Advanced maternal age and risk of adverse perinatal outcome among women with congenital heart disease: A nationwide register-based cohort study

Background: Women with maternal congenital heart disease have a higher risk of preterm birth (PTB) and giving birth to a small for gestational age (SGA) infant. Advanced maternal age (≥35 years) likewise increases the risk of PTB and SGA, probably explained by poorer cardiovascular status. It is likely that advanced maternal age is particularly detrimental in women with congenital heart disease. Objectives: We aimed to determine whether the pattern of higher risk of PTB and SGA with higher maternal age varied among women with and without congenital heart disease. We hypothesised that the effect of age is higher among women with congenital heart disease. Methods: We did a cohort study using Danish nationwide registers. Births from 1997 to 2014 were included. Cox regressions were used to estimate hazard ratios (HRs) for PTB and SGA. Universal and congenital heart disease-specific references were used for comparison. Results: We included 932 772 births among 548 314 women. HRs of PTB and SGA were 1.55 (95% confidence interval [CI] 1.37, 1.77) and 1.43 (95% CI 1.29, 1.58) in women with congenital heart disease as compared to women without. For both PTB and SGA, HRs were higher for women ≥35 years as compared to women aged 25-29 years. HRs of PTB and SGA were higher among women with congenital heart disease within all strata of maternal age as compared to women without (eg 3.71, 95% CI 1.80, 7.63 vs 1.63, 95% CI 1.56, 1.70) for SGA for women aged 40-44 years). The pattern of higher risk of PTB and SGA with higher maternal age was, however, similar among women with and without congenital heart disease. Conclusions: Women with congenital heart disease had a higher risk of PTB and giving birth to an SGA infant at all maternal ages. These two risk factors did not, however, seem to potentiate each other.