Higher risk of cerebral palsy, seizures/epilepsy, visual- and hearing impairments, cancer, injury and child abuse in children with congenital anomalies: Data from the EUROlinkCAT study.

AIM: The aim is to examine the risk of cerebral palsy, seizures/epilepsy, visual- and hearing impairments, cancer, injury/poisoning and child abuse in children with and without a congenital anomaly up to age 5 and 10 years. METHODS: This is a population-based data linkage cohort study linking information from the European Surveillance of Congenital Anomalies network (EUROCAT) and birth registries to hospital discharge databases. We included 91 504 live born children with major congenital anomalies born from 1995 to 2014 from nine EUROCAT registries in five countries and 1 960 727 live born children without congenital anomalies (reference children). Prevalence and relative risk (RR) were estimated for each of the co-morbidities using Kaplan-Meier survival estimates. RESULTS: Children with congenital anomalies had higher risks of the co-morbidities than reference children. The prevalences in the reference children were generally very low. The RR was 13.8 (95% CI 12.5-15.1) for cerebral palsy, 2.5 (95% CI 2.4-2.6) for seizures/epilepsy, 40.8 (95% CI 33.2-50.2) for visual impairments, 10.0 (95% CI 9.2-10.9) for hearing loss, 3.6 (95% CI 3.2-4.2) for cancer, 1.5 (95% CI 1.4-1.5) for injuries/poisoning and 2.4 (95% CI 1.7-3.4) for child abuse. CONCLUSION: Children with congenital anomalies were more likely to be diagnosed with the specified co-morbidities compared to reference children.

Accuracy of congenital anomaly coding in live birth children recorded in European health care databases, a EUROlinkCAT study.

Electronic health care databases are increasingly being used to investigate the epidemiology of congenital anomalies (CAs) although there are concerns about their accuracy. The EUROlinkCAT project linked data from eleven EUROCAT registries to electronic hospital databases. The coding of CAs in electronic hospital databases was compared to the (gold standard) codes in the EUROCAT registries. For birth years 2010-2014 all linked live birth CA cases and all children identified in the hospital databases with a CA code were analysed. Registries calculated sensitivity and Positive Predictive Value (PPV) for 17 selected CAs. Pooled estimates for sensitivity and PPV were then calculated for each anomaly using random effects meta-analyses. Most registries linked more than 85% of their cases to hospital data. Gastroschisis, cleft lip with or without cleft palate and Down syndrome were recorded in hospital databases with high accuracy (sensitivity and PPV ≥ 85%). Hypoplastic left heart syndrome, spina bifida, Hirschsprung's disease, omphalocele and cleft palate showed high sensitivity (≥ 85%), but low or heterogeneous PPV, indicating that hospital data was complete but may contain false positives. The remaining anomaly subgroups in our study, showed low or heterogeneous sensitivity and PPV, indicating that the information in the hospital database was incomplete and of variable validity. Electronic health care databases cannot replace CA registries, although they can be used as an additional ascertainment source for CA registries. CA registries are still the most appropriate data source to study the epidemiology of CAs.

Severe COVID-19 during pregnancy in Sweden, Norway, and Denmark.

INTRODUCTION: Pregnancy is a risk factor for severe coronavirus disease 2019 (COVID-19) and adverse pregnancy outcomes. We aimed to explore maternal characteristics, pregnancy outcomes, vaccination status, and virus variants among pregnant women admitted to intensive care units (ICU) with severe COVID-19. MATERIAL AND METHODS: We identified pregnant women admitted to ICU in Sweden (n = 96), Norway (n = 31), and Denmark (n = 16) because of severe COVID-19, from national registers and clinical databases between March 2020 and February 2022 (Denmark), August 2022 (Sweden), or December 2022 (Norway). Their background characteristics, pregnancy outcome, and vaccination status were compared with all birthing women and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test-positive pregnant women during the same time period. We calculated the number admitted to ICU per 10 000 birthing and per 1000 SARS-CoV-2 test-positive women during the Index, Alpha, Delta, and Omicron periods. RESULTS: Women admitted to ICU had a higher mean body mass index, were more often of non-Scandinavian origin, had on average lower education and income levels, had a higher proportion of chronic and pregnancy-related conditions, delivered preterm, had neonates with low Apgar scores, and had more infants admitted to neonatal care, compared with all birthing and test-positive pregnant women. Of those admitted to ICU, only 7% had been vaccinated before admission. Overall, the highest proportion of women admitted to ICU per birthing was during the Delta period (4.1 per 10 000 birthing women). In Norway, the highest proportion admitted to ICU per test-positive pregnant women was during the Delta period (17.8 per 1000 test-positive), whereas the highest proportion of admitted per test-positive in Sweden and Denmark was seen during the Index period (15.4 and 8.9 per 1000 test-positive, respectively). CONCLUSIONS: Admission to ICU because of COVID-19 in pregnancy was a rare event in the Scandinavian countries, but women who were unvaccinated, of non-Scandinavian origin, and with lower socio-economic status were at higher risk of admission to ICU. In addition, women admitted to ICU for COVID-19 had higher risk of adverse pregnancy outcomes.

Parental socio-economic position and the risk of type 1 diabetes in children and young adults in Denmark: A nation-wide register-based study.

AIM: Diabetes mellitus type 1 is one of the most common serious chronic diseases in childhood and the incidence is increasing. Insight into risk factors may inform our etiologic understanding of the disease and subsequent prevention. Any socio-economic gradient in disease risk indicates a potential for prevention, since this points towards socially patterned environmental risk factors. The aim of this study was to investigate the association between measures of parental socio-economic position and the onset of type 1 diabetes in offspring based on individual data in the entire Danish population. METHODS: In a study population of all children born in Denmark between 1 January 1987 and 31 December 2010, we examined the association between parental socio-economic position and the risk of type 1 diabetes up to the age of 25 years. The risk of type 1 diabetes was estimated according to maternal education, paternal education and household income using Cox proportional hazards regression, with adjustments for the a priori selected confounding variables: year of birth, maternal age at birth and parental type 1 diabetes. RESULTS: In the study population of 1,433,584 children, a total of 4610 developed type 1 diabetes. We found no clear pattern in type 1 diabetes risk according to parental educational attainment or parental household income. CONCLUSIONS: In this large population covering study of the risk of type 1 diabetes according to individual-level parental socio-economic position, we found no strong indication of a socially patterned disease risk.

European study showed that children with congenital anomalies often underwent multiple surgical procedures at different ages across Europe.

AIM: Children with congenital anomalies often require surgery but data on the burden of surgery for these children are limited. METHODS: A population-based record-linkage study in Finland, Wales and regions of Denmark, England, Italy and Spain. A total of 91 504 children with congenital anomalies born in 1995-2014 were followed to their tenth birthday or the end of 2015. Electronic linkage to hospital databases provided data on inpatient surgical procedures and meta-analyses of surgical procedures were performed by age groups. RESULTS: The percentage of children having surgery in the first year was 38% with some differences across regions and 14% also underwent surgery at age 1-4 years. Regional differences in age at the time of their first surgical procedure were observed for children with cleft palate, hydronephrosis, hypospadias, clubfoot and craniosynostosis. The children had a median of 2.0 (95% CI 1.98, 2.02) surgical procedures before age 5 years with children with oesophageal atresia having the highest median number of procedures (4.5; 95% CI 3.3, 5.8). CONCLUSION: A third of children with congenital anomalies required surgery during infancy and often more than one procedure was needed before age 5 years. There was no European consensus on the preferred age for surgery for some anomalies.

Temporal and geographical variations in survival of children born with congenital anomalies in Europe: A multi-registry cohort study.

BACKGROUND: Congenital anomalies are a major cause of perinatal, neonatal and infant mortality. OBJECTIVES: The aim was to investigate temporal changes and geographical variation in survival of children with major congenital anomalies (CA) in different European areas. METHODS: In this population-based linkage cohort study, 17 CA registries members of EUROCAT, the European network for the surveillance of CAs, successfully linked data on 115,219 live births with CAs to mortality records. Registries estimated Kaplan-Meier survival at 28 days and 5 years of age and fitted Cox's proportional hazards models comparing mortality at 1 year and 1-9 years of age for children born during 2005-2014 with those born during 1995-2004. The hazard ratios (HR) from each registry were combined centrally using a random-effects model. The 5-year survival conditional on having survived to 28 days of age was calculated. RESULTS: The overall risk of death by 1 year of age for children born with any major CA in 2005-2014 decreased compared to 1995-2004 (HR 0.68, 95% confidence interval [CI] 0.53, 0.89). Survival at 5 years of age ranged between registries from 97.6% to 87.0%. The lowest survival was observed for the registry of OMNI-Net (Ukraine) (87.0%, 95% CI 86.1, 87.9). CONCLUSIONS: Survival of children with CAs improved for births in 2005-2014 compared with 1995-2004. The use of CA registry data linked to mortality data enables investigation of survival of children with CAs. Factors such as defining major CAs, proportion of terminations of pregnancy for foetal anomaly, source of mortality data and linkage methods are important to consider in the design of future studies and in the interpretation of the results on survival of children with CAs.

A gold mine, but still no Klondike: Nordic register data in health inequalities research.

Aims: Future research on health inequality relies on data that cover life-course exposure, different birth cohorts and variation in policy contexts. Nordic register data have long been celebrated as a 'gold mine' for research, and fulfil many of these criteria. However, access to and use of such data are hampered by a number of hurdles and bottlenecks. We present and discuss the experiences of an ongoing Nordic consortium from the process of acquiring register data on socio-economic conditions and health in Denmark, Finland, Norway and Sweden. Methods: We compare experiences of data-acquisition processes from a researcher's perspective in the four countries and discuss the comparability of register data and the modes of collaboration available to researchers, given the prevailing ethical and legal restrictions. Results: The application processes we experienced were time-consuming, and decision structures were often fragmented. We found substantial variation between the countries in terms of processing times, costs and the administrative burden of the researcher. Concerned agencies differed in policy and practice which influenced both how and when data were delivered. These discrepancies present a challenge to comparative research. Conclusions: We conclude that there are few signs of harmonisation, as called for by previous policy documents and research papers. Ethical vetting needs to be centralised both within and between countries in order to improve data access. Institutional factors that seem to facilitate access to register data at the national level include single storage environments for health and social data, simplified ethical vetting and user guidance.

Interpregnancy Interval and Risk of Adverse Pregnancy Outcomes: A Register-Based Study of 328,577 Pregnancies in Denmark 1994-2010.

Objectives To investigate the associations of interpregnancy interval (IPI) with miscarriage, stillbirth, preterm delivery and small for gestational age delivery. Methods The study population comprised all women who had a live birth and at least one subsequent pregnancy in Denmark during the period from 1994 to 2010 (N = 328,577). Linear regression was used to estimate risk differences for miscarriage, stillbirth, preterm delivery and small for gestational age delivery according to IPI. Results The results were heterogeneous: the risk of miscarriage increased monotonically with the length of the IPI. Compared to women with IPIs of 18-23 months, women with IPIs of 0-5 months experienced 18.7 (13.1-24.2) fewer miscarriages per 1000 pregnancies, while women with IPIs of ≥ 60 months experienced 28.7 (23.4-34.0) more miscarriages per 1000 pregnancies. We found that women with IPIs of ≥ 60 months had 1.7 (0.4-3.0) more stillbirths per 1000 births compared to women with IPIs of 18-23 months. U-shaped associations were seen for preterm delivery and small for gestational age delivery with women with IPIs of 18-23 months experiencing the lowest risks of these outcomes. Conclusions for Practice The heterogeneity in associations between IPI and adverse pregnancy outcomes suggests that different mechanisms of action may be at play at various times in the antepartum period. While the finding for miscarriage suggests that fecundity is an important determinant for IPI, the findings for preterm delivery and small for gestational age delivery suggest the coexistence of the maternal depletion syndrome mechanism and the physiological regression mechanism and the finding for stillbirth speaks against a strict maternal depletion syndrome explanation.

Advanced paternal age and childhood cancer in offspring: A nationwide register-based cohort study.

Cancer initiation is presumed to occur in utero for many childhood cancers and it has been hypothesized that advanced paternal age may have an impact due to the increasing number of mutations in the sperm DNA with increasing paternal age. We examined the association between paternal age and specific types of childhood cancer in offspring in a large nationwide cohort of 1,904,363 children born in Denmark from 1978 through 2010. The children were identified in the Danish Medical Birth Registry and were linked to information from other national registers, including the Danish Cancer Registry. In total, 3,492 children were diagnosed with cancer before the age of 15 years. The adjusted hazard ratio of childhood cancer according to paternal age was estimated using Cox proportional hazards regressions. We found a 13% (95% confidence interval: 4-23%) higher hazard rate for every 5 years advantage in paternal age for acute lymphoblastic leukemia, while no clear association was found for acute myeloid leukemia (hazard ratio pr. 5 years = 1.02, 95% confidence interval: 0.80-1.30). The estimates for neoplasms in the central nervous system suggested a lower hazard rate with higher paternal age (hazard ratio pr. 5 years = 0.92, 95% confidence interval: 0.84-1.01). No clear associations were found for the remaining childhood cancer types. The findings suggest that paternal age is moderately associated with a higher rate of childhood acute lymphoblastic leukemia, but not acute myeloid leukemia, in offspring, while no firm conclusions could be made for other specific cancer types.

Advanced paternal age and stillbirth rate: a nationwide register-based cohort study of 944,031 pregnancies in Denmark.

Advanced paternal age has been associated with a variety of rare conditions and diseases of great public health impact. An increased number of de novo point mutations in sperm with increasing age have been suggested as a mechanism, which would likely also affect fetal viability. We examined the association between paternal age and stillbirth rate in a large nationwide cohort. We identified all pregnancies in Denmark from 1994 to 2010 carried to a gestational age of at least 22 completed weeks (n = 944,031) as registered in national registers and linked to individual register data about the parents. The hazard ratio of stillbirth according to paternal age was estimated, adjusted for maternal age in 1-year categories, year of outcome, and additionally parental educational levels. The relative rate of stillbirth (n = 4946) according to paternal age was found to be J-shaped with the highest hazard ratio for fathers aged more than 40 years when paternal age was modelled using restricted cubic splines. When modelled categorically, the adjusted hazard ratios of stillbirth were as follows: <25, 1.16 (95% confidence interval, CI 1.01-1.34); 25-29, 1.03 (95% CI 0.95-1.11); 35-39, 1.16 (95% CI 1.07-1.26); 40-44, 1.41 (95% CI 1.26-1.59); 45-49, 1.20 (95% CI 0.97-1.49); 50+, 1.58 (95% CI 1.18-2.11), compared with fathers aged 30-34 years. These estimates attenuated slightly when further adjusted for parental education. Our study showed that paternal age was associated with the relative rate of stillbirth in a J-shaped manner with the highest hazard ratios among fathers aged more than 40 years.

Advanced Paternal Age and Risk of Musculoskeletal Congenital Anomalies in Offspring.

OBJECTIVE: Previous research suggests that advanced paternal age increases the risk of musculoskeletal congenital anomalies (CAs) in offspring, but findings are inconsistent. This study aims to investigate the risk of musculoskeletal CAs according to paternal age at birth in an unselected population covering cohort of children. STUDY DESIGN: A register-based prospective study of 1,605,885 children born in Denmark, 1978-2004, using information from record-linked health and administrative registers. The association between paternal age and overall musculoskeletal CAs, limb anomalies, craniosynostosis, skeletal dysplasias, syndromic musculoskeletal CAs, and other musculoskeletal CAs were investigated by multiple logistic regression analysis. RESULTS: For overall musculoskeletal CAs, a slightly higher risk per 10-year increase in paternal age was found (odds ratio [OR] = 1.06 [95% CI: 1.01-1.11; where CI is confidence interval]). A 26% (95% CI: 2-56%) excess risk was found for fathers aged 50+ years compared to fathers aged 30-34 years. For syndromic musculoskeletal CAs, excess risks were found for fathers aged 40+ years, compared to fathers aged 30-34 years (40-44: OR = 1.38 [95% CI: 1.01-1.88], 45-49: OR = 1.45 [95% CI: 0.89-2.34], 50+: OR = 1.42 [95% CI: 0.73-2.79]). The risks in all other subgroups of musculoskeletal CAs were increased for fathers aged 50+ years. CONCLUSIONS: A slightly higher risk for overall musculoskeletal CAs in offspring was found with increasing paternal age, mainly due to an excess risk of syndromic musculoskeletal CAs for fathers aged 40+ years. While associations between paternal age 50+ years and increased risk of all subtypes of musculoskeletal CAs were indicated, advanced paternal age likely plays a minor role in the etiology of these anomalies.

Covid-19 infection and vaccination during first trimester and risk of congenital anomalies: Nordic registry based study.

OBJECTIVES: To evaluate the risk of major congenital anomalies according to infection with or vaccination against covid-19 during the first trimester of pregnancy. DESIGN: Prospective Nordic registry based study. SETTING: Sweden, Denmark, and Norway. PARTICIPANTS: 343 066 liveborn singleton infants in Sweden, Denmark, and Norway, with an estimated start of pregnancy between 1 March 2020 and 14 February 2022, identified using national health registries. MAIN OUTCOME MEASURE: Major congenital anomalies were categorised using EUROCAT (European Surveillance of Congenital Anomalies) definitions. The risk after covid-19 infection or vaccination during the first trimester was assessed by logistic regression, adjusting for maternal age, parity, education, income, country of origin, smoking, body mass index, chronic conditions, and estimated date of start of pregnancy. RESULTS: 17 704 (5.2%) infants had a major congenital anomaly. When evaluating risk associated with covid-19 infection during the first trimester, the adjusted odds ratio ranged from 0.84 (95% confidence interval 0.51 to 1.40) for eye anomalies to 1.12 (0.68 to 1.84) for oro-facial clefts. Similarly, the risk associated with covid-19 vaccination during the first trimester ranged from 0.84 (0.31 to 2.31) for nervous system anomalies to 1.69 (0.76 to 3.78) for abdominal wall defects. Estimates for 10 of 11 subgroups of anomalies were less than 1.04, indicating no notable increased risk. CONCLUSIONS: Covid-19 infection and vaccination during the first trimester of pregnancy were not associated with risk of congenital anomalies.

Hospital care in the first 10 years of life of children with congenital anomalies in six European countries: data from the EUROlinkCAT cohort linkage study.

OBJECTIVE: To quantify the hospital care for children born with a major congenital anomaly up to 10 years of age compared with children without a congenital anomaly. DESIGN, SETTING AND PATIENTS: 79 591 children with congenital anomalies and 2 021 772 children without congenital anomalies born 1995-2014 in six European countries in seven regions covered by congenital anomaly registries were linked to inpatient electronic health records up to their 10th birthday. MAIN OUTCOME MEASURES: Number of days in hospital and number of surgeries. RESULTS: During the first year of life among the seven regions, a median of 2.4% (IQR: 2.3, 3.2) of children with a congenital anomaly accounted for 18% (14, 24) of days in hospital and 63% (62, 76) of surgeries. Over the first 10 years of life, the percentages were 17% (15, 20) of days in hospital and 20% (19, 22) of surgeries. Children with congenital anomalies spent 8.8 (7.5, 9.9) times longer in hospital during their first year of life than children without anomalies (18 days compared with 2 days) and 5 (4.1-6.1) times longer aged, 5-9 (0.5 vs 0.1 days). In the first year of life, children with gastrointestinal anomalies spent 40 times longer and those with severe heart anomalies 20 times longer in hospital reducing to over 5 times longer when aged 5-9. CONCLUSIONS: Children with a congenital anomaly consume a significant proportion of hospital care resources. Priority should be given to public health primary prevention measures to reduce the risk of congenital anomalies.

Joint exposure to parental cancer and income loss during childhood and the child's socioeconomic position in early adulthood: a Danish and Norwegian register-based cohort study.

BACKGROUND: Parental cancer as well as economic hardship in the family during childhood can affect the child negatively. Our aim was to examine the association between the joint exposure to parental cancer and income loss in childhood and the child's socioeconomic position in early adulthood. METHODS: We conducted a register-based prospective cohort study of children born in Denmark between 1978 and 1986 and in Norway between 1979 and 1987. The children were followed from 1 January 1994 (in Denmark) or 1995 (in Norway). Educational level and personal income were measured at age 30 years. Children who experienced parental cancer between the years they turned 8 and 16 years were identified, and exposure to income loss was measured in the same period. Adjusted multinomial logistic regression model was used to estimate relative risk ratios for the joint exposure of parental cancer and income loss during childhood. RESULTS: Children who experienced parental cancer and an income loss during childhood had an increased risk of low education and lower income at age 30 years. The associations were weaker for children only exposed to income loss and less clear for those only exposed to parental cancer. Further, exposure to parental cancer with a severe cancer type was associated with lower educational level. CONCLUSION: The child's educational attainment and income level in early adulthood were negatively affected by exposure to income loss in childhood, and even more so if exposed to both parental cancer and income loss. The associations with educational attainment were stronger for more severe cancer types.

The quality and the accuracy of codes for terminations of pregnancy for fetal anomalies recorded in hospital databases in three countries in northern Europe.

BACKGROUND: The number of terminations of pregnancy for fetal anomalies in Europe (TOPFA) has increased over recent decades. Therefore, it is important that TOPFAs, in addition to all other birth outcomes, are included in the surveillance of congenital anomalies and in studies on possible teratogenic risks of pregnancy exposures. The aim of this study was to evaluate the quality and the accuracy of codes identifying TOPFA cases in hospital databases. METHODS: TOPFA cases recorded in three EUROCAT congenital anomaly registries (Finland, 2010-2014; Funen in Denmark, 2005-2014; and northern Netherlands, 2013-2014) were linked to hospital databases using maternal IDs. RESULTS: A total of 2,114 TOPFA cases over the study period were identified in the registries and 2,096 (99%) of these pregnancies were identified in the hospital databases. An end of pregnancy code was present for 91% of the cases and a code for a congenital anomaly was present for 82% (with some differences across registries). The proportion of TOPFA cases with a code for a specific congenital anomaly was <50% for cases with a structural anomaly (range 0%-50%) and 70% for cases with a chromosomal anomaly. CONCLUSION: Hospital databases have limited information or codes to identify TOPFAs for specific anomalies and the data are not detailed enough for surveillance of congenital anomalies or for studies analyzing pregnancy exposures and risk of congenital anomalies. However, hospital data may be used to identify the occurrence of a TOPFA to enable more detailed information to be obtained from the medical records.

Ten-year survival of children with trisomy 13 or trisomy 18: a multi-registry European cohort study.

OBJECTIVE: To investigate the survival to 10 years of age of children with trisomy 13 (T13) and children with trisomy 18 (T18), born 1995-2014. DESIGN: Population-based cohort study that linked mortality data to data on children born with T13 or T18, including translocations and mosaicisms, from 13 member registries of EUROCAT, a European network for the surveillance of congenital anomalies. SETTING: 13 regions in nine Western European countries. PATIENTS: 252 live births with T13 and 602 with T18. MAIN OUTCOME MEASURES: Survival at 1 week, 4 weeks and 1, 5 and 10 years of age estimated by random-effects meta-analyses of registry-specific Kaplan-Meier survival estimates. RESULTS: Survival estimates of children with T13 were 34% (95% CI 26% to 46%), 17% (95% CI 11% to 29%) and 11% (95% CI 6% to 18%) at 4 weeks, 1 and 10 years, respectively. The corresponding survival estimates were 38% (95% CI 31% to 45%), 13% (95% CI 10% to 17%) and 8% (95% CI 5% to 13%) for children with T18. The 10-year survival conditional on surviving to 4 weeks was 32% (95% CI 23% to 41%) and 21% (95% CI 15% to 28%) for children with T13 and T18, respectively. CONCLUSIONS: This multi-registry European study found that despite extremely high neonatal mortality in children with T13 and T18, 32% and 21%, respectively, of those who survived to 4 weeks were likely to survive to age 10 years. These reliable survival estimates are useful to inform counselling of parents after prenatal diagnosis.

Survival, hospitalisation and surgery in children born with Pierre Robin sequence: a European population-based cohort study.

OBJECTIVE: To evaluate survival, hospitalisations and surgical procedures for children born with Pierre Robin sequence (PRS) across Europe. DESIGN: Multicentre population-based cohort study. SETTING: Data on 463 live births with PRS from a population of 4 984 793 from 12 EUROCAT congenital anomaly registries. METHODS: Data on children with PRS born 1995-2014 were linked electronically to data on mortality, hospitalisations and surgical procedures up to 10 years of age. Each registry applied a common data model to standardise the linked data and ran common syntax scripts to produce aggregate tables. Results from each registry were pooled using random-effect meta-analyses. MAIN OUTCOME MEASURES: Probability of survival, proportion of children hospitalised and undergoing surgery, and median length of hospital stay. RESULTS: The majority of deaths occurred in the first year of life with a survival rate of 96.0% (95% CI 93.5% to 98.5%); 95.1% (95% CI 92.7% to 97.7%) survived to age 10. In the first year of life, 99.2% (95% CI 95.0% to 99.9%) of children were hospitalised with a median stay of 21.4 days (95% CI 15.6 to 27.2), and 67.6% (95% CI 46.6% to 81.8%) underwent surgery. In the first 5 years of life, 99.2% of children underwent a median of two surgical procedures. Between ages 5 and 9, 58.3% (95% CI 44.7% to 69.7%) were hospitalised with a median annual stay of 0.3 days. CONCLUSIONS: Children with PRS had high mortality and morbidity with long hospital stays in the first year of life, and almost all had surgery before 5 years of age. Survival improved after infancy with fewer hospitalisations after age 5. This study provides reliable estimates of the survival and morbidity of children with PRS for families and healthcare providers.

Hospital Length of Stay and Surgery among European Children with Rare Structural Congenital Anomalies-A Population-Based Data Linkage Study.

Little is known about morbidity for children with rare structural congenital anomalies. This European, population-based data-linkage cohort study analysed data on hospitalisations and surgical procedures for 5948 children born 1995-2014 with 18 rare structural congenital anomalies from nine EUROCAT registries in five countries. In the first year of life, the median length of stay (LOS) ranged from 3.5 days (anotia) to 53.8 days (atresia of bile ducts). Generally, children with gastrointestinal anomalies, bladder anomalies and Prune-Belly had the longest LOS. At ages 1-4, the median LOS per year was ≤3 days for most anomalies. The proportion of children having surgery before age 5 years ranged from 40% to 100%. The median number of surgical procedures for those under 5 years was two or more for 14 of the 18 anomalies and the highest for children with Prune-Belly at 7.4 (95% CI 2.5-12.3). The median age at first surgery for children with atresia of bile ducts was 8.4 weeks (95% CI 7.6-9.2) which is older than international recommendations. Results from the subset of registries with data up to 10 years of age showed that the need for hospitalisations and surgery continued. The burden of disease in early childhood is high for children with rare structural congenital anomalies.