Feasibility of predicting fetal growth restriction, by identifying plasma biomarkers

DOI

https://dx.doi.org/10.18565/aig.2022.269

Izhoykina E.V., Trifonova E.A., Kutsenko I.G., Stepanov I.A., Gavrilenko M.M., Stepanov V.A.
1) Siberian State Medical University, Ministry of Health of Russia, Tomsk, Russia; 2) Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russia; 3) I.D. Evtushenko Regional Perinatal Center, Tomsk, Russia

Fetal growth restriction (FGR) remains one of the important obstetric problems, being a risk factor for antenatal and neonatal mortality and morbidity. The timely prediction of FGR is one of the most important measures in reducing adverse pregnancy outcomes. However, despite numerous studies, practical obstetrics still lacks highly sensitive and specific prognostic biomarkers for this disease.
This paper analyzes open-access modern scientific literature data in the PubMed, Cochrane, and eLibrary databases, which characterize the role of biomarkers in predicting the risk of FGR. Meta-analyses demonstrate that beta-human chorionic gonadotropin, alpha-fetoprotein, free estriol, human chorionic somatomammotropin hormone 1, pappalysin 1, inhibin α-subunit, and placental growth factor are considered the most promising predictive biomarkers for FGR. However, the data obtained by most authors suggest that the use of individual biomarkers has insufficient sensitivity and specificity in stratifying the risk of FGR. The most promising direction in this area is the creation of models for complex multiparametric screening based on the study of maternal risk factors, the levels of biomarkers (both proteomic and molecular genetic ones) in conjunction with ultrasound data.
Conclusion: Thus, studies focused on the search for new biomarkers in order to develop a comprehensive screening program that is of high prognostic value in identifying the risk of FGR are highly relevant and determine personalized patient management tactics in the future.

Authors’ contributions: Izhoykina E.V., Gavrilenko M.M., Trifonova E.A. – material collection and processing, writing the text; Stepanov I.A., Kutsenko I.G., Stepanov V.A. – editing.
Conflicts of interest: The authors declare that there are no conflicts of interest.
Funding: The article has been prepared without sponsorship.
For citation: Izhoykina E.V., Trifonova E.A., Kutsenko I.G., Stepanov I.A., Gavrilenko M.M., Stepanov V.A. Feasibility of predicting fetal growth restriction, by identifying plasma biomarkers.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2023; (2): 18-24 (in Russian)
https://dx.doi.org/10.18565/aig.2022.269

fetal growth restriction

biomarkers

screening

Full text (in Russian)

Российское общество акушеров-гинекологов. Клинические рекомендации «Недостаточный рост плода, требующий предоставления медицинской помощи матери (задержка роста плода)». 2020. [Russian Society of Obstetricians and Gynecologists. Clinical guidelines “Inadequate fetal growth requiring maternal medical care (fetal growth restriction)”. 2020. (in Russian)].
Heazell A.E., Hayes D.Jl., Whitworth M., Takwoingi Y., Bayliss S.E., Davenport C. Biochemical tests of placental function versus ultrasound assessment of fetal size for stillbirth and small-for-gestational-age infants. Cochrane Database Syst. Rev. 2019; 5(5): CD012245. https://dx.doi.org/10.1002/14651858.
Levine T.A, Grunau R.E., McAuliffe F.M., Pinnamaneni R.M., Foran A.,Alderdice F.A. Early childhood neurodevelopment after intrauterine growth restriction: a systematic review. Pediatrics. 2015; 135(1): 126-41.https://dx.doi.org/10.1542/peds.2014-1143.
Colella M., Frérot A., Novais A.R.B., Baud O. Neonatal and long-term consequences of fetal growth restriction. Curr. Pediatr. Rev. 2018; 14(4): 212-8. https://dx.doi.org/10.2174/1573396314666180712114531.
Хачатрян З.В., Кан Н.Е., Макарова Н.П. Современные представления о молекулярных механизмах формирования задержки роста плода. Акушерство и гинекология. 2019; 10: 22-6. https://dx.doi.org/10.18565/aig.2019.10.22-26. [Khachatryan Z.V., Kan N.E., Makarova N.P. Present views on molecular mechanisms of formation of fetal growth restriction. Obstetrics and Gynecology. 2019; (10): 22-6. (in Russian)]. https://dx.doi.org/10.18565/aig.2019.10.22-26.
Burton G.J., Jauniaux E. Pathophysiology of placental-derived fetal growth restriction. Am. J. Obstet. Gynecol. 2018; 218(Suppl. 2): S745-61.https://dx.doi.org/10.1016/j.ajog.2017.11.577.
Zur R.L., Kingdom J.C., Parks W.T., Hobson S.R. The placental basis of fetal growth restriction. Obstet. Gynecol. Clin. North Am. 2020; 47(1): 81-98. https://dx.doi.org/10.1016/j.ogc.2019.10.008.
Zareaan E., Heidarpour M., Kargarzadeh E., Moshfeghi M. Association of maternal and umbilical cord blood leptin concentrations and abnormal color Doppler indices of umbilical artery with fetal growth restriction. Int. J. Reprod. Biomed. 2017; 15(3): 135-40.
Ferrero S., Mazarico E., Valls C., Di Gregorio S., Montejo R., Ibáñez L. et al. Relationship between fetal growth restriction and maternal nutrition status measured by Dual-Energy X-Ray absorptiometry, leptin, and insulin-like growth factor. Gynecol. Obstet. Invest. 2015; 80(1): 54-9.https://dx.doi.org/10.1159/000371761.
Visentin S., Lapolla A., Londero A.P., Cosma C., Dalfrà M., Camerin M. et al. Adiponectin levels are reduced while markers of systemic inflammation and aortic remodelling are increased in intrauterine growth restricted mother-child couple. Biomed. Res. Int. 2014; 2014: 401595. https://dx.doi.org/10.1155/2014/401595.
Madeleneau D., Buffat C., Mondon F., Grimault H., Rigourd V., Tsatsaris V.et al. Transcriptomic analysis of human placenta in intrauterine growth restriction. Pediatr. Res. 2015; 77(6): 799-807. https://dx.doi.org/10.1038/pr.2015.40.
Zhang C., Ding J., Li H., Wang T. Identification of key genes in pathogenesis of placental insufficiency intrauterine growth restriction. BMC Pregnancy Childbirth. 2022; 22(1): 77. https://dx.doi.org/10.1186/s12884-022-04399-3.
Cignini P., Savasta L.M., Gulino F.A., Vitale S.G., Mangiafico L., Mesoraca A., Giorlandino C. Predictive value of pregnancy-associated plasma protein-A (PAPP-A) and free beta-hCG on fetal growth restriction: results of a prospective study. Arch. Gynecol. Obstet. 2016; 293(6): 1227-33. https://dx.doi.org/10.1007/s00404-015-3947-z.
Boonpiam R., Wanapirak C., Sirichotiyakul S., Sekararithi R., Traisrisilp K., Tongsong T. Quad test for fetal aneuploidy screening as a predictor of small-for-gestational age fetuses: a population-based study. BMC Pregnancy Childbirth. 2020; 20(1): 621. https://dx.doi.org/10.1186/s12884-020-03298-9.
Kiyokoba R., Uchiumi T., Yagi M., Toshima T., Tsukahara S., Fujita Y. et al. Mitochondrial dysfunction-induced high hCG associated with development of fetal growth restriction and pre-eclampsia with fetal growth restriction. Sci. Rep. 2022; 12(1): 4056. https://dx.doi.org/10.1038/s41598-022-07893-y.
Yu N., Cui H., Chen X., Chang Y. First trimester maternal serum analytes and second trimester uterine artery Doppler in the prediction of preeclampsia and fetal growth restriction. Taiwan. J. Obstet. Gynecol. 2017; 56(3): 358-61. https://dx.doi.org/10.1016/j.tjog.2017.01.009.
Zamarian A.C.P., Araujo E.Jn., Daher S., Rolo L.C., Moron A.F., Nardozza L.M.M. Evaluation of biochemical markers combined with uterine artery Doppler parameters in fetuses with growth restriction: a case-control study. Arch. Gynecol. Obstet. 2016; 294(4): 715-23. https://dx.doi.org/10.1007/s00404-016-4024-y.
Sifakis S., Androutsopoulos V.P., Pontikaki A., Velegrakis A., Papaioannou G.I., Koukoura O. et al. Placental expression of PAPPA, PAPPA-2 and PLAC-1 in pregnacies is associated with FGR. Mol. Med. Rep. 2018; 17(5): 6435-40. https://dx.doi.org/10.3892/mmr.2018.8721.
Yazdani S., Rouholahnejad R., Asnafi N., Sharbatdaran M., Zakershob M., Bouzari Z. Correlation of pregnancy outcome with quadruple screening test at second trimester. Med. J. Islam. Repub. Iran. 2015; 29: 281.
Awamleh Z., Gloor G.B., Han V.K.M. Placental microRNAs in pregnancies with early onset intrauterine growth restriction and preeclampsia: potential impact on gene expression and pathophysiology. BMC Med. Genomics. 2019; 12: 91. https://dx.doi.org/10.1186/s12920-019-0548-x.
Nawathe A.R., Christian M., Kim S.H., Johnson M., Savvidou M.D., Terzidou V. Insulin-like growth factor axis in pregnancies affected by fetal growth disorders. Clin. Epigenetics. 2016; 8: 11. https://dx.doi.org/10.1186/s13148-016-0178-5.
Lesmes C., Gallo D.M., Gonzalez R., Poon L.C., Nicolaides K.H. Prediction of small-for-gestational-age neonates: screening by maternal serum biochemical markers at 19-24 weeks. Ultrasound Obstet. Gynecol. 2015; 46(3): 341-9. https://dx.doi.org/10.1002/uog.14899.
Komwilaisak R., Tangkiratichai P. Maternal serum angiogenic growth factors in intrauterine growth restriction versus normal pregnancies. J. Med. Assoc. Thai. 2017; 100(2): 119-24.
Ravikumar G., Mukhopadhyay A., Mani C., Kocchar P., Crasta J., Thomas T. et al. Placental expression of angiogenesis-related genes and their receptors in IUGR pregnancies: correlation with fetoplacental and maternal parameters. J. Matern. Fetal Neonatal Med. 2019; 28: 1-8. https://dx.doi.org/10.1080/14767058.2019.1593362.
Хачатрян З.В., Кан Н.Е., Вторушина В.В., Кречетова Л.В., Харченко Д.К., Мантрова Д.А., Тютюнник В.Л. Роль трансформирующего фактора роста β в формировании задержки роста плода Акушерство и гинекология. 2019; 11: 107-12. [Khachatryan Z.V., Kan N.E., Vtorushina V.V., Krechetova L.V., Kharchenko D.K., Mantrova D.A., Tyutyunnik V.L. Role of transforming growth factor-β in the formation of fetal growth restriction. Obstetrics and Gynecology. 2019; (11): 107-12. (in Russian)]. https://dx.doi.org/10.18565/aig.2019.11.107-112.
Красный А.М., Хачатурян А.А., Вторушина В.В., Кречетова Л.В., Кан Н.Е., Тютюнник В.Л. Содержание растворимой формы Е-кадгерина и фактора роста кератиноцитов в плазме крови при задержке роста плода. Акушерство и гинекология. 2020; 6: 37-42. [Krasnyi A.M., Khachaturyan A.A., Vtorushina V.V., Krechetova L.V., Kan N.E., Tyutyunnik V.L. Plasma levels of soluble E-cadherin and the keratinocytes growth factor in intrauterine growth restriction. Obstetrics and Gynecology. 2020; (6): 37-42. (in Russian)].https://dx.doi.org/10.18565/aig.2020.6.37-42.
Raia-Barjat T., Prieux C., Gris J-C., Chapelle C., Laporte S., Chauleur C. Angiogenic factors for prediction of preeclampsia and intrauterine growth restriction onset in high-risk women: AngioPred study. J. Matern. Fetal Neonatal Med. 2019; 32(2): 248-57. https://dx.doi.org/ 10.1080/14767058.2017.1378325.
Şahin B., Soyer-Çalışkan C., Çelik S., Hatırnaz Ş., Tinelli A. Midregional pro-adrenomedullin and matrix metalloproteinase-2 levels in intrauterine growth restriction and small gestational age pregnancies: biochemical diagnostic difference. J. Matern. Fetal Neonatal Med. 2021; 34(12): 1999-2005.https://dx.doi.org/10.1080/14767058.2020.1846707.
Ibrahim M.I., Ammar E.M., Ramy A., Ellaithy M.I., Abdelrahman R.M., Elkabarity R. The association between pentraxin 3 in maternal circulation and pathological intrauterine fetal growth restriction. Eur. J. Obstet. Gynecol. Reprod. Biol. 2015; 185: 1-8. https://dx.doi.org/10.1016/j.ejogrb.2014.11.010.
Andres F., Wong G.P., Walker S.P., MacDonald T.M., Keenan E., Cannon P. et al. A disintegrin and metalloproteinase 12 (ADAM12) is reduced at 36 weeks' gestation in pregnancies destined to deliver small for gestational age infants. Placenta. 2022; 117: 1-4. https://dx.doi.org/10.1016/j.placenta.2021.11.001.
Docheva N., Romero R., Chaemsaithong P., Tarca A.L., Bhatti G., Pacora P. et al. The profiles of soluble adhesion molecules in the "great obstetrical syndromes". J. Matern. Fetal Neonatal Med. 2019; 32(13): 2113-36. https://dx.doi.org/10.1080/14767058.2018.1427058.
Berbets A., Koval H., Barbe A., Albota O., Yuzko O. Melatonin decreases and cytokines increase in women with placental insufficiency. J. Matern. Fetal Neonatal Med. 2021; 34(3): 373-8. https://dx.doi.org/10.1080/14767058.2019.1608432.
Medina-Bastidas D., Guzmán-Huerta M., Borboa-Olivares H., Ruiz-Cruz C., Parra-Hernández S., Flores-Pliego A. et al. Placental microarray profiling reveals common mRNA and lncRNA expression patterns in preeclampsia and intrauterine growth restriction Int. J. Mol. Sci. 2020; 21(10): 3597.https://dx.doi.org/10.3390/ijms21103597.
Azizieh F.Y., Raghupathy R.G. Tumor necrosis factor-α and pregnancy complications: a prospective study. Med. Princ. Pract. 2015; 24(2): 165-70. https://dx.doi.org/10.1159/000369363.
Karlı P., Özdemir A.Z., Ayan D. Maternal serum and fetal cord blood C-reactive protein levels but not procalcitonin levels are increased in idiopathic intrauterine gowth restriction. Med. Sci. Monit. 2019; 25: 6512-7.https://dx.doi.org/10.12659/MSM.917397.
Dai F.F., Hu M., Zhang Y.W., Zhu R.H., Chen L.P., Li Z.D. et al. Maternal serum and fetal cord blood C-reactive protein levels but not procalcitonin levels are increased in idiopathic intrauterine gowth restriction. Expert Rev. Mol. Med. 2022; 24: e26. https://dx.doi.org/10.1017/erm.2022.18.
Pylypjuk C.L., Monarrez-Espino J. False-positive maternal serum screens in the second trimester as markers of placentally mediated complications later in pregnancy: a systematic review and meta-analysis. Dis. Markers. 2021; 2021: 5566234. https://dx.doi.org/10.1155/2021/5566234.
Heazell A.E.P., Whitworth M., Duley L., Thornton J.G. Use of biochemical tests of placental function for improving pregnancy outcome. Cochrane Database Syst. Rev. 2015; 2015(11): CD011202. https://dx.doi.org/10.1002/14651858.CD011202.pub2.
Morris R.K., Bilagi A., Devani P., Kilby M.D. Association of serum PAPP-A levels in first trimester with small for gestational age and adverse pregnancy outcomes: systematic review and meta-analysis. Prenat. Diagn. 2017; 37(3): 253-65. https://dx.doi.org/10.1002/pd.5001.
Chen W., Wei Q., Liang Q., Song S., Li J. Diagnostic capacity of sFlt-1/PlGF ratio in fetal growth restriction: a systematic review and meta-analysis. Placenta. 2022; 127: 37-42. https://dx.doi.org/10.1016/j.placenta.2022.07.020.
Kiyokoba R., Uchiumi T., Yagi M., Toshima Т., Tsukahara S., Fujita Y. et al. Mitochondrial dysfunction-induced high hCG associated with development of fetal growth restriction and pre-eclampsia with fetal growth restriction. Sci. Rep. 2022; 12: 4056.
Costa M.A. The endocrine function of human placenta: an overview. Reprod. Biomed. Online. 2016; 32(1): 14-43. https://dx.doi.org/10.1016/j.rbmo.2015.10.005.
Yu N., Cui H., Chen X., Chang Y. First trimester maternal serum analytes and second trimester uterine artery Doppler in the prediction of preeclampsia and fetal growth restriction. Taiwan. J. Obstet. Gynecol. 2017; 56(3): 358-61.https://dx.doi.org/10.1016/j.tjog.2017.01.009.

Received 14.11.2022

Accepted 17.01.2023

Ekaterina V. Izhoykina, Laboratory Assistant, Department of Obstetrics and Gynecology, Siberian State Medical University, Ministry of Health of the Russia,
+7(923)441-12-18, katushkabig@mail.ru, 634050, Russia, Tomsk, Moskovsky Trakt str., 2.
Ekaterina A. Trifonova, PhD, Senior Researcher, Research Institute of Medical Genetics, Tomsk Scientific Research Center RAS, +7(3822)51-33-34,
ekaterina.trifonova@medgenetics.ru, 634050, Russia, Tomsk, Naberezhnaya Reki Ushayka str., 10.
Irina G. Kutsenko, Dr. Med. Sci., Professor, Head of the Department of Obstetrics and Gynecology, Siberian State Medical University, Ministry of Health of Russia, +7(3822)90-11-01, 17-36, kutsenko.ig@ssmu.ru, 634050, Russia, Tomsk, Moskovsky Trakt str., 2.
Igor A. Stepanov, PhD, Chief Physician, I.D. Evtushenko Regional Perinatal Center, +7(3822)91-50-11, StepanovIA@opc.tomsk.ru,
634063, Russia, Tomsk, Ivana Chernykh str., 96/1.
Maria M. Gavrilenko, Ph.D. student, Research Institute of Medical Genetics, Tomsk Scientific Research Center RAS, +7(3822)51-33-34, maria.gavrilenko@medgenetics.ru, 634050, Russia, Tomsk, Naberezhnaya Reki Ushayka str., 10.
Vadim A. Stepanov, Academician of RAS, Dr. Bio. Sci., Professor, Director of the Research Institute of Medical Genetics, Tomsk Research Center RAS, +7(3822)51-33-34, vadim.stepanov@medgenetics.ru, 634050, Russia, Tomsk, Naberezhnaya Reki Ushayka str., 10.
Corresponding author: Ekaterina V. Izhoykina, katushkabig@mail.ru

Feasibility of predicting fetal growth restriction, by identifying plasma biomarkers

Izhoykina E.V., Trifonova E.A., Kutsenko I.G., Stepanov I.A., Gavrilenko M.M., Stepanov V.A.

Keywords

References

About the Authors

Similar Articles