Maternal age and the prevalence of congenital heart defects in Europe, 1995–2015: A register‐based study
Authors: Mamasoula Chrysovalanto , Bigirumurame Theophile , Chadwick Thomas , Addor Marie‐Claude , Cavero‐Carbonell Clara , Dias Carlos M. , Echevarría‐González‐de‐Garibay Luis‐Javier , Gatt Miriam , Khoshnood Babak , Klungsoyr Kari , Randall Kay , Stoianova Sylvia , Haeusler Martin , Nelen Vera , Neville Amanda J. , Perthus Isabelle , Pierini Anna , Bertaut‐Nativel Bénédicte , Rissmann Anke , Rouget Florence , Schaub Bruno , Tucker David , Wellesley Diana , Zymak‐Zakutnia Natalya , Barisic Ingeborg , de Walle Hermien E.K. , Lanzoni Monica , Sayers Gerardine , Mullaney Carmel , Pennington Lindsay , Rankin Judith 
Published: February 2023

Background

Evidence 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.

Objectives

To 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.

Methods

Associations 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.

Results

There 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.

Conclusions

Based 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.