Abstract
The associations of maternal history of spontaneous abortion (SA) and stillbirth with congenital heart disease (CHD) remain elusive. To evaluate the associations of maternal history of pregnancy loss with CHD in offspring and the role of maternal type 2 diabetes. This population-based cohort study included singleton live offspring born between January 1, 1977, and December 31, 2016, identified through Danish national health registries. Statistical analysis was performed from October 1, 2019, through September 1, 2021. Maternal history of SA, with frequency varying from 1 or 2 to 3 or more episodes, and maternal history of single and multiple stillbirths. Overall CHD identified by hospital diagnosis. Cox proportional hazard regression was used to estimate the hazard ratio (HR) of CHD. Diabetes was evaluated as a potential confounder and a potential effect modifier. Among 1 642 534 included offspring (mean [SD] age, 14.11 [8.39] years; 843 265 male [51.35%]), 246 669 (15.02%) were born to mothers with a history of SA and 9750 (0.59%) were born to mothers with a history of stillbirth. The HRs of CHD were 1.16 (95% CI, 1.13-1.20) for offspring with a maternal history of SA and 1.49 (95% CI, 1.32-1.68) for offspring with a maternal history of stillbirth. Significant dose-response associations were observed among offspring with a maternal history of 3 or more episodes of SA (HR, 1.60; 95% CI, 1.39-1.84) and those with maternal history of multiple stillbirths (HR, 2.75; 95% CI, 1.63-4.65). If only inpatient CHD cases were included, the risk of CHD was higher than that found in the main analysis, with HRs of 1.24 (95% CI, 1.19-1.30) for maternal history of SA and 1.78 (95% CI, 1.51-2.11) for maternal history of stillbirth. The observed associations were strengthened by maternal prepregnancy type 2 diabetes (HR for maternal history of SA, 1.65 [95% CI, 1.37-1.97]; HR for maternal history of stillbirth, 1.74 [95% CI, 1.06-2.85]). These findings suggest that offspring born to mothers with a previous SA or stillbirth, especially multiple episodes, or with prepregnancy type 2 diabetes were at a higher risk of being diagnosed with CHD. These findings may help identify women at increased risk in whom detailed fetal heart assessment may be cost-effective and highlight the importance of screening for type 2 diabetes in women of reproductive age.
Highlights
Congenital heart disease (CHD) is the most common congenital anomaly, with a global prevalence ranging from 9 to 18 per 1000 live births that resulted in 2.6 million deaths worldwide in 2017.1,2 The etiology of congenital heart disease (CHD) is complex, and epidemiological studies have suggested that a genetic or environmental cause can be identified in 20% to 30% of CHD cases.[3]
Significant dose-response associations were observed among offspring with a maternal history of 3 or more episodes of spontaneous abortion (SA) (HR, 1.60; 95% CI, 1.39-1.84) and those with maternal history of multiple stillbirths (HR, 2.75; 95% CI, 1.63-4.65)
If only inpatient CHD cases were included, the risk of CHD was higher than that found in the main analysis, with hazard ratio (HR) of 1.24 for maternal history of SA and 1.78 for maternal history of stillbirth
Summary
Congenital heart disease (CHD) is the most common congenital anomaly, with a global prevalence ranging from 9 to 18 per 1000 live births that resulted in 2.6 million deaths worldwide in 2017.1,2 The etiology of CHD is complex, and epidemiological studies have suggested that a genetic or environmental cause can be identified in 20% to 30% of CHD cases.[3]. Maternal history of pregnancy loss, including spontaneous abortion (SA) and stillbirth, was suggested as a risk factor for CHD in offspring in 2 case-control studies[10,11] and 1 cross-sectional study.[12] a null association was reported in another case-control study.[13] The inconsistent findings and less favorable design of these studies make it difficult to draw a solid conclusion. Spontaneous abortion occurs in 15% of all clinically identified pregnancies,[14] and stillbirth accounts for 18.4 per 1000 total births in the world and 3.4 per 1000 in developed regions.[15] The relatively high prevalence of pregnancy loss means that a small increased risk of CHD associated with maternal history of pregnancy loss could have major public health implications. The determination of maternal history of SA and stillbirth as risk factors for CHD warrants further investigation by well-designed studies
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
