A PEER-REVIEWED JOURNAL OF RESEARCH AND CLINICAL MEDICINEISSN 1727-2378 (Print)         ISSN 2713-2994 (Online)
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The diagnostic Value of Vascular Endothelial Growth Factor in Women with Growth-Restricted Fetuses

DOI:10.31550/1727-2378-2020-19-8-44-48
For citation: Fatkullin I.F., Akhmadeev N.R., Ulyanina E.V., Islamova L.Kh., Fatkullina L.S. The diagnostic Value of Vascular Endothelial Growth Factor in Women with Growth-Restricted Fetuses. Doctor.Ru. 2020; 19(8): 44–48. (in Russian). DOI: 10.31550/1727-2378-2020-19-8-44-48

Study Objective: To assess delivery outcomes in women with slow fetal growth (ICD-10 code P05) and study serum levels of vascular endothelial growth factor (VEGF) and its diagnostic value in patients with growth-restricted fetuses that have constitutional low weight, in order to choose an approach to pregnancy management.

Study Design: This was a prospective and retrospective comparative study.

Materials and Methods: The medical charts of 782 women who had given birth to low-weight babies in 2013 and 2014 were reviewed retrospectively. The prospective part of the study involved measuring serum levels of VEGF in 150 pregnant women: 50 women with growth-restricted fetuses (Group I), 50 women with low-weight fetuses without hemodynamic disruptions or placental abnormalities (Group II), and 50 women with healthy pregnancies (Group III). Based on the babies’ gestational term at birth, the women in each group were divided into two subgroups: between 22 weeks and 0 days and 31 weeks and 6 days (subgroup 1) and ≥32 weeks and 0 days (subgroup 2).

The data obtained were processed using descriptive statistics and compared with data obtained through other fetal assessments.

Study Results: The pregnant women with growth-restricted fetuses had higher VEGF levels by a statistically significant margin (p<0.00001) than the women in groups II and III: median levels were 310 (Q1–Q3: 270–508), 33 (Q1–Q3: 31–38), and 36 (Q1–Q3: 32–40) pg/mL, respectively, in subgroups 1 and 174 (Q1–Q3: 100–214), 78 (Q1–Q3: 73–86), and 82 (Q1–Q3: 78–88) pg/mL, respectively, in subgroups 2. VEGF levels ≥100 pg/mL were associated with fetal growth restriction (FGR) (p = 0.0001) and levels ≥200 pg/mL with a high risk of antenatal fetal death (p = 0.026) or early neonatal death (p = 0.03).

Conclusion: For women with growth-restricted fetuses, VEGF serum levels ≥200 pg/mL are an additional risk factor for unfavorable perinatal outcomes, which helps to optimize obstetrical management for these patients.

Contributions: Dr. I.F. Fatkullin suggested the idea for the article, developed the design of the study, reviewed critically important content, and approved the final version submitted for publication. Dr. N.R. Akhmadeev developed the design of the study, processed, analyzed and interpreted data, and reviewed relevant publications. Dr. E.V. Ulyanina collected clinical material, processed, analyzed and interpreted data, did statistical analysis of results, and wrote the paper. Dr. L.Kh. Islamova was responsible for selection, examination, and treatment of patients and collected clinical material. Dr. L.S. Fatkullina was the scientific editor of the manuscript.

Conflict of interest: The authors declare that they do not have any conflict of interests. 

I.F. Fatkullin (Corresponding author) — Kazan State Medical University (a Federal Government-funded Educational Institution of Higher Education), Russian Federation Ministry of Health; 49 Butlerov St., Kazan, Russian Federation 420012. eLIBRARY.RU SPIN: 6058-3137. https://orcid.org/0000-0001-9673-9077. E-mail: fatkullin@yandex.ru

N.R. Akhmadeev — Republican Clinical Hospital, Republic of Tatarstan Ministry of Health (a State Autonomous Healthcare Institution); 138 Orenburgsky Highway, Kazan, Russian Federation 420064. eLIBRARY.RU SPIN: 1969-3192. https://orcid.org/0000-0003-0908-7256. E-mail: akhmadeyevnr@gmail.com

E.V. Ulyanina — City Clinical Hospital No. 7 (a State Autonomous Healthcare Institution), 56 Chuikov St., Kazan, Russian Federation 420103. E-mail: ualena87@yandex.ru

L.Kh. Islamova — City Clinical Hospital No. 7 (a State Autonomous Healthcare Institution), 56 Chuikov St., Kazan, Russian Federation 420103. eLIBRARY.RU SPIN: 3439-9840. E-mail: leis_k@mail.ru

L.S. Fatkullina — Republican Clinical Hospital, Republic of Tatarstan Ministry of Health (a State Autonomous Healthcare Institution); 138 Orenburgsky Highway, Kazan, Russian Federation 420064. eLIBRARY.RU SPIN: 3903-5170. https://orcid.org/0000-0003-0361-2785. E-mail: lara.doctor@mail.ru

Доктор.ру

Table 1

Different types of delivery

t7_1.jpg 

Fig. Levels of vascular endothelial growth factor in various phenotypical types of low fetal weight and in healthy pregnancy, pg/mL.

Note: FGR = fetal growth restriction

r7_1.jpg

Table 2

Efficacy of the diagnostic test in respect to predicting unfavorable perinatal outcomes, %

t7_2.jpg

Note: CTG = cardiotocography, MCA = middle cerebral artery, VEGF = vascular endothelial growth factor, NPV = negative predictive value, PPV = positive predictive value, STV = short-term variation. 

Received: 21.05.2020

Accepted: 14.06.2020

LITERATURE
  1. McCowan L.M., Figueras F., Anderson N.H. Evidence-based national guidelines for the management of suspected fetal growth restriction: comparison, consensus, and controversy. Am. J. Obstet. Gynecol. 2018; 218(2S): S855–68. DOI: 10.1016/j.ajog.2017.12.004
  2. Ego A., Monier I., Skaare K., Zeitlin J. Antenatal detection of fetal growth restriction and risk of stillbirth: population-based case-control study. Ultrasound Obstet. Gynecol. 2020; 55(5): 613–20. DOI: 10.1002/uog.20414
  3. Lees C.C., Marlow N., van Wassenaer-Leemhuis A., Arabin B., Bilardo C.M., Brezinka C. et al.; TRUFFLE study group. 2 year neurodevelopmental and intermediate perinatal outcomes in infants with very preterm fetal growth restriction (TRUFFLE): a randomised trial. Lancet. 2015; 385(9983): 2162–72. DOI: 10.1016/S0140-6736(14) 62049-3
  4. Baschat A.A. Planning management and delivery of the growth-restricted fetus. Best Pract. Res. Clin. Obstet. Gynaecol. 2018; 49: 53–65. DOI: 10.1016/j.bpobgyn.2018.02.009
  5. Vayssière C., Sentilhes L., Ego A., Bernard C., Cambourieu D., Flamant C. et al. Fetal growth restriction and intra-uterine growth restriction: guidelines for clinical practice from the French College of Gynaecologists and Obstetricians. Eur. J. Obstet. Gynecol. Reprod. Biol. 2015; 193: 10–8. DOI: 10.1016/j.ejogrb.2015.06.021
  6. Sergent F., Hoffmann P., Brouillet S., Garnier V., Salomon A., Murthi P. et al. Sustained Endocrine Gland-Derived Vascular Endothelial Growth Factor Levels Beyond the First Trimester of Pregnancy Display Phenotypic and Functional Changes Associated With the Pathogenesis of Pregnancy-Induced Hypertension. Hypertension. 2016; 68(1): 148–56. DOI: 10.1161/HYPERTENSIONAHA.116.07442
  7. Borras D., Perales-Puchalt A., Ruiz Sacedón N., Perales A. Angiogenic growth factors in maternal and fetal serum in pregnancies complicated with intrauterine growth restriction. J. Obstet. Gynaecol. 2014; 34(3): 218–20. DOI: 10.3109/01443615.2013.834304
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