Timing of Cardiac Surgical Interventions and Postoperative Mortality in Children With Severe Congenital Heart Defects Across Europe: Data From the EUROlinkCAT Study.

BACKGROUND: The purpose of this study was to evaluate the timing of the first cardiac surgery, the number of cardiac surgeries performed, and 30-day postoperative mortality rate for children with severe congenital heart defects (sCHDs) in their first 5 years of life. METHODS AND RESULTS: This was a population-based data linkage cohort study linking information from 9 European congenital anomaly registries to vital statistics and hospital databases. Data were extracted for 5693 children with sCHDs born from 1995 to 2004. Subgroup analyses were performed for specific types of sCHD. Children with sCHDs underwent their first surgical intervention at a median age of 3.6 (95% CI, 2.6-4.5) weeks. The timing of the first surgery for most subtypes of sCHD was consistent across Europe. In the first 5 years of life, children with hypoplastic left heart underwent the most cardiac surgeries, with a median of 4.4 (95% CI, 3.1-5.6). The 30-day postoperative mortality rate in children aged <1 year ranged from 1.1% (95% CI, 0.5%-2.1%) for tetralogy of Fallot to 23% (95% CI, 12%-37%) for Ebstein anomaly. The 30-day postoperative mortality rate was highest for children undergoing surgery in the first month of life. Overall 5-year survival for sCHD was <90% for all sCHDs, except transposition of the great arteries, tetralogy of Fallot, and coarctation of the aorta. CONCLUSIONS: There were no major differences among the 9 regions in the timing, 30-day postoperative mortality rate, and number of operations performed for sCHD. Despite an overall good prognosis for most congenital heart defects, some lesions were still associated with substantial postoperative death.

Risk factors for mortality in infancy and childhood in children with major congenital anomalies: A European population-based cohort study.

BACKGROUND: Preterm birth and young maternal age are known risk factors for infant and childhood mortality. There is limited knowledge of the impact of these risk factors in children born with major congenital anomalies (CAs), who have inherently higher risks of death compared with other children. OBJECTIVES: To investigate the risk factors for mortality up to age 10 years in children born with specific major CAs. METHODS: This population-based cohort study involved 150,198 livebirths from 1995 to 2014 in 13 European CA registries linked to mortality data. Cox proportional hazards models estimated the association of gestational age, maternal age and child's sex with death <1 year and 1-9 years for the whole cohort and by CA subgroup. Hazard ratios (HR) from each registry were pooled using multivariate meta-analysis. RESULTS: Preterm birth had a dose-response association with mortality; compared with infants born at 37+ weeks gestation, those born at <28, 28-31 and 32-36 weeks had 14.88 (95% CI 12.57, 17.62), 8.39 (95% CI 7.16, 9.85) and 3.88 (95% CI 3.40, 4.43) times higher risk of death <1 year, respectively. The corresponding risks at 1-9 years were 4.99 (95% CI 2.94, 8.48), 3.09 (95% CI 2.28, 4.18) and 2.04 (95% CI 1.69, 2.46) times higher, respectively. Maternal age <20 years (versus 20-34 years) was a risk factor for death <1 year (HR 1.30, 95% CI 1.09, 1.54) and 1-9 years (HR 1.58, 95% CI 1.19, 2.10). Females had 1.22 (95% CI 1.07, 1.39) times higher risk of death between 1 and 9 years than males. CONCLUSION: Preterm birth was associated with considerably higher infant and childhood mortality in children with CAs, comparable to estimates reported elsewhere for the background population. Additional risk factors included young maternal age and female sex. Information on risk factors could benefit clinical care and guide counselling of parents following CA diagnoses.

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.

Prescriptions for insulin and insulin analogues in children with and without major congenital anomalies: a data linkage cohort study across six European regions.

Are children with major congenital anomalies more likely to develop diabetes requiring insulin therapy, as indicated by prescriptions for insulin, than children without congenital anomalies? The aim of this study is to evaluate prescription rates of insulin/insulin analogues in children aged 0-9 years with and without major congenital anomalies. A EUROlinkCAT data linkage cohort study, involving six population-based congenital anomaly registries in five countries. Data on children with major congenital anomalies (60,662) and children without congenital anomalies (1,722,912), the reference group, were linked to prescription records. Birth cohort and gestational age were examined. The mean follow-up for all children was 6.2 years. In children with congenital anomalies aged 0-3 years, 0.04 per 100 child-years (95% CIs 0.01-0.07) had > 1 prescription for insulin/insulin analogues compared with 0.03 (95% CIs 0.01-0.06) in reference children, increasing ten-fold by age 8-9 years. The risk of > 1 prescription for insulin/insulin analogues aged 0-9 years in children with non-chromosomal anomalies (RR 0.92, 95% CI 0.84-1.00) was similar to that of reference children. However, children with chromosomal anomalies (RR 2.37, 95% CI 1.91-2.96), and specifically children with Down syndrome (RR 3.44, 95% CIs 2.70-4.37), Down syndrome with congenital heart defects (RR 3.86, 95% CIs 2.88-5.16) and Down syndrome without congenital heart defects (RR 2.78, 95% CIs 1.82-4.27), had a significantly increased risk of > 1 prescription for insulin/insulin analogues aged 0-9 years compared to reference children. Female children had a reduced risk of > 1 prescription aged 0-9 years compared with male children (RR 0.76, 95% CI 0.64-0.90 for children with congenital anomalies and RR 0.90, 95% CI 0.87-0.93 for reference children). Children without congenital anomalies born preterm (< 37 weeks) were more likely to have > 1 insulin/insulin analogue prescription compared to term births (RR 1.28, 95% CIs 1.20-1.36). CONCLUSION: This is the first population-based study using a standardised methodology across multiple countries. Males, children without congenital anomalies born preterm and those with chromosomal anomalies had an increased risk of being prescribed insulin/insulin analogues. These results will help clinicians to identify which congenital anomalies are associated with an increased risk of developing diabetes requiring insulin therapy and allow them to reassure families of children who have non-chromosomal anomalies that their risk is similar to that of the general population. WHAT IS KNOWN: • Children and young adults with Down syndrome have an increased risk of diabetes requiring insulin therapy. • Children born prematurely have an increased risk of developing diabetes requiring insulin therapy. WHAT IS NEW: • Children with non-chromosomal anomalies do not have an increased risk of developing diabetes requiring insulin therapy compared to children without congenital anomalies. • Female children, with or without major congenital anomalies, are less likely to develop diabetes requiring insulin therapy before the age of 10 compared to male children.

Ten-Year Survival of Children With Congenital Anomalies: A European Cohort Study.

OBJECTIVES: To investigate the survival up to age 10 for children born alive with a major congenital anomaly (CA). METHODS: This population-based linked cohort study (EUROlinkCAT) linked data on live births from 2005 to 2014 from 13 European CA registries with mortality data. Pooled Kaplan-Meier survival estimates up to age 10 were calculated for these children (77 054 children with isolated structural anomalies and 4011 children with Down syndrome). RESULTS: The highest mortality of children with isolated structural CAs was within infancy, with survival of 97.3% (95% confidence interval [CI]: 96.6%-98.1%) and 96.9% (95% CI: 96.0%-97.7%) at age 1 and 10, respectively. The 10-year survival exceeded 90% for the majority of specific CAs (27 of 32), with considerable variations between CAs of different severity. Survival of children with a specific isolated anomaly was higher than in all children with the same anomaly when those with associated anomalies were included. For children with Down syndrome, the 10-year survival was significantly higher for those without associated cardiac or digestive system anomalies (97.6%; 95% CI: 96.5%-98.7%) compared with children with Down syndrome associated with a cardiac anomaly (92.3%; 95% CI: 89.4%-95.3%), digestive system anomaly (92.8%; 95% CI: 87.7%-98.2%), or both (88.6%; 95% CI: 83.2%-94.3%). CONCLUSIONS: Ten-year survival of children born with congenital anomalies in Western Europe from 2005 to 2014 was relatively high. Reliable information on long-term survival of children born with specific CAs is of major importance for parents of these children and for the health care professionals involved in their care.