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 Klungsoyr; Nathalie Lelong; Renee L Lutke; Amanda J. Neville; David Tucker; Stine K  Urhoj; Diana Wellesley; Joan K Morris

doi:10.1111/ppe.13010

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 Klungsoyr

Nathalie Lelong, Renee L Lutke, Amanda J. Neville, David Tucker, Stine K Urhoj, Diana Wellesley, Joan K Morris

Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

43 Downloads (Pure)

Abstract

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 language	English
Pages (from-to)	1-12
Number of pages	12
Journal	Paediatric and Perinatal Epidemiology
Volume	37
Issue number	8
Early online date	10 Oct 2023
DOIs	https://doi.org/10.1111/ppe.13010
Publication status	Published 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.

Funding

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.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

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

Access to Document

10.1111/ppe.13010

Paediatric Perinatal Epid - 2023 - Tan - Risk factors for mortality in infancy and childhood in children with majorFinal published version, 417 KBLicence: CC BY

Cite this

Tan, J., Glinianaia, S., Rankin, J., Pierini, A., Santoro, M., Coi, A., Garne, E., Loane, M., Given, J., Brigden, J., Ballardini, E., Cavero‑Carbonell, C., de Walle, H. EK., García-Villodre, L., Gatt, M., Gissler, M., Heino, A., Jordan, S., Khoshnood, B., ... Morris, J. K. (2023). Risk factors for mortality in infancy and childhood in children with major congenital anomalies: a European population-based cohort study. Paediatric and Perinatal Epidemiology, 37(8), 1-12. Advance online publication. https://doi.org/10.1111/ppe.13010

@article{72768cb8b13442c5b92f492b78173d8d,

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

abstract = "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{\textquoteright}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.",

keywords = "Congenital Abnormalities, Mortality, risk factor, Data linkage, Europe, Gestational Age, Maternal age, risk factors, maternal age, mortality, congenital anomalies, gestational age",

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

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: {\textcopyright} 2023 The Authors. Paediatric and Perinatal Epidemiology published by John Wiley \& Sons Ltd.",

year = "2023",

month = oct,

day = "10",

doi = "10.1111/ppe.13010",

language = "English",

volume = "37",

pages = "1--12",

journal = "Paediatric and Perinatal Epidemiology",

publisher = "Wiley-Blackwell Publishing Ltd",

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Tan, J, Glinianaia, S, Rankin, J, Pierini, A, Santoro, M, Coi, A, Garne, E, Loane, M , Given, J, Brigden, J, Ballardini, E, Cavero‑Carbonell, C, de Walle, HEK, García-Villodre, L, Gatt, M, Gissler, M, Heino, A, Jordan, S, Khoshnood, B, Klungsoyr, K, Lelong, N, Lutke, RL, Neville, AJ, Tucker, D, Urhoj, SK, Wellesley, D & Morris, JK 2023, 'Risk factors for mortality in infancy and childhood in children with major congenital anomalies: a European population-based cohort study', Paediatric and Perinatal Epidemiology, vol. 37, no. 8, pp. 1-12. https://doi.org/10.1111/ppe.13010

TY - JOUR

T1 - Risk factors for mortality in infancy and childhood in children with major congenital anomalies: a European population-based cohort study

AU - Tan, Joachim

AU - Glinianaia, Svetlana

AU - Rankin, Judith

AU - Pierini, Anna

AU - Santoro, Michele

AU - Coi, Alessio

AU - Garne, Ester

AU - Loane, Maria

AU - Given, Joanne

AU - Brigden, Joanna

AU - Ballardini,, Elisa

AU - Cavero‑Carbonell, Clara

AU - de Walle, Hermien EK

AU - García-Villodre, Laura

AU - Gatt, Miriam

AU - Gissler, Mika

AU - Heino, Anna

AU - Jordan, Sue

AU - Khoshnood, Babak

AU - Klungsoyr, Kari

AU - Lelong, Nathalie

AU - Lutke, Renee L

AU - Neville, Amanda J.

AU - Tucker, David

AU - Urhoj, Stine K

AU - Wellesley, Diana

AU - Morris, Joan K

N1 - 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.

PY - 2023/10/10

Y1 - 2023/10/10

N2 - 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.

AB - 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.

KW - Congenital Abnormalities

KW - Mortality

KW - risk factor

KW - Data linkage

KW - Europe

KW - Gestational Age

KW - Maternal age

KW - risk factors

KW - maternal age

KW - mortality

KW - congenital anomalies

KW - gestational age

UR - https://www.scopus.com/pages/publications/85173638085

U2 - 10.1111/ppe.13010

DO - 10.1111/ppe.13010

M3 - Article

C2 - 37817457

VL - 37

SP - 1

EP - 12

JO - Paediatric and Perinatal Epidemiology

JF - Paediatric and Perinatal Epidemiology

IS - 8

ER -

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

Abstract

Bibliographical note

Funding

UN SDGs

Keywords

Access to Document

Other files and links

Fingerprint

EUROlinkCAT Protocol for a European population-based data linkage study investigating the survival, morbidity and education of children with congenital anomalies

Linking a European cohort of children born with congenital anomalies to vital statistics and mortality records: a EUROlinkCAT study

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