Long term trends in prevalence of neural tube defects in Europe:population based study

STUDY QUESTIONWhat are the long term trends in the total (live births, fetal deaths, and terminations of pregnancy for fetal anomaly) and live birth prevalence of neural tube defects (NTD) in Europe, where many countries have issued recommendations for folic acid supplementation but a policy for mandatory folic acid fortification of food does not exist?METHODSThis was a population based, observational study using data on 11 353 cases of NTD not associated with chromosomal anomalies, including 4162 cases of anencephaly and 5776 cases of spina bifida from 28 EUROCAT (European Surveillance of Congenital Anomalies) registries covering approximately 12.5 million births in 19 countries between 1991 and 2011. The main outcome measures were total and live birth prevalence of NTD, as well as anencephaly and spina bifida, with time trends analysed using random effects Poisson regression models to account for heterogeneities across registries and splines to model non-linear time trends.SUMMARY ANSWER AND LIMITATIONSOverall, the pooled total prevalence of NTD during the study period was 9.1 per 10 000 births. Prevalence of NTD fluctuated slightly but without an obvious downward trend, with the final estimate of the pooled total prevalence of NTD in 2011 similar to that in 1991. Estimates from Poisson models that took registry heterogeneities into account showed an annual increase of 4% (prevalence ratio 1.04, 95% confidence interval 1.01 to 1.07) in 1995-99 and a decrease of 3% per year in 1999-2003 (0.97, 0.95 to 0.99), with stable rates thereafter. The trend patterns for anencephaly and spina bifida were similar, but neither anomaly decreased substantially over time. The live birth prevalence of NTD generally decreased, especially for anencephaly. Registration problems or other data artefacts cannot be excluded as a partial explanation of the observed trends (or lack thereof) in the prevalence of NTD.WHAT THIS STUDY ADDSIn the absence of mandatory fortification, the prevalence of NTD has not decreased in Europe despite longstanding recommendations aimed at promoting peri-conceptional folic acid supplementation and existence of voluntary folic acid fortification.</p

Survival of infants born with esophageal atresia among 24 international birth defects surveillance programs

Background: Esophageal atresia (EA) affects around 2.3–2.6 per 10,000 births world-wide. Infants born with this condition require surgical correction soon after birth. Most survival studies of infants with EA are locally or regionally based. We aimed to describe survival across multiple world regions. Methods: We included infants diagnosed with EA between 1980 and 2015 from 24 birth defects surveillance programs that are members of the International Clearinghouse for Birth Defects Surveillance and Research. We calculated survival as the proportion of liveborn infants alive at 1 month, 1- and 5-years, among all infants with EA, those with isolated EA, those with EA and additional anomalies or EA and a chromosomal anomaly or genetic syndrome. We also investigated trends in survival over the decades, 1980s–2010s. Results: We included 6,466 liveborn infants with EA. Survival was 89.4% (95% CI 88.1–90.5) at 1-month, 84.5% (95% CI 83.0–85.9) at 1-year and 82.7% (95% CI 81.2–84.2) at 5-years. One-month survival for infants with isolated EA (97.1%) was higher than for infants with additional anomalies (89.7%) or infants with chromosomal or genetic syndrome diagnoses (57.3%) with little change at 1- and 5-years. Survival at 1 month improved from the 1980s to the 2010s, by 6.5% for infants with isolated EA and by 21.5% for infants with EA and additional anomalies. Conclusions: Almost all infants with isolated EA survived to 5 years. Mortality was higher for infants with EA and an additional anomaly, including chromosomal or genetic syndromes. Survival improved from the 1980s, particularly for those with additional anomalies

Major Congenital Anomalies in Babies Born With Down Syndrome: A EUROCAT Population-Based Registry Study

Previous studies have shown that over 40% of babies with Down syndrome have a major cardiac anomaly and are more likely to have other major congenital anomalies. Since 2000, many countries in Europe have introduced national antenatal screening programs for Down syndrome. This study aimed to determine if the introduction of these screening programs and the subsequent termination of prenatally detected pregnancies were associated with any decline in the prevalence of additional anomalies in babies born with Down syndrome. The study sample consisted of 7,044 live births and fetal deaths with Down syndrome registered in 28 European population-based congenital anomaly registries covering seven million births during 2000-2010. Overall, 43.6% (95% CI: 42.4-44.7%) of births with Down syndrome had a cardiac anomaly and 15.0% (14.2-15.8%) had a non-cardiac anomaly. Female babies with Down syndrome were significantly more likely to have a cardiac anomaly compared to male babies (47.6% compared with 40.4%, P&#8201;<&#8201;0.001) and significantly less likely to have a non-cardiac anomaly (12.9% compared with 16.7%, P&#8201;<&#8201;0.001). The prevalence of cardiac and non-cardiac congenital anomalies in babies with Down syndrome has remained constant, suggesting that population screening for Down syndrome and subsequent terminations has not influenced the prevalence of specific congenital anomalies in these babies.

A multi-program analysis of cleft lip with cleft palate prevalence and mortality using data from 22 International Clearinghouse for Birth Defects Surveillance and Research programs, 1974-2014

Background Cleft lip with cleft palate (CLP) is a congenital condition that affects both the oral cavity and the lips. This study estimated the prevalence and mortality of CLP using surveillance data collected from birth defect registries around the world. Methods Data from 22 population- and hospital-based surveillance programs affiliated with the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR) in 18 countries on live births (LB), stillbirths (SB), and elective terminations of pregnancy for fetal anomaly (ETOPFA) for CLP from 1974 to 2014 were analyzed. Prevalence and survival (survival for LB only) estimates were calculated for total and subclassifications of CLP and by pregnancy outcome. Results The pooled prevalence of total CLP cases was 6.4 CLP per 10,000 births. The prevalence of CLP and all of the pregnancy outcomes varied across programs. Higher ETOPFA rates were recorded in most European programs compared to programs in other continents. In programs reporting low ETOPFA rates or where there was no ascertainment of ETOPFA, the rate of CLP among LB and SB was higher compared to those where ETOPFA rates were ascertained. Overall survival for total CLP was 91%. For isolated CLP, the survival was 97.7%. CLP associated with multiple congenital anomalies had an overall survival of 77.1%, and for CLP associated with genetic/chromosomal syndromes, overall survival was 40.9%. Conclusions Total CLP prevalence reported in this study is lower than estimates from prior studies, with variation by pregnancy outcomes between programs. Survival was lower when CLP was associated with other congenital anomalies or syndromes compared to isolated CLP

Analysis of Mortality among Neonates and Children with Spina Bifida: An International Registry-Based Study, 2001-2012.

Medical advancements have resulted in better survival and life expectancy among those with spina bifida, but a significantly increased risk of perinatal and postnatal mortality for individuals with spina bifida remains. To examine stillbirth and infant and child mortality among those affected by spina bifida using data from multiple countries. We conducted an observational study, using data from 24 population- and hospital-based surveillance registries in 18 countries contributing as members of the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR). Cases of spina bifida that resulted in livebirths or stillbirths from 20 weeks' gestation or elective termination of pregnancy for fetal anomaly (ETOPFA) were included. Among liveborn spina bifida cases, we calculated mortality at different ages as number of deaths among liveborn cases divided by total number of liveborn cases with spina bifida. As a secondary outcome measure, we estimated the prevalence of spina bifida per 10 000 total births. The 95% confidence interval for the prevalence estimate was estimated using the Poisson approximation of binomial distribution. Between years 2001 and 2012, the overall first-week mortality proportion was 6.9% (95% CI 6.3, 7.7) and was lower in programmes operating in countries with policies that allowed ETOPFA compared with their counterparts (5.9% vs. 8.4%). The majority of first-week mortality occurred on the first day of life. In programmes where information on long-term mortality was available through linkage to administrative databases, survival at 5 years of age was 90%-96% in Europe, and 86%-96% in North America. Our multi-country study showed a high proportion of stillbirth and infant and child deaths among those with spina bifida. Effective folic acid interventions could prevent many cases of spina bifida, thereby preventing associated childhood morbidity and mortality.This research received no specific grant from any funding agency in the public, commercial, or not‐for‐profit sectors. The programmes participating in this study may receive local funding.S

Surveillance of adverse fetal effects of medications (SAFE-Med):Findings from the International Clearinghouse of Birth Defects Surveillance and Research

To evaluate whether the routinely collected data in birth defect registries could be used to assess association between medications and risk for congenital anomalies an "exposed case-only" design was performed. Twelve registries provided 18,131 cases exposed to a medication during the first trimester of pregnancy and with at least one major malformation. Odds ratios for malformations associated with maternal use of selected medications were computed. Among seven most commonly used medications very few significant associations with malformations were identified. Among fourteen potentially teratogenic medications several strong associations were found, including valproic acid with spina bifida, and insulin (as proxy for diabetes) with several types of cardiac defects. Finding known associations provides assurance on the validity of this approach, whereas identifying new associations provides a signal to be followed by confirmatory studies. Through this activity, international networks of birth defect registries can contribute with limited resources to post-marketing surveillance of the teratogenicity of medications. (C) 2010 Elsevier Inc. All rights reserved

Surveillance of Adverse Fetal Effects of Medications (SAFE-Med): findings from the International Clearinghouse of Birth Defects Surveillance and Research (ICBDSR).

To evaluate whether the routinely collected data in birth defect registries could be used to assess association between medications and risk for congenital anomalies an "exposed case-only" design was performed. Twelve registries provided 18,131 cases exposed to a medication during the first trimester of pregnancy and with at least one major malformation. Odds ratios for malformations associated with maternal use of selected medications were computed. Among seven most commonly used medications very few significant associations with malformations were identified. Among fourteen potentially teratogenic medications several strong associations were found, including valproic acid with spina bifida, and insulin (as proxy for diabetes) with several types of cardiac defects. Finding known associations provides assurance on the validity of this approach, whereas identifying new associations provides a signal to be followed by confirmatory studies. Through this activity, international networks of birth defect registries can contribute with limited resources to post-marketing surveillance of the teratogenicity of medications

Prenatal diagnosis and prevalence of critical congenital heart defects: an international retrospective cohort study

OBJECTIVES: To assess international trends and patterns of prenatal diagnosis of critical congenital heart defects (CCHDs) and their relation to total and live birth CCHD prevalence and mortality. SETTING: Fifteen birth defect surveillance programmes that participate in the International Clearinghouse for Birth Defects Surveillance and Research from 12 countries in Europe, North and South America and Asia. PARTICIPANTS: Live births, stillbirths and elective terminations of pregnancy for fetal anomaly diagnosed with 1 of 12 selected CCHD, ascertained by the 15 programmes for delivery years 2000 to 2014. RESULTS: 18 243 CCHD cases were reported among 8 847 081 births. The median total prevalence was 19.1 per 10 000 births but varied threefold between programmes from 10.1 to 31.0 per 10 000. CCHD were prenatally detected for at least 50% of the cases in one-third of the programmes. However, prenatal detection varied from 13% in Slovak Republic to 87% in some areas in France. Prenatal detection was consistently high for hypoplastic left heart syndrome (64% overall) and was lowest for total anomalous pulmonary venous return (28% overall). Surveillance programmes in countries that do not legally permit terminations of pregnancy tended to have higher live birth prevalence of CCHD. Most programmes showed an increasing trend in prenatally diagnosed CCHD cases. DISCUSSION AND CONCLUSIONS: Prenatal detection already accounts for 50% or more of CCHD detected in many programmes and is increasing. Local policies and access likely account for the wide variability of reported occurrence and prenatal diagnosis. Detection rates are high especially for CCHD that are more easily diagnosed on a standard obstetric four-chamber ultrasound or for fetuses that have extracardiac anomalies. These ongoing trends in prenatal diagnosis, potentially in combination with newborn pulse oximetry, are likely to modify the epidemiology and clinical outcomes of CCHD in the near future

Gastroschisis and associated defects:An international study

Our objective was to evaluate the frequency and type of malformations associated with gastroschisis in Large 11001 of international data, to identify malformation patterns, and to evaluate the role of maternal age in non-isolated cases. Case-by-case information from 24 registries, all members of the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR), WERE evaluated. After the exclusion of other abdominal wall defects cases were classified as: (a) isolated: (h) recognizable syndrome, chromosomal or not; (c) multiple congenital anomalies (MCA). Our results showed that out of 3,322 total cases 469 non-isolated cases were registered (14.1%): 41 chromosomal syndromes. 24 other syndromes, and 404 MCA. Among MCA four groups of anomalies were most frequent: CNS (4.5%), cardiovascular (2.5%), limb (2.2%), and kidney anomalies (1.9%). No similar patterns emerged except two patterns resembling limb-body wall complex and OEIS. In both of them the gastroschisis could he however misclassified. Chromosomal trisomies and possibly non-syndromic MCA are associated, with,in older Maternal age more than isolated cases. On consideration of our Data and the most valid studies published in the literature, the best estimate of the proportion of gastroschisis associated with major unrelated defects is about 10%, with a few cases associated to recognizable syndromes. Recognized syndromes with gastroschisis seem to be so exceptional that the well documented and validated cases are worth being published as interesting case report. An appropriate case definition in etiological studies should include only isolated gastroschisis after an appropriate definition of isolated and non-isolted cases and a thorough case-by-case review. (c) 2007 Wiley-Liss, Inc