Creating a population-based cohort of children born with and without congenital anomalies using birth data matched to hospital discharge databases in 11 European regions: Assessment of linkage success and data quality.

Linking routinely collected healthcare administrative data is a valuable method for conducting research on morbidity outcomes, but linkage quality and accuracy needs to be assessed for bias as the data were not collected for research. The aim of this study was to describe the rates of linking data on children with and without congenital anomalies to regional or national hospital discharge databases and to evaluate the quality of the matched data. Eleven population-based EUROCAT registries participated in a EUROlinkCAT study linking data on children with a congenital anomaly and children without congenital anomalies (reference children) born between 1995 and 2014 to administrative databases including hospital discharge records. Odds ratios (OR), adjusted by region, were estimated to assess the association of maternal and child characteristics on the likelihood of being matched. Data on 102,654 children with congenital anomalies were extracted from 11 EUROCAT registries and 2,199,379 reference children from birth registers in seven regions. Overall, 97% of children with congenital anomalies and 95% of reference children were successfully matched to administrative databases. Information on maternal age, multiple birth status, sex, gestational age and birthweight were >95% complete in the linked datasets for most regions. Compared with children born at term, those born at ≤27 weeks and 28-31 weeks were less likely to be matched (adjusted OR 0.23, 95% CI 0.21-0.25 and adjusted OR 0.75, 95% CI 0.70-0.81 respectively). For children born 32-36 weeks, those with congenital anomalies were less likely to be matched (adjusted OR 0.78, 95% CI 0.71-0.85) while reference children were more likely to be matched (adjusted OR 1.28, 95% CI 1.24-1.32). Children born to teenage mothers and mothers ≥35 years were less likely to be matched compared with mothers aged 20-34 years (adjusted ORs 0.92, 95% CI 0.88-0.96; and 0.87, 95% CI 0.86-0.89 respectively). The accuracy of linkage and the quality of the matched data suggest that these data are suitable for researching morbidity outcomes in most regions/countries. However, children born preterm and those born to mothers aged <20 and ≥35 years are less likely to be matched. While linkage to administrative databases enables identification of a reference group and long-term outcomes to be investigated, efforts are needed to improve linkages to population groups that are less likely to be linked.

The burden of disease for children born alive with Turner syndrome-A European cohort study.

BACKGROUND: Turner syndrome is a rare congenital anomaly caused by complete or partial X chromosome monosomy that may affect mortality and morbidity in childhood. METHODS: This population-based data-linkage cohort study, as part of the EUROlinkCAT project, investigated mortality and morbidity for the first 5 years of life for liveborn European children diagnosed with Turner syndrome. Thirteen population-based registries in 10 countries from the European surveillance of congenital anomalies (EUROCAT) network participated. Data on children born 1995-2014 and diagnosed with Turner syndrome were linked to mortality, hospital and prescription records. Children with any congenital anomaly and children without a congenital anomaly were included for comparison on morbidity. RESULTS: Out of a population of 5.8 million livebirths 404 were diagnosed with Turner syndrome prenatally or in infancy and 95.5% survived to their fifth birthday. During the first year of life 72.3% (95% CI 59.5;81.6) of children with Turner syndrome were hospitalized, the median length of stay was 5.6 days (95% CI 3.5;7.7) and 18.7% (95% CI 13.9;23.9) underwent surgery. After the first year of life hospitalizations and length of stay decreased but more children underwent surgery (30.8% [95% CI 17.6;44.7]). In the first 5 years the percentage of children with Turner syndrome having a prescription for antibiotics was 12%-20% per year and increased with the age of child. CONCLUSIONS: In the first year of life, the burden of disease was relatively high for children with Turner syndrome. The outlook is more positive beyond the first year, though overall morbidity still exceeded that of children without congenital anomalies.

Estimating Global Burden of Disease due to congenital anomaly: an analysis of European data.

OBJECTIVE: To validate the estimates of Global Burden of Disease (GBD) due to congenital anomaly for Europe by comparing infant mortality data collected by EUROCAT registries with the WHO Mortality Database, and by assessing the significance of stillbirths and terminations of pregnancy for fetal anomaly (TOPFA) in the interpretation of infant mortality statistics. DESIGN, SETTING AND OUTCOME MEASURES: EUROCAT is a network of congenital anomaly registries collecting data on live births, fetal deaths from 20 weeks' gestation and TOPFA. Data from 29 registries in 19 countries were analysed for 2005-2009, and infant mortality (deaths of live births at age <1 year) compared with the WHO Mortality Database. Eight EUROCAT countries were excluded from further analysis on the basis that this comparison showed poor ascertainment of survival status. RESULTS: According to WHO, 17%-42% of infant mortality was attributed to congenital anomaly. In 11 EUROCAT countries, average infant mortality with congenital anomaly was 1.1 per 1000 births, with higher rates where TOPFA is illegal (Malta 3.0, Ireland 2.1). The rate of stillbirths with congenital anomaly was 0.6 per 1000. The average TOPFA prevalence was 4.6 per 1000, nearly three times more prevalent than stillbirths and infant deaths combined. TOPFA also impacted on the prevalence of postneonatal survivors with non-lethal congenital anomaly. CONCLUSIONS: By excluding TOPFA and stillbirths from GBD years of life lost (YLL) estimates, GBD underestimates the burden of disease due to congenital anomaly, and thus declining YLL over time may obscure lack of progress in primary, secondary and tertiary prevention.

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

STUDY QUESTION: What 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? METHODS: This 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 LIMITATIONS: Overall, 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 ADDS: In 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. FUNDING, COMPETING INTERESTS, DATA SHARING: The study was funded by the European Public Health Commission, EUROCAT Joint Action 2011-2013. HD and ML received support from the European Commission DG Sanco during the conduct of this study. No additional data available.

European recommendations for primary prevention of congenital anomalies: a joined effort of EUROCAT and EUROPLAN projects to facilitate inclusion of this topic in the National Rare Disease Plans.

Congenital anomalies (CA) are the paradigm example of rare diseases liable to primary prevention actions due to the multifactorial etiology of many of them, involving a number of environmental factors together with genetic predispositions. Yet despite the preventive potential, lack of attention to an integrated preventive strategy has led to the prevalence of CA remaining relatively stable in recent decades. The 2 European projects, EUROCAT and EUROPLAN, have joined efforts to provide the first science-based and comprehensive set of recommendations for the primary prevention of CA in the European Union. The resulting EUROCAT-EUROPLAN 'Recommendations on Policies to Be Considered for the Primary Prevention of Congenital Anomalies in National Plans and Strategies on Rare Diseases' were issued in 2012 and endorsed by EUCERD (European Union Committee of Experts on Rare Diseases) in 2013. The recommendations exploit interdisciplinary expertise encompassing drugs, diet, lifestyles, maternal health status, and the environment. The recommendations include evidence-based actions aimed at reducing risk factors and at increasing protective factors and behaviors at both individual and population level. Moreover, consideration is given to topics specifically related to CA (e.g. folate status, teratogens) as well as of broad public health impact (e.g. obesity, smoking) which call for specific attention to their relevance in the pre- and periconceptional period. The recommendations, reported entirely in this paper, are a comprehensive tool to implement primary prevention into national policies on rare diseases in Europe.