The role of vasculogenic and angiogenic factors in perinatal outcomes, neonatal morbidity, and mortality in complicated monochorionic multiple pregnancies

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Abstract

Relevance: Selective fetal growth restriction (sFGR) and twin-to-twin transfusion syndrome (TTTS) are the most common complications of monochorionic multiple pregnancies (10–35%) and are characterized by high perinatal mortality and a wide range of neonatal complications. The main etiological factor in the development of TTTS and sFGR is placental dysfunction, which is primarily associated with vasculogenic and angiogenic factors during monochorionic pregnancy.

Objective: This study aimed to investigate the role of vascular endothelial growth factors in perinatal outcomes, neonatal morbidity, and mortality in complicated monochorionic twin pregnancies.

Materials and methods: This was a prospective study with comparative analysis of the relationship between vasculogenic and angiogenic factors and perinatal outcomes, neonatal morbidity, and mortality in monochorionic multiple pregnancies complicated by sFGR and TTTS. The study included 84 pregnant women with monochorionic diamniotic twins and 152 newborns. An analysis of the course of pregnancy and childbirth, perinatal outcomes, and neonatal morbidity was also performed. The study also analyzed vasculogenic and angiogenic factors in the second trimester of pregnancy depending on the development of specific complications.

Results: Antenatal losses occurred in 6.45% (n=2) of patients in the TTTS group (p=0.249). Early neonatal mortality was observed in 14.3% (n=4) of the TTTS group and in 5% (n=1) of the sFGR group (p=0.272). The gestational age at delivery was significantly different in the complicated pregnancy groups (32.2–32.4 weeks) compared to the control group (36.2 weeks); (p<0.001). A study of vasculogenic and angiogenic factors in the second trimester of pregnancy showed an increase in maternal blood VEGF-C to 0.66 ng/ml and HIF-1a to 0.69 ng/ml, a decrease in VEGF-R1 to 0.73 ng/ml with neonatal mortality. In case of stillbirth, a high concentration of HIF-1a was observed (0.69 ng/ml). Changes in maternal blood concentrations of VEGF-R1 (0.787 ng/ml) and ANGPT2 (8255.91 pg/ml) were associated with the risk of fetal growth restriction. Analysis of the early neonatal period showed high respiratory, cardiovascular, and gastrointestinal morbidity in neonates from the TTTS and sFGR groups associated with prematurity and intrauterine deficits.

Conclusion: An association was found between changes in vasculogenic and angiogenic factors in the blood of pregnant women and high neonatal morbidity and mortality in complicated monochorionic twins. Specifically, the concentrations of VEGF-C and HIF-1a increased while VEGF-R1 decreased. The data obtained make it possible to predict antenatal and neonatal risks, improve perinatal outcomes, and minimize the risk of severe neonatal complications.

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About the authors

Kristina A. Gladkova

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation

Author for correspondence.
Email: k_gladkova@oparina4.ru
ORCID iD: 0000-0001-8131-4682

MD, Ph.D, Senior Researcher at the Fetal Medicine Unit, Institute of Obstetrics, Head of the 1st Obstetric Department of Pregnancy Pathology, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Russian Federation, Moscow

Zulfiya S. Khodzhaeva

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation

Email: z_khodzhaeva@oparina4.ru
ORCID iD: 0000-0001-8159-3714

Dr. Med. Sci., Professor, Deputy Director of Obstetrics Institute, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Russian Federation, Moscow

Viktoriya A. Sakalo

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation

Email: v_sakalo@oparina4.ru
ORCID iD: 0000-0002-5870-4655

MD, Ph.D, Junior Researcher at the Department of Pregnancy Pathology, Institute of Obstetrics, Obstetrician-Gynecologist at the 1st Obstetric Department of Pregnancy Pathology, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Russian Federation, Moscow

Ekaterina R. Frolova

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation

Email: kattirella@gmail.com
ORCID iD: 0000-0003-2817-3504

PhD Student at the High-Risk Pregnancy Department, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Russian Federation, Moscow

Marika N. Shakaya

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation; I.M. Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation (Sechenov University)

Email: k_gladkova@oparina4.ru
ORCID iD: 0000-0002-3838-3321

Neonatologist the A.G. Antonov Neonatal Intensive Care Unit, Institute of Neonatology and Pediatrics, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia; Teaching Assistant at the N.F. Filatov Department of Neonatology, Faculty of Pediatrics, I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia

Russian Federation, Moscow; Moscow

Аnna R. Kirtbaya

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation; I.M. Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation (Sechenov University)

Email: a_kirtbaya@oparina4.ru
ORCID iD: 0000-0002-7628-8157

Dr. Med. Sci., Clinical Care Supervisor at the A.G. Antonov Neonatal Intensive Care Unit, Institute of Neonatology and Pediatrics, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia; Professor at the N.F. Filatov Department of Neonatology, Faculty of Pediatrics, I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia

Bouvet Island, Moscow; Moscow

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Supplementary files

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2. Fig. 1. ROC curve of the relationship between the probability of giving birth to newborns with low body weight and the level of VEGF-R1 in the blood plasma of a pregnant woman

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3. Fig. 2. ROC curve of the relationship between the probability of giving birth to newborns with low body weight and the level of ANGPT2 in the blood plasma of a pregnant woman

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