Diagnosis of fetal hypoxia

Istomina N.G., Makarovskaya E.A., Baranov A.N., Revako P.P.

Northern State Medical University, Ministry of Health of the Russian Federation, Arkhangelsk, Russia
The predominant role in the overall pattern of perinatal mortality is currently played by antenatal fetal death (73%), the most considerable contribution to the pattern of which is made by chronic hypoxia. The pathophysiological processes of chronic fetal hypoxia are multicomponent and have not been fully explored. Its diagnostic methods used in obstetric practice have their limitations and disadvantages; they are often set up to register secondary or indirect signs, which cannot accurately predict severe neonatal outcomes or stillbirth. The most promising areas for research can be considered methods for the early diagnosis of placental insufficiency and noninvasive techniques for the functional assessment of fetal hypoxia, which is fundamentally important for initiating its maintenance therapy. This paper considers the general issues related to the pathophysiology of chronic hypoxia in the fetus and study methods for its assessment. It describes the new criteria for Doppler study, the widely used diagnostic method, which can assess the functional state of the fetal cardiovascular system in case of cardiac sparing and brain sparing effects. There are also the results of some pilot studies concerning the determination of specific hypoxia-induced RNA of the fetus in maternal blood, which have a high potential for the clinical biomarkers of obstetric complications. Attention is paid to a study method, such as MRI, the value of which will be able to significantly increase in the coming years. MRI allows a detailed study of the anatomical features of the placenta, identifying the causes of placental insufficiency. Furthermore, diffusion-weighted MRI (DW-MRI) or diffuse-tensor imaging (DTI) can provide additional functional information about the placenta, by detecting the areas of hypoperfusion. MRI also holds great promise to assess the fetal functional state: the markers of heart failure and lung tissue maturity are only part of new noninvasive fetal state imaging techniques that have the potential for further investigation and implementation in obstetric practice.
Conclusion. Doppler blood flow study remains promising in the antenatal period; at the same time, great hopes are associated with MRI of placental insufficiency and the functional assessment of the fetal state, analysis of circulating fetal nucleic acids in maternal blood as markers of obstetric or fetal pathology.

Keywords

chronic fetal hypoxia
fetal growth retardation syndrome
MRI diagnosis of placental perfusion
hypoxia-induced RNA of the fetus

References

  1. McClure E.M., Saleem S., Goudar S.S., Garces A., Whitworth R., Esamai F. et al. Stillbirth 2010–2018: a prospective, population-based, multi-country study from the Global Network. Reprod. Health. 2020; 17(Suppl. 2): 146. https://dx.doi.org/10.1186/s12978-020-00991-y.
  2. Основные показатели здоровья матери и ребенка, деятельность службы охраны детства и родовспоможения в Российской Федерации. М.: ФГБУ «ЦНИИОИЗ» Минздрава Российской Федерации; 2019. [The main indices of maternal and child health, child protection and obstetric services in the Russian Federation M.: FSBI "TsNIIOIZ" of Ministry of Health of the Russian Federation; 2019 (in Russian)].
  3. Lawn J.E., Lee A.C., Kinney M., Sibley L., Carlo W.A., Paul V.K., Pattinson R., Darmstadt G.L. Two million intrapartum-related stillbirths and neonatal deaths: where, why, and what can be done? Int. J. Gynaecol. Obstet. 2009; 107(Suppl. 1): S5-18. https://dx.doi.org/10.1016/j.ijgo.2009.07.016.
  4. Beth J.A., Kirsty L.B., Youguo Niu, Andrew D.K., Emilio A.H., Avnesh S.T. et al. Use of umbilical cord blood gas analysis in the assessment of the newborn. Arch. Dis. Child. Fetal Neonatal Ed. 2007; 92: F430-4. https://dx.doi.org/10.1016/j.yebeh.2007.08.010.
  5. Lees C.C., Stampalija T., Baschat A.A., da Silva Costa F., Ferrazzi E., Figueras F. et al. ISUOG Practice Guidelines: diagnosis and management of small-for-gestational-age fetus and fetal growth restriction. Ultrasound Obstet. Gynecol. 2020; 56(2): 298-312. https://dx.doi.org/10.1002/uog.22134.
  6. Кузнецов П.А., Козлов П.В. Гипоксия плода и асфиксия новорожденного. Лечебное дело. 2017; 4: 9-15. [Kuznetsov P.A., Kozlov P.V. Fetal hypoxia and asphyxia of the newborn. Lechebnoe delo/General Medicine. 2017; 4: 9-15. (in Russian)].
  7. Уразов М.Д., Астраханова Т.А., Усенко А.В., Мищенко Т.А., Щелчкова Н.А., Кравченко Г.А., Ведунова М.В., Митрошина Е.В. Новые аспекты адаптации центральной нервной системы к пренатальной гипоксии. Современные технологии в медицине. 2018; 4: 60-7. [Urazov M.D., Astrakhanova T.A., Usenko A.V., Mishchenko T.A., Shchelchkova N.A., Kravchenko G.A., Vedunova M.V., Mitroshina E.V. New aspects of the central nervous system adaptation to prenatal hypoxia. Modern technologies in medicine. 2018; 4: 60-7. (in Russian)].
  8. Gravett C., Eckert L.O., Gravett M.G., Dudley D.J., Stringer E.M., Mujobu T.B. et al. Non-reassuring fetal status Working Group. Non-reassuring fetal status: Case definition & guidelines for data collection, analysis, and presentation of immunization safety data. Vaccine. 2016; 34(49): 6084-92. https://dx.doi.org/10.1016/j.vaccine.2016.03.043.
  9. Савельева Г.М., Сухих Г.Т., Серов В.Н., Радзинский В.Е., ред. Акушерство. Национальное руководство. 2-е изд. М.: ГЭОТАР-Медиа; 2018. [Savelyeva G.M., Sukhikh G.T., Serov V.N., Radzinsky V.E., eds. Obstetrics. National guidelines. 2nd ed., revised and add. Moscow: GEOTAR-Media, 2018. (in Russian)].
  10. Yakıştıran B., Katlan D.C., Yüce T., Koç A. Neural and cardiac injury markers in fetal growth restriction and their relation to perinatal outcomes. Turk. J. Obstet. Gynecol. 2019; 16(1): 50-4. https://dx.doi.org/10.4274/tjod.galenos.2019.84665.
  11. Miller S.L., Huppi P.S., Mallard C. The consequences of fetal growth restriction on brain structure and neurodevelopmental outcome. J Physiol. 2016; 594(4): 807-23. https://dx.doi.org/10.1113/JP271402.
  12. Yildirim A., Ozgen F., Ucar B., Alatas O., Tekin N., Kilic Z. The diagnostic value of troponin T level in the determination of cardiac damage in perinatal asphyxia newborns. Fetal Pediatr. Pathol. 2016; 35: 29-36. https://dx.doi.org/10.3109/15513815.2015.1122128.
  13. Fan H.C., Blumenfeld Y.J., Chitkara U., Hudgins L., Quake S.R. Noninvasive diagnosis of fetal aneuploidy by shotgun sequencing DNA from maternal blood. Proc. Natl. Acad. Sci. USA. 2008; 105(42): 16266-71. https://dx.doi.org/10.1073/pnas.0808319105.
  14. Moufarrej M.N., Wong R.J., Shaw G.M., Stevenson D.K., Quake S.R. Investigating pregnancy and its complications using circulating cell-free RNA in women's blood during gestation. Front. Pediatr. 2020; 8: 605219. https://dx.doi.org/10.3389/fped.2020.605219.
  15. Kosaka N., Yoshioka Y., Hagiwara K., Tominaga N., Katsuda T., Ochiya T. Trash or treasure: extracellular microRNAs and cell-to-cell communication. Front. Genet. 2013; 4: 173. https://dx.doi.org/10.3389/fgene.2013.00173.
  16. Valadi H., Ekstrom K., Bossios A., Sjostrand M., Lee J.J., Lotvall J.O. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat. Cell Biol. 2007; 9(6): 654-9. https://dx.doi.org/10.1038/ncb1596.
  17. Ngo T.T.M., Moufarrej M.N., Rasmussen M.H., Camunas-Soler J., Pan W., Okamoto J. et al. Noninvasive blood tests for fetal development predict gestational age and preterm delivery. Science. 2018; 360(6393): 1133-6. https://dx.doi.org/10.1126/science.aar3819.
  18. Whitehead C.L., Walker S.P., Lappas M., Tong S. Circulating RNA coding genes regulating apoptosis in maternal blood in severe early onset fetal growth restriction and pre‐eclampsia. J. Perinatol. 2013; 33(8): 600-4. https://dx.doi.org/10.1038/jp.2013.16.
  19. Whitehead C.L., Walker S.P., Tong S. Measuring circulating placental RNAs to non-invasively assess the placental transcriptome and to predict pregnancy complications. Prenat. Diagn. 2016; 36(11): 997-1008. https://dx.doi.org/10.1002/pd.4934.
  20. Hannan N.J., Stock O., Spencer R., Whitehead C., David A.L., Groom K. et al. Circulating mRNAs are differentially expressed in pregnancies with severe placental insufficiency and at high risk of stillbirth. BMC Med. 2020; 18(1):145. https://dx.doi.org/10.1186/s12916-020-01605-x.
  21. Görkem S.B., Coşkun A., Eşlik M., Kütük M.S., Öztürk A. Diffusion-weighted imaging of placenta in intrauterine growth restriction with worsening Doppler US findings. Diagn. Interv. Radiol. 2019; 25(4): 280-4. https://dx.doi.org/10.5152/dir.2019.18358.
  22. Morita S., Ueno E., Fujimura M., Muraoka M., Takagi K., Fujibayashi M. Feasibility of diffusion-weighted MRI for defining placental invasion. J. Magn. Reson. Imaging. 2009; 30(3): 666-71. https://dx.doi.org/10.1002/jmri.21875.
  23. Bonel H.M., Stolz B., Diedrichsen L., Frei K., Saar B., Tutschek B. et al. Diffusion-weighted MR imaging of the placenta in fetuses with placental insufficiency. Radiology. 2010; 257(3): 810-9. https://dx.doi.org/10.1148/radiol.10092283.
  24. Perrone S., Santacroce A., de Bernardo G., Alagna M.G., Carbone S.F., Paternò I., Buonocore G. Magnetic resonance imaging in pregnancy with intrauterine growth restriction: A Pilot Study. Dis. Markers. 2019: 4373490. https://dx.doi.org/10.1155/2019/4373490.

Received 16.12.2020

Accepted 08.02.2021

About the Authors

Natalia G. Istomina, M.D., CSc (med.), Associate Professor, Department of Obstetrics and Gynecology, Northern State Medical University, Ministry of Health of Russia.
Tel.: +7(8182)24-03-46, +7(921)477-47-84. E-mail: nataly.istomina@gmail.com. 163000, Russia, Arkhangelsk, Troitskiy str., 5.
Alexey N. Baranov, PhD, DSc, Professor, Head of the Department of Obstetrics and Gynecology, Northern State Medical University, Ministry of Health of Russia.
Tel.: +7(8182)24-03-46, +7(921)246-90-58. 163000, Russia, Arkhangelsk, Troitskiy str., 5.
Elizaveta A. Makarovskaya, postgraduate student, Northern State Medical University, Ministry of Health of Russia. Tel.: +7(8182)24-03-46, +7(911)572-20-79.
163000, Russia, Arkhangelsk, Troitskiy str., 5.
Pavel P. Revako, M.D., CSc (med.), Associate Professor, Department of Obstetrics and Gynecology, Northern State Medical University, Ministry of Health of Russia.
Tel.: +7(8182)24-03-46, +7(911)875-54-41. 163000, Russia, Arkhangelsk, Troitskiy str., 5.

For citation: Istomina N.G., Makarovskaya E.A., Baranov A.N., Revako P.P. Diagnosis of fetal hypoxia.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2021; 6: 29-33 (in Russian)
https://dx.doi.org/10.18565/aig.2021.6.29-33

Similar Articles

By continuing to use our site, you consent to the processing of cookies that ensure the proper functioning of the site.