Elena Alekseenkova

Background: Several scenarios of abnormal fetal growth develop during pregnancy in women with pregestational diabetes. A trend towards a higher incidence of large-for-gestational-age (LGA) births among women with type 1 diabetes (T1D) is observed worldwide despite novel approaches to maternal glycaemic control. Fetal growth restriction (FGR) is commonly recognised as a severe condition. However, the risk of adverse outcomes in LGA fetuses generally remains underestimated. Methods: We conducted a comparative analysis of pregnancy outcomes across different birthweight categories in pregnancies with T1D based on published data (2001–2026). Results: Interactions between disorders of early placentation, impaired nutrient transfer, fetal overnutrition, and genetic background result in alterations in birthweight and disproportionate fetal adipose tissue deposition. Both FGR and macrosomia are associated with increased risks of adverse perinatal outcomes. Although stillbirth occurs at both extremes of fetal growth, term LGA fetuses may remain particularly vulnerable because routine surveillance methods, including arterial Doppler assessment, fail to identify compromised fetuses with excessive growth. Accelerated fetal growth in T1D pregnancies, when placentation is initially impaired, may cause growth-restricted fetuses to appear appropriate for gestational age (AGA). Routine assessment may classify these vulnerable fetuses as being at low risk of perinatal complications. Disproportionate growth, even among infants classified as AGA, is associated with shoulder dystocia, birth trauma, and operative delivery. Neonatal hypoglycaemia and respiratory disorders remain frequent complications across the spectrum of abnormal fetal growth. Conclusions: Increased glucose variability may explain differences in placental and fetal growth trajectories and the high rate of pregnancy complications in patients with target glycated haemoglobin levels and routine capillary glucose monitoring results. Fetal overgrowth reflects impaired intrauterine development and should be considered a high-risk condition requiring careful consideration of the timing and mode of delivery.

Aim: to evaluate the effectiveness of low-molecular-weight heparins (LMWHs) in preventing placenta-associated complications (РАС), such as preeclampsia (PE), fetal growth restriction (FGR), intrauterine fetal death (IUFD) and placental abruption (PА), in women at high risk for these complications but without thrombophilia or thromboembolic disorders, based on a review and meta-analysis of publications released within the last twenty years. Materials and Methods. A search for relevant randomized controlled trials was conducted in electronic databases (PubMed/MEDLINE, Embase, Web of Science, etc.) spanning from 2005 to 2025. The meta-analysis included 11 trials involving a total of 1965 women. PE, FGR, IUFD, and PA were considered as the primary outcomesFixed-effects models were used for analysis, and the results were presented as risk ratios with 95 % confidence intervals. Results. LMWHs use was associated with a reduced IUFD risk (0.77 [0.65; 0.90]; p = 0.001), PA (0.67 [0.52; 0.86]; p = 0.002), and PE occurrence (0.74 [0.62; 0.89]; p = 0.001). No significant effect of LMWHs use on FGR risk was found (0.93 [0.69; 1.25]; p = 0.62). Considerable heterogeneity (I² > 60 %) was observed while analyzing IUFD, PE and PA. Funnel plot assessment did not rule out a potential risk of publication bias and requires further investigation. Conclusion. Prophylactic LMWHs use in women at high risk for РАС without thrombophilia may reduce the incidence of complications such as PE, IUFD, and PA. These findings indicate the need for multicenter studies with detailed analyses to identify patient cohorts where prophylactic LMWHs use for complication prevention provides a clear clinical and pathogenetic rationale.

BACKGROUND: Despite national reports on diabetes mellitus in pregnancy, the impact of different types of the disease on the features of anesthesia and the postoperative period in patients has not been studied well enough. AIM: The aim of this study was to evaluate the features of anesthesia during abdominal cesarean section and the postoperative period in patients with different types of diabetes mellitus. METHODS: We conducted a non-randomized controlled clinical study to examine the details of anesthetic management for cesarean section in patients with various types of diabetes mellitus. The patients underwent cesarean section under spinal anesthesia (10–12.5 mg of hyperbaric bupivacaine) using standard techniques. We studied the development and regression of motor block, as measured by the Bromage scale, and the progression of sensory block to the Th4–Th5 level. RESULTS: The study included 190 patients. Pregestational and gestational metabolic disorders contributed to a slowing of the blockade of sensorimotor fibers of the spinal nerves after spinal anesthesia with 0.5% hyperbaric bupivacaine. In all groups of patients with diabetes mellitus, the development of motor block to Bromage score 3 and sensory block to the Th4–Th5 level differed from the control group (p 0.001), but did not differ between groups with different types of glycemic disorders. The rate of regression of sensorimotor block in the study groups differed from rate of its development. In patients with type 1 or type 2 diabetes mellitus, regression of both sensory and motor blocks was longer by an average of 20 minutes (134.0–140.0 [128; 140] and 184.0–188.0 [180; 190] minutes, respectively) compared to healthy parturients. In patients with gestational diabetes mellitus, we observed the opposite reaction, namely, regression of sensory and motor blocks occurred on average 10 minutes faster (110.0–112.0 [110; 114] and 155.0 [150; 160] minutes, respectively) than in patients of the control group (121.0 [115; 128] and 165.0 [160; 170] minutes, respectively). CONCLUSION: Spinal anesthesia, as the preferred anesthetic option for cesarean section, has its own unique challenges for women with pregestational and gestational diabetes. However, the longer time to achieve sensory and motor block in these patients should be taken into account when choosing an anesthesia method based on abdominal delivery urgency.

BACKGROUND: Neonates with excessive body fat deposition are at increased risk of adverse short- and long-term outcomes. The potential of fractional fetal thigh (TVol) and arm (AVol) volume assessment to predict fetal body composition at birth, including but not limited to neonates of mothers with diabetes mellitus, is to be investigated. AIM: The aim of this study was to investigate the association between the extended fetal biometry measurements, based on the calculation of fetal fractional limb volumes, the neonatal body composition, and the development of neonatal hypoglycemia. METHODS: This single-center cohort study included patients with singleton pregnancies divided into the study groups: pregestational diabetes mellitus, gestational diabetes mellitus, and no carbohydrate metabolism disorders. Routine fetal biometry and TVol and AVol assessment were performed within 7 days before delivery. Body fat mass at birth was calculated using the Catalano et al. (1995) equation. RESULTS: The study included 46 patients with diabetes mellitus (pregestational, n = 32; gestational, n = 14) and 18 healthy control individuals, as well as their children. In newborns with diabetic fetopathy, the percentage of body fat was the highest — 25.0 [22.1; 26.1]% (p 0.001). Neonates in the pregestational diabetes mellitus group had a higher weight-for-length Z-score (INTERGROWTH-21st) — 1.253 [0.663; 2.058] (p = 0.001), in the gestational diabetes mellitus group — 0.247 [0.014; 0.411] (p = 0.001), and in the control group — 0.485 [0.059; 0.887] (p = 0.004). The percentage of body fat mass was strongly associated (p 0.001) with neonatal weight (r = 0.706) and its Z-score (r = 0.840), the weight-for-length ratio and its Z-score (r = 0.843), TVol (r = 0.639), and AVol (r = 0.532). The percentage of body fat mass did not correlate with the estimated fetal weight (r = 0.135, p = 0.288). A linear regression model including TVol and gestational age at birth had r2 = 0.64 (p 0.001) for body fat mass prediction. Generalized linear models identified pregestational diabetes mellitus as independent risk factor (p 0.001) for higher body fat mass percentage with comparable TVol. For neonatal hypoglycemia prediction, the birth weight Z-score (sensitivity 66.7%, specificity 70.0%) and the weight-for-length Z-score (sensitivity 66.7%, specificity 75.0%) were unreliable estimates, whereas the percentage of body fat mass had better performance (sensitivity 70.8%, specificity 80.0% at a percentage of greater than or equal to 20.2%). CONCLUSION: The accuracy of fetal adiposity detection and assessing the risk of neonatal hypoglycemia can be improved by using fetal fractional limb volume measurements. TVol is a sonographic predictor for excessive fat deposition, which can be used for body fat mass calculation, while parameters measured during routine fetometry poorly reflect the distribution of fat tissue in the fetus.

Recent research has demonstrated the effectiveness of continuous glucose monitoring systems in improving obstetric and perinatal outcomes in women with diabetes mellitus. Furthermore, these systems have opened up opportunities for stratifying patients based on their glycemic profiles, known as glucotypes, which, in turn, enables a more personalized approach to predicting complications and choosing treatment strategies. This article was aimed to analyze glycemic profile data obtained, using continuous glucose monitoring systems in pregnant women with pregestational diabetes mellitus, in order to study predictors of obstetric and perinatal complications, according to the available literature. We conducted a systematic review of publications from MEDLINE, PubMed, EMBASE and CSCD databases from 2005 to 2024. Fourteen studies that met the inclusion criteria were included in the analysis. The primary endpoints were continuous glucose monitoring data, glycated hemoglobin levels, and the incidence of preeclampsia, preterm birth, macrosomia, and neonatal hypoglycemia. Continuous glucose monitoring has been shown to be associated with lower glycated hemoglobin levels, increased time spent in the target glucose range, and decreased incidence of macrosomia, neonatal hypoglycemia, and neonatal intensive care unit admissions. The use of new methods of glycemic profile assessment such as glucotype allocation based on continuous glucose monitoring data opens up new opportunities for personalized pregnancy management. Continuous glucose monitoring can significantly improve glycemic control in pregnant women with pregestational types of diabetes mellitus and optimize insulin therapy, while helping to reduce the incidence of adverse obstetric and perinatal outcomes. Stratification by glucotype may be a promising avenue for personalization of therapy.

BACKGROUND: Growth disturbances are common in pregnancies complicated by pregestational diabetes mellitus. Identifying the relationship between the structural and functional characteristics of the placenta and abnormal fetal growth is important for understanding its formation and the possibility of its prediction. AIM: The aim of this study was to conduct a comparative analysis of the postnatal morphological and prenatal ultrasound features of the structure of placentas in cases of fetal growth disorders in pregnant women with pregestational diabetes mellitus. METHODS: In this retrospective single-center cohort study, we analyzed the results of the morphological studies of 1200 placentas, including those with fetal growth disorders in pregnant women with pregestational diabetes mellitus. Ultrasound prenatal fetometry, placentometry and Doppler measurements were used in this study. The studied placentas were weighed, with their size and cotyledonous structure assessed. Placental histopathological parameters were diagnosed using standardized criteria. Statistical analysis was carried out using SPSS Statistics version 23.0. RESULTS: The comparison groups included patients with pregestational diabetes mellitus types 1 and 2 with the absence (n = 394) or the presence of various fetal growth disturbances such as fetal growth restriction (n = 109), small (n = 118) and large (n = 352) for gestational age fetuses. The control group (n = 157) consisted of pregnant women with normal fetal growth rates and normal carbohydrate metabolism. In the placentas from pregnant women with pregestational diabetes mellitus, regardless of the presence of fetal growth disorders, we identified a number of distinctive features compared to patients in the control group. These were abnormal size, inconsistency of the structure of the placenta and the gestational age with a predominance of dissociated villous maturation, the presence of circulatory disorders of varying degrees, the presence of inflammatory changes in the placenta, deposition of calcium salts, and the development of chronic placental insufficiency and placental infarction. Moreover, in pregestational diabetes mellitus, the placentas of fetuses with macrosomic and normal growth often demonstrated similar features of the morphological structure. In intrauterine growth restriction, signs of pathological immaturity, premature and abnormal maturation of the villi prevailed in the structure of the placenta, with sclerosis of the villous stroma, placental infarctions, and circulatory disorders being more common. We demonstrated an association of grade II and III hemodynamic disorders with the features of maturation and structure of the villi and the presence of placental insufficiency. Critical blood flow disorders in the umbilical artery were associated with severe circulatory disorders in the placentas. CONCLUSION: In analyzing the morphofunctional and ultrasound characteristics of the placenta in cases of fetal growth disorders in pregestational diabetes mellitus, we found changes associated with both impaired carbohydrate metabolism and the influence of concomitant conditions. Some features of placental morphology in pregestational diabetes mellitus appeared to be morphofunctional adaptations. A relationship was found between fetoplacental hemodynamics Doppler disturbances and the histological structure of the placentas.

Objectives: To evaluate fetal thigh (TVol) and arm (AVol) fractional volume in pregnant women with pregestational diabetes (PGD) and normal glucose tolerance and to assess its ability to predict fetal macrosomia, defined as a birth weight of 4000 g or greater.Methods: A single‐center prospective cohort longitudinal study was conducted from February 2022 to November 2023. Women with a singleton pregnancy were enrolled in the study. Patients with severe extragenital pathology other than PGD, with fetal growth restriction, hemolytic disease, fetal malformations and anomalies, and gestational diabetes were excluded. The groups were those with PGD (n = 60) and the control group (n = 35). All patients underwent ultrasound examination three times during the third trimester, including standard biometry and assessment of fractional limb volume using 5D Limb Vol™ software (Samsung Medison). The primary outcome was a fetal macrosomia.Results: Fractional limb volumes in the PGD group (TVol 64.8, AVol 30.2 mL) exceeded those in the control group (TVol 51.7, AVol 22.5 mL, P < 0.001). Large‐for‐gestational age fetuses had significantly higher TVol and AVol compared with appropriate‐for‐gestational age fetuses in both the PGD and control groups. Fractional thigh volume (TVol) measured within 7 days before delivery can predict fetal macrosomia with a sensitivity of 81.82% and a specificity of 84.93% at a cut‐off of 82.71 mL.Conclusion: Fetal limb fractional volume can be used as a predictor for fetal macrosomia in women having diabetes or normal glucose tolerance. Further investigation implementing automatized methods can improve estimated fetal weight assessment in birth weight extremes.

Background: Chronic hyperglycemia and abnormal glucose variability are established risk factors for perinatal complications. Abnormal fetal growth and diabetic fetopathy can be associated not only with carbohydrate metabolism disorders, but also with impaired production of cytokines, chemokines, and growth factors that regulate intercellular interactions. Aim: The aim of this study was to evaluate cytokine and growth factor levels in the blood serum of pregnant women with type 1 diabetes mellitus and in umbilical cord blood of their neonates, as well as assessing the associations of these levels with the development of fetal macrosomia and diabetic fetopathy. Materials and methods: This prospective study included 88 women with a singleton pregnancy and cesarean delivery. All the patients provided informed consent for participation. The study groups comprised individuals with type 1 diabetes mellitus (n = 32) and non-impaired glucose tolerance (n = 56). The levels of interferons alfa 2 and gamma, monokine induced by interferon-gamma, interleukin-1α, -1β, -2, -3, -4, -5, -6, -7, -8, -9, -10, -13, -15, -16, -17, -18, interleukin-1 receptor antagonist, interleukin-2 receptor alpha subunits, p40 and p70 subunits of interleukin-12, monocyte chemotactic protein-1, -3, macrophage inflammatory protein-1α, -1β, leukemia inhibitory factor, macrophage ingibitory factor, nerve growth factor beta, stem cell factor, cutaneous T-cell-attracting chemokine, growth-regulated oncogene alpha, hepatocyte growth factor, stem cell growth factor beta, stromal cell-derived factor-1 alfa, interferon gamma inducible protein 10, platelet-derived growth factor-bb, vascular endothelial growth factor, basic fibroblast growth factor, eotaxin, chemokine ligand 5, and macrophage, granulocyte, and granulocyte/macrophage colony-stimulating factors, tumor necrosis factor alfa and beta, and tumor necrosis factor-related apoptosis-inducing ligand were measured with multiplex immunoassay in the blood serum of women at 36–40 weeks of gestation and in the umbilical cord blood serum of their neonates. Results: Cytokine levels varied widely in the both study groups. Women with type 1 diabetes mellitus had higher levels of interleukin-1β, -6, -17, basic fibroblast growth factor, macrophage inflammatory protein-1α, -1β, and lower levels of interleukin-1ra compared to the control group. Their neonates had higher levels of interleukin-6, -8, granulocyte colony-stimulating factor, macrophage inflammatory protein-1α, -1β. Higher levels of interleukin-1β, -6, -17, and basic fibroblast growth factor in the blood serum of the women were associated with time in range less than 70% and the development of diabetic fetopathy. Time in range was inversely associated with the interferon gamma / interleukin-5 (ρ = −0.531; p = 0.013), interferon gamma / interleukin-10 (ρ = −0.441; p = 0.045), interleukin-2 / -10 (ρ = −0.473; p = 0.030), interleukin-1β / -10 (ρ = −0.561; p = 0.008), interleukin-1β / -1ra (ρ = −0.635; p = 0.002), and interleukin-6 / -10 (ρ = −0.540; p = 0.012) ratios. Conclusions: Cytokine profile alterations were the most pronounced in pregnant women with non-target time in range values and in those with diabetic fetopathy development. Serum cytokine levels correlate with glycemic profile parameters but are considered non-specific markers of pregnancy complications.

BACKGROUND: During pregnancy complicated by diabetes mellitus, the risks of developing fetal macrosomia and other perinatal complications increase. Redistribution of blood flow in the fetal umbilical-portal venous system may be an important but poorly understood compensatory mechanism that affects macrosomic fetal growth. AIM: The aim of this study was to determine the features of the fetal umbilical-portal venous hemodynamics in pregnant women with various types of diabetes mellitus and the absence of carbohydrate metabolism disorders, taking into account the gestational age and the macrosomic fetal growth. MATERIALS AND METHODS: In this prospective cohort study, 86 pregnant women with pregestational diabetes mellitus, 44 pregnant women with gestational diabetes mellitus and 58 patients without carbohydrate metabolism disorders underwent ultrasound examinations from 30+0 to 41+3 weeks of gestation. During ultrasound, we performed Doppler assessment of venous hemodynamic parameters in the vessels of the umbilical-portal venous system, with volumetric blood flow calculated for each vessel. Additionally, the total liver volumetric blood flow and ductus venosus shunt fraction were calculated. RESULTS: The presence of fetal macrosomia in patients from the pregestational diabetes mellitus group is associated with an increase in the volumetric blood flow of the umbilical vein by 89.5 ml/min (p = 0.003) and the left portal vein by 33.3 ml/min (p = 0.008), as well as the total volumetric blood flow of the fetal liver by 95.7 ml/min (p = 0.001) compared with normal-weight fetuses. At the same time, the ductus venosus shunt fraction decreased in macrosomic fetuses by 3.83% (p = 0.001). In the gestational diabetes mellitus and control groups, despite the tendency for these parameters to increase in fetuses with macrosomia, the differences did not reach statistical significance. With a left portal vein volume flow threshold of 94.51 ml/min, the sensitivity and specificity for predicting large births were 84.46 and 72.09%, respectively. CONCLUSIONS: Pregestational diabetes mellitus in the mother is associated with a priority redistribution of blood flow to the fetal liver and is accompanied by a decrease in the ductus venosus shunt fraction. The severity of these hemodynamic changes increases in the presence of fetal macrosomia, which confirms the role of liver perfusion in the regulation of fetal growth in uncomplicated pregnancy and maternal diabetes mellitus.

BACKGROUND: Being strongly affected by maternal and fetal genetic factors, intrauterine environment plays a critical role in fetal growth. Intrauterine conditions, in turn, are largely determined by the genetic factors. AIM: The aim of this study was to evaluate the effect of the IGF1R rs907806 and GHSR rs572169 genetic variants on the weight of newborns. MATERIALS AND METHODS: This prospective study included 221 mother-newborn pairs. The inclusion criteria were singleton pregnancy and informed consent to participate in the study. The exclusion criteria were severe somatic, oncological and acute illnesses three months prior or during pregnancy, gestational diabetes mellitus, refusal to participate in the study at any stage, and insufficient data. The study groups included patients with type 1 diabetes mellitus (group I), type 2 diabetes mellitus (group II), and no carbohydrate metabolism disorders (group III). Cord blood samples were obtained after delivery. The IGF1R rs907806 and GHSR rs572169 genotypes were determined by polymerase chain reaction with restriction fragment length polymorphism analysis. The main outcomes were delivery of a large for gestational age fetus (weight of more than the 90th percentile INTERGROWTH-21st). The secondary outcomes were diabetic fetopathy, diabetic cardiomyopathy, and neonatal hypoglycemia. RESULTS: In group III, the minor G allele of the IGF1R rs907806 variant was more frequent in large-for-gestational-age newborns (p = 0.017; odds ratio 3.039; 95% confidence interval 1.244–7.424) than in those with a weight of less than 90th percentile. For the GHSR rs572169 variant, no similar trend was observed. This pattern was pronounced in the male newborns only (rs907806 AA vs. AG+GG; p = 0.046; odds ratio 4.229, 95% confidence interval 1.181–15.139). In newborns with hypoglycemia, a higher frequency of the GG genotype of the GHSR rs572169 (GA) variant was observed in the total sample (p = 0.004) and the type 1 diabetes mellitus group (p = 0.0496). CONCLUSIONS: The IGF1R rs907806 variant may affect birthweight in the male newborns of mothers without carbohydrate metabolism disorders. The observed association of neonatal hypoglycemia with the GG genotype of the GHSR rs572169 variant requires further investigation. Genetic factors can contribute to prognostic models of perinatal complications, while improving their early diagnosis opportunities.