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Anne Sofie Dam Laursen

Association of Maternal History of Spontaneous Abortion and Stillbirth with Risk of Congenital Heart Disease in Offspring of Women with vs without Type 2 Diabetes

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  • Honglei Ji, Fudan University, Aarhus Universitet
  • ,
  • Hong Liang
  • ,
  • Yongfu Yu, Fudan University
  • ,
  • Ziliang Wang, Fudan University
  • ,
  • Wei Yuan, Fudan University
  • ,
  • Xu Qian, Fudan University
  • ,
  • Ellen Margrethe Mikkelsen
  • Anne Sofie Dam Laursen
  • Guanghong Fang, Fudan University
  • ,
  • Guoying Huang, Fudan University
  • ,
  • Maohua Miao, Fudan University
  • ,
  • Jiong Li

Importance: The associations of maternal history of spontaneous abortion (SA) and stillbirth with congenital heart disease (CHD) remain elusive. Objective: To evaluate the associations of maternal history of pregnancy loss with CHD in offspring and the role of maternal type 2 diabetes. Design, Setting, and Participants: 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. Exposures: Maternal history of SA, with frequency varying from 1 or 2 to 3 or more episodes, and maternal history of single and multiple stillbirths. Main Outcomes and Measures: 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. Results: 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]). Conclusions and Relevance: 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.

TidsskriftJAMA network open
StatusUdgivet - nov. 2021

Bibliografisk note

Funding Information:
Funding/Support: This study was supported by grants 2016YFC1000500 (Dr Huang) and 2018YFC1002801 (Dr Liang) from the National Key Research and Development Program, Innovation-Oriented Science and Technology Grant CX2017-06 from NHC Key Laboratory of Reproduction Regulation (Dr Miao), grant 82073570 from the National Natural Science Foundation of China (Dr Li), grants DFF-6110-00019B and DFF 9039-00010B from the Independent Research Fund Denmark (Dr Li), grant R275-A15770 from the Nordic Cancer Union (Dr Li), the Karen Elise Jensens Fond (2016) (Dr Li), and grant NNF18OC0052029 from the Novo Nordisk Foundation (Dr Li).

Publisher Copyright:
© 2021 Ji H et al.

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