Search

Background: Prenatal diagnosis of several major congenital anomalies can be achieved in the first trimester of pregnancy., Objective: This study investigates the timing of diagnosis and pregnancy outcome of foetuses and neonates with selected structural anomalies in the Northern Netherlands over a 10-year period when the prenatal screening programme changed significantly, but no first-trimester anatomical screening was implemented., Methods: We performed a population-based retrospective cohort study with data from the EUROCAT Northern Netherlands database on pregnancies with delivery or termination of pregnancy for fetal anomaly (TOPFA) date between 2010 and 2019. The analysis was restricted to anomalies potentially detectable in the first trimester of pregnancy in at least 50% of cases, based on previously published data. These included: anencephaly, encephalocele, spina bifida, holoprosencephaly, tricuspid/pulmonary valve atresia, hypoplastic left heart, abdominal wall and limb reduction defects, lethal skeletal dysplasia, megacystis, multiple congenital anomalies. The primary outcome was the timing of diagnosis of each structural anomaly. Information on additional investigations, genetic testing and pregnancy outcome (live birth, TOPFA and foetal/neonatal death) was also collected., Results: A total of 478 foetuses were included; 95.0% (n = 454) of anomalies were detected prenatally and 5.0% (n = 24) postpartum. Among the prenatally detected cases, 31% (n = 141) were diagnosed before 14 weeks of gestation, 65.6% (n = 298) between 14-22 weeks and 3.3% (n = 15) after 22 weeks. Prenatal genetic testing was performed in 80.4% (n = 365) of cases with prenatally diagnosed anomalies, and the results were abnormal in 26% (n = 95). Twenty-one% (n = 102) of pregnancies resulted in live births and 62.8% (n = 300) in TOPFA. Spontaneous death occurred in 15.9% (n = 76) of cases: in-utero (6.1%, n = 29), at delivery (7.7%, n = 37) or in neonatal life (2.1%, n = 10)., Conclusion: Major structural anomalies amenable to early diagnosis in the first trimester of pregnancy are mostly diagnosed during the second trimester in the absence of a regulated first-trimester anatomical screening programme in the Netherlands and are associated with TOPFA and spontaneous death, especially in cases with underlying genetic anomalies., (© 2022 The Authors. Paediatric and Perinatal Epidemiology published by John Wiley & Sons Ltd.)

Background: Perinatal mortality in foetuses/children with congenital anomalies remains high. Prenatal diagnosis, essential for risk assessment and organisation of perinatal/postnatal care, offers parents the opportunity to consider the termination of pregnancy. In times of quick changes in prenatal screening programmes, it is relevant to evaluate the effect of prenatal screening on perinatal mortality rates., Objectives: The objective of this study was to study trends in early foetal and perinatal mortality associated with congenital anomalies before/after the introduction of the Dutch prenatal screening programme., Methods: This population-based cohort study included 8535 foetuses/neonates with congenital anomalies born in the Northern Netherlands between 2001 and 2017. Total deaths were defined as sum of early foetal (before 24 weeks' gestation) and perinatal deaths (from 24 weeks' gestation till day 7 post-partum). Foetal deaths were categorised into spontaneous or elective termination of pregnancy for foetal anomalies (TOPFA). Trends in total mortality as well as early foetal and perinatal mortality were studied. Joinpoint regression was used to calculate the average annual percentage chance (AAPC) and identify linear trends in mortality within subperiods., Results: Total and perinatal mortality were 17% and 4%. Total mortality was higher in abnormal karyotype and central nervous system anomalies. We observed an increase in total mortality over time: 11.9% in 2001 versus 21.9% in 2017 (AAPC 2.6, 95% confidence interval [CI] 1.5, 3.7), caused by an increase in early foetal mortality from 5.5% to 19.2% (AAPC 8.7, 95% CI 4.7, 12.9) and a decrease in perinatal mortality from 6.4% to 2.7% (AAPC -5.6, 95% CI -10.0, -1.0). The increase in early foetal mortality reflects an increase in TOPFA from 3.6% to 16.9% (AAPC 8.3, 95% CI 4.2, 12.7), mostly occurring at 13-14 and 20-23 weeks' gestation., Conclusions: The introduction of the prenatal screening programme led to a decrease in perinatal mortality among foetuses and neonates with congenital anomalies and a marked increase in early foetal mortality before 24 weeks' gestation due to higher rates of TOPFA., (© 2021 The Authors. Paediatric and Perinatal Epidemiology published by John Wiley & Sons Ltd.)

Introduction: The primary aim of this study is to investigate the impact of a 13-week anomaly scan on the experienced levels of maternal anxiety and well-being. Secondly, to explore women's knowledge on the possibilities and limitations of the scan and the preferred timing of screening for structural abnormalities., Material and Methods: In a prospective-cohort study conducted between 2013-2015, pregnant women in the North-Netherlands underwent a 13-week anomaly scan. Four online-questionnaires (Q1, Q2, Q3 and Q4) were completed before and after the 13- and the 20-week anomaly scans. In total, 1512 women consented to participate in the study and 1118 (74%) completed the questionnaires at Q1, 941 (64%) at Q2, 807 (55%) at Q3 and 535 (37%) at Q4. Psychological outcomes were measured by the state-trait inventory-scale (STAI), the patient's positive-negative affect (PANAS) and ad-hoc designed questionnaires., Results: Nine-nine percent of women wished to be informed as early as possible in pregnancy about the absence/presence of structural abnormalities. In 87% of women levels of knowledge on the goals and limitations of the 13-week anomaly scan were moderate-to-high. In women with a normal 13-week scan result, anxiety levels decreased (P < .001) and well-being increased over time (P < .001). In women with false-positive results (n = 26), anxiety levels initially increased (STAI-Q1: 39.8 vs. STAI-Q2: 48.6, P = 0.025), but later decreased around the 20-week anomaly scan (STAI-Q3: 36.4 vs. STAI-Q4: 34.2, P = 0.36)., Conclusions: The 13-week scan did not negatively impact the psychological well-being of pregnant women. The small number of women with screen-positive results temporarily experienced higher anxiety after the scan but, in false-positive cases, anxiety levels normalized again when the abnormality was not confirmed at follow-up scans. Finally, most pregnant women have moderate-to-high levels of knowledge and strongly prefer early screening for fetal structural abnormalities., Competing Interests: The authors have declared that no competing interests exist.

Background: Maternal nutrition status (e.g. dietary/nutrient intake) during pregnancy has been associated with pregnancy outcomes including birth weight, infant survival and metabolic health of the offspring during later life. During the past few years, maternal dietary intake, at least three months before conception, has been shown to affect pregnancy outcomes also. However, literature investigating this link is still scarce. The studies that have looked at preconception dietary intake in relation to pregnancy outcome were either animal studies, had small sample sizes or focused on only selected macronutrient intake rather than complete (macro)nutrient composition or dietary intakes (e.g. food groups). Therefore, we aim to investigate the association between preconception diet and pregnancy outcomes in a linked birth cohort. The main objective of this manuscript is to describe the methodology of establishing this birth cohort and to describe both the characteristics of the study population included as well as the representativeness in terms of dietary intake., Methods: We created the birth cohort by linking two existing databases; a large population-based cohort study in the Netherlands (The Lifelines Cohort study) and the Dutch national birth registry (Perined), through a 'trusted third party'. The birth cohort contains information on maternal dietary intake during preconception as well as pregnancy outcomes., Results and Discussion: In the Lifelines Cohort study, 3,418 pregnancies were available for linking with Perined. In total, 2,368 pregnancies (86.9%) were linked with Perined, resulting in the birth cohort. With this linked cohort we are able to provide insights on the associations between dietary intake before conception and pregnancy outcomes. Such data could potentially improve nutritional care for women of childbearing age. Lifestyle changes in the period preceding pregnancy may be most effective in improving pregnancy outcomes. A focus on this window of opportunity may provide both sufficient time, as well as a period when women are potentially motivated to adopt health optimizing behaviours., Competing Interests: Author EB is part-time employee of Danone Nutricia Research, Utrecht, The Netherlands. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

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 (PM 10 , PM 2.5 , PM 10-2.5 , NO 2 , NO X , 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 (NO 2 , PM 2.5 , PM 10-2.5 , 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., (Copyright © 2018. Published by Elsevier GmbH.)

Background: To evaluate the impact of the introduction of prenatal screening on time of detection and pregnancy outcome for trisomy 21 (T21), trisomy 18 (T18) and trisomy 13 (T13)., Methods: We performed a retrospective, population-based cohort study in the Northern Netherlands including 503 trisomy cases born between 2005 and 2012. Screening tests and invasive procedures, timing of diagnosis and pregnancy outcome were compared between the period before (2005-2006) and after introduction (2007-2012) using X 2 tests., Results: There was an increase in proportion of women who had a prenatal screening and/or invasive test, from 62% in 2005-2006 to 84% in 2010-2012 (p < 0.01), while the proportion of prenatally diagnosed cases did not change (60% overall). In women < =35 years 47% of the cases were diagnosed prenatally vs 73% in women >35 years (p < 0.01). More T13/T18 cases were diagnosed <24 weeks after introduction (62% vs 84%; p < 0.01). In T13/T18 intra-uterine death decreased (26% vs 15%), while terminations increased: 55% vs 72%., Conclusion: The introduction of prenatal screening had limited impact on the time of detection and outcome of the most common trisomies. The introduction of the 20-week anomaly scan has resulted in more trisomy cases diagnosed <24 weeks and a shift from fetal death to terminations.

Unlabelled: We aimed to study the association between use of antihistamines in early pregnancy and congenital heart defects (CHD) in the offspring., Design: Two case-control studies., Setting: HAVEN study, Erasmus MC, University Medical Centre, Rotterdam, and Eurocat Northern Netherlands (NNL), University Medical Center Groningen, Groningen, the Netherlands. We studied 361 children with CHD and 410 controls without congenital malformations from the HAVEN study and replicated the analyses in 445 children with CHD and 530 controls from the Eurocat NNL registry. Information about antihistamine use in early pregnancy and potential confounders was obtained from questionnaires postpartum. We calculated the association between antihistamines and CHD risk by multivariable logistic regression analysis., Main Outcome Measures: Odds ratios (OR) with 95% confidence intervals (CI). In the HAVEN study, 25 of 771 mothers used antihistamines that were associated with an increased CHD risk (OR 3.0, 95% CI 1.2-7.3), particularly atrioventricular septal defects (AVSD) (OR 5.1, 95 % CI 1.3-20.5) and perimembranous ventricular septal defects (pVSD) (OR 5.1, 95% CI 1.8-14.4). Mothers with severe nausea who did not use antihistamines had a reduced risk (OR 0.7, 95% CI 0.5-0.98), whereas nauseous mothers using antihistamines showed an almost fivefold increased risk of pVSD (OR 4.8, 95% CI 1.1-21.8). The association between antihistamines and AVSD was confirmed in the Eurocat cohort (OR 3.5, 95% CI 1.4-8.7), but we could not replicate the association with overall CHD risk. We found a positive association between antihistamine use in early pregnancy and CHD risk, particularly AVSD, which seemed to be independent of nausea/vomiting.

Objectives: To evaluate in a population-based cohort the effect of the introduction of the 20-week ultrasound scan in 2007 on the time of diagnosis, pregnancy outcome and total prevalence and liveborn prevalence of cases with selected congenital heart defects (CHDs) in The Netherlands., Methods: We included children and fetuses diagnosed with selected severe CHD, born in the 11-year period from 2001 to 2011. Two groups of CHD were defined: those associated with an abnormal four-chamber view at ultrasound (Group 1), and those associated with a normal four-chamber view at ultrasound (Group 2). The time of diagnosis, pregnancy outcome and total liveborn prevalence were compared for both groups over two 5-year periods, before and after the introduction of the 20-week ultrasound scan. Trends in total and liveborn prevalence were examined over 2001 to 2011., Results: Information was collected on 269 children and fetuses. After the introduction of the 20-week ultrasound scan, the prenatal detection rate of CHDs increased in both groups (Group 1, 34.6% in 2001-2005 vs 84.8% in 2007-2011 (P < 0.001); Group 2, 14.3% in 2001-2005 vs 29.6% in 2007-2011 (P = 0.037)). The rate of termination of pregnancy (TOP) increased significantly only for Group 1 (15.4% vs 51.5% (P < 0.001)). The total prevalence of CHD in Group 1 increased over time from 2.9 per 10 000 births in 2001 to 6.4 per 10 000 births in 2011 (P = 0.016). The liveborn prevalence did not show a trend over time. For Group 2, no trends in total or liveborn prevalence could be detected over time., Conclusions: Since the implementation of the routine 20-week ultrasound scan in The Netherlands, prenatal detection rate of selected severe CHDs increased significantly. Improved prenatal detection was accompanied by a more than three-fold increase in TOP, although only in those CHDs with an abnormal four-chamber view at prenatal ultrasound., (Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.)

Purpose: To describe the prescription of antibiotics before, during and after pregnancy, and the trends over a 16-year period in the Netherlands, and to determine whether they were prescribed according to national guidelines., Methods: The IADB (http://iadb.nl) contains prescriptions dispensed by community pharmacies in the Netherlands. We extracted information on 18,873 pregnancies for 14,969 women between 1994 and 2009, focusing on antibiotics dispensed in the four trimesters before conception to two trimesters after birth (nine trimesters in total). We calculated trends in prescription rates during pregnancy and over time, and also compared the prescription of antibiotics in the Netherlands with safety category based on the Australian Drug Evaluation Committee., Results: During pregnancy 20.8% of the women were prescribed at least one antibiotic. The 'beta-lactam antibacterials/penicillins' group and the specific antibiotic amoxicillin were most commonly prescribed in the nine trimesters covered. The prescription rate of the 'other antibacterials' group during pregnancy increased over the years, in contrast to that of the 'sulphonamides/trimethoprim' group, which decreased. In total, 2.0% of pregnancies were exposed to a 'potentially harmful' antibiotic and 0.8% to a 'harmful' antibiotic. Compared with the period before conception, 'safe' antibiotics were prescribed more often during pregnancy than the other groups., Conclusions: One in five women was prescribed at least one antibiotic during pregnancy in the Netherlands, which is comparable with rates in other European countries. Our results suggest that antibiotics appear to be prescribed to pregnant women generally in accordance with national recommendations., (Copyright © 2013 John Wiley & Sons, Ltd.)

Periconceptional folic acid has been associated with a reduced risk of neural tube defects, but findings on its effect in oral clefts are largely inconclusive. This case-control study assesses the effects of periconceptional folic acid on cleft risk, using complementary data from the Dutch Oral Cleft Registry and a population-based birth defects registry (Eurocat) of children and foetuses born in the Northern Netherlands between 1997 and 2009. Cases were live-born infants with non-syndromic clefts (n = 367) and controls were infants or foetuses with chromosomal/syndromal (n = 924) or non-folate related anomalies (n = 2,021). We analyzed type/timing/duration of supplement use related to traditional cleft categories as well as to their timing (early/late embryonic periods) and underlying embryological processes (fusion/differentiation defects). Consistent supplement use during the aetiologically relevant period (weeks 0-12 postconception) was associated with an increased risk of clefts (adjusted odds ratio 1.72, 95% confidence interval 1.19-2.49), especially of cleft lip/alveolus (3.16, 1.69-5.91). Further analysis systematically showed twofold to threefold increased risks for late differentiation defects-mainly clefts of the lip/alveolus-with no significant associations for early/late fusion defects. Effects were attributable to folic acid and not to other multivitamin components, and inclusion of partial use (not covering the complete aetiologically relevant period) generally weakened associations. In conclusion, this study presents several lines of evidence indicating that periconceptional folic acid in the Northern Netherlands is associated with an increased risk of clefts, in particular of cleft lip/alveolus. This association is strengthened by the specificity, consistency, systematic pattern, and duration of exposure-response relationship of our findings, underlining the need to evaluate public health strategies regarding folic acid and to further investigate potential adverse effects.

Background: The effects of many drugs on the unborn child are unknown. In a case-population design, drug exposure of cases is compared with that of a source population; this kind of study can be useful for generating signals., Objective: To see whether a comparison of drug use rates from the birth defect registry EUROCAT NNL (cases) with prescription rates from a population-based prescription database, the IADB (population), could be used to detect signals of teratogenic risk of drugs., Methods: We defined 3,212 cases from the EUROCAT NNL database, a population-based birth defect registry in the Northern Netherlands and 29,223 population controls from the IADB, a prescription database with data from community pharmacies in the same geographical area, born between 1998 and 2008. We classified the malformations of the 3,212 cases into several malformation groups according to organ system (based on the International Classification of Diseases codes and the EUROCAT guidelines). If a child had multiple malformations in several organ systems (n = 253, 7.9 %), he/she was counted in all the categories represented. For several groups of malformations we calculated rate ratios (RR) and 95 % confidence intervals for drugs acting on the central nervous system and for drugs considered to be safe for use in pregnancy. The RRs were based on first-trimester drug use rates from the cases in the EUROCAT NNL database and prescription rates from the population controls in the IADB., Results: For drugs acting on the central nervous system we found significantly increased RRs for the anti-epileptic drug valproic acid and for some selective serotonin reuptake inhibitors. For drugs considered to be safe only the anti-hypertensive methyldopa showed significantly increased RRs., Conclusion: We show that a case-population study is a suitable method for detecting signals of possible teratogenicity, provided that the teratogenic effects and the drugs under study are as specific as possible and the drugs are widely used.

Background: In case-control studies that assess associations between medication use and birth defects, detailed information on type of medication and timing of use is essential to prevent misclassification. However, data on the accuracy of recall of medication use during pregnancy are scarce., Objective: The aim of this study was to validate a self-administered questionnaire to assess prescription medication use in the 3 months before and during pregnancy., Methods: This validation study was embedded in Eurocat Northern Netherlands, a population-based birth defects registry that covers 10% of all births in The Netherlands. The questionnaire was validated among 560 mothers of infants with major birth defects registered from 1 January 2009 through 30 June 2010 by comparing it with a reference standard consisting of pharmacy data which were checked for compliance by maternal interviews. Sensitivity and specificity were calculated to quantify validity for any prescription medication use, groups of medications and individual medications. In addition, we determined whether maternal characteristics influenced disagreement between the questionnaire and the reference standard using logistic regression analyses., Results: The sensitivity for any prescription medication use was 0.57, ranging between 0.07 (dermatological corticosteroids) and 0.83 (antihypertensives) for medication groups, and between 0.00 (naproxen) and 0.73 (salbutamol) for individual medications. Overall, specificity was high (0.93-1.00). Smoking during pregnancy and completing the questionnaire>2 years after delivery were associated with increased disagreement between the questionnaire for prescription medication use and the reference standard., Conclusions: The validity of the self-administered questionnaire for prescription medication use during pregnancy was moderate to poor for most medications and disagreement differed by some maternal characteristics. As many epidemiological studies use similar questionnaires to assess medication use these studies may need additional data sources such as pharmacy records or prescription databases for medication use next to self-reported methods. Also, previous knowledge on the effect of questionnaire design should be taken into account.

The Eurocat registry Northern Netherlands (NNL) has been used in regional context, as well as in national/international context, to describe the epidemiology of oral clefts (OC). However, the region NNL seems to have prevalence data different from Dutch national registries and certain other European areas. This may be due to differences in registration methods or geographical variation. To investigate whether the prevalence of OC live births varies regionally in the Netherlands, we established time trends for NNL and the rest of the Netherlands over 1997-2007 using data from two national registries (the OC Registry and The Netherlands Perinatal Registry) and a regional registry (Eurocat NNL). We found that the overall live-birth prevalence-comprising cleft lip/alveolus ± cleft palate and cleft palate only-was significantly higher in NNL (15.1-21.4 per 10,000) than in the rest of the Netherlands (13.2-16.1 per 10,000). None of the registries showed significant trends for NNL, whereas both national registries showed that the live-birth prevalence of cleft lip/alveolus ± cleft palate decreased significantly in the rest of the Netherlands. Despite some differences in prevalence between the registries, they showed similar regional variation in prevalence and trends. In conclusion, the prevalence of OC live births varies significantly in the Netherlands, not only between but also within registries. This underlines that extrapolation of regional cleft data should be done with caution. To further investigate OC etiology and evaluate preventive strategies, future studies should consider geographical differences-between and within countries-regarding the various cleft sub-phenotypes among live births, stillbirths, and pregnancy terminations., (Copyright © 2011 Wiley Periodicals, Inc.)

Background: Infertility is a growing problem in western societies. Few studies have examined the drug utilization of common treatments for infertility. Clomiphene citrate (CC) is the first-line treatment for normogonadotropic women with absent or irregular ovulation. We examined CC use among women at reproductive age in the northern Netherlands., Methods: Drug dispensing data of CC between 1998 and 2007 were retrieved from the IADB.nl database. Two-year prevalences of CC use per 1000 women covered by the database were calculated and stratified by 5-year age group. The duration of CC use was analyzed using Kaplan-Meier survival analysis., Results: From the IADB.nl database, a total of 1854 women aged 20-44 years initiated ovulation induction treatment with CC only in the northern Netherlands during 1998 and 2007. The 2-year prevalence of CC use increased from 6.66 per 1000 women during 1998-1999 to 7.24 per 1000 during 2002-2003, followed by a decrease to 4.82 per 1000 in 2006-2007 (P < 0.05). Median duration of CC use was four cycles for women <30 years of age, three cycles for women aged 30-39 and two cycles for women aged above 40., Conclusions: There is no increase of CC use during 1998-2007, and indeed a decrease of CC use during recent years, among women at reproductive age in northern Netherlands.

Background: There is a need for case-control studies of the effect of paroxetine on the occurrence of specific heart defects., Methods: We performed a case-control study with data from a population-based birth defects registry in the Netherlands. All the children born between 1997 and 2006 were selected. Cases were defined as fetuses and children with isolated heart defects, and the controls were fetuses and children with a genetic disorder with no heart defect. We excluded children for whom there was no information on maternal medication use and deceased children and fetuses who were not examined postmortem. First-trimester exposure to paroxetine was compared between cases and controls by calculating adjusted odds ratios (AOR)., Results: We included 678 cases with isolated heart defects and 615 controls. The first trimester exposure rate was 1.5% for cases and 1.0% for controls. After excluding mothers who used paroxetine outside the first trimester, or who had used another SSRI, we found no significantly increased risk for heart defects overall (10 exposed cases; AOR, 1.5; 95% confidence interval [CI], 0.5-4.0), but we did find a significantly increased risk for atrium septum defects (three exposed cases; AOR, 5.7; 95% CI, 1.4-23.7)., Conclusions: Our results suggest that the use of paroxetine in early pregnancy is associated with an increased risk of atrium septum defects. The results stress the importance of studying possible teratogenic effects of a drug, preferably in regard to well-specified malformations.

Aims: To investigate the potentially protective of periconceptional folic acid use on the risk of congenital heart defects (CHDs) relative to other non-folate related malformations., Methods and Results: We analysed data from a large regional register of birth defects (EUROCAT-Northern Netherlands), over a 10 year period (1996-2005) for a case-control study. The cases were mothers who had delivered infants with isolated or complex heart defects, without any related syndrome or genetic abnormality (n = 611). We used two control groups; one from the EUROCAT database and another from the general population. The registry controls consisted of mothers of children with a known chromosomal or genetic defect, and with infants with other non-folate related congenital malformations (n = 2401). Additional folic acid was taken as a single supplement or as a multivitamin containing folic acid in a dose of >or=400 microg daily. Mothers who had used folate antagonists or who had diabetes, and mothers of children with oral clefts, hypospadias, limb reduction- or neural tube defects, were excluded from both groups. Potentially confounding factors of periconceptional folic acid use in relation to CHD were explored, including baby's birth year, maternal body mass index, education, maternal age at delivery of index baby, smoking behaviour, and alcohol use during pregnancy. Periconceptional folic acid use revealed an odds ratio (OR) of 0.82 (95% CI 0.68-0.98) for all types of CHD relative to other malformations. The estimated relative risk for CHDs of additional folic acid use compared with the general population was comparable [OR 0.74 (95%CI 0.62-0.88)]. Subgroup analysis showed an OR of 0.62 (95% CI 0.47-0.82) for isolated septal defects. The proportions of the potential confounders between mothers of case and control infants did not differ significantly., Conclusion: Our results support the hypothesis that additional periconceptional folic acid use reduces CHD risk in infants. Use of periconceptional folic acid supplements was related to approximately 20% reduction in the prevalence of any CHD. Given the relatively high prevalence of CHD worldwide, our findings are important for public health.

Objective: To describe the prevalence of congenital anomalies in children born in Amsterdam and to analyse potential differences between groups based on risk factors such as ethnicity and maternal age., Design: Secondary analysis of a prospective cohort study., Methods: Between 2003 and 2004, mothers filled in questionnaires on their newborn children on behalf of the Amsterdam-Born Children and their Development study (ABCD study). Data from 5,276 liveborn children in this cohort were used to calculate the prevalence rates of congenital anomalies in Amsterdam. These were compared with expected prevalence rates based on Eurocat data for the Northern region of the Netherlands during the years 2000-2005. Prevalence rates were compared between subgroups which had been divided according to risk factors: maternal ethnic origin, maternal age, parity, gender of child, inter-pregnancy interval, years of maternal education, smoking, alcohol use, and periconceptional folate use., Results: The total prevalence of major congenital anomalies among liveborn children in the ABCD cohort was as expected based on the figures from the Eurocat registration. Digestive anomalies were reported significantly less frequently (n = 1) than expected (n = 10). Mothers of Surinam descent more frequently reported a child with a musculoskeletal anomaly. Older mothers were more likely to report congenital anomalies. No significant trends regarding other risk factors were observed., Conclusions: No significant trends regarding ethnicity and congenital anomalies were detected. The interpretation of the other results was hampered by methodological differences between the ABCD study and Eurocat. Nationwide registration with active case detection of congenital anomalies is therefore recommended.

What Is Already Known About This Subject: * Recently, the use of selective serotonin reuptake inhibitors (SSRIs), particularly paroxetine, in pregnancy has been associated with an increased risk on specific birth defects or other adverse pregnancy outcomes. * However, the extent of SSRI use in pregnancy is largely unknown., What This Study Adds: * In the last decade the use of SSRIs in the year preceding delivery has increased twofold. * This increase runs parallel with the increase in use of SSRIs among women of fertile age. * Paroxetine is one of the most commonly used SSRIs. * Only recently have sufficient data become available on the use of paroxetine to detect moderate increased risks for specific malformations. * The safety of SSRIs which are less frequently used is not yet established. * Case-control birth defect-monitoring systems may be helpful in providing safety and risk estimates that become more precise as data accumulate for these drugs., Aims: Recent case-control studies suggest a relationship between the use of selective serotonin reuptake inhibitors (SSRIs) and the occurrence of birth defects and other adverse pregnancy outcomes. The aim was to determine the extent of the use of SSRIs before and during pregnancy and its trend over the years 1995-2004 in the Netherlands., Methods: The study was performed with data from a population-based prescription database. Within this database, women giving birth to a child between 1995 and 2004 were identified. The exposure rate and 95% confidence interval (CI) were calculated as the number of pregnancies per 1000 that were exposed to an SSRI in a defined period (per trimester or in the year preceding delivery). Exposure rates were calculated for 2-year periods: 1995/1996, 1997/1998, 1999/2000, 2001/2002 and 2003/2004. Trends in exposure rates were analysed using the chi(2) test for trend., Results: Included were 14,902 pregnancies for which complete pharmacy records were available from 3 months before pregnancy until delivery. A total of 310 pregnancies were exposed to an SSRI in the year preceding delivery. The exposure rate increased from 12.2 (95% CI 7.0, 19.8) in 1995/1996 to 28.5 (95% CI 23.0, 34.9) in 2003/2004., Conclusion: There has been a significant increase in the use of SSRIs among pregnant women in the Netherlands over the last 10 years, parallel with the increase in exposure in women of fertile age. In light of the recent warnings about the use of SSRIs in pregnancy, healthcare professionals should be careful in prescribing SSRIs to women planning a pregnancy.

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 fetal risk., Design: A cohort study based on pharmacy records of women giving birth to a child between 1994 and 2003., Setting: The study was performed with data from the InterAction database, containing prescription-drug-dispensing data from community pharmacies., Population: The study population included 5412 women for whom complete pharmacy records were available., Methods: Drugs were classified into three categories: (1) drugs for chronic conditions, (2) drugs for occasional use and (3) drugs for pregnancy-related symptoms and also classified according to the Australian classification system., Main Outcome Measures: 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., Conclusions: 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 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.