Maternal Age and the Prevalence of Congenital Heart Defects in Europe, 1995 to 2015; a register-based study

Background: Evidence on the direction and strength of association betweenmaternal age and the prevalence of congenital heart defects (CHD) in differentage group categories is conflicting. Some studies have illustrated differenttrends with an increase in prevalence in younger and older age groups whileother studies have reported a linear relationship. Given the increase in mater-nal age over recent years, it is important to study the CHD prevalence bymaternal age.Objectives: To examine the association between maternal age and the preva-lence of CHD in Europe between 1995 and 2015 using population-based datafrom 24 registries belonging to the European Surveillance of Congenital Anom-alies (EUROCAT) network.Methods: Associations over time of all nonsyndromic CHD according tomaternal age category and for three CHD severity groupings (severity group I:very severe; severity group II: severe; severity group III: less severe) were exam-ined using Bayesian multilevel Poisson regression modeling. Further subgroupanalyses were undertaken within four maternal age-bands: <=24, 25-29, 30-34and 35-44 years. Descriptive summaries are also presented.Results: There were 51,608 nonsyndromic CHD cases in Europe over the20-year study period. Total prevalence for all CHD combined was increased foryounger mothers (<=24 years) and for mothers 35-44 years of age when com-pared 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 sub-types: double outlet right ventricle (IRR:1.33, 95% CI: 1.09, 1.60), hypoplasticleft heart syndrome (IRR: 1.18, 95% CI: 1.05, 1.32), hypoplastic right heart syn-drome (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) andatrial 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 inthe prevalence for severity group II (IRR: 1.09, 95% CI: 1.03, 1.14), severitygroup III (IRR: 1.05, 95% CI: 1.01, 1.08) and an increased prevalence of theCHD 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 categoriescompared to the reference category, different associations of ASD and anincreased 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 andthe total prevalence of CHD for younger (<=24 years old) and older (35-44 yearsold) mothers was observed. The results suggest that young maternal age(<=24 years old) is a factor associated with severe CHD phenotypes while a posi-tive association between advanced maternal age (35-44 years old) and mildCHD phenotypes was observed.