Maternal age and the prevalence of congenital heart defects in Europe, 1995–2015: A register‐based study

Author:

Mamasoula Chrysovalanto1,Bigirumurame Theophile1,Chadwick Thomas1,Addor Marie‐Claude2,Cavero‐Carbonell Clara3,Dias Carlos M.14,Echevarría‐González‐de‐Garibay Luis‐Javier5,Gatt Miriam6,Khoshnood Babak7,Klungsoyr Kari89,Randall Kay10,Stoianova Sylvia11,Haeusler Martin12,Nelen Vera13,Neville Amanda J.14,Perthus Isabelle15,Pierini Anna16,Bertaut‐Nativel Bénédicte17,Rissmann Anke18ORCID,Rouget Florence19,Schaub Bruno20,Tucker David21,Wellesley Diana22,Zymak‐Zakutnia Natalya23,Barisic Ingeborg24,de Walle Hermien E.K.25,Lanzoni Monica26,Sayers Gerardine27,Mullaney Carmel28,Pennington Lindsay1,Rankin Judith1

Affiliation:

1. Population Health Sciences Institute Newcastle University Newcastle UK

2. Department of Woman‐Mother‐Child University Medical Center CHUV Lausanne Switzerland

3. Rare Diseases Research Unit Foundation for the Promotion of Health and Biomedical Research in the Valencian Region Valencia Spain

4. Epidemiology Department National Institute of Health Doutor Ricardo Jorge Lisbon Portugal

5. Ministry of Health of the Basque Government. Directorate for Healthcare Planning, Organisation and Evaluation Registries and Health Information Unit Vitoria‐Gasteiz Spain

6. Malta Congenital Anomalies Register Directorate for Health Information and Research Pietà Malta

7. Université de Paris INSERM U1153, CRESS, Obstetrical Perinatal and Pediatric Epidemiology Research Team (EPOPé) Paris France

8. Department of Global Public Health and Primary Care University of Bergen Bergen Norway

9. Division for Mental and Physical Health Norwegian Institute of Public Health Bergen Norway

10. National Perinatal Epidemiology Unit, Nuffield Department of Population Health University of Oxford Oxford UK

11. South West Congenital Anomaly Register, Bristol Medical School University of Bristol Bristol UK

12. Styrian Malformation Registry Med. University of Graz Graz Austria

13. Provinciaal Instituut voor Hygiene (PIH) Antwerp Belgium

14. Registro IMER ‐ IMER Registry (Emilia Romagna Registry of Birth Defects), Center for Clinical and Epidemiological Research University of Ferrara Ferrara Italy

15. Auvergne registry of congenital anomalies (CEMC‐Auvergne), Department of clinical genetics, Centre de Référence des Maladies Rares University Hospital of Clermont‐Ferrand Clermont‐Ferrand France

16. Tuscany Registry of Congenital Defects (RTDC) Institute of Clinical Physiology ‐ National Research Council/ Fondazione Toscana Gabriele Monasterio Pisa Italy

17. Register of Congenital Malformations of Reunion Island CHU Réunion Saint‐Denis France

18. Malformation Monitoring Centre Saxony‐Anhalt Medical Faculty Otto‐von‐Guericke University Magdeburg Germany

19. Brittany Registry of Congenital Anomalies, CHU Rennes, University Rennes, Inserm, EHESP Irset (Institut de recherche en santé, environnement et travail) Rennes France

20. French West Indies Registry, Registre des Malformations des Antilles (REMALAN), Maison de la Femme de la Mère et de l'Enfant University Hospital of Martinique Fort‐de‐France France

21. CARIS, Public Health Wales Singleton Hospital Swansea UK

22. Wessex Clinical Genetics Department Princess Anne Hospital Southampton UK

23. OMNI‐Net Ukraine Birth Defects Program and Khmelnytsky City Children's Hospital Khmelnytsky Ukraine

24. Centre of Excellence for Reproductive and Regenerative Medicine, Children's Hospital Zagreb Medical School University of Zagreb Zagreb Croatia

25. University of Groningen, University Medical Center Groningen Department of Genetics Groningen Netherlands

26. European Commission Joint Research Centre (JRC) Ispra Italy

27. Health Service Executive Dr Steeven's Hospital Dublin Ireland

28. Department of Public Health Service Executive (HSE) South East Area Limerick Ireland

Abstract

AbstractBackgroundEvidence on the direction and strength of association between maternal age and the prevalence of congenital heart defects (CHD) in different age group categories is conflicting. Some studies have illustrated different trends with an increase in prevalence in younger and older age groups while other studies have reported a linear relationship. Given the increase in maternal age over recent years, it is important to study the CHD prevalence by maternal age.ObjectivesTo examine the association between maternal age and the prevalence of CHD in Europe between 1995 and 2015 using population‐based data from 24 registries belonging to the European Surveillance of Congenital Anomalies (EUROCAT) network.MethodsAssociations over time of all nonsyndromic CHD according to maternal age category and for three CHD severity groupings (severity group I: very severe; severity group II: severe; severity group III: less severe) were examined using Bayesian multilevel Poisson regression modeling. Further subgroup analyses were undertaken within four maternal age‐bands: ≤24, 25–29, 30–34 and 35–44 years. Descriptive summaries are also presented.ResultsThere were 51,608 nonsyndromic CHD cases in Europe over the 20‐year study period. Total prevalence for all CHD combined was increased for younger mothers (≤24 years) and for mothers 35–44 years of age when compared with mothers aged 25–29 years (reference group) (IRR: 1.05, 95% CI: 1.02, 1.07). The total prevalence was increased for severity group I (very severe) only for younger mothers compared to those aged 25–29 years (IRR: 1.14, 95% CI: 1.04, 1.23). We found an increased prevalence of the following CHD subtypes: double outlet right ventricle (IRR:1.33, 95% CI: 1.09, 1.60), hypoplastic left heart syndrome (IRR: 1.18, 95% CI: 1.05, 1.32), hypoplastic right heart syndrome (IRR: 1.41, 95% CI: 1.05, 1.84), atrioventricular septal defect (IRR: 1.15, 95% CI: 1.01, 1.32), coarctation of aorta (IRR: 1.15, 95% CI: 1.03, 1.28) and atrial septal defect (IRR: 1.08, 95% CI: 1.02, 1.13). For older mothers (35–44 years) compared to the reference category, we observed an increased risk in the prevalence for severity group II (IRR: 1.09, 95% CI: 1.03, 1.14), severity group III (IRR: 1.05, 95% CI: 1.01, 1.08) and an increased prevalence of the CHD subtypes: Pulmonary valve stenosis (IRR: 1.22, 95% CI: 1.09, 1.34), ASD (IRR: 1.07, 95% CI: 1.02, 1.13), CoA (IRR: 1.18, 95% CI: 1.06, 1.32) and Tetralogy of Fallot (IRR: 1.14, 95% CI: 1.01, 1.28). Finally, for all age categories compared to the reference category, different associations of ASD and an increased prevalence of CoA was also observed.ConclusionsBased on data for cases of CHD from 24 European population‐based registries, evidence of a positive association between maternal age and the total prevalence of CHD for younger (≤24 years old) and older (35–44 years old) mothers was observed. The results suggest that young maternal age (≤24 years old) is a factor associated with severe CHD phenotypes while a positive association between advanced maternal age (35–44 years old) and mild CHD phenotypes was observed.

Publisher

Wiley

Subject

Health, Toxicology and Mutagenesis,Developmental Biology,Toxicology,Embryology,Pediatrics, Perinatology and Child Health

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