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Background: There are a growing number of reports on the association between air pollution and the risk of congenital anomalies. However, the results are inconsistent and most studies have only focused on the association of air pollution with congenital heart defects and orofacial clefts.Objectives: Using an exploratory study design, we aimed to identify congenital anomalies that may be sensitive to maternal exposure to specific air pollutants during the periconceptional period.Methods: We conducted a case-control study of 7426 subjects born in the 15 years between 1999 and 2014 and registered in the European Registration of Congenital Anomalies and Twins Northern Netherlands (EUROCAT NNL). Concentrations of various air pollutants (PM10, PM2.5, PM10-2.5, NO2, NOx, absorbance) were obtained using land use regression models from the European Study of Cohorts for Air Pollution Effects (ESCAPE). We linked these data to every subject in the EUROCAT NNL registry via their full postal code. Cases were classified as children or fetuses born in the 15-year period with a major congenital anomaly that was not associated with a known monogenic or chromosomal anomaly. Cases were divided into anomaly subgroups and compared with two different control groups: control group 1 comprised children or fetuses with a known monogenic or chromosomal anomaly, while control group 2 comprised all other non-monogenic and non-chromosomal registrations.Results: Using control group 1 (n = 1618) for analysis, we did not find any significant associations, but when we used control group 2 (ranges between n = 4299 and n = 5771) there were consistent positive associations between several air pollutants (NO2, PM2.5, PM10-2.5, absorbance) and the genital anomalies subgroup.Conclusion: We examined various congenital anomalies and their possible associations with a number of air pollutants in order to generate hypotheses for future research. We found that air pollution exposure was positively associated with genital anomalies, mainly driven by hypospadias. These results broaden the evidence of associations between air pollution exposure during gestation and congenital anomalies in the child. They warrant further research, which should also focus on possible underlying mechanisms.

Background: Surveillance of congenital anomalies is important to identify potential teratogens. Despite known associations between different anomalies, current surveillance methods examine trends within each subgroup separately. We aimed to evaluate whether hierarchical statistical methods that combine information from several subgroups simultaneously would enhance current surveillance methods using data collected by EUROCAT, a European network of population-based congenital anomaly registries. Methods: Ten year trends (2003 to 2012) in 18 EUROCAT registries over 11 countries were analysed for the following groups of anomalies: neural tube defects, congenital heart defects, digestive system and chromosomal anomalies. Hierarchical Poisson regression models that combined related subgroups together according to EUROCAT’s hierarchy of subgroup coding were applied. Results from hierarchical models were compared to those from Poisson models that consider each congenital anomaly separately. Results: Hierarchical models gave similar results as those obtained when considering each anomaly subgroup in a separate analysis. Hierarchical models that included only around three subgroups showed poor convergence and were generally found to be over-parameterised. Larger sets of anomaly subgroups were found to be too heterogeneous to group together in this way. Conclusions: There were no substantial differences between independent analyses of each subgroup and hierarchical models when using the EUROCAT anomaly subgroups. Considering each anomaly separately therefore remains an appropriate method for the detection of potential changes in prevalence by surveillance systems. Hierarchical models do, however, remain an interesting alternative method of analysis when considering the risks of specific exposures in relation to the prevalence of congenital anomalies, which could be investigated in other studies.

We describe the case of a 56-year-old man presenting a primary pulmonary epithelioid angiosarcoma versus malignant epithelioid hemangioendothelioma still alive, without recurrence at nearly two years after the beginning of the symptoms. The primary pulmonary angiosarcoma is extremely rare, being reported only in a handful of cases. Metastatic involvement of the lung (90%) is far more common than primary pulmonary involvement (10%). Various predisposing condition for the development of angiosarcoma have been described. Early diagnosis is not common, because of the rarity of angiosarcoma in the lung and consequent low index of suspicion. Due to the paucity of cases, there are no defined treatment regimens for this entity. However, there is a tendency for surgical intervention in all reported cases.

Background: The use of topiramate (TPM) has been increased among pregnant women. Safety data for TPM in human pregnancy are limited. Recent studies have suggested that exposure to TPM early in gestation has a higher risk of orofacial clefts (OCs), particularly cleft lip with or without palate, and there has been a Food Drug Administration (FDA) alert. Objectives: The aim of this study was to assess the risk of OCs relative to other malformations in infants whose mothers had taken TPM during the first trimester of pregnancy. Methods: A population-based case-control study with malformed controls was performed using the EUROCAT Antiepileptic (AED) Drug Database including data from 19 population-based registries of congenital anomaly in Europe with a total coverage of 8.0 million births from 1995 to 2011. Cases were 10 802 nonsyndromic OC registrations, of whom 8919 were isolated, and 6827 were cleft lip with or without cleft palate (CL/P). Controls were 136 838 nonchromosomal, non-OC registrations. We compared first trimester TPM use versus no-AED use, for monotherapy and polytherapy. Results: Exposure to TPM monotherapy was recorded for a total of 12 registrations, with one registration in the case group (isolated cleft palate) and 11 in the control group (odds ratio (OR) 1.15, 95% CI 0.03-7.95 for OC relative to other malformations, OR 4.03, 95%CI 0.09-27.8 for isolated cleft palate). No registration of CL/P was in TPM monotherapy exposure. There were 36 registrations exposed to TPM polytherapy, of whom six with isolated CL/P, three with cleft palate. Out of 36 of TPM polytherapy, 19 included valproic acid, 8 included carbamazepine and 4 included lamotrigine. The OR for TPM polytherapy versus no-AED use was 4.23 (95%CI 1.75-9.28) for OC, 4.35 (95%CI 1.31- 11.5) for isolated CL/P and 3.85 (95%CI 0.75- 12.5) for isolated cleft palate. Conclusions: The prevalence of TPM monotherapy exposure was five times lower in these data than reported in the United States, which limited our ability to confirm or refute previous findings. We found an excess of OCs, particularly CL/P, associated with TPM polytherapy. Further attention to TPM polytherapy is warranted.

Objective: To compare the prescription of drugs in women over a period from 2 years before until 3 months after pregnancy, regarding the type of drugs used and the foetal risk. Design: A cohort study based on pharmacy records of women giving birth to a child between 1994 and 2003. Methods: The study was performed with data from the InterAction database, containing prescription drug dispensing data from community pharmacies. The study population included 5412 women for whom complete pharmacy records were available. Drugs were classified into three categories: (1) drugs for chronic conditions, (2) drugs for occasional use and (3) drugs for pregnancy-related symptoms. Drugs were also classified according to the Australian classification system. The prescription rate was calculated as the number of women per 100 women who received one or more prescriptions for a given drug within a specified time period. Results: About 79.1 % of the women received at least one prescription during pregnancy. The prescription rate for most drugs for chronic diseases and for occasional use decreased during pregnancy, whereas, as expected, the prescription rate for pregnancy-related drugs increased. During the first trimester of pregnancy, 1.7 % of all drugs prescribed for chronic conditions and 2.3 % of the occasional drugs were classified as harmful. Conclusion: The increase in prescription rate during pregnancy is caused by an increase in prescription rate of drugs for pregnancy-related symptoms. The prescription of harmful drugs is more commonly associated with drugs for occasional use rather than with drugs for chronic conditions. Therefore, a more cautious prescribing of drugs to healthy women in the fertile age is necessary.

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 nonwestern 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.

Glycol ethers are found in a wide range of domestic and industrial products, many of which are used in women's work environments. Motivated by concern about their potential reproductive toxicity, we have evaluated the risk of congenital malformations related to glycol ether exposure during preg nancy as part of a multicenter case-control study, conducted in six regions in Europe. The study comprised 984 cases of major congenital malformations and 1,134 controls matched for place and date of birth. Interviews of the mothers provided information about occupation during pregnancy, sociodemographic variables, and other potential risk factors (medical history, tobacco, alcohol, drugs). A chemist specializing in glycol ethers evaluated exposure during pregnancy, using the job description given by the mother, without knowledge of case or control status. We classified malformations into 22 subgroups. The overall odds ratio (OR) of congenital malformation associated with glycol ether exposure was 1.44 [95% confidence interval (CI) = 1.10-1.90], after adjustment for several potential confounders. The association with exposure to glycol ethers appeared particularly strong in three subgroups: neural tube defects (OR = 1.94; 95% CI = 1.16-3.24), multiple anomalies (OR = 2.00; 95% CI = 1.24-3.23), and cleft lip (OR = 2.03; 95% CI = 1.11-3.73). In this last subgroup, risk, especially of an isolated defect, tended to increase with level of exposure.

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