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

Joachim Tan, Svetlana Glinianaia, Judith Rankin, Anna Pierini, Michele Santoro, Alessio Coi, Ester Garne, Maria Loane, Joanne Given, Joanna Brigden, Elisa Ballardini,, Clara Cavero‑Carbonell, Hermien EK de Walle, Laura García-Villodre, Miriam Gatt, Mika Gissler, Anna Heino, Sue Jordan, Babak Khoshnood, Kari KlungsoyrNathalie Lelong, Renee L Lutke, Amanda J. Neville, David Tucker, Stine K Urhoj, Diana Wellesley, Joan K Morris

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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 1995-2014 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 (HRs) 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) tmes 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 1-9 years than males.

Conclusions: 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.
Original languageEnglish
Pages (from-to)1-12
Number of pages12
JournalPaediatric and Perinatal Epidemiology
Issue number8
Early online date10 Oct 2023
Publication statusPublished online - 10 Oct 2023

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. Start Date: 1 Jan 2017. Duration: 5 years 5 months. ( https://ec.europa.eu/programmes/horizon2020/en ).

Funding Information:
We thank EUROlinkCAT contributors to this paper for their work on the project (including data provision, linkage and standardisation; writing and running of syntax scripts). Ms Abigail Reid (St George's, University of London, London, United Kingdom); Ms Nicole Siemensma-Muhlenberg (University Medical Center Groningen, Groningen, Netherlands); Sandra Moreno Marro, Laia Barrachina Bonet (Foundation for the Promotion of Health and Biomedical Research in the Valencian Region, Valencia, Spain); Dr Sonja Kiuru-Kuhlefelt, 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 Makan Rahshenas (INSERM, Paris, France); Mr Daniel Thayer (Faculty of Medicine, Health and Life Science, Swansea University, Swansea, Wales, UK); Professor Elizabeth Draper (University of Leicester, Leicester, United Kingdom); Professor Jenny Kurinczuk (University of Oxford, Oxford, United Kingdom). We also thank Mr Hugh Claridge for the project management.

Publisher Copyright:
© 2023 The Authors. Paediatric and Perinatal Epidemiology published by John Wiley & Sons Ltd.


  • Congenital Abnormalities
  • Mortality
  • risk factor
  • Data linkage
  • Europe
  • Gestational Age
  • Maternal age
  • risk factors
  • maternal age
  • mortality
  • congenital anomalies
  • gestational age


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