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JACC Adv
JACC Adv
JACC: Advances
2772-963X
Elsevier

S2772-963X(24)00479-4
10.1016/j.jacadv.2024.101248
101248
Letters
To the Editor
Preeclampsia and Congenital Heart Disease in Offspring
Unresolved Issues
Tang Wei-Zhen MD ab
Li Ying-Bo PhD b
Liu Tai-Hang PhD liuth@cqmu.edu.cn
b∗
Lan Xia MD 18623177325@163.com
a∗∗
a Women and Children’s Hospital of Chongqing Medical University, Chongqing, China
b School of Basic Medical Sciences, Chongqing Medical University, Chongqing, China
∗ Department of Bioinformatics, School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China liuth@cqmu.edu.cn
∗∗ Women and Children's Hospital of Chongqing Medical University, No. 120 Longshan Rd, Yubei District, Chongqing 401147, China. 18623177325@163.com
14 9 2024
10 2024
14 9 2024
3 10 101248© 2024 The Authors
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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pmcThe latest study findings by Isabel Katlaps and colleagues have revealed a persistent association between preeclampsia and congenital heart disease (CHD) in offspring, an association that extends beyond a single pregnancy and may span multiple gestations.1 These findings are enlightening, suggesting that the etiology of preeclampsia and its connection to the embryonic development of cardiovascular structures warrant further investigation. However, we believe there are several key issues in the study that could potentially affect the interpretation of the results and need to be addressed to enhance the study’s accuracy.

First, it is not clear whether the study excluded mothers with CHD. Pregnant women with CHD could influence the cardiac development of the fetus through genetic or other biological mechanisms, increasing the risk of CHD in newborns. Moreover, a substantial body of research indicates that women with CHD are at a significantly increased risk of developing preeclampsia, possibly due to reduced placental perfusion.2,3 This could affect the observed association between preeclampsia and CHD. Additionally, the increased risk of preterm birth in pregnant women with CHD could further impact the accuracy of subgroup analyses for early-onset and late-onset preeclampsia.

Second, the study does not specify whether an adjustment was made for the maternal history of miscarriage or stillbirth. Research has shown that a maternal history of miscarriage is associated with an increased risk of CHD in offspring, potentially through common pathological mechanisms such as placental defects and genetic variations in the niacin synthesis pathway.4 Furthermore, a history of miscarriage or stillbirth is related to an increased risk of preeclampsia and preterm birth.5 Women with such histories may be more inclined to take preventative measures in subsequent pregnancies, such as folic acid supplementation, which has been shown to have a potential positive effect on preventing CHD and preeclampsia. Therefore, failing to consider these prior pregnancy events could mask the true strength and nature of the association between preeclampsia and CHD, especially when assessing the interrelationship between index pregnancies and subsequent pregnancies.

The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.
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References

1 Isabel K. Ronai C. Garg B. Mandelbaum A. Ghafari-Saravi A. Caughey A.B. The ongoing relationship between offspring congenital heart disease and preeclampsia across pregnancies JACC Adv 3 7P1 2024 101009 10.1016/j.jacadv.2024.101009
2 Hayward R.M. Foster E. Tseng Z.H. Maternal and fetal outcomes of admission for delivery in women with congenital heart disease JAMA Cardiol 2 2017 664 671 10.1001/jamacardio.2017.0283 28403428
3 Hardee I. Wright L. McCracken C. Lawson E. Oster M.E. Maternal and neonatal outcomes of pregnancies in women with congenital heart disease: a meta-analysis J Am Heart Assoc 10 2021 e017834 10.1161/JAHA.120.017834
4 Ji H. Liang H. Yu Y. 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 JAMA Netw Open 4 2021 e2133805 10.1001/jamanetworkopen.2021.33805
5 Zhang J. Liu X. Rao L. Adverse obstetric and perinatal outcomes of patients with history of recurrent miscarriage: a retrospective cohort study Fertil Steril 120 2023 626 634 10.1016/j.fertnstert.2023.04.028 37121567
