Placenta crucially affects formation of fetal congenital heart disease
V. I. Tsibizova,
T. M. Pervunina,
V. A. Artemenko,
V. O. Bitsadze,
K. E. Gotsiridze,
I. I. Averkin,
D. V. Blinov,
N. Yu. Novikova https://doi.org/10.17749/2313-7347/ob.gyn.rep.2022.262
Abstract
It has been increasingly recognized that structural abnormalities and functional changes in the placenta can adversely affect developing fetal heart. In this article, we examine a role of the placenta as well as potential impact of placental insufficiency on a fetus with congenital heart disease (CHD). The fetal heart and placenta are directly connected because they develop simultaneously with common regulatory and signaling pathways. Moreover, placenta-associated complications are more common in pregnant women carrying fetus with CHD, and the fetal response to placental insufficiency may lead to postnatal preservation of remodeled heart. The mechanisms underlying this placenta–fetus axis potentially consists of genetic factors, oxidative stress, chronic hypoxia, and/or angiogenic imbalance. Thus, the mother–placenta–fetus circulation is critical in understanding the CHD formation. It is necessary to study the changing factors involved in these processes for early identification, imaging, quantification of placental insufficiency, and development of new prenatal therapies in the CHD patient population.
About the Authors
V. I. Tsibizova
Almazov National Medical Research Centre, Health Ministry of Russian Federation
Russian Federation
Russian Federation
MD, PhD, Obstetrician-Gynecologist, Research Laboratory of Operative Gynecology, Institute of Perinatology and Pediatrics; Physician, Department of Functional and Ultrasound Diagnostics,
2 Akkuratova Str., Saint Petersburg 197341
T. M. Pervunina
Almazov National Medical Research Centre, Health Ministry of Russian Federation
Russian Federation
Russian Federation
MD, Dr Sci Med, Director of the Institute of Perinatology and Pediatrics,
2 Akkuratova Str., Saint Petersburg 197341
V. A. Artemenko
Almazov National Medical Research Centre, Health Ministry of Russian Federation
Russian Federation
Russian Federation
MD, Obstetrician-Gynecologist, Junior Researcher, Research Laboratory of Operative Gynecology, Institute of Perinatology and Pediatrics,
2 Akkuratova Str., Saint Petersburg 197341
V. O. Bitsadze
Sechenov University
Russian Federation
Russian Federation
MD, Dr Sci Med, Professor of RAS, Professor, Department of Obstetrics and Gynecology, Filatov Clinical Institute of Children’s Health,
2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow 119991
K. E. Gotsiridze
Chachava Clinic
Georgia
Georgia
MD, Obstetrician-Gynecologist, Head of the Center for Reproductive Health,
38 Merab Kostava Str., Tbilisi 0179
I. I. Averkin
Almazov National Medical Research Centre, Health Ministry of Russian Federation
Russian Federation
Russian Federation
MD, Pediatric Cardiologist, Department of Pediatric Cardiology,
2 Akkuratova Str., Saint Petersburg 197341
D. V. Blinov
Institute for Preventive and Social Medicine;
Lapino Clinical Hospital, GC «Mother and Child»
Russian Federation
Russian Federation
MD, PhD, MBA, Head of Medical and Scientific Affairs, 4–10 Sadovaya-Triumfalnaya Str., Moscow 127006;
Neurologist, 111, 1st Uspenskoe Highway, Lapino, Odintsovo District, Moscow region 143081
N. Yu. Novikova
Mechnikov North-Western State Medical University, Health Ministry of Russian Federation
Russian Federation
Russian Federation
5th year Student,
47 Piskarevskiy Prospect, Saint Petersburg 195067
References
1. van Deutekom A.W., Lewandowski A.J. Physical activity modification in youth with congenital heart disease: a comprehensive narrative review. Pediatr Res. 2020;89(7):1650–8. https://doi.org/10.1038/s41390-020-01194-8.
2. Lim T.B., Foo S.Y.R., Chen C.K. The role of epigenetics in congenital heart disease. Genes (Basel). 2021;12(3):390. https://doi.org/10.3390/genes12030390.
3. Reddy D.P., Viswamitra S. Cardiac embryology. In: CT and MRI in ongenital heart diseases. Springer, 2021. 29–54. https://doi.org/10.1007/978-981-15-6755-1_2.
4. Salman H.E., Alser M., Shekhar A. et al. Effect of left atrial ligation-driven altered inflow hemodynamics on embryonic heart development: Clues for prenatal progression of hypoplastic left heart syndrome. Biomech Model Mechanobiol. 2021;20(2):733–50. https://doi.org/10.1007/s10237-020-01413-5.
5. Burton G.J., Jauniaux E. Development of the human placenta and fetal heart: synergic or independent? Front Physiol. 2018;9:373. https://doi.org/10.3389/fphys.2018.00373.
6. Neufeld G., Cohen T., Gengrinovitch S., Poltorak Z. Vascular endothelial growth factor (VEGF) and its receptors. FASEB J. 1999;13(1):9–22.
7. Fowden A., Forhead A., Coan P., Burton G. The placenta and intrauterine programming. J Neuroendocrinol. 2008;20(4):439–50. https://doi.org/10.1111/j.1365-2826.2008.01663.x.
8. Saleemuddin A., Tantbirojn P., Sirois K. et al. Obstetric and perinatal complications in placentas with fetal thrombotic vasculopathy. Pediatr Dev Pathol. 2010;13(6):459–64. https://doi.org/10.2350/10-01- 0774-OA.1.
9. Verburg B.O., Jaddoe V., Wladimiroff J.W. et al. Fetal hemodynamic adaptive changes related to intrauterine growth: the Generation R Study. Circulation. 2008;117(5):649–59. https://doi.org/10.1161/CIRCULATIONAHA.107.709717.
10. Matthiesen N.B., Henriksen T.B., Agergaard P. et al. Congenital heart defects and indices of placental and fetal growth in a nationwide study of 924 422 liveborn infants. Circulation. 2016;134(20):1546–56. https://doi.org/10.1161/CIRCULATIONAHA.116.021793.
11. Khong T.Y., Mooney E.E., Ariel I. et al. Sampling and definitions of placental lesions: Amsterdam placental workshop group consensus statement. Arch Pathol Lab Med. 2016;140(7):698–713. https://doi.org/10.5858/arpa.2015-0225-CC.
12. Rychik J., Goff D., McKay E. et al. Characterization of the placenta in the newborn with congenital heart disease: distinctions based on type of cardiac malformation. Pediatr Cardiol. 2018;39(6):1165–71. https://doi.org/10.1007/s00246-018-1876-x.
13. Johnson J.A., Canavan T. Placental expression of vascular endothelial growth factor in patients with hypoplastic left heart syndrome. J Am Coll Cardiol. 2020;75(11 Suppl 1):630. https://doi.org/10.1016/s0735-1097(20)31257-2.
14. Barker D.J., Godfrey K.M., Gluckman P.D. et al. Fetal nutrition and cardiovascular disease in adult life. Lancet. 1993;341(8850):938–41. https://doi.org/10.1016/0140-6736(93)91224-a.
15. Menendez-Castro C., Rascher W., Hartner A. Intrauterine growth restriction-impact on cardiovascular diseases later in life. Mol Cell Pediatr. 2018;5(1):4. https://doi.org/10.1186/s40348-018-0082-5.
16. Zhao F., Lei F., Yan X. et al. Protective effects of hydrogen sulfide against cigarette smoke exposure-induced placental oxidative damage by alleviating redox imbalance via Nrf2 pathway in rats. Cell Physiol Biochem. 2018;48(5):1815–28. https://doi.org 10.1159/000492504.
17. Lu L., Kingdom J., Burton G.J., Cindrova-Davies T. Placental stem villus arterial remodeling associated with reduced hydrogen sulfide synthesis contributes to human fetal growth restriction. Am J Pathol. 2017;187(4):908–20. https://doi.org/10.1016/j.ajpath.2016.12.002.
18. Shen Y., Shen Z., Luo S. et al. The cardioprotective effects of hydrogen sulfide in heart diseases: from molecular mechanisms to therapeutic potential. Oxid Med Cell Longev. 2015;2015:925167. https://doi.org/10.1155/2015/925167.
19. Russell M.W., Moldenhauer J.S., Rychik J. et al. Damaging variants in proangiogenic genes impair growth in fetuses with cardiac defects. J Pediatr. 2019;213:103–9. https://doi.org/10.1016/j.jpeds.2019.05.013.
20. Laakkonen J.P., Lähteenvuo J., Jauhiainen S. et al. Beyond endothelial cells: vascular endothelial growth factors in heart, vascular anomalies and placenta. Vascul Pharmacol. 2019;112:91–101. https://doi.org/10.1016/j.vph.2018.10.005.
21. Llurba E., Sanchez O., Ferrer Q. et al. Maternal and foetal angiogenic imbalance in congenital heart defects. Eur Heart J. 2014;35(11):701–7. https://doi.org/10.1093/eurheartj/eht389.
22. Brodwall K., Leirgul E., Greve G. et al. Possible common aetiology behind maternal preeclampsia and congenital heart defects in the child: a cardiovascular diseases in Norway project study. Paediatr Perinat Epidemiol. 2016;30(1):76–85. https://doi.org/10.1111/ppe.12252.
23. Hertig A., Berkane N., Lefevre G. et al. Maternal serum sFlt1 concentration is an early and reliable predictive marker of preeclampsia. Clin Chem. 2004;50(9):1702–3. https://doi.org/10.1373/clinchem.2004.036715.
24. Cahill L.S., Stortz G., Chandran A.R. et al. Wave reflections in the umbilical artery measured by Doppler ultrasound as a novel predictor of placental pathology. EBioMedicine. 2021;67:103326. https://doi.org/10.1016/j.ebiom.2021.103326.
25. Yagel S., Cohen S.M., Goldman-Wohl D. An integrated model of preeclampsia: a multifaceted syndrome of the maternal cardiovascularplacental-fetal array. Am J Obstet Gynecol. 2021 Mar 9;S0002- 9378(20)31197-2. https://doi.org/10.1016/j.ajog.2020.10.023. [Online ahead of print].
26. Hanna J., Goldman-Wohl D., Hamani Y. et al. Decidual NK cells regulate key developmental processes at the human fetal-maternal interface. Nat Med. 2006;12(9):1065–74. https://doi.org/10.1038/nm1452.
27. Tayade C., Hilchie D., He H. et al. Genetic deletion of placenta growth factor in mice alters uterine NK cells. J Immunol. 2007;178(7):4267–75. https://doi.org/10.4049/jimmunol.178.7.4267.
28. Yagel S. The developmental role of natural killer cells at the fetal-maternal interface. Am J Obstet Gynecol. 2009;201(4):344–50. https://doi.org/10.1016/j.ajog.2009.02.030.
29. Hanna J., Wald O., Goldman-Wohl D. et al. CXCL12 expression by invasive trophoblasts induces the specific migration of CD16- human natural killer cells. Blood. 2003;102(5):1569–77. https://doi.org/10.1182/blood-2003-02-0517.
30. Gamliel M., Goldman-Wohl D., Isaacson B. et al. Trained memory of human uterine NK cells enhances their function in subsequent pregnancies. Immunity. 2018;48(5):951–62.e5. https://doi.org/10.1016/j.immuni.2018.03.030.
31. Goldman-Wohl D., Gamliel M., Mandelboim O., Yagel S. Learning from experience: cellular and molecular bases for improved outcome in subsequent pregnancies. Am J Obstet Gynecol. 2019;221(3):183–93. https://doi.org/10.1016/j.ajog.2019.02.037.
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For citations:
Tsibizova V.I., Pervunina T.M., Artemenko V.A., Bitsadze V.O., Gotsiridze K.E., Averkin I.I., Blinov D.V., Novikova N.Yu. Placenta crucially affects formation of fetal congenital heart disease. Obstetrics, Gynecology and Reproduction. 2022;16(1):66-72. (In Russ.) https://doi.org/10.17749/2313-7347/ob.gyn.rep.2022.262
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