Survival of children with rare structural congenital anomalies: a multi‑registry cohort study

Alessio Coi, Michele Santoro, Anna Pierini, Judith Rankin, Svetlana Glinianaia, Joachim Tan, Abigail-Kate Reid, Ester Garne, Maria Loane, Joanne Given, E Ballardini, Clara Cavero-Carbonell, Hermien de Walle, Miriam Gatt, Laura Garcia-Villodre, Mika Gissler, Sue Jordan, Sonja Kiuru-Kuhlefelt, Stine Kjaer Urhoj, Kari KlungsøyrNatalie Lelong, L Renee Lutke, Amanda Neville, Makan Rahshenas, Ieuan Scanlon, Diana Wellesley, Joan K Morris

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Background: Congenital anomalies are the leading cause of perinatal, neonatal and infant mortality in developed countries. Large long-term follow-up studies investigating survival beyond the first year of life in children with rare congenital anomalies are costly and sufficiently large standardized cohorts are difficult to obtain due to the rarity of
some anomalies. This study aimed to investigate the survival up to 10 years of age of children born with a rare structural congenital anomaly in the period 1995–2014 in Western Europe.
Methods: Live births from thirteen EUROCAT (European network for the epidemiological surveillance of congenital anomalies) population-based registries were linked to mortality records. Survival for 12,685 live births with one of the 31 investigated rare structural congenital anomalies (CAs) was estimated at 1 week, 4 weeks and 1, 5 and 10 years
of age within each registry and combined across Europe using random effects meta-analyses. Differences between registries were evaluated for the eight rare CAs with at least 500 live births.
Results: Amongst the investigated CAs, arhinencephaly/holoprosencephaly had the lowest survival at all ages (58.1%, 95% Confidence Interval (CI): 44.3–76.2% at 1 week; 47.4%, CI: 36.4–61.6% at 1 year; 35.6%, CI: 22.2–56.9% at 10 years). Overall, children with rare CAs of the digestive system had the highest survival (> 95% at 1 week, > 84% at
10 years). Most deaths occurred within the first four weeks of life, resulting in a 10-year survival conditional on surviving 4 weeks of over 95% for 17 out of 31 rare CAs. A moderate variability in survival between participating registries was observed for the eight selected rare CAs.
Conclusions: Pooling standardised data across 13 European CA registries and the linkage to mortality data enabled reliable survival estimates to be obtained at five ages up to ten years. Such estimates are useful for clinical practice and parental counselling.
Original languageEnglish
Article number142
Pages (from-to)1-11
Number of pages11
JournalOrphanet Journal of Rare Diseases
Issue number142
Publication statusPublished (in print/issue) - 29 Mar 2022

Bibliographical note

Funding Information:
This project has received funding from the European Union’s Horizon 2020 research and innovation programme under Grant Agreement No. 733001 (Jan 2017–May 2022) ). The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, or review; and decision to submit the manuscript for publication. The views presented here are those of the authors only and the European Commission is not responsible for any use that may be made of the information presented here.

Funding Information:
We are very grateful to the whole EUROlinkCAT Working Group for their contribution to the project (data linkage and standardization, running syntax scripts): Dr Nicole Siemensma-M?hlenberg (University Medical Center Groningen, Groningen, The Netherlands); ?scar Zurriaga, Ana Ruiz Palacio, Sandra Moreno Marro and Laia Barrachina Bonet (Foundation for the Promotion of Health and Biomedical Research in the Valencian Region, Valencia, Spain); Anna Heino and Tuuli Puroharju (THL Finnish Institute for Health and Welfare. Helsinki, Finland); Drs Gianni Astolfi, Aurora Puccini, Annarita Armaroli (Center for Clinical and Epidemiological Research, University of Ferrara, Ferrara, Italy); Nathalie Bertille and Babak Khoshnood (INSERM, Paris, France); Professor Elizabeth Draper (University of Leicester, Leicester, United Kingdom); Professor Jenny Kurinczuk (University of Oxford, Oxford, United Kingdom). We also thank Mr Hugh Claridge (Population Health Research Institute, St George?s, University of London, London, United Kingdom) for the project management.

Publisher Copyright:
© 2022, The Author(s).


  • Child
  • Cohort Studies
  • Europe/epidemiology
  • Female
  • Humans
  • Infant
  • Newborn
  • Pregnancy
  • Registries
  • Europe


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