Congenital heart disease and the risk of impaired fertility: A Danish nationwide cohort study using time to pregnancy.

BACKGROUND: The number of women with congenital heart disease (CHD) becoming pregnant are increasing. Although menstrual irregularities appear to occur more often in these patients, knowledge on their fertility is limited. In this nationwide cohort study, we evaluated the risk of impaired fertility in women with CHD compared with unaffected women using time to pregnancy (TTP). METHODS: The Danish National Birth Cohort (DNBC) of pregnant women constituted the study population. Information on TTP and use of medically assisted reproduction (MAR) treatment was reported at a first trimester interview. Women with CHD were identified by linkage to the Danish National Patient Registry. TTP was divided into three categories; 0-5 months, 6-12 months (i.e. subfertile), and > 12 months or use of MAR treatment (i.e. infertile). Relative risk ratios (RRR) for subfertility and infertility with 95% confidence intervals were estimated using multinomial logistic regression. RESULTS: Among 93,832 pregnancies in 84,922 women, CHD was diagnosed in 333 women (0.4%), contributing with 360 pregnancies. The CHD was of simple complexity in 291 women (87.4%). No association was found between CHD and longer TTP (RRR of 1.02 (95% CI: 0.75-1.40) for subfertility, and RRR of 0.86 (95% CI: 0.61-1.20) for infertility). Similar was observed when comparing women with simple CHD and unaffected women. The number of women with complex CHD was too low for evaluation. CONCLUSIONS: Women with CHD had no increased risk of impaired fertility, assessed by TTP, when compared with unaffected women. Separate analysis of women with complex CHD was hampered by low numbers.

Congenital Heart Disease and Fertility: A Danish Nationwide Cohort Study Including Both Men and Women.

Background Despite an increasing number of patients with congenital heart disease (CHD) reaching reproductive age, the fertility of these patients remains undescribed. Therefore, the aim of the study was to evaluate the fertility in men and women with CHD by estimating the risk of infertility and comparing the birth rates, proportions of individuals becoming parents or remaining childless, and the number of children per parent with unaffected individuals. Methods and Results The study population consisted of individuals born between 1977 and 2000. Information on CHD, infertility, and live born children were obtained from the Danish health registries. Hazard ratios for infertility were analyzed using a Cox regression model. Differences of proportions and birth rates were calculated and compared between groups. Among 1 385 895 individuals, a total of 8679 (0.6%) were diagnosed with CHD. Men and women with simple or moderate CHD had no increased risk of infertility when compared with the reference population. Estimates for complex CHD groups were too imprecise for evaluation. Individuals with CHD were more often childless with consequently lower birth rates compared with unaffected individuals. However, those becoming parents had the same number of children as the reference population. Conclusions Men and women with simple or moderate CHD had the same risk of infertility as the reference population. Despite patients with CHD more often being childless, those becoming parents had the same number of children as parents without CHD. The current findings increase the knowledge regarding fertility in the CHD population.

Timing of Pubertal Development in Boys and Girls With Congenital Heart Defects: A Nationwide Cohort Study.

Background Children with congenital heart defects (CHD) have an increased risk of developmental delay. It remains sparsely investigated if these patients also have a delayed pubertal development. In this nationwide cohort study, we evaluated if CHD was associated with timing of puberty using longitudinally collected data on pubertal milestones. Methods and Results We used data from the Danish nationwide Puberty Cohort. Information on CHD was obtained from the Danish National Patient Register. Information on pubertal development was obtained from 15 780 children through questionnaires answered half-yearly from 11 years until 18 years or full maturity. Using a multivariable regression model for censored time-to-event data, mean difference in age at attaining each pubertal milestone was estimated, including a combined pubertal marker. Compared with children without CHD, analyses were performed for both CHD overall and subdivided into simple and complex CHD. In a subanalysis, analyses were repeated in children born at term. In total, 137 children (62 boys and 75 girls) had a CHD diagnosis. Overall, no difference in age at pubertal timing was observed for children with CHD compared with unaffected children. The average differences were small for both boys (1.6 [95% CI, -2.6 to 5.7] months) and girls (1.0 [95% CI, -2.5 to 4.4] months). The same differences were observed when subdividing into simple or complex CHD and when restricting to children born at term. Conclusions We found no association between CHD and pubertal timing. For the group of children with complex CHD, we were unable to exclude a later pubertal timing.

Pregnancy outcome in women with atrial septal defect: associated with in vitro fertilisation and pre-eclampsia.

Objective: To investigate in vitro fertilisation (IVF) in women with atrial septal defect (ASD), and to examine the maternal characteristics and outcome of pregnancy, as well as the fetal outcome of infants born by women with ASD. Methods: We used population-based registries in this nationwide cohort study, including Danish individuals born before 1994 who received an ASD diagnosis between 1959 and 2014. Patients were compared with a random reference sample (ratio of 10 citizens per patient) matched by sex and age. The Danish Medical Birth Register (DMBR) contains data on all pregnancies and births in Denmark from 1977 to present. Risk of IVF treatment as well as maternal, pregnancy and fetal outcomes were compared. Results: A total of 2277 Danish patients had a validated ASD diagnosis. Of these, 310 women were identified in the DMBR. Women with ASD had an increased risk of receiving IVF treatment (HR 3.14, 95% CI 2.1 to 4.7, p<0.0001), and a higher proportion of patients received IVF treatment when compared with the reference cohort (10.6% vs 3.2%; p<0.001). Furthermore, patients had more multiple births. Looking at singleton pregnancies (n=519), pre-eclampsia occurred more frequently in patients with ASD during pregnancy (6.7% vs 2.3%; p<0.001). Infants from mothers with ASD were found to have perinatal outcomes comparable to those of infants from the reference group. Conclusion: Women with ASD had an increased risk of and received more IVF treatment than the reference group. The outcome of pregnancy in these patients were generally uneventful, however, we did confirm that pre-eclampsia occurred more frequently.