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Aims: Information about medication safety in pregnancy is inadequate. We aimed to develop a signal detection methodology to routinely identify unusual associations between medications and congenital anomalies using data collected by 15 European congenital anomaly registries., Methods: EUROmediCAT database data for 14 950 malformed foetuses/babies with first trimester medication exposures in 1995-2011 were analyzed. The odds of a specific medication exposure (coded according to chemical substance or subgroup) for a specific anomaly were compared with the odds of that exposure for all other anomalies for 40 385 medication anomaly combinations in the data. Simes multiple testing procedure with a 50% false discovery rate (FDR) identified associations least likely to be due to chance and those associations with more than two cases with the exposure and the anomaly were selected for further investigation. The methodology was evaluated by considering the detection of well-known teratogens., Results: The most common exposures were genitourinary system medications and sex hormones (35.2%), nervous system medications (28.0%) and anti-infectives for systemic use (25.7%). Fifty-two specific medication anomaly associations were identified. After discarding 10 overlapping and three protective associations, 39 associations were selected for further investigation. These associations included 16 which concerned well established teratogens, valproic acid (2) and maternal diabetes represented by use of insulin (14)., Conclusions: Medication exposure data in the EUROmediCAT central database can be analyzed systematically to determine a manageable set of associations for validation and then testing in independent datasets. Detection of teratogens depends on frequency of exposure, level of risk and teratogenic specificity., (© 2016 The British Pharmacological Society.)

Objectives: Our main objective was to assess sociodemographic differences in the probability of prenatal diagnosis of congenital heart defects (CHD); we also looked at differences in termination of pregnancy for fetal anomaly (TOPFA)., Design: Prospective cohort observational study., Setting: Population-based cohort of CHD (live births, TOPFA, fetal deaths) born to women residing in the Greater Paris area (Paris and its surrounding suburbs, N=317,538 total births)., Participants: 2867 cases of CHD, including 2348 (82%) live births, 466 (16%) TOPFA and 53 (2%) fetal deaths., Primary and Secondary Outcome Measures: Differences in the probability of prenatal diagnosis by maternal occupation, geographic origin and place of residence; differences in the probability of TOPFA., Results: 29.1% (95% CI 27.5% to 30.8%) of all CHD were prenatally diagnosed. Probability of prenatal diagnosis was similar by maternal occupation, geographic origin and place of residence. In contrast, there were substantial differences in the probability of TOPFA by maternal geographic origin; differences by maternal occupation and place of residence were generally smaller and not statistically significant., Conclusions: Our findings suggest that an appropriate health system organisation aimed at providing universal, reimbursed specialised services to all women can provide comparable access to prenatal diagnosis for all sociodemographic groups. In contrast, we found substantial differences in TOPFA for women of different geographic origins, which may reflect women's preferences that should be respected, but that can nonetheless lead to the situation where families with fewer resources will be disproportionately responsible for care of newborns with more severe forms of CHD., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Pregnant women with asthma need to take medication during pregnancy., Objective: We sought to identify whether there is an increased risk of specific congenital anomalies after exposure to antiasthma medication in the first trimester of pregnancy., Methods: We performed a population-based case-malformed control study testing signals identified in a literature review. Odds ratios (ORs) of exposure to the main groups of asthma medication were calculated for each of the 10 signal anomalies compared with registrations with nonchromosomal, nonsignal anomalies as control registrations. In addition, exploratory analyses were done for each nonsignal anomaly. The data set included 76,249 registrations of congenital anomalies from 13 EUROmediCAT registries., Results: Cleft palate (OR, 1.63; 95% CI, 1.05-2.52) and gastroschisis (OR, 1.89; 95% CI, 1.12-3.20) had significantly increased odds of exposure to first-trimester use of inhaled β2-agonists compared with nonchromosomal control registrations. Odds of exposure to salbutamol were similar. Nonsignificant ORs of exposure to inhaled β2-agonists were found for spina bifida, cleft lip, anal atresia, severe congenital heart defects in general, or tetralogy of Fallot. None of the 4 literature signals of exposure to inhaled steroids were confirmed (cleft palate, cleft lip, anal atresia, and hypospadias). Exploratory analyses found an association between renal dysplasia and exposure to the combination of long-acting β2-agonists and inhaled corticosteroids (OR, 3.95; 95% CI, 1.99-7.85)., Conclusions: The study confirmed increased odds of first-trimester exposure to inhaled β2-agonists for cleft palate and gastroschisis and found a potential new signal for renal dysplasia associated with combined long-acting β2-agonists and inhaled corticosteroids. Use of inhaled corticosteroids during the first trimester of pregnancy seems to be safe in relation to the risk for a range of specific major congenital anomalies., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Antiretroviral (ARV) regimens during pregnancy are highly effective in preventing mother-to-child transmission of human immunodeficiency virus (HIV). Congenital heart defects (CHDs) and anomalies in cardiac function have been reported in zidovudine (ZDV)-exposed uninfected children. We explored these associations in a large observational cohort and a randomized clinical trial., Methods: Since 1986, the French Perinatal Cohort prospectively enrolled all HIV-infected women in 90 centers and collected follow-up on their children through 2 years of age. All CHDs were reviewed by a specialist blinded to exposures. Additionally, in a randomized trial (PRIMEVA ANRS 135) of 2 ARV regimens during pregnancy, 1 of which was without nucleoside reverse transcriptase inhibitors, infants had a specific follow-up including echocardiography at 1 month and 12 months., Results: Among 12 888 children included, ZDV exposure in the first trimester was significantly associated with CHD (1.5% vs 0.7%; adjusted odds ratio, 2.2 [95% confidence interval, 1.3-3.7]; P < .001). This association was significant for ventricular septal defects (1.1% vs 0.6%; P = .001) and other CHDs (0.31% vs 0.11%; P = .02). In the randomized trial, among 50 infants, girls (but not boys) exposed in utero to ZDV/lamivudine/ritonavir-boosted lopinavir (LPV/r) had a higher left ventricular shortening fraction at 1 month (40% vs 36%; P = .008), and an increased posterior wall thickness at 1 year (5.4 mm vs 4.4 mm; P = .01) than the LPV/r group., Conclusions: This study confirms a specific association between in utero exposure to ZDV and CHDs, and a long-lasting postnatal myocardial remodeling in girls. A potential common mechanism, including the involvement of mitochondrial dysfunction, must be explored, and long-term consequences on cardiac function warrant specific attention., Clinical Trials Registration: NCT00424814., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Objective: To compare the probability of prenatal diagnosis (PND) and termination of pregnancy for fetal anomaly (TOPFA) between fetuses conceived by assisted reproductive techniques (ART) and spontaneously-conceived fetuses with congenital heart defects (CHD)., Design: Population-based observational study., Setting: Paris and surrounding suburbs., Population: Fetuses with CHD in the Paris registry of congenital malformations and cohort of children with CHD (Epicard)., Methods: Comparison of ART-conceived and spontaneously conceived fetuses taking into account potential confounders (maternal characteristics, multiplicity and year of birth or TOPFA)., Main Outcome Measures: Probability and gestational age at PND and TOPFA for ART-conceived versus spontaneously conceived fetuses., Results: The probability of PND (28.1% versus 34.6%, P = 0.077) and TOPFA (36.2% versus 39.2%, P = 0.677) were not statistically different between ART-conceived (n = 171) and spontaneously conceived (n = 4620) fetuses. Estimates were similar after adjustment for potential confounders. Gestational age at PND tended to be earlier for ART fetuses (23.1 versus 24.8 weeks, P = 0.05) but no statistical difference was found after adjustment for confounders. Gestational age at TOPFA was comparable between ART-conceived and spontaneously conceived fetuses., Conclusions: In our population, ART conception was not significantly associated with the probability of PND or TOPFA for CHD. One implication of our results is that live births may be adequate for assessing the overall risk of CHD related to ART. However, total prevalence, in particular of severe CHD, would not be adequately assessed if TOPFA are not included., (© 2015 Royal College of Obstetricians and Gynaecologists.)

Objectives: The aim of this study is to describe the prenatal diagnosis and epidemiology of multicystic kidney dysplasia (MCKD)., Methods: The study is based on routinely collected data from a European database of major congenital anomalies including 13 registries with cases born in 1997-2006 and covering 1 458 552 births., Results: There were 601 MCKD cases giving an overall prevalence of 4.12 per 10 000 births with regional variation. In live births, 87% of cases had an isolated renal anomaly and 13% had associated major nonrenal anomalies (chromosomal, syndrome or other major anomalies). For the cases with isolated renal anomalies, 51/386 (11%) and 7/386 (2%) choose to terminate the pregnancy or resulted in an intrauterine fetal death, respectively. The prenatal detection rate was 88% in both unilateral and bilateral cases. Birth outcome differed with 92% of unilateral MCKD cases being liveborn compared with 33% of bilateral MCKD cases. For unilateral MCKD cases, 84% had an isolated renal anomaly compared with 51% of bilateral MCKD cases (p < 0.001)., Conclusions: Cases with unilateral MCKD are mainly liveborn, and only 16% have associated major malformations or a syndrome. Cases with bilateral MCKD are often associated with nonrenal major congenital anomalies or part of a syndrome, and only one third of bilateral MCKD cases in this study were liveborn. Prenatal detection rate of MCKD was high for both unilateral and bilateral cases. © 2014 John Wiley & Sons, Ltd., (© 2014 John Wiley & Sons, Ltd.)

Objective: To determine risk of Down syndrome (DS) in multiple relative to singleton pregnancies, and compare prenatal diagnosis rates and pregnancy outcome., Design: Population-based prevalence study based on EUROCAT congenital anomaly registries., Setting: Eight European countries., Population: 14.8 million births 1990-2009; 2.89% multiple births., Methods: DS cases included livebirths, fetal deaths from 20 weeks, and terminations of pregnancy for fetal anomaly (TOPFA). Zygosity is inferred from like/unlike sex for birth denominators, and from concordance for DS cases., Main Outcome Measures: Relative risk (RR) of DS per fetus/baby from multiple versus singleton pregnancies and per pregnancy in monozygotic/dizygotic versus singleton pregnancies. Proportion of prenatally diagnosed and pregnancy outcome., Statistical Analysis: Poisson and logistic regression stratified for maternal age, country and time., Results: Overall, the adjusted (adj) RR of DS for fetus/babies from multiple versus singleton pregnancies was 0.58 (95% CI 0.53-0.62), similar for all maternal ages except for mothers over 44, for whom it was considerably lower. In 8.7% of twin pairs affected by DS, both co-twins were diagnosed with the condition. The adjRR of DS for monozygotic versus singleton pregnancies was 0.34 (95% CI 0.25-0.44) and for dizygotic versus singleton pregnancies 1.34 (95% CI 1.23-1.46). DS fetuses from multiple births were less likely to be prenatally diagnosed than singletons (adjOR 0.62 [95% CI 0.50-0.78]) and following diagnosis less likely to be TOPFA (adjOR 0.40 [95% CI 0.27-0.59])., Conclusions: The risk of DS per fetus/baby is lower in multiple than singleton pregnancies. These estimates can be used for genetic counselling and prenatal screening., (© 2014 The Authors. BJOG An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists.)

Background: Antiretroviral therapy (ART) has major benefits during pregnancy, both for maternal health and to prevent mother-to-child transmission of HIV. Safety issues, including teratogenic risk, need to be evaluated. We estimated the prevalence of birth defects in children born to HIV-infected women receiving ART during pregnancy, and assessed the independent association of birth defects with each antiretroviral (ARV) drug used., Methods and Findings: The French Perinatal Cohort prospectively enrolls HIV-infected women delivering in 90 centers throughout France. Children are followed by pediatricians until 2 y of age according to national guidelines. We included 13,124 live births between 1994 and 2010, among which, 42% (n = 5,388) were exposed to ART in the first trimester of pregnancy. Birth defects were studied using both European Surveillance of Congenital Anomalies (EUROCAT) and Metropolitan Atlanta Congenital Defects Program (MACDP) classifications; associations with ART were evaluated using univariate and multivariate logistic regressions. Correction for multiple comparisons was not performed because the analyses were based on hypotheses emanating from previous findings in the literature and the robustness of the findings of the current study. The prevalence of birth defects was 4.4% (95% CI 4.0%-4.7%), according to the EUROCAT classification. In multivariate analysis adjusting for other ARV drugs, maternal age, geographical origin, intravenous drug use, and type of maternity center, a significant association was found between exposure to zidovudine in the first trimester and congenital heart defects: 2.3% (74/3,267), adjusted odds ratio (AOR) = 2.2 (95% CI 1.3-3.7), p = 0.003, absolute risk difference attributed to zidovudine +1.2% (95% CI +0.5; +1.9%). Didanosine and indinavir were associated with head and neck defects, respectively: 0.5%, AOR = 3.4 (95% CI 1.1-10.4), p = 0.04; 0.9%, AOR = 3.8 (95% CI 1.1-13.8), p = 0.04. We found a significant association between efavirenz and neurological defects (n = 4) using the MACDP classification: AOR = 3.0 (95% CI 1.1-8.5), p = 0.04, absolute risk +0.7% (95% CI +0.07%; +1.3%). But the association was not significant using the less inclusive EUROCAT classification: AOR = 2.1 (95% CI 0.7-5.9), p = 0.16. No association was found between birth defects and lopinavir or ritonavir with a power >85% for an odds ratio of 1.5, nor for nevirapine, tenofovir, stavudine, or abacavir with a power >70%. Limitations of the present study were the absence of data on termination of pregnancy, stillbirths, tobacco and alcohol intake, and concomitant medication., Conclusions: We found a specific association between in utero exposure to zidovudine and heart defects; the mechanisms need to be elucidated. The association between efavirenz and neurological defects must be interpreted with caution. For the other drugs not associated with birth defects, the results were reassuring. Finally, whatever the impact that some ARV drugs may have on birth defects, it is surpassed by the major role of ART in the successful prevention of mother-to-child transmission of HIV. Please see later in the article for the Editors' Summary.

Background: The Mastersizer X (Malvern Instruments) used to be the reference device for assessing droplet size distribution of aerosols by laser diffraction, but it has not been updated and has gradually been replaced by the Spraytec (Malvern Instruments), which is considered to provide greater accuracy and higher acquisition speed., Methods: The aim of this study was to compare the use of the two diffractometers to characterize medical liquid aerosols in a wide range of droplet sizes, using four nasal sprays to produce large droplets (10-180 μm) and 10 nebulizers to produce smaller droplets (0.5-20 μm). The influence of the inhalation cell provided with the Spraytec on the measurements was also determined., Results: Correlation between the devices was low for large droplets (R(2)=0.37) and high for smaller droplets (R(2)=0.97). The Spraytec overestimated the median diameter of small droplets by 14%, and Bland-Altman tests showed no equivalence (limits of agreement over 20%). An artifact peak in the large size range was observed with the Spraytec, which could be due to difficulty for the multiple scattering algorithm to process high-density aerosol clouds. The difference was reduced to 5% by using the inhalation cell provided by the Spraytec with a 15 L/min aspiration., Conclusion: The Mastersizer X and the Spraytec cannot be considered as equivalent laser diffraction devices, but the difference can be reduced with the Spraytec inhalation cell.

Background: Assisted reproductive techniques (ART) are associated with a higher risk of tetralogy of Fallot (TOF) and multiple pregnancies may be associated with a higher risk of congenital anomalies. We assessed the extent to which the association between ART and risk of TOF may be mediated by the higher risk of multiple pregnancies associated with ART., Methods: We conducted a case-control study using population-based data from the Paris Registry of Congenital Malformations for the period 1987-2009 and a cohort study of congenital heart defects (EPICARD). The study population included 395 cases of TOF and 4104 malformed controls with no known associations with ART. The analysis was based on a path-analysis model using a counterfactual approach, which allows decomposition of the total effect of ART into an indirect effect (that mediated by the association between ART and multiple pregnancies) and a direct effect., Results: ART (all methods combined) were associated with a 2.6-fold higher odds of TOF after adjustment for maternal and paternal characteristics and year of birth (adjusted OR 2.6, 95% CI, 1.5-4.5). Most (79%) of the effect associated with ART was a direct effect (i.e., not mediated by multiple pregnancies), whereas 21% of the effect of ART was due to its association with multiple pregnancies (i.e., the indirect effect). In vitro fertilization with intracytoplasmic sperm injection was associated with a 3.5-fold higher odds of TOF (adjusted OR 3.5, 95% CI, 1.1-11.2); 11% of this effect was mediated through the association of ICSI with multiple pregnancies., Conclusions: By far, most of the higher risk of TOF associated with ART is a direct effect and only a small proportion of the effect may be mediated by multiple pregnancies.

Objectives: To estimate the national prevalence and analyse the factors associated with preconceptional folic acid supplementation, including maternal sociodemographic characteristics, region of residence, birth control use and chronic diseases requiring medical care before conception., Design: Cross-sectional population-based study., Setting: All maternity units in France., Population: A nationally representative sample of women giving birth in 2010 (n = 12,646)., Methods: Data came from mothers' interviews 2-3 days after delivery. Statistical analyses included multivariable logistic regressions., Main Outcome Measure: Folic acid supplementation starting at least 1 month before conception., Results: 14.8% (95% confidence interval [95% CI] 14.2-15.4) of women used folic acid before pregnancy; this percentage varied from 10.4% to 18.7% across regions. Supplementation was more frequent in primiparae, French citizens, women with higher educational levels and those needing medical monitoring or treatment before conception. Women who stopped contraception to become pregnant (75% of our population) used folic acid more often (intrauterine device or implant: 19%, pill: 17%, other methods which did not need medical monitoring: 17%) than other women (7%). The adjusted odds ratios were 3.3 (95% CI 2.6-4.3) for intrauterine device and implant, 2.2 (95% CI 1.8-2.6) for pill and 1.9 (95% CI 1.5-2.4) for other methods, compared with women who did not use birth control., Conclusion: The absence of preconceptional folic acid supplementation for most women, even those needing consultations with healthcare professionals before pregnancy, shows that campaigns to promote folic acid supplementation should address not only women but also healthcare professionals involved in birth control and obstetric care before pregnancy., (© 2013 Royal College of Obstetricians and Gynaecologists.)

The development of jet nebulizers for medical purposes is an important challenge of aerosol therapy. The performance of a nebulizer is characterized by its output rate of droplets with a diameter under 5 µm. However the optimization of this parameter through experiments has reached a plateau. The purpose of this study is to design a numerical model simulating the nebulization process and to compare it with experimental data. Such a model could provide a better understanding of the atomization process and the parameters influencing the nebulizer output. A model based on the Updraft nebulizer (Hudson) was designed with ANSYS Workbench. Boundary conditions were set with experimental data then transient 3D calculations were run on a 4 µm mesh with ANSYS Fluent. Two air flow rate (2 L/min and 8 L/min, limits of the operating range) were considered to account for different turbulence regimes. Numerical and experimental results were compared according to phenomenology and droplet size. The behavior of the liquid was compared to images acquired through shadowgraphy with a CCD Camera. Three experimental methods, laser diffractometry, phase Doppler anemometry (PDA) and shadowgraphy were used to characterize the droplet size distributions. Camera images showed similar patterns as numerical results. Droplet sizes obtained numerically are overestimated in relation to PDA and diffractometry, which only consider spherical droplets. However, at both flow rates, size distributions extracted from numerical image processing were similar to distributions obtained from shadowgraphy image processing. The simulation then provides a good understanding and prediction of the phenomena involved in the fragmentation of droplets over 10 µm. The laws of dynamics apply to droplets down to 1 µm, so we can assume the continuity of the distribution and extrapolate the results for droplets between 1 and 10 µm. So, this model could help predicting nebulizer output with defined geometrical and physical parameters.

Objective: To evaluate the contribution of examination of specific anatomical features of the fetal posterior brain on mid-sagittal first-trimester ultrasound examination to the early detection of open spina bifida., Methods: Four independent observers reviewed a series of 260 mid-sagittal first-trimester ultrasound images from 52 cases of open spina bifida and 208 normal fetuses. The following analysis was performed by each reviewer for each image: Herman score calculation, intracranial translucency score (CFEF-IT) calculation and determination of presence or absence of three anatomical criteria: intracranial translucency (IT), caudal displacement of the brainstem and cisterna magna. The sensitivity and the false-positive rate for spina bifida detection were calculated for each of the latter three criteria. A secondary analysis was performed on the subset of images achieving a Herman score ≥ 7., Results: The highest detection rate for spina bifida was achieved by non-visualization of the cisterna magna, with associated sensitivity of 50-73% and 39-76%, respectively, for all images and for the subset of images achieving a Herman score ≥ 7. Posterior shift of the brainstem achieved the highest detection rate (86%), but for a single reviewer only. The level of variation in performance between observers was also greatest for this sign. Absence of IT was associated with a lower detection rate for all observers. Overall, an abnormal posterior brain presenting at least one of these three criteria was associated with a detection rate ranging from 50 to 90%., Conclusion: In the detection of spina bifida, non-visualization of the cisterna magna achieved the best screening performance. Both non-visualization of the IT and posterior shift of the brainstem were associated with acceptable but lower detection rates. A prospective evaluation of changes in the posterior brain is needed to allow assessment of the most pertinent criteria for first-trimester screening for spina bifida., (Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To identify pregnancy-related risk factors for different manifestations of congenital anorectal malformations (ARMs)., Design: A population-based case-control study., Setting: Seventeen EUROCAT (European Surveillance of Congenital Anomalies) registries, 1980-2008., Population: The study population consisted of 1417 cases with ARM, including 648 cases of isolated ARM, 601 cases of ARM with additional congenital anomalies, and 168 cases of ARM-VACTERL (vertebral, anal, cardiac, tracheo-esophageal, renal, and limb defects), along with 13 371 controls with recognised syndromes or chromosomal abnormalities., Methods: Multiple logistic regression analyses were used to calculate adjusted odds ratios (ORs) for potential risk factors for ARM, such as fertility treatment, multiple pregnancy, primiparity, maternal illnesses during pregnancy, and pregnancy-related complications., Main Outcome Measures: Adjusted ORs for pregnancy-related risk factors for ARM., Results: The ARM cases were more likely to be firstborn than the controls (OR 1.6, 95% CI 1.4-1.8). Fertility treatment and being one of twins or triplets seemed to increase the risk of ARM in cases with additional congenital anomalies or VACTERL (ORs ranging from 1.6 to 2.5). Maternal fever during pregnancy and pre-eclampsia were only associated with ARM when additional congenital anomalies were present (OR 3.9, 95% CI 1.3-11.6; OR 3.4, 95% CI 1.6-7.1, respectively), whereas maternal epilepsy during pregnancy resulted in a five-fold elevated risk of all manifestations of ARM (OR 5.1, 95% CI 1.7-15.6)., Conclusions: This large European study identified maternal epilepsy, fertility treatment, multiple pregnancy, primiparity, pre-eclampsia, and maternal fever during pregnancy as potential risk factors primarily for complex manifestations of ARM with additional congenital anomalies and VACTERL., (© 2013 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2013 RCOG.)

Objective: To assess the public health consequences of the rise in multiple births with respect to congenital anomalies., Design: Descriptive epidemiological analysis of data from population-based congenital anomaly registries., Setting: Fourteen European countries., Population: A total of 5.4 million births 1984-2007, of which 3% were multiple births., Methods: Cases of congenital anomaly included live births, fetal deaths from 20 weeks of gestation and terminations of pregnancy for fetal anomaly., Main Outcome Measures: Prevalence rates per 10,000 births and relative risk of congenital anomaly in multiple versus singleton births (1984-2007); proportion prenatally diagnosed, proportion by pregnancy outcome (2000-07). Proportion of pairs where both co-twins were cases., Results: Prevalence of congenital anomalies from multiple births increased from 5.9 (1984-87) to 10.7 per 10,000 births (2004-07). Relative risk of nonchromosomal anomaly in multiple births was 1.35 (95% CI 1.31-1.39), increasing over time, and of chromosomal anomalies was 0.72 (95% CI 0.65-0.80), decreasing over time. In 11.4% of affected twin pairs both babies had congenital anomalies (2000-07). The prenatal diagnosis rate was similar for multiple and singleton pregnancies. Cases from multiple pregnancies were less likely to be terminations of pregnancy for fetal anomaly, odds ratio 0.41 (95% CI 0.35-0.48) and more likely to be stillbirths and neonatal deaths., Conclusions: The increase in babies who are both from a multiple pregnancy and affected by a congenital anomaly has implications for prenatal and postnatal service provision. The contribution of assisted reproductive technologies to the increase in risk needs further research. The deficit of chromosomal anomalies among multiple births has relevance for prenatal risk counselling., (© 2013 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2013 RCOG.)

This article examines the role of public health registries, based on the example of congenital abnormalities. In addition to their main role in epidemiological surveillance, registries can be useful for conducting research and for evaluating public health interventions such as primary prevention and prenatal diagnosis. Congenital abnormalities are relatively frequent, affecting about 3% of births, but many are due to rare diseases. Known teratogens increase the risk of one or afew specific, often rare anomalies. Consequently, continuous monitoring of large, geographically defined populations is needed, particularly to establish the "baseline "prevalence of birth defects. Networks of registries can make an important contribution to this goal, as exemplified by the EUROCAT network, which plays a key role in coordinating surveillance and research on birth defects in Europe.

Study Question: Are the risks of hypoplastic left heart syndrome, transposition of great arteries, tetralogy of Fallot (TOF) and coarctation of the aorta increased in infants conceived by different assisted reproductive techniques (ARTs)?, Study Answer: ARTs, and particularly intracytoplasmic sperm injection (ICSI), are specifically associated with a higher risk of TOF., What Is Already Known: ARTs are associated with an increase in the overall risk of birth defects. The risk for congenital heart defects (CHDs) associated with ARTs has been evaluated as a whole but there is limited information on the risks for specific CHDs. STUDY DESIGN, MATERIAL AND METHODS: We conducted a case-control study using population-based data from the Paris registry of congenital malformations for the period 1987-2009 and a cohort study of CHD (EPICARD) on 1583 cases of CHDs and 4104 malformed controls with no known associations with ARTs. ARTs included ovulation induction only, IVF and ICSI., Results: Exposure to ARTs was significantly higher for TOF than controls (6.6 versus 3.5%, P = 0.002); this was not the case for the other three CHDs. ARTs (all methods combined) were associated with a 2.4-fold higher odds of TOF after adjustment for maternal characteristics, paternal age and year of birth [adjusted odds ratios (OR): 2.4, 95% confidence interval (CI): 1.5-3.7] with the highest risk associated with ICSI (adjusted OR: 3.0, 95% CI: 1.0-8.9). No statistically significant associations were found for the other CHDs., Limitations: Our study cannot disentangle to what extent the observed associations between the risk of TOF and ARTs are due to causal effects of ARTs and/or the underlying infertility problems of couples who conceive following ART., Implications: The developmental basis of the specific association between the risk of TOF and ARTs need to be further investigated.

Objectives: This study aims to (1) evaluate the probability and timing of termination of pregnancy for fetal anomaly (TOPFA) for all congenital heart defects (CHD) and categories of CHD and (2) assess clinical and socioeconomic predictors of TOPFA for isolated CHD excluding ventricular septal defects (VSD)., Methods: Using population-based data from the Paris Registry of Congenital Malformations, we assessed the probability of TOPFA and gestational age at TOPFA. We used logistic regression to estimate the adjusted effects of maternal characteristics, clinical factors (CHD type, fetal growth restriction, nuchal translucency measurement and gestational age at prenatal diagnosis) on the odds of TOPFA., Results: The proportion of TOPFA for prenatally diagnosed CHD was 46% for all CHD combined, 82% for CHD associated with chromosomal anomalies and 27% for isolated CHD-VSD excluded. Isolated CHD-VSD excluded diagnosed before 22 weeks of gestational age had a 3.2-fold higher odds of TOPFA (adjusted OR 3.2, 95%CI 1.4-7.1). Maternal occupation was not associated with the odds of TOPFA. Women of African origin had a tenfold lower odds of TOPFA than women of French origin (adjusted OR 0.1, 95%CI 0.02-0.4)., Conclusion: In addition to severity of CHD, early prenatal diagnosis and maternal characteristics were highly associated with the probability of TOPFA for CHD., (© 2013 John Wiley & Sons, Ltd.)

Objective: To assess the prevalence, timing of diagnosis and infant mortality of congenital heart defects (CHD) with population-based data and using a classification that allows regrouping of the International Paediatric and Congenital Cardiac Code into a manageable number of categories based on anatomic and clinical criteria (ACC-CHD)., Design: Population-based cohort study., Setting: Greater Paris., Patients: All cases (live births, terminations of pregnancy for foetal anomaly (TOPFA), foetal deaths) diagnosed prenatally, or up to 1 year of age in the birth cohorts, May 2005-April 2008, for women in Greater Paris (n=317 538 births). Diagnoses were confirmed in specialised centres and subsequently coded and classified into the categories of ACC-CHD by paediatric cardiologists in the study group., Results: The total number of CHD was 2867, including 2348 live births (82%), 466 TOPFA (16.2%) and 53 foetal deaths (1.8%). The total prevalence of CHD was 90 per 10 000. After exclusion of ventricular septal defects (VSD), 40% of 'isolated' CHD was diagnosed prenatally with about one half of the remaining diagnosed before 7 days of age. Nevertheless, one in five cases of these major CHD was diagnosed after the fourth week. Infant mortality of 'isolated' CHD-VSD excluded was 8.5% with 40% of deaths occurring after the fourth week of life. These outcomes varied substantially across categories of ACC-CHD., Conclusions: Timing of diagnosis, TOPFA, risk and timing of infant mortality were highly variable across the categories of CHD in ACC-CHD, suggesting that it may be a useful measure of severity, and hence, predictor of outcomes of CHD.

Background: The prevalence of esophageal atresia (EA) has been shown to vary across different geographical settings. Investigation of geographical differences may provide an insight into the underlying etiology of EA., Methods: The study population comprised infants diagnosed with EA during 1998 to 2007 from 18 of the 46 birth defects surveillance programs, members of the International Clearinghouse for Birth Defects Surveillance and Research. Total prevalence per 10,000 births for EA was defined as the total number of cases in live births, stillbirths, and elective termination of pregnancy for fetal anomaly (ETOPFA) divided by the total number of all births in the population., Results: Among the participating programs, a total of 2943 cases of EA were diagnosed with an average prevalence of 2.44 (95% confidence interval [CI], 2.35-2.53) per 10,000 births, ranging between 1.77 and 3.68 per 10,000 births. Of all infants diagnosed with EA, 2761 (93.8%) were live births, 82 (2.8%) stillbirths, 89 (3.0%) ETOPFA, and 11 (0.4%) had unknown outcomes. The majority of cases (2020, 68.6%), had a reported EA with fistula, 749 (25.5%) were without fistula, and 174 (5.9%) were registered with an unspecified code., Conclusions: On average, EA affected 1 in 4099 births (95% CI, 1 in 3954-4251 births) with prevalence varying across different geographical settings, but relatively consistent over time and comparable between surveillance programs. Findings suggest that differences in the prevalence observed among programs are likely to be attributable to variability in population ethnic compositions or issues in reporting or registration procedures of EA, rather than a real risk occurrence difference. Birth Defects Research (Part A), 2012., (Copyright © 2012 Wiley Periodicals, Inc.)

Objectives: To assess overall and malformation-specific trends in the prevalence and prenatal diagnosis of congenital anomalies in the Parisian population., Methods: The Paris Registry of Congenital Malformations is population-based and since 1981 has registered all cases with structural birth defects or chromosomal anomalies in the Parisian population. The total and livebirth prevalence and the proportion of cases with prenatal diagnosis were calculated for all anomalies and 20 malformations selected based on their higher frequency and their impact on health outcomes., Results: The overall prevalence was 3.30% (95% CI 3.27-3.33), and the livebirth prevalence 2.42% (95% CI 2.39-2.45). The proportion of cases diagnosed prenatally increased from 16.5% (95% CI 14.1-19.1) in 1983 to 70.7% (95% CI 68.3-73.1) in 2007. Terminations of pregnancy for fetal anomaly (TOPFA) increased from 8.8% (95% CI 7.0-10.8) in 1983 to 35.6% (95% CI 33.1-38.1) in 2007. These results varied substantially for the 20 congenital anomalies studied., Conclusion: We found an increase in the overall prevalence of all anomalies, especially for chromosomal abnormalities. The observed increase is at least to a large extent due to trends in delayed childbearing and an increase in both pre- and postnatal diagnosis of congenital anomalies in our population., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Background and Objectives: Preterm birth (PTB) and congenital heart defect (CHD) are 2 major causes of mortality and disability of perinatal origin. There are limited data on the relation between CHD and PTB. Our objective was to use population-based data to estimate the risk of PTB in newborns with CHD and to study specific associations between categories of CHD and PTB., Methods: We used data from a population-based cohort study of CHD (EPIdémiologique sur le devenir des enfants porteurs de CARDiopathies congénitales study), including 2189 live births with CHD (excluding isolated atrial septal defects) born between 2005 and 2008. We categorized CHD by using an anatomic and clinical classification. Data from the French National Perinatal Survey of 2003 were used to compare PTB in the EPIdémiologique sur le devenir des enfants porteurs de CARDiopathies congénitales study to that of the general population., Results: Of the newborns with CHD, 13.5% were preterm. The odds of PTB were twofold higher than for the general population (odds ratio 2.0, 95% confidence interval 1.6-2.5), essentially due to an increase in spontaneous PTB for newborns with CHD. The risk of PTB associated with CHD persisted after exclusion of chromosomal or other anomalies. There were significant variations in risk of PTB across the categories of CHD after adjustment for known risk factors of PTB and factors related to medical management of pregnancy and delivery., Conclusions: We found a higher risk of PTB in newborns with CHD, which was essentially due to spontaneous PTB. Risk of PTB varied for categories of CHD. Our finding may be helpful for generating hypotheses about the developmental links between CHD and PTB.

Background: In many countries the closure of small maternity units has raised concerns about how the concentration of low-risk pregnancies in large specialized units might affect the management of childbirth. We aimed to assess the role of maternity unit characteristics on obstetric intervention rates among low-risk women in France., Methods: Data on low-risk deliveries came from the 2010 French National Perinatal Survey of a representative sample of births (n = 9,530). The maternity unit characteristics studied were size, level of care, and private or public status; the interventions included induction of labor; cesarean section; operative vaginal delivery (forceps, spatulas or vacuum); and episiotomy. Multilevel logistic regression analyses were adjusted for maternal confounding factors, gestational age, and infant birthweight., Results: The rates of induction, cesarean section, operative delivery, and episiotomy in this low-risk population were 23.9 percent, 10.1 percent, 15.2 percent, and 19.6 percent, respectively, and 52.0 percent of deliveries included at least one of them. Unit size was unrelated to any intervention except operative delivery (adjusted odds ratio [aOR] = 1.47 (95% CI, 1.10-1.96) for units with >3,000 deliveries per year vs units with <1,000). The rate of every intervention was higher in private units, and the aOR for any intervention was 1.82 (95% CI, 1.59-2.08). After adjustment for maternal characteristics and facility size and status, significant variations in the use of interventions remained between units, especially for episiotomies. Results for level of care were similar to those for unit size., Conclusions: The concentration of births in large maternity units in France is not associated with higher rates of interventions for low-risk births. The situation in private units could be explained by differences in the organization of care. Additional research should explore the differences in practices between maternity units with similar characteristics., (© 2012, Copyright the Authors Journal compilation © 2012, Wiley Periodicals, Inc.)

Objective: To study trends in the main indicators of health, medical practices and risk factors in France., Population and Method: We collected data from samples of all births in France during one week in 1995 (n=13318), 1998 (n=13718), 2003 (n=14737) and 2010 (n=14903) and have compared them., Results: Between 1995 and 2010, maternal age and body mass index increased steadily, but tobacco use decreased. In 2010, 39.4% of pregnant women had a visit with a midwife in a maternity unit, versus 26.6% in 2003. Deliveries occurred in large public hospitals more and more frequently. The increase in caesarean sections was no longer significant between 2003 and 2010. In general, medical decisions during pregnancy and delivery were closer to professional recommendations in 2010 than in earlier years. Live births before 37 weeks increased steadily from 5.4% in 1995 to 6.6% in 2010, but the proportion of birth weights below 2500g or the 10th percentile stopped increasing after 2003., Conclusion: Routine national perinatal surveys highlight major trends in maternal characteristics, obstetric practices, organisation of services, and perinatal health., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Objective: To study trends in the main indicators of health, medical practice and risk factors in France., Population and Method: A sample of all births during one week was set-up in 1995 (n=13,318), 1998 (n=13,718), 2003 (n=14,737) and 2010 (n=14,903), and we compared data from these four years., Results: Between 1995 and 2010, maternal age and body mass index increased steadily, but tobacco smoking decreased. In 2010, 39.4% of pregnant women had a visit with a midwife in maternity unit, versus 26.6% in 2003. Deliveries occurred in large public hospitals more and more frequently. The increase in caesarean sections was no longer significant between 2003 and 2010. In general medical decisions during pregnancy and delivery were closer to professional recommendations in 2010 than in the previous years. Live births before 37 weeks increased steadily from 5.4% in 1995 to 6.6% in 2010, but the proportion of births below 2500g or under the 10th percentile stopped increasing since 2003., Conclusion: Routine national perinatal surveys highlight major trends in maternal characteristics, obstetric practice, organisation of services and perinatal health., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Introduction: Little is known on the prevalence of tooth decay among pregnant women. Better knowledge of tooth decay risk indicators during pregnancy could help to develop follow-up protocols for women at risk, along with better prevention strategies. The aim of this study was to assess the frequency of tooth decay and the number of decayed teeth per woman in a large sample of pregnant women in France, and to study associated risk indicators., Methods: A secondary cross-sectional analysis of data from a French multicentre case-control study was performed. The sample was composed of 1094 at-term women of six maternity units. A dental examination was carried out within 2 to 4 days post-partum. Socio-demographic and behavioural characteristics were obtained through a standardised interview with the women. Medical characteristics were obtained from the women's medical records. Risk indicators associated with tooth decay were identified using a negative binomial hurdle model., Results: 51.6% of the women had tooth decay. The mean number of decayed teeth among women having at least one was 3.1 (s.d. = 2.8). Having tooth decay was statistically associated with lower age (aOR = 1.58, 95%CI [1.03,2.45]), lower educational level (aOR = 1.53, 95%CI [1.06,2.23]) and dental plaque (aOR = 1.75, 95%CI [1.27,2.41]). The number of decayed teeth was associated with the same risk indicators and with non-French nationality and inadequate prenatal care., Discussion: The frequency of tooth decay and the number of decayed teeth among pregnant women were high. Oral health promotion programmes must continue to inform women and care providers about the importance of dental care before, during and after pregnancy. Future research should also assess the effectiveness of public policies related to oral health in target populations of pregnant women facing challenging social or economic situations.

Objective: In small-for-gestational-age neonates, parental and fetal characteristics can be used to distinguish between constitutionally small size and growth restriction, which is associated with a higher risk of morbidity and mortality. The aim of this study was to quantify relationships of parental and fetal characteristics with fetal ultrasound measurements., Methods: The EDEN mother-child cohort included 2002 pregnant women with singleton pregnancies attending one of two university hospitals. Data from two routine ultrasound examinations for fetal biometry were recorded, at 20-25 and 30-35 weeks of gestation. Biparietal diameter (BPD), head circumference (HC), femur length (FL), abdominal circumference (AC) and estimated fetal weight (EFW) were studied as a function of prepregnancy maternal body mass index (BMI), maternal height, paternal height, fetal sex and gestational age., Results: Data were obtained at the first scan from 1833 women and at the second scan from 1752 women. Parental anthropometric characteristics were significantly associated with ultrasound measurements at both scans. Maternal BMI was more strongly associated with AC and EFW, whereas both maternal and paternal height were more strongly associated with FL. An association was also found between fetal sex and all ultrasound measurements other than FL., Conclusion: Maternal and paternal anthropometric characteristics are significantly associated with ultrasound measurements in mid to late pregnancy. These relationships provide support for the use of these characteristics in ultrasound fetal size reference charts., (Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.)

Objectives: (1) Assess sensitivity of the measurement of nuchal translucency (NT), for the prenatal screening of congenital heart defect (CHD) on population-based data; (2) examine whether the sensitivity of NT varies for specific types of cardiac defects., Methods: Using population-based data of the Paris Registry of Congenital Malformation for 935 fetuses with CHD and without chromosomal anomalies for the period 2001 to 2007, we calculated sensitivity of NT, its positive predictive value and likelihood ratio, for all CHD and for six types of CHD., Results: Sensitivity of NT was 7.1 and 4.2% for the 2.5 and 3.5 mm cut-off values, respectively; when isolated ventricular septal defects were excluded, sensitivity increased to 9.9 and 6.3%. Positive predictive values were 1.1 and 3.2% for 2.5 and 3.5 mm cut-offs, respectively. Of the six defects examined, sensitivity of NT was highest for heterotaxy followed by hypoplastic left heart syndrome and coarctation of aorta., Conclusion: Prevalence of CHD was about fourfold higher for fetuses with NT ≥ 3.5 mm (3.2%) than in the general population. This higher risk is comparable to that of other risk factors commonly used for early referral to specialized echocardiography. Nevertheless, our results, suggest that NT is not a very effective or efficient tool for the prenatal screening of CHD., (Copyright © 2011 John Wiley & Sons, Ltd.)

Objective: To evaluate the ability to confidently identify intracranial translucency (IT) in a clinical practice and following specific training of 10 operators., Methods: Two experienced observers reviewed 11-13-week nuchal translucency (NT) images for IT visibility in (1) a series of 50 randomly selected images obtained by 10 skilled operators certified by the Collège Français d'Echographie Foetale (CFEF) (retrospective analysis) and (2) a series of 315 images obtained by 10 different operators following specific training for IT visualization (prospective analysis). We calculated proportions of images for which IT was deemed visible and the agreement between the two observers. Data were also stratified by Herman and CFEF quality-score intervals., Results: In the retrospective analysis, IT was visualized by both reviewers in 52% of images, with a moderate level of agreement (κ = 0.63). The rate of IT visualization by both reviewers increased very slightly to 56-58% when only considering images with the best NT quality-control scores. Following specific training of the operators the proportion of images for which both reviewers could identify the fourth ventricle increased to 85%, but the level of agreement remained moderate (κ = 0.66). When considering images with the best NT quality-control scores, IT visualization by both reviewers increased to 91-92%., Conclusions: In a clinical practice that focuses on NT measurement IT cannot be visualized in a substantial proportion of the images obtained, which limits the utility of this approach for the early prenatal diagnosis of open spina bifida. However, the ability to identify the fourth ventricle significantly increases following specific training., (Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.)

Background: Classification of the overall spectrum of congenital heart defects (CHD) has always been challenging, in part because of the diversity of the cardiac phenotypes, but also because of the oft-complex associations. The purpose of our study was to establish a comprehensive and easy-to-use classification of CHD for clinical and epidemiological studies based on the long list of the International Paediatric and Congenital Cardiac Code (IPCCC)., Methods: We coded each individual malformation using six-digit codes from the long list of IPCCC. We then regrouped all lesions into 10 categories and 23 subcategories according to a multi-dimensional approach encompassing anatomic, diagnostic and therapeutic criteria. This anatomic and clinical classification of congenital heart disease (ACC-CHD) was then applied to data acquired from a population-based cohort of patients with CHD in France, made up of 2867 cases (82% live births, 1.8% stillbirths and 16.2% pregnancy terminations)., Results: The majority of cases (79.5%) could be identified with a single IPCCC code. The category "Heterotaxy, including isomerism and mirror-imagery" was the only one that typically required more than one code for identification of cases. The two largest categories were "ventricular septal defects" (52%) and "anomalies of the outflow tracts and arterial valves" (20% of cases)., Conclusion: Our proposed classification is not new, but rather a regrouping of the known spectrum of CHD into a manageable number of categories based on anatomic and clinical criteria. The classification is designed to use the code numbers of the long list of IPCCC but can accommodate ICD-10 codes. Its exhaustiveness, simplicity, and anatomic basis make it useful for clinical and epidemiologic studies, including those aimed at assessment of risk factors and outcomes.

OBJECTIVE. The aim of this study was to analyse the association between maternal dental caries and pre-term birth (PTB), with a particular focus on the infection-suspected causes of pre-term births. MATERIALS AND METHODS. A secondary analysis was performed on data from the EPIPAP study, a French multi-centre case-control study. Cases were 1107 women giving birth to a singleton live-born infant before 37 weeks of gestation and controls were 1094 women delivering at 37 weeks or more. A sub-group of cases was defined as women with spontaneous labour and/or pre-term premature rupture of membranes (PPROM, n = 620). A full-mouth dental examination was performed after delivery. The main factor of interest was the presence of decay on at least one tooth. RESULTS. Crude associations between presence of tooth decay and PTB or spontaneous PTB/PPROM were significant (OR = 1.21 [1.01-1.45] and OR = 1.25 [1.01-1.55], respectively). After adjustment for two sets of potential confounders (four pre-term birth risk factors and four social characteristics), for periodontitis status and for inter-examiner variability, tooth decay was not significantly associated with either PTB or spontaneous PTB/PPROM (aOR = 1.10 [0.91-1.32] and aOR = 1.14 [0.91-1.42], respectively). CONCLUSIONS. This study failed to demonstrate a significant association between tooth decay and pre-term birth. However, future well-designed studies are needed to further assess the link between dental caries and adverse pregnancy outcomes.

The purpose of this investigation was to study the impact of using various definitions of periodontitis on the frequency of periodontitis and on the associations with some known risk factors for periodontitis in a population of postpartum women in France. A clinical examination was performed within 2-4 d postpartum in 932 at-term women at five maternity units. We studied six definitions of periodontitis; five were applicable if at least two teeth were found to have the following: (i) a proximal clinical attachment level (CAL) of ≥ 3 mm; (ii) a probing depth (PD) of ≥ 4 mm; (iii) a PD of ≥ 4 mm and a CAL of ≥ 3 mm at the same site; (iv) a proximal PD of ≥ 5 mm or a proximal CAL of ≥ 4 mm; or (v) a PD of ≥ 4 mm and a CAL ≥ 3 mm and bleeding on probing at the same site. The sixth definition required the involvement of four teeth with a PD of ≥ 4 mm and a CAL of ≥ 3 mm at the same site. Associations between case status according to each definition and maternal characteristics (age, educational level, smoking before pregnancy, and time since last dental visit) were analyzed using generalized estimating equation models. The definition of periodontitis had an impact on the frequency of periodontitis, which ranged from 12.1% to 37.7%, and produced different ORs for the associations with risk factors for periodontitis., (© 2011 Eur J Oral Sci.)

Objective: To study trends in smoking before and during pregnancy in national samples of pregnant women and changes in characteristics of smokers over time, and describe the current relation between maternal smoking during pregnancy and fetal growth., Population and Methods: Five nationally representative samples of singleton live births in metropolitan France (1972, 1981, 1995, 1998 and 2003) were used to study the change in smoking rates during pregnancy over the past 30 years. We further examined changes in smoking rates between 1998 and 2003 according to maternal characteristics. Finally, we estimated the effect of smoking on fetal growth in 2003., Results: Prevalence of smoking decreased over time, but the rate remained high, 21 % in 2003. The decrease was more important among women at low risk of adverse pregnancy outcomes, resulting in increased social disparities. We confirmed the strong dose-response relation between tobacco use during pregnancy and fetal growth., Conclusion: It is important to verify that smoking during pregnancy is still decreasing and to develop policies to encourage women to quit smoking during pregnancy, especially for highly exposed groups., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Aims: To estimate the risk of congenital heart defects (CHD) associated with assisted reproductive technologies (ART)., Methods and Results: We used data from the Paris Registry of Congenital Malformations on 5493 cases of CHD and 3847 malformed controls for which no associations with ART were reported in the literature. Assisted reproductive technologies included inductors of ovulation only, in vitro fertilization, and intracytoplasmic sperm injection. Exposure to ART was higher for cases than controls (4.7 vs. 3.6%, P= 0.008) and was associated with a 40% increase in the maternal age, socioeconomic factors, and year of birth-adjusted odds of CHD without chromosomal abnormalities [adjusted odds ratio (OR) 1.4, 95% confidence interval (CI) 1.1-1.7]. Assisted reproductive technologies were specifically associated with significant increases in the odds of malformations of the outflow tracts and ventriculoarterial connections (adjusted OR 1.7, 95% CI 1.2-2.4) and of cardiac neural crest defects and double outlet right ventricle (adjusted OR 1.7, 95% CI 1.1-2.7). In general, we found specific associations between methods of ART and subcategories of CHD., Conclusion: Cases with CHD were more likely to have been conceived following ART when compared with malformed controls. This higher risk for CHD varied specifically according to the method of ART and the type of CHD and may be due to ART per se and/or the underlying infertility of couples.

Aim: To analyse the association between maternal periodontitis and preterm birth (<37 weeks' gestation) according to the causes of preterm birth., Materials and Methods: Epipap is a case-control multi-centre study of singleton livebirths. One thousand one hundred and eight women with preterm deliveries and 1094 with deliveries at term (> or =37 weeks) at six French maternity units were included. Periodontal examinations after delivery identified localized and generalized periodontitis. Cases were classified according to four causes of preterm birth. Polytomous logistic regression analysis was used to control for confounders (maternal age, parity, nationality, educational level, marital status, employment during pregnancy, body mass index before pregnancy, smoking status) and the examiner., Results: Localized periodontitis was identified in 129 (11.6%) cases and in 118 (10.8%) control women and generalized periodontitis in 148 (13.4%) and 118 (10.8%), respectively. A significant association was observed between generalized periodontitis and induced preterm birth for pre-eclampsia [adjusted odds ratio 2.46 [95% confidence intervals (95% CI)1.58-3.83]. Periodontitis was not associated with spontaneous preterm birth or preterm premature rupture of membranes or with the other causes., Conclusion: Maternal periodontitis is associated with an increased risk of induced preterm birth due to pre-eclampsia.

Objectives: To estimate the sensitivity of nuchal-translucency measurement and compare it with that of second-trimester serum screening using population-based data and to evaluate the effect of nuchal-translucency measurement on the gestational age at prenatal diagnosis of Down syndrome and pregnancy termination., Methods: We used The Paris Registry of Congenital Malformation data on 594 cases of Down syndrome (live births, fetal deaths, and pregnancy terminations) from 2001-2006. Analyses were done separately for women younger than 38 years and women aged 38 years or older. Analyses included binomial regression and fractional polynomials to model time trends in gestational age at diagnosis and at pregnancy termination., Results: Ninety percent of the fetuses had undergone nuchal-translucency measurement as compared with only 22% that underwent second-trimester serum screening. This was principally because half of the pregnant women were given a diagnosis of Down syndrome during the first trimester after an abnormal result of nuchal-translucency measurement. Second-trimester serum screening had a higher sensitivity than did nuchal-translucency measurement (72% compared with 56%). The increasing use of nuchal-translucency measurement led to an increase in early diagnosis of Down syndrome in women younger than 38 years of age; diagnosis before 15 weeks of gestation increased from 21.7% in 2001 to 51.6% in 2006 (P=.016). Pregnancy termination before 15 weeks also increased from 18.8% in 2001 to 47.5% in 2006 (P=.02)., Conclusion: The main effect of the increased use of nuchal-translucency measurement was a substantial increase in the early detection of Down syndrome, principally in younger women. This is an important advantage because several studies have shown that women prefer early diagnosis of Down syndrome., Level of Evidence: III.

This study explored the extent to which the psychological distress of women is related to their motherhood status. A representative sample of 6970 women, aged 20-59, living in France, was interviewed. This analysis was restricted to the 2799 women aged between 25 and 39, 307 of whom had had a baby in the last year. Several indicators of psychological distress were used, including the 12-item General Health Questionnaire, psychotropic drug use and suicide attempts. Women with babies under the age of 12 months presented no more psychological problems than the other women. The proportion of respondents with scores above 5 for the GHQ was 8.7% for mothers with young babies, 11.4% for mothers of an older child and 12.0% for childless women. Adjusting for age, education, employment and couple status, no differences were observed between the three groups of women, except for a lower level of psychotropic drug use among the mothers of young babies. Overall, regardless of maternal status, a high proportion of women showed symptoms of anxiety and depression. Thus, research and clinical efforts should focus on risk factors for psychological distress in women and on preventive measures beyond the post-partum period.

This study aimed to analyse the relationship between smoking and preterm birth (22-36 weeks) according to the main obstetric complications leading to the preterm birth, both overall and by parity. The EUROPOP study is a case-control study carried out between 1994 and 1997; 3,787 preterm and 5,602 full-term births were included, from maternity units in 10 countries, using the same protocol. Social, demographic and medical information was collected after delivery, from obstetric records and interviews with the mothers. Cases were classified according to the main obstetric complication (hypertension, haemorrhage, preterm premature rupture of membranes (PPROM), idiopathic spontaneous preterm labour, intrauterine growth retardation, all other causes). Multiple logistic regression analysis was used to control for confounders. Twenty four percent of cases and 20% of controls were smokers. Smoking during pregnancy, heavy smoking (>or=10 cigarettes per day) in particular, was a risk factor for preterm birth (aOR = 1.39, 95% CI:1.20-1.60). Smoking increased the risk of preterm delivery due to all obstetric complications other than hypertension. For these complications, the risk of preterm delivery associated with smoking was higher for multiparae (aOR = 1.46, 95% CI:1.24-1.71) than for primiparae (aOR = 1.18, 95% CI:1.00-1.38). In conclusion, smoking during pregnancy increases the risk of preterm birth among women with all obstetric complications except hypertension. This association is stronger in multiparae than in primiparae and the risk is higher for heavy smokers.

Background: Despite the widespread use of highly effective contraception in France, the incidence of abortion is high. A retrospective population-based cohort study was designed to analyse women's contraceptive history., Method: We compared the contraceptive use of 163 women, whose last pregnancy ended in abortion, 6 months before, at the time of, 1 month and 6 months after the event with that of 1787 women who had never had an abortion., Results: A total of 46% of women who experienced an abortion used a highly effective form of contraception 6 months before the event (versus 76% among women who had never had an abortion, P < 0.001). This proportion dropped to 33% at the time of the abortion and increased to 71%, 1 month after. In addition, 50% of women who had an abortion had changed their contraceptive method in the 6 months before the event (compared with 16% in the 6 months before the interview in women who had not had an abortion, P < 0.001). Women with socially deprived backgrounds were less likely to use a highly effective contraception after an abortion., Conclusions: Abortion is a good opportunity for intervention, but especially so for socially disadvantaged women. It is essential to draw the attention of prescribers and women to the higher risk of contraceptive failure at the start of use of a method.

Objective: The aim of this article is to describe conditions of abortions practices in France., Materials and Methods: The study was based on the COCON survey. This survey was carried out among a representative sample of 2863 women aged 18 to 44 living in metropolitan France. Women were interviewed by telephone. The analysis was performed among a sub-sample of 320 women who had had an abortion between 1996 and 2000. Results were compared with those of the national notification of induced abortions., Results: Altogether, the way in which abortions were carried out was appropriate, but differences were observed according to the type of hospital: access to care was easier in the private sector; however a pre-abortion interview was less often carried out and a post-abortion interview less often proposed in the private sector. Besides, in both sectors, women were rarely allowed to choose the abortion technique, or the type of anesthesia in the case of a surgical abortion., Conclusion: The COCON study is the first population based survey describing the characteristics of care regarding voluntary abortion. It shows the persistence of differences in practices between the public and the private sectors.

After a review of medical literature on domestic violence during pregnancy, this paper shows the results of a survey carried out in 16 European countries. The percentage of women reporting domestic violence during pregnancy varies with the country; it is specially high in Russia, Poland and Czech Republic. Women who live without partner, those whose the couple has been separated during the pregnancy or those living in an overcrowded house have been more often victim of domestic violence. Domestic violence is significantly related to preterm birth risk.

Study Objective: To analyse the relation between preterm birth and working conditions in Europe using common measures of exposure and to test whether employment related risks varied by country of residence., Design: A case-control study in which cases included all consecutive singleton preterm births and controls included one of every ten singleton term births in each participating maternity unit. Data about working conditions were obtained by interview from women after delivery., Setting: Sixteen European countries., Participants: The analysis included 5145 preterm and 7911 term births of which 2369 preterm and 4098 term births were to women employed during pregnancy. Analyses of working conditions were carried out for women working through at least the third month of pregnancy., Main Results: Employed women did not have an excess risk of preterm birth. Among working women, a moderate excess risk was observed for women working more than 42 hours a week (OR = 1.33, CI = 1.1 to 1.6), standing more than six hours a day (OR = 1.26, CI = 1.1 to 1.5), and for women with low job satisfaction (OR = 1.27, CI = 1.1 to 1.5). There were stronger links in countries with a lower overall level of perinatal health and a common practice of long prenatal leaves., Conclusion: These findings show that specific working conditions affect the risk of preterm birth. They also suggest employment related risks could be mediated by the social and legislative context.

Background: Postpartum depression is a common, severe, yet often undetected condition. Between 10 and 15 percent of new mothers suffer from depressive disorders in the first year after childbirth. The objective of this study was to investigate whether asking women questions about their daily life constituted a useful strategy to detect women at risk of developing psychological distress after childbirth., Methods: A prospective study of 330 first- and second-time mothers was conducted. Structured interviews with women were performed at the maternity unit 1 to 2 days after childbirth, and postal questionnaires were sent to participants 5 months later. An interviewer wrote down her perception of the mood of participants, in the form of three short statements, immediately after the interview. This perception was compared with the score of the woman on the General Health Questionnaire scale, which was included in the 5 months' questionnaire., Results: The interviewer's perception of women's mood was significantly associated with the score on the General Health Questionnaire scale 5 months later. Multivariate analysis showed that the interviewer's perception of anxiety was a better predictor of postpartum psychological distress at 5 months than women's answers to questions about their mood before pregnancy and 1 to 2 days after delivery., Conclusions: Asking the new mother questions about her private and occupational life can be considered as one of many possible ways to improve the identification of women at risk of developing postpartum depression.

Background: The objective of this study was to investigate the relationship between history of induced abortion and preterm delivery in various parts of Europe, and according to the main cause of preterm birth., Methods: We used data from a case-control survey, the EUROPOP study; 2938 preterm births and 4781 controls at term from ten European countries were included. Based on national statistics, we distinguished three groups of countries with high, intermediate and low rates of induced abortion., Results: Previous induced abortions were significantly associated with preterm delivery and the risk of preterm birth increased with the number of abortions. Odds ratios did not differ significantly between the three groups of countries. The extent of association with previous induced abortion varied according to the cause of preterm delivery. Previous induced abortions significantly increased the risk of preterm delivery after idiopathic preterm labour, preterm premature rupture of membranes and ante-partum haemorrhage, but not preterm delivery after maternal hypertension. The strength of the association increased with decreasing gestational age at birth., Conclusions: Identifying subgroups of preterm births on the basis of the complications involved in delivery increases our understanding of the mechanisms by which previous induced abortion affects subsequent pregnancy outcomes.

Background: Many women stop smoking while they are pregnant, but the majority resume smoking in the postpartum. The objective is to describe postpartum tobacco use of women who quit during pregnancy and factors predicting postpartum smoking relapse., Methods: Secondary analysis of two surveys of new mothers. Survey A conducted in three maternity hospitals, including 685 women interviewed after birth and who answered a postal questionnaire at 5 months postpartum; survey B conducted in four 'départements' (administrative areas), including 636 women who answered a postal questionnaire at 6 months postpartum. Response rates were respectively 90% and 68%. Smoking status was recorded for three time periods: before pregnancy, during pregnancy, and at 5-6 months. Social characteristics and preventive behaviour were compared for regular smokers who had quit smoking during pregnancy and those who had not, and among quitters, who had resumed smoking postpartum and those who had not., Results: In survey A, 37% were smokers before pregnancy, 34% of them stopped during pregnancy, and among the latter, 48% had resumed smoking 5-6 months after delivery. In survey B, the percentages were respectively 43, 54 and 57%. The most predictive factor of postpartum smoking relapse was the partner's smoking behaviour., Conclusion: Return to smoking after delivery is frequent, but nearly half of the regular smokers who had stopped during pregnancy were still non-smokers 5-6 months after the birth. However, to increase this proportion, interventions need to include partners, especially if they are smokers.

Objectives: To study the psychological health of the mothers and their difficulties seven years after the birth of triplets and to compare these results with those obtained at four years., Data and Methods: Eleven mothers of triplets were followed up from birth to seven. At four and seven years the psychological status of the mothers and their relationships with the triplets were evaluated using a semi-structured interview and the level of depression was measured using a standardized scale (CES-D). At seven years the scores were compared to those of mothers having a singleton child of the same age., Results: At seven years three mothers of triplets out of 11 still suffered of depressive symptoms. These symptoms were more frequent than among control mothers but non significantly. One mother of triplets out of two (6/11), twice more than at four years, appreciated the increase of her educative tasks and the decrease of practical problems. In the other half of the sample problems still persisted between adults and children., Conclusion: Although the situation seemed to improve at seven years, the mother's psychological distress and quality of relationship with the children remained preoccupying in one family out of two.

Objective: To describe the prevalence of various symptoms five months and twelve months after childbirth in two European countries, according to employment, financial difficulties and relationship with partner., Design: Longitudinal multicentre survey with a similar design in France and Italy. Women were interviewed three times: at birth and twice after childbirth. At 12 months after childbirth, the survey was postal in both countries., Population: Women who had been delivered of their first or second baby in three maternity units in France and five units in Italy. Women who had multiple pregnancies, a stillbirth or known neonatal death were excluded., Results: The response rates were 83% in France and 88% in Italy. Fifteen symptoms were considered. The results were similar in the two countries and showed that the prevalence of most symptoms was higher at 12 months than at five months after childbirth. When their baby was one year old, more than half of the women reported backache, anxiety and extreme tiredness. Around one-third of women reported headache, lack of sexual desire, sleep disorders and depression. Piles, constipation and painful intercourse were also common. One year postpartum women with financial problems or a difficult relationship reported poor psychological health more frequently., Conclusion: Physical and emotional problems are common after birth, and they tend to increase over time. Backache, headache and piles can seriously interfere with day-to-day life. Sexual problems also may be a source of unhappiness for the woman and her partner. Extreme tiredness, anxiety and depression may make a woman feel guilty for not corresponding to the image of a healthy, happy and well-coping mother. There is a link between financial problems or a difficult relationship with her partner and her own wellbeing. Health professionals should be aware of the high prevalence of health problems among new mothers, and of the social context of women who are more likely to suffer from them. They should counsel the women in their care, in order to help them to find the best solution, be it medical or social in nature.

Introduction: A pilot study has been conducted in France to estimate the extent of underreporting of induced abortion and the factors linked to underreporting., Methods: A representative random sample of 300 women aged between 18 and 44 years of age who had been pregnant during the previous 2 years and 100 women who had not was selected from the telephone directory. Interviews were conducted by telephone., Results: The annual incidence of induced abortion for the 18-44-year-old age group was 6.9 per 1000 (95% confidence interval 2.2-11.6), while the rate derived from national statistics was 15 per 1000. Five women who reported a therapeutic abortion in their lifetime had confused induced abortion and therapeutic abortion. There was no significant difference in the proportion of women reporting induced abortion in their lifetime between those answering with another adult present and those who were alone when answering (13.1% versus 11.1%, p = 0.8). There was also no significant difference according to the sex of the interviewer (10.0% for men versus 12.2% for women, p = 0.6)., Conclusion: The results suggest that the context in which the questions were asked does not affect the validity of the answers and that there is a problem in the comprehension of the terminology used. Extensive rewriting and reformulation of the questions is required to minimize the underreporting of induced abortion.

Study Objective: To analyse the relation between unemployment and the psychological distress of mothers one year after childbirth., Design: Multicentric survey concerning births occurring between September 1993 and July 1994., Setting: In France: two maternity units in the Parisian area and one in Champagne-Ardennes, in the east of France, comprising both urban and rural areas., Participants: Primipara and secondipara women were interviewed three times: at birth by a face to face interview, five months and 12 months after the birth, by postal questionnaires, with a 83% response rate for the two postal questionnaires. The analysis includes 632 women who answered all three stages of the survey., Measurements: Psychological distress was mainly assessed one year after birth by the 12-item General Health Questionnaire., Results: After adjustment for unwanted pregnancy, marital conflicts, marital status, hospitalisation of the baby during the last year, lack of confiding relationship, depressive or anxious troubles before pregnancy, age, educational level and parity, unemployed women had an excess of psychological distress compared with employed women (OR = 1.87; 95% CI = 1.12, 3.13). The ratios for housewives were very close to those of employed women. Among the unemployed women, 60% had recently been without a job, since a few months before or after the birth. An excess of psychological distress among unemployed compared with employed women was observed in all social groups defined by the current or last occupation, but with various extents. Psychological distress was specially linked to the employment status in the group of women with the more qualified occupations., Conclusion: Even after a birth, when women are very much involved in their maternal role, those seeking a job have worse mental health than those in a stable situation, either employed or housewives. In France, the unemployment rate among young women is high. It is specially important that social regulations protecting employment during and after pregnancy are adequately applied. Employers, legislators, such as medical doctors, have to be aware to this situation.