Comparison of prenatal functional markers of retardation of fetal growth and delayed fetal development with expression of vascular growth factors in the placenta

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Abstract

AIM: The study aimed to investigate and compare Doppler metric indicators in the main arteries of the functional system of the mother, placenta, and fetus as well as the parameters of the activity–rest cycle in fetuses with vascular endothelial growth factor (VEGF) expression and placenta growth factor (PlGF) in the presence of physiological pregnancy and placental insufficiency to analyze morphofunctional parallels between these indicators in the third trimester of pregnancy.

MATERIALS AND METHODS: Twenty-nine women on the 34–35 weeks of pregnancy (period of physiological maturity of the activity–rest cycle in the fetus) were screened. The main group consisted of 19 patients. The inclusion criteria were as follows: single-fetal pregnancy, fetometric indicators below the 10th percentile, and presence of blood flow disorders in the main vessels of the mother–placenta–fetus functional system. The comparison group included 10 relatively healthy women. The criteria for inclusion in the comparison group were as follows: single-fetal physiological pregnancy, fetometric indicators above the 10th percentile, and absence of Doppler disorders of placental blood flow. Fetometry and Doppler studies of the placental blood flow in the main arteries of the functional system of the mother, placenta, fetus were performed using the Voluson 730 Expert ultrasound device (GE, USA). The activity–rest cycle in the fetus was evaluated using Sonicaid Team Care fetal monitor (Oxford, UK). Placental tissue was taken from the central placental area for immunohistochemical analysis of VEGF and PlGF expression with primary monoclonal antibodies of the main women group and comparison group after childbirth (1:100, Abcam, UK).

RESULTS: A direct correlation between the expression of VEGF in the central zone of the placenta and index resistance (IR), ripple index (RI) in the uterine arteries, as well as the cerebroplacental relationship — CPR (r1=0.487; p1=0.035; r2=0.487; p2=0.035; r3=0.578; p3=0.030, respectively) in women of the main group was found. A direct correlation was established between the expression of VEGF in the central zone of the placenta and IR in the umbilical artery (r=0.49; p=0.033) in patients of the main group. The analysis of the rest–activity cycle in fetuses of women of the main group showed that at 34–35 weeks 73% of them do not form it: the behavior of fetuses is represented only by the activated state. An inverse relationship was found between VEGF expression and the motor-cardiac reflex amplitude (r=–0.866; p=0.05) as well as the heart rate oscillation amplitude (r=–0.866; p=0.05) in fetuses of women of the main group.

CONCLUSIONS: The identified morphofunctional parallels will allow to develop non-invasive pathogenetic prognostic models for prenatal diagnosis of fetal development delay with different degrees of growth restriction.

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About the authors

Sholpan D. Dyusembinova

Maternity hospital No. 6 named after prof. V.F. Snegirev

Author for correspondence.
Email: sholpan8-d@mail.ru
ORCID iD: 0000-0001-9483-7335

ultrasound diagnostics doctor

Russian Federation, 5 Mayakovsky str., Saint Petersburg, 191014

Nataliya G. Pavlova

The First Saint Petersburg State Medical University named after I.P. Pavlov

Email: ngp05@yandex.ru
ORCID iD: 0000-0002-2886-4578

M.D., Dr. Sci. (Med.), professor

Russian Federation, Saint Petersburg

Kseniya A. Klikunova

Saint Petersburg State Pediatric Medical University

Email: kliksa@gmail.com
ORCID iD: 0000-0002-5978-5557

MD, Cand. Sci. (Phys. and Mathem.), assistant professor

Russian Federation, Saint Petersburg

References

  1. Strizhakov AN, Ignatko IV, Timokhina EV, Belotserkovtseva LD. Fetal growth retardation syndrome: pathogenesis, diagnosis, treatment, obstetric tactics. Moscow: GEOTAR-Media; 2013. (In Russ).
  2. Pavlova NG, Dyusembinova ShD. Features of the formation of the activity–rest cycle in fruits with delayed growth and development. Obstetrics and Gynecology. 2020;(1):104–109. (In Russ). doi: 10.18565/aig.2020.1.104-109
  3. Bose C, Van Marter LJ, Laughon M, et al. Fetal growth restriction and chronic lung disease among infants born before the 28th week of gestation. Pediatrics. 2009;124(3):450–458. doi: 10.1542/peds.2008-3249
  4. Gordijn SJ, Beune IM, Thilaganathan B, et al. Consensus definition of fetal growth restriction: a Delphi procedure. Ultrasound Obstet Gynecol. 2016;48(3):333–339. doi: 10.1002/uog.15884
  5. Strizhakov AN, Kushlinskiy NE, Timokhina EV. The role of angiogenic growth factors in predicting placental insufficiency. Voprosy ginekologii, akusherstva i perinatologii. 2009;8(4):5–11. (In Russ).
  6. Makarov OV, Volkova EV, Lysyuk EYu, Kopylova YuV. Fetoplacental angiogenesis in pregnant women with placental insufficiency. Obstetrics, Gynecology and Reproduction. 2013;7(3):13–19. (In Russ).
  7. Shu-Wei Li, Yi Ling, Song Jin, et al. Expression of soluble vascular endothelial growth factor receptor-1 and placental growth factor in fetal growth restriction cases and intervention effect of tetramethylpyrazine. Asian Pacific Journal of Tropical Medicine. 2014;7(8):663–667. doi: 10.1016/s1995-7645(14)60112-7
  8. Dyusembinova ShD, Drobintseva AO, Sosnina AK, et al. Local expression of signaling molecules and the state of intra-placental blood flow. Molecular medicine. 2017;15(2). (In Russ).
  9. Pavlova NG, Arzhanova ON, Zaynulina MS. Placental insufficiency: an educational and methodological guide. Ed. E.K. Aylamazyan. Saint Petersburg: N-L; 2007. (In Russ).
  10. Khankin EV, Royle C, Karumanchi SA. Placental vasculature in health and disease. Semin Thromb Hemost. 2010;36(3):309–320. (In Russ). doi: 10.1055/s-0030-1253453
  11. Sokolov DI. Vasculogenesis and angiogenesis in placental development. Journal of Obstetrics and Women's Diseases. 2007;LVI(3):129–133. (In Russ).
  12. Akolekar R, Syngelaki A, Poon LC, Wright D, Nicolaides KH. Competing risks model in early screening for preeclampsia by biophysical and biochemical markers. Fetal Diagn Ther. 2013;33(1):8–15. doi: 10.1159/000341264
  13. Smirnova TL, Alekseeva TA, Sergeeva VE. Placental morphology in placental insufficiency. Fundamental Research. 2009;(7 suppl.):62–63. (In Russ).
  14. Zakurina AN, Korzhevskii DE, Pavlova NG. Placental insufficiency ― morphofunctional parallels. Journal of Obstetrics and Women's Diseases. 2010;LIX(5):51–55. (In Russ).
  15. Torry DS, Hinrichs M, Torry RJ. Determinants of placental vascularity. Am J Reprod Immunol. 2004;51(4):257–268.
  16. Burton GJ, Charnock-Jones DS, Jauniaux E. Regulation of vascular growth and function in the human placenta. Reproduction. 2009;138(6):895–902. doi: 10.1530/REP-09-0092
  17. Yagel S. Angiogenesis in gestational vascular complications. Thromb Res. 2011;127 Suppl.3:S64–S66. doi: 10.1016/S0049-3848(11)70018-4
  18. Strizhakov AN, Kushlinskii NE, Timokhina EV, Tarabrina TV. The role of angiogenic growth factors in predicting placental insufficiency. Gynecology, Obstetrics and Perinatology. 2009;8(4):5–11. (In Russ).
  19. Bose C, Van Marter LJ, Laughon M, et al. Fetal growth restriction and chronic lung disease among infants born before the 28th week of gestation. Pediatrics. 2009;124(3):450–458. doi: 10.1542/peds.2008-3249
  20. Degtyareva EA, Zakharova OA, Kufa MA, Kantemirova MG, Radzinskii VE. Effectiveness of predicting and early diagnosis of fetal growth retardation. Russian Bulletin of perinatology and pediatrics. 2018;63(6):37–45. (In Russ). doi: 10.21508/1027-4065-2018-63-5-37-45
  21. Belich AI. An evolutionary approach to the study of the development of the fetal central nervous system. Journal of Obstetrics and Women's Diseases. 2010;LIX(5):12–16. (In Russ).

Supplementary files

Supplementary Files
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1. Fig. 1. Comparison of the PlGF expression area in the terminal villi of the central part of the placenta: a — patients of the main group; b — patients of the control group. Arrows indicate PlGF expression; color: immunohistochemical reaction to PlGF.

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2. Fig. 2. Comparison of the area of VEGF expression in chorionic villi of the central part of the placenta: a — patients of the main group; b — patients of the control group. The arrows indicate VEGF expression; color: immunohistochemical reaction to VEGF.

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