Advanced maternal age and critical congenital cardiac malformations in Nevada

Abstract

BackgroundControversy exists regarding an association between advanced maternal age and the occurrence of fetal congenital heart disease and whether advanced maternal age is an indication for fetal echocardiography. ObjectivesOur purpose was to undertake a retrospective, multi-year review of critical congenital heart disease in Nevada to investigate a possible association with advanced maternal age. MethodsWe identified all those prenatally and postnatally diagnosed between September 2012 and August 2020. For each identified case, we tabulated each pregnant woman’s age at the estimated date or actual date of delivery. Using Nevada population demographic data, we calculated the percentages of pregnant women ≥ 35 years old (defined as advanced maternal age) and of pregnant women < 35 years old. Subsequently, we calculated occurrence rates for critical congenital cardiac malformations in advanced and non-advanced maternal age populations. A chi-square risk ratio analysis, excluding aneuploidy cases, was used to determine statistical significance for each malformation. ResultsWe identified 467 total cases. Of the 467, 39 (8.4%) had aneuploidy. Of the 467, 413 (88.4%) were live born, 32 (6.9%) had fetal demise, and 22 (4.7%) had elective termination. There were approximately 280,000 live births during the study period for a prevalence of 14.8 cases (inclusive of both those with and without aneuploidies) per 10,000 live births. From the 428 cases exclusive of aneuploidy, the following malformations were statistically significantly associated with advanced maternal age (risk ratios with 95% CI): 1) coarctation ± ventricular septal defect 1.75 (1.12, 2.73) p = 0.01, 2) D-transposition of the great arteries ± ventricular septal defect 2.13 (1.18, 2.83) p = 0.01, 3) double outlet right ventricle 2.10 (1.01, 4.35) p = 0.04, and 4) tetralogy of Fallot ± pulmonary atresia 2.40 (1.39, 4.31) p = 0.001. ConclusionExcluding aneuploidy cases, advanced maternal age was statistically significantly associated with some critical congenital cardiac malformations and lacked association with others.