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Study Question: What are the long term trends in the total (live births, fetal deaths, and terminations of pregnancy for fetal anomaly) and live birth prevalence of neural tube defects (NTD) in Europe, where many countries have issued recommendations for folic acid supplementation but a policy for mandatory folic acid fortification of food does not exist?, Methods: This was a population based, observational study using data on 11,353 cases of NTD not associated with chromosomal anomalies, including 4162 cases of anencephaly and 5776 cases of spina bifida from 28 EUROCAT (European Surveillance of Congenital Anomalies) registries covering approximately 12.5 million births in 19 countries between 1991 and 2011. The main outcome measures were total and live birth prevalence of NTD, as well as anencephaly and spina bifida, with time trends analysed using random effects Poisson regression models to account for heterogeneities across registries and splines to model non-linear time trends., Summary Answer and Limitations: Overall, the pooled total prevalence of NTD during the study period was 9.1 per 10,000 births. Prevalence of NTD fluctuated slightly but without an obvious downward trend, with the final estimate of the pooled total prevalence of NTD in 2011 similar to that in 1991. Estimates from Poisson models that took registry heterogeneities into account showed an annual increase of 4% (prevalence ratio 1.04, 95% confidence interval 1.01 to 1.07) in 1995-99 and a decrease of 3% per year in 1999-2003 (0.97, 0.95 to 0.99), with stable rates thereafter. The trend patterns for anencephaly and spina bifida were similar, but neither anomaly decreased substantially over time. The live birth prevalence of NTD generally decreased, especially for anencephaly. Registration problems or other data artefacts cannot be excluded as a partial explanation of the observed trends (or lack thereof) in the prevalence of NTD., What This Study Adds: In the absence of mandatory fortification, the prevalence of NTD has not decreased in Europe despite longstanding recommendations aimed at promoting peri-conceptional folic acid supplementation and existence of voluntary folic acid fortification., Funding, Competing Interests, Data Sharing: The study was funded by the European Public Health Commission, EUROCAT Joint Action 2011-2013. HD and ML received support from the European Commission DG Sanco during the conduct of this study. No additional data available., (© Khoshnood et al 2015.)

Background: Two crucial issues relative to the benefits and impact of folic acid in the prevention of birth defects are whether supplementation recommendations alone, without fortification, are effective in reducing the population-wide rates of neural tube defects (NTDs), and whether such policies can reduce the occurrence of other birth defects. Using data from 15 registries, we assessed rates and trends of 14 major defects, including NTDs, in areas with official recommendations or fortification to assess the effectiveness of recommendations and fortification on a wide range of major birth defects., Methods: We evaluated surveillance data through 2003 on major birth defects from population-based registries from Europe, North America, and Australia. All included ascertainment of pregnancy terminations (where legal). Trends before and after policies or fortification were assessed via Poisson regression and were compared via rate ratios., Results: Significant changes in trends were seen for NTDs in areas with fortification but not in areas with supplementation recommendations alone. For other major birth defects, there was an overall lack of major trend changes after recommendations or fortification. However, some significant declines were observed for select birth defects in individual areas., Conclusions: Recommendations alone remain an ineffective approach in translating the known protective effect of folic acid in population-wide decline in NTD rates. Fortification appears to be effective in reducing NTDs. The effect on other birth defects remains unclear., ((c) 2006 Wiley-Liss, Inc.)

The European Registration Of Congenital Anomalies and Twins (EUROCAT), a network of 40 European registries of congenital anomalies, has published a special report on the prevention of neural-tube defects by, periconceptional folic-acid supplementation in Europe. This report reviews the progress made in 17 European countries since i99I in terms of developing and implementing public health policies to raise periconceptional folate status. Data on the prevalence of neural-tube defects in 1980-2000 were also analysed. - At the beginning of 2002, 10 of the 17 countries had an official government recommendation that women planning a pregnancy should take folic-acid supplementation daily. Only 7 countries implemented official health-education initiatives. - Despite the various measures taken to date, the majority of women in all countries surveyed are not taking periconceptional folic-acid supplements. Even in the Netherlands, where the percentage of planned pregnancies is estimated at 85%, only 36% of women take folic-acid supplements during the advised period. - Overall, the number of neural-tube defects has not decreased in Europe. A slight decrease was seen in those countries with an official policy regarding periconceptional folic-acid supplementation. - It is clear from the report that more effective prevention of neuraltube defects could be achieved with folic-acid fortification of staple foods; this approach has led to a reduction in the prevalence of neuraltube defects in the US and Canada. This approach can also prevent the majority of neural-tube defects in unplanned pregnancies and reduce the socioeconomic differences in prevalence.

Each year, more than 4500 pregnancies in the European Union are affected by neural tube defects (NTD). Unambiguous evidence of the effectiveness of periconceptional folic acid in preventing the majority of neural tube defects has been available since 1991. We report on trends in the total prevalence of neural tube defects up to 2002, in the context of a survey in 18 European countries of periconceptional folic acid supplementation (PFAS) policies and their implementation. EUROCAT is a network of population-based registries in Europe collaborating in the epidemiological surveillance of congenital anomalies. Representatives from 18 participating countries provided information about policy, health education campaigns and surveys of PFAS uptake. The yearly total prevalence of neural tube defects including livebirths, stillbirths and terminations of pregnancy was calculated from 1980 to 2002 for 34 registries, with UK and Ireland estimated separately from the rest of Europe. A meta-analysis of changes in NTD total prevalence between 1989-1991 and 2000-2002 according to PFAS policy was undertaken for 24 registries. By 2005, 13 countries had a government recommendation that women planning a pregnancy should take 0.4mg folic acid supplement daily, accompanied in 7 countries by government-led health education initiatives. In the UK and Ireland, countries with PFAS policy, there was a 30% decline in NTD total prevalence (95% CI 16-42%) but it was difficult to distinguish this from the pre-existing strong decline. In other European countries with PFAS policy, there was virtually no decline in NTD total prevalence whether a policy was in place by 1999 (2%, 95% CI 28% reduction to 32% increase) or not (8%, 95% CI 26% reduction to 16% increase). The potential for preventing NTDs by periconceptional folic acid supplementation is still far from being fulfilled in Europe. Only a public health policy including folic acid fortification of staple foods is likely to result in large-scale prevention of NTDs.

Objectives: To evaluate the effectiveness of policies and recommendations on folic acid aimed at reducing the occurrence of neural tube defects., Design: Retrospective cohort study of births monitored by birth defect registries., Setting: 13 birth defects registries monitoring rates of neural tube defects from 1988 to 1998 in Norway, Finland, Northern Netherlands, England and Wales, Ireland, France (Paris, Strasbourg, and Central East), Hungary, Italy (Emilia Romagna and Campania), Portugal, and Israel. Cases of neural tube defects were ascertained among liveborn infants, stillbirths, and pregnancy terminations (where legal). Policies and recommendations were ascertained by interview and literature review., Main Outcome Measures: Incidences and trends in rates of neural tube defects before and after 1992 (the year of the first recommendations) and before and after the year of local recommendations (when applicable)., Results: The issuing of recommendations on folic acid was followed by no detectable improvement in the trends of incidence of neural tube defects., Conclusions: Recommendations alone did not seem to influence trends in neural tube defects up to six years after the confirmation of the effectiveness of folic acid in clinical trials. New cases of neural tube defects preventable by folic acid continue to accumulate. A reasonable strategy would be to quickly integrate food fortification with fuller implementation of recommendations on supplements.

Objective: To investigate the influence of ethnicity on the awareness and use of folic acid by pregnant women., Design: Secondary data analysis., Method: Using the data on 1555 women, collected during a cross-sectional study conducted among pregnant women with good knowledge of the Dutch language in 1996, the authors determined what was known about the recommendation to use folic acid around the time of conception and what the actual use was. Women were defined as either 'western' or 'non-western' on the basis of the place of birth of the woman and her parents., Results: Of the 1555 pregnant women, 74 (5%) were non-western or of non-western descent. Non-western women more often had a lower educational level than western women (51% versus 34%; p = 0.002) and more often had an unintended pregnancy (24% versus 8%; p < 0.0001). 41% of the non-western women had heard of the recommendation to use folic acid before pregnancy, compared to 79% of the western women (p < 0.0001). However, the use of folic acid was not significantly different between non-western and western women (56% versus 69%) if they had been aware of the recommendation to use folic acid before pregnancy. Awareness of the recommendation to use folic acid was higher in older women (OR: 1.46; 95% CI: 1.13-1.89), women of western descent (0.27; 0.16-0.47), women with a higher level of education (0.35; 0.27-0.45) and in case of planned pregnancy (0.45; 0.31-0.67). The use of folic acid, restricted to women who were aware of the recommendation to use folic acid before their pregnancy, was higher in older women (1.37; 1.05-1.80) and lower in those with more previous pregnancies (0.57; 0.43-0.75) and in case of an unplanned pregnancy (0.55; 0.34-0.88)., Conclusion: Although non-western women had less knowledge of the recommendation to use folic acid than western women, the use of folic acid was not significantly different from that by western women if they had been aware of the recommendation to use folic acid before pregnancy. Continued education on folic acid targeting non-western and western women is important.

Background: We investigated periconceptional awareness and the use of folic acid tablets 3 years after the 1995 campaign in the northern Netherlands. We studied whether the socioeconomic differences we found in 1996 with respect to awareness and use of folic acid remained in 1998., Methods: The present study took place in 1998. Pregnant women were asked to complete a questionnaire., Results: A total of 452 women completed the questionnaire in 1998. Sixty percent of the women with a lower level of education and 85% of the women with a higher level of education had heard of folic acid before pregnancy. Newspapers and magazines were the most often cited sources of information. Fifty percent of the women with a lower educational level used folic acid, while this figure was 80% for the group with higher education., Conclusion: Awareness and use of folic acid increased after the 1995 campaign. However, socioeconomic differences with respect to awareness of folic acid remained and even increased with respect to knowledge of the advised period. Use of folic acid is also associated with level of education more strongly than in 1996. Therefore, fortification of staple foods is an attractive option.

Background: Supplementation of folic acid prior to and in the beginning of pregnancy may prevent neural tube defects (NTDs) in newborns--such as spina bifida--and possibly other congenital malformations., Objective: To estimate cost effectiveness of periconceptional supplementation of folic acid using pharmaco-economic model calculation., Method: Probabilities for NTDs, risk reductions through periconceptional supplementation of folic acid and lifetime costs of care for children with spina bifida were estimated using Dutch registrations and international literature., Main Outcome Measure: Cost effectiveness was expressed in net costs per discounted life-year gained. Cost effectiveness was calculated in the baseline and in sensitivity analysis., Results: Estimated cost effectiveness of periconceptional supplementation of folic acid amounts to NLG 3900 ([symbol: see text] 1800) in the base case. In sensitivity analysis cost effectiveness mostly remains below NLG 10,000 ([symbol: see text] 4500)., Conclusion: Periconceptional supplementation of folic acid shows a favorable cost effectiveness. From pharmaco-economic point of view this justifies further stimulation of folic-acid supplementation prior to pregnancy. This can be done through targeted education by health-care workers, such as pharmacists.

Periconceptional folic acid use considerably reduces the risk of neural tube defects. The aim of this study was to measure the effect of the national and the local 'Folic Acid Campaign' on periconceptional folic acid use. Before (1995 survey) and 1 year after the campaign (1996 survey), the awareness and use of folic acid was measured among pregnant women in four regions of the Netherlands. To this end, pregnant women who visited the midwife, general practitioner or obstetrician for the first or second prenatal visit were asked to complete a questionnaire. The results showed that use of folic acid for any period around conception increased from 25.1% in 1995 to 53.5% in 1996. Appropriate use (4 weeks before until 8 weeks after conception) increased from 4.8% in 1995 to 21.0% in 1996. No additional effect of the local Folic Acid Campaign was found (adjusted odds ratio= 1.0; 95% confidence interval = 0.7, 1.4). It was possible to conclude that folic acid use at the recommended time increased considerably as a result of the national and the local Folic Acid Campaign, but the target (use in 46% of women wishing to conceive) was not achieved. New health education programmes are needed to increase further its use at the appropriate times.

Objective: Evaluation of prenatal diagnosis of neural tube defects by ultrasound examination in unselected populations across Europe., Setting: Prenatal ultrasound units in areas that report to contributing congenital malformation registers., Methods: All cases with a suspected or confirmed neural tube defect and delivered within the 30 month study period were identified from 18 Congenital Malformation Registers from 11 European countries. Data on the pregnancy, prenatal scans, outcome of pregnancy, and information on different screening policies for each country were analysed., Results: 670766 deliveries occurred in the area covered by the registers during the study period. A neural tube defect was diagnosed at delivery in 542 cases. In 84% of these, the lesion was isolated (166 anencephaly, 252 spina bifida, 35 encephalocele). Of the 166 isolated cases with anencephaly, 96% were correctly identified prenatally; one was missed on scan, two were wrongly diagnosed, and four were not scanned (sensitivity 98%). 84% of the prenatal diagnoses were made before 24 weeks' gestation; 86% of isolated anencephalic pregnancies were terminated. Of the 252 cases of isolated spina bifida, 171 (68%) were correctly identified prenatally; 66% of these before 24 weeks' gestation. The diagnosis was missed on scan in 60 cases and 21 were not scanned (sensitivity 75%). The mean reduction in birth prevalence because of termination of pregnancy for spina bifida was 49% (range 6-100%). There was a wide variation between centres in prenatal detection rate (33-100%), termination of pregnancy of prenatally diagnosed cases (17-100%), and gestation both at diagnosis and termination of pregnancy., Conclusion: A high prenatal detection rate for anencephaly was reported by all registers. There is a large variation in prenatal detection and termination rates for spina bifida between centres, reflecting differences both in policy and culture.

Objective: In November 1993, Dutch health authorities advised that women planning a pregnancy should take folic acid in the periconceptional period to reduce the risk of fetal neural tube defects. In the autumn of 1995 a national campaign was organized to inform women and health care professionals in a systematic way., Methods: We assessed the awareness and behaviour of women at their first or second antenatal visit in two surveys in the spring of 1994 and the autumn of 1995, in order to evaluate the impact of non-systematic information during that period, and to collect baseline data to evaluate the effect of the national folic acid campaign. The two surveys were carried out in the north and the west of The Netherlands., Results: The proportion of women who had heard of folic acid increased from 28% to 78%. The proportion that used folic acid during any period in pregnancy increased from 7.8% to 26%. The proportion that took folic acid tablets during the whole of the recommended period increased from 0.8 to 4.4%. In the group of women who did not take folic acid, the proportion who did "not like to use anything during pregnancy" decreased, as did the proportion who did "not think it is useful"., Conclusion: In the Netherlands, non-systemic information about periconceptional folic acid use has already led to significant changes in awareness and behaviour before the start of the national folic acid campaign.

Objective: To describe the epidemiological impact of prenatal diagnosis and selective abortion on the frequency of neural tube defects (NTD) in the period 1980-1992 in the Northern Netherlands in comparison with data from other European regions., Design: Descriptive., Setting: 17 'European registration of congenital anomalies' (EUROCAT) registrations, localized in 10 European countries., Method: Data were collected actively and retrospectively from multiple sources fed by voluntary registration of congenital anomalies in live births, stillbirths and pregnancies terminated because of congenital anomalies., Results: In Europe the total birth prevalence of NTD in the period 1980-1992 ranged from 5.3 per 10,000 in Switzerland to 29.0 per 10,000 in Glasgow, a difference of a factor 5.5. In live births the difference was ninefold: ranging from 2.0 per 10,000 in Paris to 18.8 per 10,000 in Dublin. The Netherlands had a conspicuously high prevalence among live births, higher than in other regions in continental Europe. For spina bifida the live birth prevalence both in other continental regions and in Glasgow was also lower than in the Netherlands. In Glasgow serum alpha-foetoprotein screening apparently led to frequent early prenatal diagnosis of NTD and to frequent termination of pregnancy. In Paris the use of ultrasound screening appears to lead to frequent later prenatal diagnosis, as well as frequent termination of pregnancy., Conclusion: In the Netherlands the impact of prenatal diagnosis and selective abortion is limited, so that primary prevention (periconceptional use of folic acid) is more important than in some other European countries.

Objective: To determine the live birth prevalence of neural tube defects (NTD) in the Netherlands and describe the clinical picture., Design: Descriptive., Setting: TNO Prevention and Health, Leiden, the Netherlands., Method: Data collected through active surveillance of NTD on a monthly basis by paediatricians throughout the country., Results: From October 1993 to September 1995, 203 infants with NTD were registered. Six were diagnosed with anencephaly, 10 with encephalocele and 157 with spina bifida. On 30 children no further information was available. Seventy-nine per cent of children with spina bifida had a myelomeningocele and 11% had a meningocele. Hydrocephalus was found in 75% of all registered infants and in 81% of infants with myelomeningocele. In 18% of the latter group a kyphosis was diagnosed. In 45% of 131 children prognosis of ambulation fair: they were expected to learn to walk. In 32% prognosis for motor disorder was very poor, and unsupported sitting was considered to be unlikely. At the time of registration, when most children were less than a month old, 55 (27%) had died; in infants with a myelomeningocele this was 35%. In many children treatment had not been started, probably because the prognosis was poor. Some had not been referred to a multidisciplinary team and only one of them received a hydrocephalus valve., Conclusion: The prevalence of spina bifida in the Netherlands is at least 100 live-born children per year among 195,000 total births. Mortality in the first month is high and for many surviving infants a severe handicap can be expected. Preventive strategies (such as folic acid supplementation) are urgently needed.

Study Question: Is there an association between maternal occupational exposure to solvents, pesticides and metals as assessed by expert-based assessment and congenital anomalies in the offspring?Summary Answer: There is an association between maternal occupational exposure to solvents and congenital anomalies in the offspring, including neural tube defects, congenital heart defects and orofacial clefts.What Is Known Already: One important environmental risk factor for development of congenital anomalies is maternal occupational exposure to chemicals in the workplace prior to and during pregnancy. A number of studies have assessed the association with often conflicting results, possibly due to different occupational exposure assessing methods.Study Design, Size, Duration: For this systematic review with meta-analysis, the search terms included maternal occupation, exposure, congenital anomalies and offspring. Electronic databases MEDLINE and EMBASE were searched for English studies up to October 2017.Participants/materials, Setting, Methods: Two reviewers independently screened all citations identified by the search. Case-control studies and cohort studies were included if (I) they reported on the association between maternal occupational exposure to solvents, pesticides or metals and congenital anomalies, and (II) assessment of occupational exposure was performed by experts. Data on study characteristics, confounders and odds ratios (ORs) were extracted from the included studies for four subgroups of congenital anomalies. Methodological quality was assessed using the Newcastle-Ottawa Scale. In the meta-analysis, random effects models were used to pool estimates.Main Results and the Role Of Chance: In total, 2806 titles and abstracts and 176 full text papers were screened. Finally, 28 studies met the selection criteria, and 27 studies could be included in the meta-analysis. Our meta-analysis showed that maternal occupational exposure to solvents was associated with neural tube defects (OR: 1.51, 95%CI: 1.09-2.09) and congenital heart defects (OR: 1.31, 95%CI:1.06-1.63) in the offspring. Also maternal occupational exposure to glycol ethers, a subgroup of solvents, was associated with neural tube defects (OR: 1.93, 95%CI: 1.17-3.18) and orofacial clefts (OR: 1.95, 95%CI: 1.38-2.75) in the offspring. Only one study investigated the association between maternal occupational exposure to solvents and hypospadias and found an association (OR: 3.63, 95%CI: 1.94-7.17). Results of the included studies were consistent. In our meta-analysis, we found no associations between occupational exposure to pesticides or metals and congenital anomalies in the offspring.Limitations, Reasons For Caution: A limited number of studies was included, which made it impossible to calculate pooled estimates for all congenital anomalies, analyse individual chemicals or calculate exposure-response relations. Bias could have been introduced because not all included studies corrected for potentially confounding factors.Wider Implications Of the Findings: Employers and female employees should be aware of the possible teratogenic effects of solvent exposure at the workplace. Therefore, is it important that clinicians and occupational health specialist provide women with preconception advice on occupational solvent exposure, to reduce the congenital anomaly risk.Study Funding/competing Interest(s): NSp was paid by the Graduate School of Medical Sciences (MD/PhD program), UMCG, Groningen, the Netherlands. EUROCAT Northern Netherlands is funded by the Dutch Ministry of Health, Welfare and Sports. There are no competing interests.Registration Number: CRD42017053943. [ABSTRACT FROM AUTHOR]

An abstract of the article "Prenatal detection of neural tube defects in the Netherlands: timing of diagnosis and pregnancy outcome," by M. Bakker and colleagues is presented.