester of pregnancy, with one meta-analysis indicating that around 25% of women did so. An estimated 14,600 NTD pregnancies may have been prevented if the European countries had implemented fortification at the level adopted by the USA in 1998 and 25% of women took folic acid supplements. An estimated 19,500 NTD pregnancies would have been prevented if no women took folic acid supplements.Conclusions: This study suggests that failure to implement mandatory folic acid fortification in the 28 European countries has caused, and continues to cause, neural tube defects to occur in almost 1,000 ...

International audience ; Objective: Thirty years ago it was demonstrated that folic acid taken before pregnancy and in early pregnancy reduced the risk of a neural tube defect (NTD). Despite Public Health Initiatives across Europe recommending that women take 0.4 mg folic acid before becoming pregnant and during the first trimester, the prevalence of NTD pregnancies has not materially decreased in the EU since 1998, in contrast to the dramatic fall observed in the USA. This study aimed to estimate the number of NTD pregnancies that would have been prevented if flour had been fortified with folic acid in Europe from 1998 as it had been in the USA.Design and Setting: The number of NTD pregnancies from 1998 to 2017 that would have been prevented if folic acid fortification had been implemented in the 28 countries who were members of the European Union in 2019 was predicted was predicted using data on NTD prevalence from 35 EUROCAT congenital anomaly registries and literature searches for population serum folate levels and folic acid supplementation.Results: From 1998 to 2017 an estimated 95,213 NTD pregnancies occurred amongst 104 million births in the 28 countries in the EU, a prevalence of 0.92 per 1,000 births. The median serum folate level in Europe over this time period was estimated to be 14.1 mu g/L. There is a lack of information about women taking folic acid supplements before becoming pregnant and during the first trimester of pregnancy, with one meta-analysis indicating that around 25% of women did so. An estimated 14,600 NTD pregnancies may have been prevented if the European countries had implemented fortification at the level adopted by the USA in 1998 and 25% of women took folic acid supplements. An estimated 19,500 NTD pregnancies would have been prevented if no women took folic acid supplements.Conclusions: This study suggests that failure to implement mandatory folic acid fortification in the 28 European countries has caused, and continues to cause, neural tube defects to occur in almost 1,000 ...

International audience ; Objective: Thirty years ago it was demonstrated that folic acid taken before pregnancy and in early pregnancy reduced the risk of a neural tube defect (NTD). Despite Public Health Initiatives across Europe recommending that women take 0.4 mg folic acid before becoming pregnant and during the first trimester, the prevalence of NTD pregnancies has not materially decreased in the EU since 1998, in contrast to the dramatic fall observed in the USA. This study aimed to estimate the number of NTD pregnancies that would have been prevented if flour had been fortified with folic acid in Europe from 1998 as it had been in the USA.Design and Setting: The number of NTD pregnancies from 1998 to 2017 that would have been prevented if folic acid fortification had been implemented in the 28 countries who were members of the European Union in 2019 was predicted was predicted using data on NTD prevalence from 35 EUROCAT congenital anomaly registries and literature searches for population serum folate levels and folic acid supplementation.Results: From 1998 to 2017 an estimated 95,213 NTD pregnancies occurred amongst 104 million births in the 28 countries in the EU, a prevalence of 0.92 per 1,000 births. The median serum folate level in Europe over this time period was estimated to be 14.1 mu g/L. There is a lack of information about women taking folic acid supplements before becoming pregnant and during the first trimester of pregnancy, with one meta-analysis indicating that around 25% of women did so. An estimated 14,600 NTD pregnancies may have been prevented if the European countries had implemented fortification at the level adopted by the USA in 1998 and 25% of women took folic acid supplements. An estimated 19,500 NTD pregnancies would have been prevented if no women took folic acid supplements.Conclusions: This study suggests that failure to implement mandatory folic acid fortification in the 28 European countries has caused, and continues to cause, neural tube defects to occur in almost 1,000 ...

Objective: Thirty years ago it was demonstrated that folic acid taken before pregnancy and in early pregnancy reduced the risk of a neural tube defect (NTD). Despite Public Health Initiatives across Europe recommending that women take 0.4 mg folic acid before becoming pregnant and during the first trimester, the prevalence of NTD pregnancies has not materially decreased in the EU since 1998, in contrast to the dramatic fall observed in the USA. This study aimed to estimate the number of NTD pregnancies that would have been prevented if flour had been fortified with folic acid in Europe from 1998 as it had been in the USA. Design and Setting: The number of NTD pregnancies from 1998 to 2017 that would have been prevented if folic acid fortification had been implemented in the 28 countries who were members of the European Union in 2019 was predicted was predicted using data on NTD prevalence from 35 EUROCAT congenital anomaly registries and literature searches for population serum folate levels and folic acid supplementation. Results: From 1998 to 2017 an estimated 95,213 NTD pregnancies occurred amongst 104 million births in the 28 countries in the EU, a prevalence of 0.92 per 1,000 births. The median serum folate level in Europe over this time period was estimated to be 14.1 μg/L. There is a lack of information about women taking folic acid supplements before becoming pregnant and during the first trimester of pregnancy, with one meta-analysis indicating that around 25% of women did so. An estimated 14,600 NTD pregnancies may have been prevented if the European countries had implemented fortification at the level adopted by the USA in 1998 and 25% of women took folic acid supplements. An estimated 19,500 NTD pregnancies would have been prevented if no women took folic acid supplements. Conclusions: This study suggests that failure to implement mandatory folic acid fortification in the 28 European countries has caused, and continues to cause, neural tube defects to occur in almost 1,000 pregnancies every year.