Association between advanced paternal age and congenital heart defects: a systematic review and meta-analysis.

STUDY QUESTION: Is there an association between advanced paternal age and congenital heart defects (CHD)? SUMMARY ANSWER: Advanced paternal age is associated with a 16% increase in the overall odds of CHD. WHAT IS KNOWN ALREADY: CHD are the most common congenital malformations. Several risk factors for CHD have been identified in the literature, but the association between advanced paternal age and CHD remains unclear. STUDY DESIGN, SIZE, DURATION: We conducted a systematic literature search on MEDLINE and EMBASE (1960-2019) to identify studies assessing the association between advanced paternal age (≥35 years) and the risk of CHD, unrestrictive of language or sample size. We used a combination of Medical Subject Headings (MeSH) terms and free text words such as 'paternal age', 'paternal factors', 'father's age', 'parental age', 'heart', 'cardiac', 'cardiovascular', 'abnormalities, congenital', 'birth defects', 'congenital malformations' and 'congenital abnormalities'. PARTICIPANTS/MATERIALS, SETTING, METHODS: We included observational studies aiming at assessing the association between paternal age and CHD. The included population could be live births, fetal deaths and terminations of pregnancy for fetal anomaly. To be included, studies had to provide either odds ratios (OR) with their 95% confidence interval (CI) or sufficient information to recalculate ORs with 95% CIs per paternal age category. We excluded studies if they had no comparative group and if they were reviews or case reports. Two independent reviewers selected the studies, extracted the data and assessed risk of bias using a modified Newcastle-Ottawa Scale. We used random-effects meta-analysis to produce summary estimates of crude OR. Associations were also tested in subgroups. MAIN RESULTS AND THE ROLE OF CHANCE: Of 191 studies identified, we included nine studies in the meta-analysis (9 917 011 participants, including 34 447 CHD), including four population-based studies. Five studies were judged at low risk of bias. Only one population-based study specifically investigated isolated CHD. The risk of CHD was higher with advanced paternal age (summary OR 1.16, 95% CI, 1.07-1.25). Effect sizes were stable in population-based studies and in those with low risk of bias. LIMITATIONS AND REASONS FOR CAUTION: The available evidence did not allow to assess (i) the risk of isolated CHD in population-based studies, (ii) the association between paternal age and the risk for specific CHD and (iii) the association between paternal age and CHD after adjustment for other risk factors, such as maternal age. WIDER IMPLICATIONS OF THE FINDINGS: Our findings suggest that advanced paternal age may be a risk factor for CHD. However, because the association is modest in magnitude, its usefulness as a criterion for targeted screening for CHD seems limited. STUDY FUNDING/COMPETING INTEREST(S): None. PROSPERO REGISTRATION NUMBER: CRD42019135061.

Prenatal natural history of congenital pulmonary malformations: MALFPULM population-based cohort study.

OBJECTIVES: To assess prenatal changes in the volume of congenital pulmonary malformations (CPM) and examine whether these changes differ in lesions that appear cystic on ultrasound compared with hyperechoic lesions, and to study the relationship between CPM volume and risk of fetal compression. METHODS: We conducted a nationally representative, multicenter, prospective cohort study, which included 579 ultrasound examinations in 176 pregnant women with a diagnosis of fetal CPM, between March 2015 and November 2016. Several ultrasound examinations were performed between diagnosis and delivery, including measurement of CPM volume. We modeled changes in CPM volume ratio (CVR) as a function of gestational age, overall and for cystic/mixed vs hyperechoic malformations, and examined the association between CVR and signs of compression during pregnancy. RESULTS: When modeling CVR changes over time, there was a statistically significant decrease in CVR with increasing gestational age (P < 0.001), but the pattern of change differed according to CPM phenotype at first ultrasound examination: cystic/mixed CPM were characterized by a monotonic decrease in CVR with increasing gestational age (P = 0.002), whereas hyperechoic CPM showed an initial increase in CVR up to 27 weeks of gestation, followed by a decrease thereafter (P < 0.001). Peak CVR values were predicted as early as 21-22 weeks for cystic/mixed CPMs compared with 25-26 weeks for hyperechoic malformations. Regardless of CPM phenotype, fetuses that showed no sign of compression at any point had substantially lower CVR at first CVR measurement, and the CVR remained relatively constant thereafter. Among the subpopulation of fetuses with no sign of compression at first CVR measurement, the odds of a subsequent compression was 7-fold higher (adjusted odds ratio, 7.0; 95% CI, 1.6-29.9) if initial CVR was > 0.4 vs CVR ≤ 0.4 cm2 . CONCLUSIONS: Predicted changes in CVR during pregnancy differ between cystic and hyperechoic malformations. This may be the result of different pathophysiological mechanisms or differences in the timing of occurrence of these different types of CPM. CVR measured at the initial diagnostic ultrasound examination was strongly associated with the odds of subsequent compression. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Urm1: an essential regulator of JNK signaling and oxidative stress in Drosophila melanogaster.

Ubiquitin-related modifier 1 (Urm1) is a ubiquitin-like molecule (UBL) with the dual capacity to act both as a sulphur carrier and posttranslational protein modifier. Here we characterize the Drosophila melanogaster homologues of Urm1 (CG33276) and its E1 activating enzyme Uba4 (CG13090), and show that they function together to induce protein urmylation in vivo. Urm1 conjugation to target proteins in general, and to the evolutionary conserved substrate Peroxiredoxin 5 (Prx5) specifically, is dependent on Uba4. A complete loss of Urm1 is lethal in flies, although a small number of adult zygotic Urm1 (n123) mutant escapers can be recovered. These escapers display a decreased general fitness and shortened lifespan, but in contrast to their S. cerevisiae counterparts, they are resistant to oxidative stress. Providing a molecular explanation, we demonstrate that cytoprotective JNK signaling is increased in Urm1 deficient animals. In agreement, molecular and genetic evidence suggest that elevated activity of the JNK downstream target genes Jafrac1 and gstD1 strongly contributes to the tolerance against oxidative stress displayed by Urm1 (n123) null mutants. In conclusion, Urm1 is a UBL that is involved in the regulation of JNK signaling and the response against oxidative stress in the fruit fly.

Is the probability of prenatal diagnosis or termination of pregnancy different for fetuses with congenital anomalies conceived following assisted reproductive techniques? A population-based evaluation of fetuses with congenital heart defects.

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.

Colorectal cancer screening: factors associated with colonoscopy after a positive faecal occult blood test.

BACKGROUND: Contextual socio-economic factors, health-care access, and general practitioner (GP) involvement may influence colonoscopy uptake and its timing after positive faecal occult blood testing (FOBT). Our objectives were to identify predictors of delayed or no colonoscopy and to assess the role for GPs in colonoscopy uptake. METHODS: We included all residents of a French district with positive FOBTs (n = 2369) during one of the two screening rounds (2007-2010). Multilevel logistic regression analysis was performed to identify individual and area-level predictors of delayed colonoscopy, no colonoscopy, and no information on colonoscopy. RESULTS: A total of 998 (45.2%) individuals underwent early, 989 (44.8%) delayed, and 102 (4.6%) no colonoscopy; no information was available for 119 (5.4%) individuals. Delayed colonoscopy was independently associated with first FOBT (odds ratio, (OR)), 1.61; 95% confidence interval ((95% CI), 1.16-2.25); and no colonoscopy and no information with first FOBT (OR, 2.01; 95% CI, 1.02-3.97), FOBT kit not received from the GP (OR, 2.29; 95% CI, 1.67-3.14), and socio-economically deprived area (OR, 3.17; 95% CI, 1.98-5.08). Colonoscopy uptake varied significantly across GPs (P=0.01). CONCLUSION: Socio-economic factors, GP-related factors, and history of previous FOBT influenced colonoscopy uptake after a positive FOBT. Interventions should target GPs and individuals performing their first screening FOBT and/or living in socio-economically deprived areas.

Maternal and health care determinants of preconceptional use of folic acid supplementation in France: results from the 2010 National Perinatal Survey.

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.

Screening for fetal spina bifida at the 11-13-week scan using three anatomical features of the posterior brain.

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.

Specific obstetrical risk factors for urinary versus anal incontinence 4 years after first delivery.

AIM: Delivery can be complicated by urinary or anal incontinence (UI or AI). We hypothesized that the mechanisms of injury may differ for UI and AI. Hence, obstetrical risk factors may be specific for different types of incontinence. DESIGN: Data on maternal characteristics were collected at first delivery. Data on incontinence were obtained by a questionnaire completed by 627 women 4 years after first delivery. UI was defined by "Do you have involuntary loss of urine" and AI by "Do you have involuntary loss of flatus or stool". A multinomial logistic regression analysis was conducted to assess risk factors for UI only, AI only, and UI+AI. RESULTS: Twenty-two percent of women reported UI only, 6.5% AI only, and 6.5% both. Risk factors associated with UI only were age (at first delivery)≥ 30 (OR 2.27 [95% CI 1.47-3.49]), pre-existing UI (6.44 [2.19-19.0]) and pregnancy UI (3.64 [2.25-5.91]). Risk factors associated with AI only were length of the second active stage> 20minutes (2.86 [1.15-7.13]) and third degree perineal tear (20.9 [1.73-252]). Significant predictors of UI+AI were age ≥ 30 (2.65 [1.29-5.46]), no epidural (4.29 [1.65-11.1]), third degree perineal tear (20.0 [1.28-314]), and UI before pregnancy (32.9 [9.00-120]). Cesarean delivery was not significantly associated with UI, AI, or UI+AI, although for all three outcomes, the adjusted odds ratios were substantially less than one. CONCLUSION: We found specific associations between obstetrical risk factors and urinary versus anal incontinence 4 years after first delivery. Our results are consistent with the hypothesis that the underlying mechanisms of injury differ for UI and AI.

Impact of prenatal estimation of the risk of respiratory distress in neonates with congenital pulmonary malformations on the choice of delivery site.

BACKGROUND: The vast majority of prenatally diagnosed congenital pulmonary malformations (CPM) remain asymptomatic at birth. The maximal value of the CPM volume ratio (CVRmax) predicts the risk of neonatal respiratory distress (NRD), and should allow for better assessment of the level of expertise needed at the delivery site. AIM: This study evaluated the level of maternity units currently chosen for the delivery of CPMs, and determined the impact of the choice of delivery site based on the CVRmax, with a threshold of 0.4 cm2. METHODS: Data were extracted from the French prospective MALFPULM cohort, with inclusion between March 2015 and June 2018. RESULTS: The final study population consisted of 383 women. Deliveries in level 1 or 2 maternity units (n = 98, 25%) involved CPMs with lower CVRmax (p<0.001), causing fewer signs of prenatal compression (p = 0.025). Among the 62 children (16%) who presented with NRD, only seven (11%) were born in level 1 or 2 units (p = 0.0078). Choosing the maternity level according to the CVRmax would have increased the number of births in level 1 or 2 maternity hospitals by 70%. In these maternity units, the percentage of children with NRD would have increased from 8% in the actual distribution to 10% in the new strategy. CONCLUSION: Our results showed an overuse of level 3 maternity hospitals for the delivery of newborns with a prenatal diagnosis of CPM. The use of CVRmax should enable a reduction in the use of expertise centers without an adverse impact on newborns.

Visualization of intracranial translucency at the 11-13-week scan is improved after specific training.

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.

Respiratory morbidity in children with congenital heart disease.

OBJECTIVE: To evaluate the respiratory outcome in children with congenital heart disease (CHD), considering recent management procedures and the CHD pathophysiology. DESIGN AND SETTING: Clinical and functional respiratory outcome were evaluated in 8-year-old children with isolated CHD followed up from birth in the prospective population-based EPICARD cohort. PATIENTS: Children were assigned to two groups, based on the pathophysiology of the CHD: CHDs with left-to-right shunt (n = 212) and CHDs with right outflow tract obstruction (n = 113). RESULTS: Current wheezing episodes were observed in 15% of the children with isolated CHD and left-to-right shunt, and 11% of the children with isolated CHD and right outflow tract obstruction (not significant). Total lung capacity (TLC) was the only respiratory function parameter that significantly differed between the two groups. It was lower in children with left-to-right shunt (88.72 ± 0.65% predicted) than in those with right outflow tract obstruction (91.84 ± 0.96, p = 0.006). In multivariate analysis, CHD with left-to-right shunt (coeff. [95% CI]: -3.17 [-5.45; -0.89]) and surgery before the age of 2 months (-6.52 [-10.90; -2.15]) were identified as independent factors associated with significantly lower TLC values. CONCLUSION: Lower TLC remains a long-term complication in CHD, particularly in cases with left-to-right shunt and in patients requiring early repair. These findings suggest that an increase in pulmonary blood flow may directly impair lung development.

Linking a European cohort of children born with congenital anomalies to vital statistics and mortality records: A EUROlinkCAT study.

EUROCAT is a European network of population-based congenital anomaly (CA) registries. Twenty-one registries agreed to participate in the EUROlinkCAT study to determine if reliable information on the survival of children born with a major CA between 1995 and 2014 can be obtained through linkage to national vital statistics or mortality records. Live birth children with a CA could be linked using personal identifiers to either their national vital statistics (including birth records, death records, hospital records) or to mortality records only, depending on the data available within each region. In total, 18 of 21 registries with data on 192,862 children born with congenital anomalies participated in the study. One registry was unable to get ethical approval to participate and linkage was not possible for two registries due to local reasons. Eleven registries linked to vital statistics and seven registries linked to mortality records only; one of the latter only had identification numbers for 78% of cases, hence it was excluded from further analysis. For registries linking to vital statistics: six linked over 95% of their cases for all years and five were unable to link at least 85% of all live born CA children in the earlier years of the study. No estimate of linkage success could be calculated for registries linking to mortality records. Irrespective of linkage method, deaths that occurred during the first week of life were over three times less likely to be linked compared to deaths occurring after the first week of life. Linkage to vital statistics can provide accurate estimates of survival of children with CAs in some European countries. Bias arises when linkage is not successful, as early neonatal deaths were less likely to be linked. Linkage to mortality records only cannot be recommended, as linkage quality, and hence bias, cannot be assessed.

Termination of pregnancy for fetal anomaly after 23 weeks of gestation: a European register-based study.

OBJECTIVE: To determine the prevalence of termination of pregnancy for fetal anomaly (TOPFA) after 23 weeks of gestation in European countries, and describe the spectrum of anomalies for which late TOPFA is recorded. DESIGN: Population-based study. SETTING: Twelve European countries. POPULATION: Nineteen registries of congenital anomaly in 12 European countries between 2000 and 2005. The number of total births covered was 2 695 832. METHODS: TOPFAs in singleton pregnancies from the European Surveillance of Congenital Anomalies and Twins (EUROCAT) database. MAIN OUTCOME MEASURES: The prevalence of TOPFA and type of anomaly. RESULTS: There were 10 233 TOPFAs, 678 (6.6%) of which were performed at 24 weeks or more. The rate of TOPFA before 24 weeks was 3.4 per 1000 births, at 24-25 weeks 0.14 per 1000 births and at 26 weeks or more 0.11 per 1000 births. There was significant variation in the prevalence of TOPFA at >or=24 weeks between countries (P < 0.001), with all countries in the range 0-0.55 per 1000 births, except France (Paris) at 2.65 per 1000 births. The large majority of late TOPFAs had a gestational age of 24-27 weeks (516/678, 76%). The proportion of TOPFAs from 24 weeks or more varied by type of anomaly, with 4% of all TOPFAs for chromosomal anomalies and 9% of all TOPFAs for nonchromosomal anomalies resulting in late TOPFA (P < 0.001). For transposition of the great arteries, single ventricle, hypoplastic left heart and hydrocephaly, the percentage of late TOPFA was 12-23%. The median time interval between diagnosis and late TOPFA was 2 weeks for most anomalies, but longer (>or=5 weeks) for diaphragmatic hernia, omphalocoele, arthrogryposis multiplex and Turner's syndrome. CONCLUSION: Late TOPFA is rare in Europe, and varies in prevalence between countries. Compared with earlier TOPFA, late TOPFA is more often performed for a nonchromosomal isolated major structural anomaly and less often for a fetus with a chromosomal syndrome or multiple anomalies.

Transforming scales of measurement of visual acuity at the group level.

AIM: To provide formulae that may be used to transform sample-based estimates of group-level mean and standard deviation of visual acuity (VA) across different scales of measurement. METHODS: We focused on 3 transformations: (1) ETDRS letters - LogMAR (2) Decimal - LogMAR and (3) Snellen - LogMAR. We assumed that logMAR follows a normal distribution in the underlying population and used the empirical asymptotic normal approximation of the joint distribution of average and standard deviation in order to derive formulae for transformation of group-level estimates. We considered that the true population parameters are not known and are to be estimated using data from a sample of patients (which is essentially always the case). We compared estimates obtained with the proposed sample-based approach with those based on a "naïve" approach in which individual-level formulae are used directly for transformation of means and standard deviations at the group-level. RESULTS: Applying formulae that are appropriate for transformations of scales of measurement for data at the individual- (or patient-) level, to transform VA at the group level, can lead to biased estimates of means and standard deviations. In particular, it could lead to underestimation of the average logMAR VA in studies that use decimal VA. Such bias will be greater in magnitude when disease strongly affects VA. CONCLUSIONS: This paper provides formulae that can be easily implemented in standard spreadsheet software programs, and which allow appropriate transformations of group-level estimates of mean and standard deviation of VA across different scales of measurement. These transformations are helpful for performing meta-analyses or for comparisons of results across studies when VA is expressed in different units.

Survey of prenatal screening policies in Europe for structural malformations and chromosome anomalies, and their impact on detection and termination rates for neural tube defects and Down's syndrome.

OBJECTIVE: To 'map' the current (2004) state of prenatal screening in Europe. DESIGN: (i) Survey of country policies and (ii) analysis of data from EUROCAT (European Surveillance of Congenital Anomalies) population-based congenital anomaly registers. SETTING: Europe. POPULATION: Survey of prenatal screening policies in 18 countries and 1.13 million births in 12 countries in 2002-04. METHODS: (i) Questionnaire on national screening policies and termination of pregnancy for fetal anomaly (TOPFA) laws in 2004. (ii) Analysis of data on prenatal detection and termination for Down's syndrome and neural tube defects (NTDs) using the EUROCAT database. MAIN OUTCOME MEASURES: Existence of national prenatal screening policies, legal gestation limit for TOPFA, prenatal detection and termination rates for Down's syndrome and NTD. RESULTS: Ten of the 18 countries had a national country-wide policy for Down's syndrome screening and 14/18 for structural anomaly scanning. Sixty-eight percent of Down's syndrome cases (range 0-95%) were detected prenatally, of which 88% resulted in termination of pregnancy. Eighty-eight percent (range 25-94%) of cases of NTD were prenatally detected, of which 88% resulted in termination. Countries with a first-trimester screening policy had the highest proportion of prenatally diagnosed Down's syndrome cases. Countries with no official national Down's syndrome screening or structural anomaly scan policy had the lowest proportion of prenatally diagnosed Down's syndrome and NTD cases. Six of the 18 countries had a legal gestational age limit for TOPFA, and in two countries, termination of pregnancy was illegal at any gestation. CONCLUSIONS: There are large differences in screening policies between countries in Europe. These, as well as organisational and cultural factors, are associated with wide country variation in prenatal detection rates for Down's syndrome and NTD.

Long-term trends for socio-economic differences in prenatal diagnosis of Down syndrome: diffusion of services or persistence of disparities?

OBJECTIVE: To assess long-term trends in disparities for prenatal diagnosis of Down syndrome in relation to policy changes. DESIGN: Population-based observational study. SETTING: Paris. POPULATION: Residents of Paris who gave birth or had a termination of pregnancy in Paris during 1983-2003 (approximately 23,000 births per year). METHODS: Using population-based data from the Paris Registry of Congenital Malformations on 1934 cases of Down syndrome, we assessed differences in prenatal diagnosis proportions by maternal profession and geographical origin for the years 1983-2003. Analyses included locally weighted scatter plot smoother curves and binomial regression. MAIN OUTCOME MEASURE: Trends in proportion of Down syndrome cases diagnosed prior to birth for different maternal occupation groups and women of different geographical origins. RESULTS: The proportion of prenatally diagnosed cases increased substantially, reaching to about 85-90% of cases in 2003 for most socio-economic groups. This increase was accompanied by a significant decrease in disparities in prenatal diagnosis. Nonetheless, the proportion of prenatally diagnosed cases remained 12% lower for women without a profession compared with those in the highest occupational category (maternal age-adjusted risk difference -12.0%, 95% CI -17.1 to -6.9). CONCLUSIONS: Together with the implementation of policies aimed at providing access to prenatal screening for all women, socio-economic differences in prenatal diagnosis of Down syndrome decreased over time. These trends need to be monitored, particularly in light of technical advances and alternative strategies for prenatal testing. However, while monitoring the proportion of cases with prenatal diagnosis is important, the ideal evaluation of prenatal testing programmes should also include measures of informed choice.

[Prenatal diagnosis and prevalence of Down syndrome in the Parisian population, 2001-2005]. / Diagnostic prénatal et prévalence de la trisomie 21 en population parisienne, 2001-2005.

OBJECTIVES: To assess recent trends in the prevalence of Down syndrome and the proportion of cases with a prenatal diagnosis in the Parisian population. PATIENTS AND METHODS: Four hundred and ninety-nine cases of Down syndrome were registered by the Paris Registry of Congenital Anomalies during the period 2001-2005. All cases with prenatal diagnosis were confirmed by cytogenetic examination. We analyzed trends in the total and live birth prevalence, the proportion of cases with a prenatal diagnosis and those with a pregnancy termination, as well as gestational age at diagnosis and termination. Analyses were stratified by maternal age and trends were tested by the Cochran-Armitage test and Anova. RESULTS: Total prevalence of Down syndrome remained high (37.6 per 10,000 births, 95%CI 34.2-40.9) during this period because of advanced maternal age in Paris. The proportion of cases with a prenatal diagnosis (overall average 85.5%, 95% CI 81.8-88.1), and live birth prevalence of Down syndrome (7.1 per 10,000 live births, 95%CI 5.7-8.6) have remained fairly stable over time. The great majority of women (95% CI 95% 92.7-96.9) opted for a pregnancy termination following a prenatal diagnosis of Down syndrome. A trend towards an earlier gestational age at prenatal diagnosis was noted among women less than 30 years of age. DISCUSSION AND CONCLUSION: It is important to continue to evaluate changes in the prenatal diagnosis of Down syndrome, notably in view of potential changes in screening practices and policies, and particularly if a first trimester strategy is adopted following recent recommendation by the "Haute Autorité de santé".

[Socioeconomic disparities for maternal serum screening of Down's syndrome: trends between 1998 and 2003 in France]. / Disparités socioéconomiques dans le dépistage prénatal de la trisomie 21 par marqueurs sériques: évolution entre 1998 et 2003 en France.

OBJECTIVES: To compare trends in the use of and the opportunity for making an informed choice, regarding maternal serum screening for Down's syndrome. METHODS: Data were based on the national perinatal surveys of 1998 and 2003, which comprise representative samples of births in France. We used logistic regression models and likelihood ratio tests for testing the statistical significance of interactions between time trends and socioeconomic factors. RESULTS: We found a generalized increase between 1998 and 2003 in both the use of screening and in the opportunity for making an informed choice. The use of screening increased more however, for women with primary or no education (OR=3.0; 95% CI, 2.2-4.1) as compared with those with education levels beyond a high school diploma (OR: 1.8; 95% CI, 1.7-2.0). On the contrary, trends in informed choice were comparable across socioeconomic groups. Hence, disparities in the opportunity for informed choice were essentially unchanged. CONCLUSIONS: The use of serum screening, and the opportunity for informed choice regarding the test, became more widespread for women from all socioeconomic categories between 1998 and 2003. These trends were accompanied by a decrease in socioeconomic disparities in the use of screening but not in the opportunity for making an informed choice.

[Impact of advanced maternal age on fecundity and women's and children's health]. / Impact de l'âge maternel élevé sur la fertilité, la santé de la mère et la santé de l'enfant.

OBJECTIVE: There has been a consistent trend towards delayed childbearing in most Western countries. We present a review of the current epidemiological understanding of the effects of advanced maternal age on fecundity, maternal and child health. MATERIALS AND METHODS: A narrative review of the literature based mostly on the key population-based studies on the subject. RESULTS: Delayed childbearing results in a substantial decrease in fecundity and a considerable increase in fetal loss; risk of the latter is doubled between 20-24 and 40-44 years of age. Other risks include those related to maternal health (maternal mortality and morbidity) and adverse pregnancy outcomes (multiple births, preterm delivery, fetal growth retardation and congenital anomalies). CONCLUSION: Risks associated with delayed childbearing become significant for maternal age greater than 35 years, and are particularly high for women aged 40 years and greater. Knowledge about the risks associated with advancing age can be helpful for couples in their decisions regarding childbearing.