PREDICTION OF FETAL GROWTH REST IN WOMEN WITH OBESITY

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Introduction. With maternal obesity, fetal development and placenta formation occur under metabolically altered conditions with an imbalance of vital microelements and vitamins [1, 2]. Copper is an essential nutrient for humans. Observational studies associate elevated copper levels with the development of diseases of the cardiovascular system, liver pathology, and musculoskeletal system [3, 4, 5]. Elevated levels of free copper in the body increase oxidative stress and accelerate tissue and organ damage, contributing to the development of disease [Footnote 1].

Obese women are more likely to experience obstetric complications during pregnancy [6]. Impaired uteroplacental circulation, despite maternal overnutrition, can lead to progressive placental insufficiency (PI) and the birth of small children for their gestational age [7]. In addition, the gestational process in maternal obesity occurs against the background of changes in the rheological and coagulation properties of the blood - an increase in the overall coagulant potential, a decrease in fibrinolytic activity, which leads to disturbances in intraplacental hemodynamics and the development of pregnancy complications [6]. Placental insufficiency leads to disruption of nutritional, endocrine, immune, and gas exchange functions with the formation of fetal growth restriction syndrome (FGR) [8]. Morphological criteria for placental insufficiency are formed during the first or second wave of trphooblast invasion (6-8 and 14-16 weeks, respectively) [9], but clinical manifestations in the form of impaired blood flow in the uteroplacental bed and delayed fetal development are formed in the second half of pregnancy. Obese mothers are 2 times more likely to give birth to fetuses with fetal growth restriction, which is associated with impaired placental function and the production of insulin-like growth factor in the fetus in utero [10]. The main methods for predicting FGR are based on ultrasound measurement of fetal size during pregnancy [Footnote 2], the presence of biochemical and genetic markers [11].

Thus, fetal growth retardation remains a difficult pathology to predict and requires further work to study it, including in obese women. Purpose of the study. Development of a method for predicting fetal growth restriction in obese women in the first trimester of pregnancy. Materials and methods. The study was conducted in accordance with the ethical principles for medical research involving human subjects as outlined in the Declaration of Helsinki of the World Health Organization. 85 obese pregnant women at 6-9 weeks of pregnancy were examined at the Center for Family Planning and Prenatal Diagnostics of the Polyclinic of the Federal State Budgetary Educational Institution of Higher Education Perm State Medical University named after. Academician E.A. Wagner of the Russian Ministry of Health. Obesity was determined by body mass index, as the ratio of height squared (m) to weight (kg), with a BMI > 30 kg/m2. All pregnant women were ranked into two groups depending on the percentage of free copper: group A – pregnant women with obesity and free copper content >25% (n=26); group B - obese pregnant women with a percentage of free copper <25%, (n=59). The control group consisted of 20 pregnant women with normal body weight. For all patients, the content of total copper (Cuvol.) in the blood serum was determined by the colorimetric method [12], ceruloplasmin (CP) according to the method [13], and the percentage of free copper (Cusfree) was calculated. The calculation of the free copper index was carried out using the formula: Cufree = (Cuob. – (CPx3)) / Cuob. x 100, where Cufree is the percentage of free copper in the blood serum, %; Cuob. – content of total copper in blood serum, µmol/l; CP – content of ceruloplasmin in blood serum, mg/ml; 3- conversion factor. Descriptive statistics methods were used to analyze the results obtained; the reliability of intergroup differences was assessed using the t-test for independent samples. The difference was considered significant at a significance level of p<0.05. The relative risk was calculated using a 95% confidence interval. The construction of a prognostic model of the risk of a certain outcome was carried out using the binary logistic regression method.

Results and its discussion. The copper content in the blood serum of pregnant women with normal body weight was 33.7±2.1 µmol/l, significantly different from the copper content in the blood of women from group A (45.4±8.6 µmol/l, p=0.01 ) and group B (41.5±7.3 µmol/l, p=0.01), while no differences were found between the indicators of groups A and B, p=0.71. The content of ceruloplasmin in the blood serum of obese women from group A was lower than that of women from group B (631.4±94.6 versus 734.3±81.8 mg/l), and did not differ significantly from that of patients with normal body weight (677.4±83.4 mg/l). Using the formula, the percentage of free copper was calculated, which reflects the amount of this element not associated with proteins, mainly with ceruloplasmin. When calculating the free copper index in women with normal body weight, a value of 9.8±1.1% was revealed. The level of free copper in group A in obese pregnant women was 2.5 times higher than in pregnant women from group B (34.6±6.9% versus 14.3±7.0%, p=0.05). It has been shown that free divalent copper in excess amounts can damage cells and induce the expression of tissue procoagulant factor [14]. Such changes in the body can lead to the development of intravascular coagulation and the formation of blood clots. Severe endothelial dysfunction develops with disorders of copper metabolism during pregnancy [15].

In group A, pregnant women with a free copper content of >25% in the placental tissue are 1.5 times more likely to develop changes characteristic of chronic placental insufficiency (Table 1), while the syndrome of fetal growth retardation is 6.4 times more likely to form than in group of patients with free copper content less than 25% [OR=6.38; 95% CI 2.39-16.99 p=0.01]. In case of obesity in combination with a high content of Cufree (>25%), PN was detected in 61.5% of cases, which in 38.5% was realized in the FGR in comparison with obese women, where PN was detected in 39%, and FGR only in 6% (p=0.001) (Fig. 1). Table 1 - Relative risk of developing placental pathology (histological signs) in obese women, %.

 

Histological features	Group А, n=26   abs/%	Group В, n=59 abs /%	OR	95% CI [LL-UL]	p
Villous stromal fibrosis	15/57,7	20/33,9	1,70	1,04-2,76	0,04
Thrombosis of the intervillous space	10/38,5	9/15,2	2,52	1,16-5,46	0,01
Umbilical vein thrombosis	7/26,9	1/1,7	15,88	1,16-122,64	<0,001
Dissociation	21/80,8	16/27,1	2,98	1,88-4,71	<0,001
Sclerosis	3/11,5	6/10,1	1,12	0,30-4,19	0,85
Obliterating angiopathy of stem supporting villi	9/34,6	8/13,6	2,55	1,11-5,87	0,02
Chronic placental insufficiency (total) compensated subcompensated decompensated	16/61,5 6/23,0 4/15,4 6/23,0	23/39,0 10/16,9 6/10,1 7/11,9	1,57 1,36 1,51 1,62	1,01-2,45 0,55-3,35 0,46-4,91 0,56-4,63	0,05 0,50 0,49 0,36
OR-,relative risk  95% CI [LL-UL]- confidence interval lower and upper limits

 

The formation of fetal growth restriction in the presence of placental insufficiency in women with a BMI of more than 30 kg/m2 is accompanied by a significantly higher percentage of free copper (34.6±6.9% versus 14.3±7.0%, p=0.05 ).

About the authors

Elena Makarova

E.A.Vagner Perm State Medical University

Author for correspondence.
Email: makarova_803@mail.ru
ORCID iD: 0000-0002-1330-8341
SPIN-code: 4535-0467
Scopus Author ID: 278641

кандидат медицинских наук

Russian Federation, 614000, Perm, St. Petropavlovskaya, d. 26 614600, Perm, Brothers Ignatiev St., 2

Michail Padrul

E.A.Vagner Perm State Medical University

Email: m-padrul@mail.ru
ORCID iD: 0000-0002-6111-5093
SPIN-code: 3347-1977

доктор медицинских наук, профессор кафедры акушерства и гинекологии №1

Russian Federation, 614000, Perm, St. Petropavlovskaya, d. 26

Natalya Aleхandrovna Terekhina

E.A.Vagner Perm State Medical University

Email: terekhina@list.ru
ORCID iD: 0000-0002-0168-3785
SPIN-code: 7663-4110
Scopus Author ID: 7004162006

доктор медицинских наук, заведующая кафедрой биологической химии

Russian Federation, 614000, Perm, St. Petropavlovskaya, d. 26

References

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