Gestational Complications Research Articles

Chronic kidney disease and pregnancy: an interdisciplinary assessment of gestational risks and complications. A literature review

Chronic kidney disease represents a heterogeneous group of diseases characterized by changes in the kidneys structure and functions. It significantly increases the risks of adverse maternal and perinatal outcomes. These risks increase with worsening renal dysfunction corresponding to an increase in the degree of proteinuria and arterial hypertension. Anatomical and physiological changes in the kidneys during pregnancy are characterized by dilatation of the pelvicalyceal system, a decrease in systemic and renal vascular resistance, and an increase in the glomerular filtration rate. These clinically significant changes can complicate the diagnosis of the renal dysfunction, as well as its progression. Pregnancy can affect the kidney as it can manifest as declining kidney function, especially in the context of concomitant arterial hypertension and proteinuria, while chronic kidney disease, regardless of the stage, contributes to a higher risk of adverse pregnancy outcomes including preeclampsia, premature birth and fetal growth restriction.
 Optimization strategies of pregnancy outcomes include strict control of blood pressure, treatment of hypertension and proteinuria, and prevention of preeclampsia. The latter is difficult to diagnose in pregnant women with chronic kidney disease. Serum markers such as soluble fms-like tyrosine kinase 1 and placental growth factor may aid in definitive diagnosis. The choice of delivery mode in women with chronic kidney disease should be based on common obstetric indications. A multidisciplinary team, including an obstetrician-gynecologist, a nephrologist, an anaesthesiologist and a neonatologist, must focus on preconception medical care, antenatal care and treatment of pregnant women with chronic kidney disease for a successful pregnancy outcome.

Судинні фактори та їхня роль у розвитку акушерських і перинатальних ускладнень у жінок з вірусним гепатитом В

Purpose - to assess the role of vascular factors in the development of obstetric and perinatal complications in women with hepatitis B virus (HBV). Materials and methods. The serum parameters of peripheral venous blood were studied in 86 pregnant women with HBV (the main group, which was divided into 2 subgroups: HBV1 - 38 women with obstetric and perinatal complications; HBV2 - 48 pregnant women without significant gestational complications) and in 50 women without infectious liver disease (the control group). The state of the platelet and coagulation links of the haemostasis system and the main indicators of endothelial function (nitric oxide and endothelin-1) were determined. Results. In the vascular platelet system of pregnant women with HBV, a relative decrease in the number of platelets with an increase in their aggregation capacity and von Willebrand factor concentration was found, in the coagulation system - a decrease in fibrinogen with a slight decrease in the prothrombin index, recalcification time, international normalized ratio and an increase in activated partial thromboplastin time. The detected changes are even more pronounced in women with obstetric and perinatal complications (HBV1 subgroup): against the background of relative thrombocytopenia, the indicators of anisocytosis increase and the aggregation ability of platelets, the level of D-dimer and von Willebrand factor increase significantly. Endothelial dysfunction was found in women of the HBV1 subgroup (a decrease in the concentration of nitric oxide with an increase in endothelin-1). Conclusions. The state of the haemostatic system in pregnant women with HBV can be characterized as an unstable equilibrium, which can be easily disturbed by various exo- and endogenous factors, which is observed in women with obstetric and perinatal complications and is manifested by prothrombotic changes. Established endothelial dysfunction in pregnant women with HBV is a leading link in the pathogenesis of obstetric and perinatal complications in this category of patients. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Sialylation status in placentas from pregnancies with SARS-CoV-2 infection

IntroductionRecent investigations suggest the potential negative impact of SARS-CoV-2 infection on pregnant women and pregnancy outcome. In addition, some studies have described pathological changes in the placental tissue of SARS-CoV-2-positive mothers, which are related or not to the infection severity and/or infection trimester. Among the various molecules involved in the normal structure and functionality of the placenta, sialic acids (Sias) seem to play an important role. Hence, we aimed to investigate possible changes in the distribution and content of Sias with different glycosidic linkages, namely α2,3 and α2,6 Galactose- or N-acetyl-Galactosamine-linked Sias and polymeric Sia (PolySia), in placentas from pregnant women infected by SARS-CoV-2 during the three different pregnancy trimesters. Methodsα2,3 and α2,6 Galactose-linked Sias were evaluated by lectin histochemistry (Maackia amurensis agglutinin (MAA) and Sambucus nigra agglutinin (SNA), respectively), while immunohistochemistry was used for PolySia detection. ResultsData showed lower levels of α2,3 Galactose-linked Sias in the trophoblast and underlying basement membrane/basal plasma membrane in placentas from women infected during the second and third infection trimester compared with uninfected cases and those infected during first trimester. On the other hand, higher levels of PolySia were detected in the trophoblast during the second and third infection trimester. ConclusionsOur findings suggest that changes in the sialylation status of trophoblast and its basement membrane/basal plasma membrane, together with other concomitant factors, could be at the basis of the most common placental histopathological alterations and gestational complications found especially in pregnancies with SARS-CoV-2 infection during the second and third trimester.

Features management of very early preterm birth

The objective: to determine features of tactics of very early preterm birth depending on the gestational age with the assessment of perinatal consequences. Materials and methods. The study involved 166 women of reproductive age with very early preterm birth (VEPB) at 22–27 weeks of gestation (the main criterion of inclusion). The patients were divided into two groups depending on the criteria of live birth: group 1 – 79 women, whose labor was regarded as late miscarriage (retrospective study); group 2 – 87 women, whose labor occurred as a very early premature (prospective study). Exclusion criteria: congenital malformations of the fetus. Patients of both groups had serious general and obstetric anamnesis, high frequency of inflammatory processes of the genitals, surgery and hormonal disorders with diseases caused by them. All women have got a comprehensive examination using clinical, instrumental and laboratory research methods. Results. The main complications of gestation in pregnant women of both groups in the second trimester were the threat of abortion and insufficiency of the fetoplacental (IFP), which caused fetal growth retardation syndrome (FGRS) in both groups – 66% and 63% of children, respectively. IFP in VEPB was confirmed histologically in 68% and 72% of cases in each group of mothers. Vaginal delivery occurred with 55 patients of group 1 and 26 women of group 2 (69,6% and 29,9%), among them in the period of 22–24 weeks – 100% and 57,1%, 25 weeks – 83,3% and 26,7%, 26–27 weeks – 57,7% and 24,1%, respectively, in each group. Indications for cesarean section (CS) in group 1 were mainly from the mother (75%), in group 2 – 27,8% from the mother, from the fetus – 4,9% (IFP), according to the combined indications – 65,6% (deep prematurity). Expansion of indications for CS in VEPB by 41% led to a decrease in perinatal mortality by 1,5 times (p<0,05). In the postpartum period, patients in both groups showed a decrease in purulent-septic complications on the background of preventive treatment from 13,9% (group 1) to 4,6% (group 2) (p<0,05). In the analysis of perinatal mortality, the highest rates were observed at 22–24 weeks of gestation, while they are 1,5 times lower at 25 weeks and 3,5 times lower at 26–27 weeks. The study found that the method of delivery did not affect perinatal outcomes at 22–25 weeks, but at 26–27 weeks, the survival of children born by CS surgery is higher than in spontaneous births, by 10% (p<0,05). Expansion of indications for the prevention of respiratory distress syndrome (RDS) of the fetus from 22 weeks in group 2 (in group 1 was not performed) by 10,7% led to an increase in survival of children with extremely low body weight (ELBW) by 11% (p<0,05). Conclusions. Under threat of VEPB the choice of delivery tactics is determined by the gestation period, the state of health of the mother and fetus, the degree of readiness of the birth canal for delivery. Premature pregnancy is not an indication for CS, except the specific obstetric indications, but abdominal delivery is possible for children in early pregnancy (22–25 weeks). The questions concerning the usage of instrumental care at birth, determination of gestational dates for the beginning of RDS prophylaxis with glucocorticoids, the necessity of using tocolysis remains ambiguous. Proper definition of management of women who give birth prematurely will allow timely implementation of measures aimed at improving the results for mother and newborn, and can be prognostic.

Contribution of labor related gene subtype classification on heterogeneity of polycystic ovary syndrome.

As one of the most common endocrine disorders in women of reproductive age, polycystic ovary syndrome (PCOS) is highly heterogeneous with varied clinical features and diverse gestational complications among individuals. The patients with PCOS have 2-fold higher risk of preterm labor which is associated with substantial infant morbidity and mortality and great socioeconomic cost. The study was designated to identify molecular subtypes and the related hub genes to facilitate the susceptibility assessment of preterm labor in women with PCOS. Four mRNA datasets (GSE84958, GSE5090, GSE43264 and GSE98421) were obtained from Gene Expression Omnibus database. Twenty-eight candidate genes related to preterm labor or labor were yielded from the researches and our unpublished data. Then, we utilized unsupervised clustering to identify molecular subtypes in PCOS based on the expression of above candidate genes. Key modules were generated with weighted gene co-expression network analysis R package, and their hub genes were generated with CytoHubba. The probable biological function and mechanism were explored through Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis. In addition, STRING and Cytoscape software were used to identify the protein-protein interaction (PPI) network, and the molecular complex detection (MCODE) was used to identify the hub genes. Then the overlapping hub genes were predicted. Two molecular subtypes were found in women with PCOS based on the expression similarity of preterm labor or labor-related genes, in which two modules were highlighted. The key modules and PPI network have five overlapping five hub genes, two of which, GTF2F2 and MYO6 gene, were further confirmed by the comparison between clustering subgroups according to the expression of hub genes. Distinct PCOS molecular subtypes were identified with preterm labor or labor-related genes, which might uncover the potential mechanism underlying heterogeneity of clinical pregnancy complications in women with PCOS.

НЕОБХОДИМОСТЬ СОЗДАНИЯ ИНДИВИДУАЛЬНОГО ПРОГНОСТИЧЕСКОГО КРИТЕРИЯ ОЦЕНКИ СОСТОЯНИЯ ЗДОРОВЬЯ БЕРЕМЕННОЙ

Due to the clear depopulation trends in the country, the problem of protecting the health of mother and child, preserving the reproductive potential has become extremely acute. The current situation causes reasonable concern of the state and the medical community for the quality of health of future generations. The increase in extragenital and gynecological morbidity, the negative nuances of the reproductive behavior of adolescent girls and women creates a real threat to the successful implementation of their reproductive function and replenishment of the country's demographic reserve in the near future.The real improvement in statistics was due to the rationalization of the prevention of full-term pregnancy. The purpose of the study: to improve the outcomes of gestation for the mother and fetus based on the creation of an individual prognostic criterion for assessing the state of health. Results and discussion. In order to determine the effectiveness of the proposed set of measures to reduce the risk of adverse pregnancy outcomes, a prospective study was conducted in the "organizational modeling" group in 174 pregnant women. In order to determine the predictors of gestational complications in the process of a comprehensive examination of patients during pregnancy registration, it was found that the predictive factors for the development of pregnancy complications that subsequently affect the realization of reproductive potential are: menstrual dysfunction, somatic and gynecological pathology, previously transferred infectious diseases, as well as neuro-metabolic-endocrine diseases. The main methodological principle of the stage-by-stage monitoring of pregnancy management is the inseparable unity of the implementation of all points, control of the full scope of a single strategy and evaluation of the result obtained. The specified components of the methodology are mandatory. Conclusions: the informational significance of evaluative and prognostic predictors (calculation of pregnancy health indices by trimesters) determines the possibility of stratifying tactics by perinatal risk groups: exclusion of obstetric aggression at a low degree (index I), therapeutic and preventive measures at an average (index II, III) and high degree of risk (index IV, V).

Associations of maternal and placental extracellular vesicle miRNA with preeclampsia.

Introduction: Gestational vascular complications (GVCs), including gestational hypertension and preeclampsia, are leading causes of maternal morbidity and mortality. Elevated levels of extracellular vesicles (EVs), in GVC have been linked to vascular injury. This study aims to characterize placental and circulating EV miRNA in GVCs, and explores the involvement of EV-miRNA in GVC, and whether they may be used to distinguish between placental and maternal pathologies. Methods: Blood samples were obtained from 15 non-pregnant (NP), 18 healthy-pregnant (HP), and 23 women with GVC during the third trimester. Placental sections were obtained after caesarian section. Platelet-poor-plasma (PPP) and EV pellets were characterized: EV size/concentration, protein content and miRNA expression were measured by nanoparticle tracking analysis, western blot, nano-string technology and RT-PCR. The effects of EVs on trophoblasts and EC miRNA expression were evaluated. Results: Higher EVs concentrations were observed in HP-PPP and GVC-PPP (p < 0.0001) compared to the NP-PPP. The concentration of large EVs (>100nm) was higher in PPP and EV pellets of HP and GVC compared to the NP group. EV pellets of pregnant women demonstrated lower expression of exosomal markers CD63/CD81 compared to NP-EVs. GVC-EVs expressed more human placental lactogen (hPL) hormone than HP-EVs, reflecting their placental origin. Screening of miRNAs in EV pellets and in PPP identified certain miRNAs that were highly expressed only in EVs pellets of the HP (13%) and GVC groups (15%), but not in the NP group. Differences were detected in the expression of hsa-miR-16-5p, hsa-miR-210, and hsa-miR-29b-3p. The expression of hsa-miR-16-5p and hsa-miR-210 was low in EV pellets obtained from NP, higher in HP-EVs, and significantly lower in GVC-EVs. Except for hsa-miR-29b-3p, which was upregulated in GVC, no significant differences were found in the levels of other miRNAs in placental sections. Exposure to GVC-EVs resulted in higher expression of hsa-miR-29b-3p compared to cells exposed to HP-EVs in villous trophoblasts, but not in EC. Conclusion: Expression of hsa-miR-16-5p and hsa-miR-210 reflects maternal pathophysiological status, while hsa-miR-29b-3p reflects placental status. These findings suggest that EV-miRNA are involved in GVC, and that they may be used to distinguish between pathologies of placental and maternal origins in preeclampsia.

Chronic glomerulonephritis and pregnancy: predictors of preterm birth

Background: Chronic kidney disease (CKD) in pregnant women, with one of its most important causes being chronic glomerulonephritis (CGN), increases the incidence of adverse perinatal outcomes and gestational complications, including preterm birth (PB). Being the main cause of infant morbidity and mortality, PB has serious medical and social significance.&#x0D; Aim: To identify clinical predictors and develop a predictive model of PB in pregnant women with CGN.&#x0D; Materials and methods: A retrospective/prospective study included 122 CGN patients, whose 128 pregnancies resulted in childbirth from January 2009 to November 2022. Eighty-eight pregnancies were in the patients with CKD stage 1, 15 in stage 2, 21 in stage 3a, 3 in stage 3b, and one in stage 4. One hundred and nine (109) patients (115 pregnancies) delivered on term (at least 37 weeks of gestation) and were included into the group of term deliveries, whereas 13 women with 13 pregnancies had PB within the range of 22 weeks to 36 weeks 6 days. In the patients of both groups, we assessed nephrological and obstetric history, proteinuria and arterial hypertension at baseline and during pregnancy, complications of the index pregnancy, such as preeclampsia (PE) and severe PE, anemia, urinary tract infections, acute kidney injury, placental insufficiency, and cervical insufficiency. Binary logistic regression was used for prediction modeling of PB in women with CGN.&#x0D; Results: The proportion of PB in total cohort of the CGN patients was 10.2%. PB was spontaneous only in 2/13 (15.4%) cases, while in the rest of 11 pregnancies (84.6%) the delivery was induced due to maternal and fetal indications. Six independent predictors of PB were identified: body mass index, CKD stage, history of non-developing pregnancies, proteinuria during pregnancy 1 g/day, PE and placental insufficiency. The predictive model had sensitivity of 76.9%, specificity 99.1%, diagnostic efficiency 96.9%, positive predictive value 90.9%, and negative predictive value 97.4%.&#x0D; Conclusion: Predicting PB and targeting modifiable factors associated with PB may improve pregnancy outcomes in patients with CGN.

RISK FACTORS OF UMBILICAL CORD PATHOLOGY AND FACTORS OF NEGATIVE PERINATAL CONSEQUENCES AND NEWBORN INCIDENCE

According to literature sources, the real frequency of many umbilical cord pathologies differs significantly from the statistical data indicated by researchers in their works (from 15% to 38%). The implementation of a system of diagnostic and treatment and preventive measures, based on mandatory antenatal and postnatal assessment of the features and characteristics of the umbilical cord, allows to improve perinatal outcomes and reduce perinatal morbidity. The aim of the work was to identify the main risk factors of umbilical cord pathology and negative perinatal consequences; to develop elements of standardization of antenatal and postnatal diagnosis of umbilical cord pathology. Research materials and methods. A retrospective assessment of medical documentation data (3,280 individual medical records of pregnant women) made it possible to establish the frequency of umbilical cord pathology in the population. In the future, a more detailed extended antenatal and postnatal examination of the umbilical cord and placenta after delivery was carried out in 637 patients of reproductive age with pregnancy complicated by pathology of the umbilical cord (main group). The control group was formed by 40 patients with an uncomplicated course of pregnancy and live birth of full-term healthy children. The study was conducted taking into account the main principles of the Helsinki Declaration on Biometric Research and the powers of the GCH ICH, in accordance with biometric norms with compliance with the principles of confidentiality and ethics (excerpt from protocol No. 128/22 of the meeting of the Bioethics Commission dated September 29, 2022, Ivano-Frankivsk National Medical University, Ministry of Health of Ukraine).Data analysis was performed using the Statistica 7.0 package of statistical programs (StatSoftInc., USA). The association of independent variables with the condition being studied is presented as odds ratio (OR) and 95% confidence interval (CI).The materials of the article are the result of the research of the complex research work fragment of the Department of Obstetrics and Gynecology named after I.D. Lanovyi of the Ivano-Frankivsk National Medical University: “Development of diagnostic tactics and pathogenetic substantiation of effective methods of preserving and restoring reproductive potential and improving parameters of a woman’s quality of life in obstetric and gynecological pathology” (state registration number 0121U109269, implementation dates 2021-2026 ), the author is a co-executor of the topic.Research results and their discussion. The following data were noted: an excess of the population norm of the length of the umbilical cord, a high proportion of eccentric and marginal insertion of the umbilical cord (22.14%) and umbilical cord coiling (33.28%), a decrease in the proportion of the reference limits of the umbilical cord tortuosity index (15.86%), in 56.7% of observations, the specific gravity of the umbilical cord was lower. Probable risk factors for umbilical cord pathology with a predominance of age over 35 years, nicotine addiction in pregnant women, multiple fertility, use of IVF programs, change in the amniotic fluid index, overweight and obesity, other clinical conditions associated with metabolic disorders (gestational diabetes, insulin resistance) were identified. Conclusion. The share of the umbilical cord pathology both in the isolated type and in the combination of characteristic features of the umbilical cord is 40.98%. The increase in the risk of negative perinatal consequences has a close relationship with the umbilical cord pathology and the combination of different types of pathology, as well as the addition of gestational complications, which allows for the formation of screening programs and optimization of the diagnostic algorithm.

Developmental Ultrasound Characteristics in Guinea Pigs: Similarities with Human Pregnancy.

Biometrical and blood flow examinations are fundamental for assessing fetoplacental development during pregnancy. Guinea pigs have been proposed as a good model to study fetal development and related gestational complications; however, longitudinal growth and blood flow changes in utero have not been properly described. This study aimed to describe fetal and placental growth and blood flow of the main intrauterine vascular beds across normal guinea pig pregnancy and to discuss the relevance of this data for human pregnancy. Pregnant guinea pigs were studied from day 25 of pregnancy until term (day ~70) by ultrasound and Doppler assessment. The results were compared to human data from the literature. Measurements of biparietal diameter (BPD), cranial circumference (CC), abdominal circumference, and placental biometry, as well as pulsatility index determination of umbilical artery, middle cerebral artery (MCA), and cerebroplacental ratio (CPR), were feasible to determine across pregnancy, and they could be adjusted to linear or nonlinear functions. In addition, several of these parameters showed a high correlation coefficient and could be used to assess gestational age in guinea pigs. We further compared these data to ultrasound variables from human pregnancy with high similarities. BPD and CC are the most reliable measurements to assess fetal growth in guinea pigs. Furthermore, this is the first report in which the MCA pulsatility index and CPR are described across guinea pig gestation. The guinea pig is a valuable model to assess fetal growth and blood flow distribution, variables that are comparable with human pregnancy.

Preeclampsia: Recent Advances in Predicting, Preventing, and Managing the Maternal and Fetal Life-Threatening Condition.

Preeclampsia accounts for one of the most common documented gestational complications, with a prevalence of approximately 2 to 15% of all pregnancies. Defined as gestational hypertension after 20 weeks of pregnancy and coexisting proteinuria or generalized edema, and certain forms of organ damage, it is life-threatening for both the mother and the fetus, in terms of increasing the rate of mortality and morbidity. Preeclamptic pregnancies are strongly associated with significantly higher medical costs. The maternal costs are related to the extra utility of the healthcare system, more resources used during hospitalization, and likely more surgical spending due to an elevated rate of cesarean deliveries. The infant costs also contribute to a large percentage of the expenses as the babies are prone to preterm deliveries and relevant or causative adverse events. Preeclampsia imposes a considerable financial burden on our societies. It is important for healthcare providers and policy-makers to recognize this phenomenon and allocate enough economic budgets and medical and social resources accordingly. The true cellular and molecular mechanisms underlying preeclampsia remain largely unexplained, which is assumed to be a two-stage process of impaired uteroplacental perfusion with or without prior defective trophoblast invasion (stage 1), followed by general endothelial dysfunction and vascular inflammation that lead to systemic organ damages (stage 2). Risk factors for preeclampsia including race, advanced maternal age, obesity, nulliparity, multi-fetal pregnancy, and co-existing medical disorders, can serve as warnings or markers that call for enhanced surveillance of maternal and fetal well-being. Doppler ultrasonography and biomarkers including the mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), and serum pregnancy-associated plasma protein A (PAPP-A) can be used for the prediction of preeclampsia. For women perceived as high-risk individuals for developing preeclampsia, the administration of low-dose aspirin on a daily basis since early pregnancy has proven to be the most effective way to prevent preeclampsia. For preeclamptic females, relevant information, counseling, and suggestions should be provided to facilitate timely intervention or specialty referral. In pregnancies complicated with preeclampsia, closer monitoring and antepartum surveillance including the Doppler ultrasound blood flow study, biophysical profile, non-stress test, and oxytocin challenge test can be arranged. If the results are unfavorable, early intervention and aggressive therapy should be considered. Affected females should have access to higher levels of obstetric units and neonatal institutes. Before, during, and after delivery, monitoring and preparation should be intensified for affected gravidas to avoid serious complications of preeclampsia. In severe cases, delivery of the fetus and the placenta is the ultimate solution to treat preeclampsia. The current review is a summary of recent advances regarding the knowledge of preeclampsia. However, the detailed etiology, pathophysiology, and effect of preeclampsia seem complicated, and further research to address the primary etiology and pathophysiology underlying the clinical manifestations and outcomes is warranted.

Predictors of late complications in pregnant women with arterial hypertension

Arterial hypertension occurs in 829% of pregnant women and is a common form of endothelial dysfunction during gestation. In recent decades, the prevalence of arterial hypertension has increased several times largely due to the increasing maternal age of primiparous women and the increased incidence of obesity, diabetes mellitus, and carbohydrate metabolism disorders.&#x0D; The aim of this study was to formulate the management tactics for pregnant patients with high blood pressure, based on the current understanding of the causes and mechanisms of the disease and the ability to influence the molecular links of pathogenesis, and to identify possible markers for predicting the progression of endothelial dysfunction in pregnant women with arterial hypertension. This review, based on the literature, raises the problem of modern diagnosis of arterial hypertension in pregnancy. We discuss the consequences of late initiation of the therapy and evaluate possible complications.&#x0D; The severity of arterial hypertension is assessed differently in pregnant and non-pregnant women, according to current clinical guidelines. Thus, chronic arterial hypertension in pregnant women corresponds to grade II arterial hypertension in non-pregnant women, according to the American Heart Association and American College of Cardiology classification. Both untimely diagnosis and delayed or inadequate treatment result in adverse obstetric outcomes. Recent studies indicate the ability of earlier antihypertensive therapy (already at stage I according to the American Heart Association and American College of Cardiology classification) to reduce maternal and fetal adverse effects and prolong pregnancy. The CHAP 2022 study showed that using a blood pressure treatment threshold of 140/90 mmHg for pregnant women with chronic arterial hypertension provides better outcomes compared to treatment at higher numbers. Despite early initiation of therapy, some patients with elevated blood pressure subsequently develop thrombotic and gestational complications associated with endothelial dysfunction. There is an obvious need to introduce early preclinical diagnostic methods that would narrow the risk group and prevent late complications. The authors consensus on personalization of acetylsalicylic acid intake has emerged. The review analyzes the potential mechanisms of aspirin resistance, as well as the influence of genetic (the PTGS1, PTGS2, ITGB3, ITGA2, GP6, GP1BA, P2RY1, P2RY12 genes, other genes, and associated microRNA) and biochemical markers (11-dehydrotromboxane B2), which presumably may have prognostic value and applicability in clinical practice.&#x0D; Our current understanding of the problem of diagnosis and early treatment of arterial hypertension in pregnancy can reduce the number of complications. The problem of predicting the development of endothelial dysfunction remains unresolved to the end. Active implementation of the studied markers into practice requires a further more detailed study of this area and the optimization of research design.

Adverse Childbirth and Perinatal Outcomes Among Healthy, Low-Risk Pregnant Women with Abnormal Total Gestational Weight Gain.

Purpose: Little is known on the potential effects of abnormal gestational weight gain (GWG) among low-risk, healthy pregnant women with no comorbidities or gestational complications. We investigated perinatal outcomes of these pregnancies according to GWG as per the 2009 National Academy of Medicine (NAM) recommendations. Materials and Methods: A retrospective analysis of prospectively collected data of low-risk pregnant women giving birth at term between January 2016 and December 2020. Inclusion criteria were normal pregestational body mass index (pBMI) (18.5-24.9 kg/m2) and no pregestational or gestational complication. Self-reported prepregnancy weight was used to calculate pBMI; GWG was the difference between maternal weight at childbirth and prepregnancy weight. Women were classified according to the 2009 NAM guidelines for GWG: insufficient (iGWG, <11.5 kg), adequate (aGWG, 11.5-16 kg), and excessive (eGWG, >16 kg). Logistic regression analysis with aGWG as referent was performed to independently estimate dose-response associations. Results: During the study period, there were 4,127 (33.1%) births fulfilling the inclusion criteria. Fifty-two percent of women gained outside the recommended range: 33.5% had iGWG and 18.7% had eGWG. iGWG women were 40% more likely to have early-term births and small for gestational age neonates. In turn, eGWG women displayed increased odds of prolonged pregnancy (adjusted odds ratio [aOR] 1.32), cesarean section in labor (aOR 1.50), high-degree perineal tears (aOR 2.04), postpartum hemorrhage ≥1,000 mL (aOR 1.54), and large for gestational age newborns (aOR 1.83). Conclusion: Our data show that abnormal GWG independently associates with heightened risk of adverse outcomes among healthy, low-risk pregnant women with normal pBMI and no comorbidity or gestational complication.

Associations between maternal complications during pregnancy and childhood asthma: a retrospective cohort study.

Studies on the associations between maternal complications during pregnancy and childhood asthma are exclusively conducted in Western countries. The findings are mixed and may not be translated to other populations. We aimed to investigate the associations among the Chinese population and to determine whether the associations were mediated through pre-term birth, caesarean delivery, low birthweight and not breastfeeding in the first 6 months. We conducted a retrospective cohort study of 166 772 children in Guangzhou, China. Information on maternal gestational hypertension, gestational diabetes and gestational anaemia during pregnancy was extracted from medical records. Ever-diagnosis of asthma in children aged 6-12 years was obtained by questionnaire. Logistic regression models and mediation analyses were used to estimate the adjusted odds ratios (aORs) and 95% confidence intervals for childhood asthma. Gestational hypertension, gestational diabetes and gestational anaemia during pregnancy were associated with an increased risk of ever-diagnosed childhood asthma: aOR 1.48 (95% CI 1.37-1.60), 1.71 (95% CI 1.65-1.78) and 1.34 (95% CI 1.26-1.45), respectively. A stronger association was observed for two or three gestational complications (aOR 2.02 (95% CI 1.93-2.16)) than one gestational complication (aOR 1.64 (95% CI 1.52-1.77)). The aOR for the three gestational complications was 1.35 (95% CI 1.26-1.45), 1.63 (95% CI 1.58-1.70) and 1.32 (95% CI 1.24-1.43), respectively, after controlling for the mediators, including pre-term birth, caesarean delivery, low birthweight and not breastfeeding in the first 6 months. Gestational hypertension, gestational diabetes and gestational anaemia were associated with childhood asthma, and the associations were partially explained by the mediation effects.

Laparoscopic Removal of Nonseparated Cavitated Horn in Unicornuate Uterus: Surgical Aspects and Long-Term follow-up.

In unicornuate uterus cases, when the rudimentary horn is very close to the uterus and is firmly attached, laparoscopic surgery can be very challenging due to the danger of massive bleeding and the possiblity of damaging the healthy hemiuterus. The aim of study is to verify if the laparoscopic resection of the horn site of hematometra, when solidly attached to the unicornuate uterus, is safe and effective. This is a retrospective analysis of prospectively collected data in a tertiary referral centre. From 2005 to 2021, a total of 19 women were diagnosed with unicornuate uterus with cavitated noncommunicating horn (class II B). We reviewed the original documentations of the patients and created a database. The follow-up results were assessed by questionnaires answered by the patients. In all cases, the chosen treatment was: laparoscopic removal of the rudimentary horn together with the ipsilateral salpinx and reconstruction of the myometrium of the hemiuterus. Statistical Package for Social Science (SPSS) version 21.0 was used to perform data analysis. We decided to calculate continuous variables in terms of mean and standard deviation (SD) or as median and interquartile range (IQR), as appropriate. Instead, categorical variables were expressed in terms of percentage. Five patients (12-18 years old) with unicornuate uterus and rudimentary horn with hematometra and broadly connected to the hemiuterus were operated laparoscopically. The surgical procedure was successfull in all cases. No major complications were recorded. Postoperative course was uneventfull. In the follow-up in all cases dysmenorrhea and pelvic pain disappeared. Three patients sought to become pregnant and have children. They had in total 4 pregnancies with 2 abortions in the 1st trimester and two pregnancies with premature births at the 34th and 36th weeks. No serious gestational complications were recorded and the pregnancies ended with caesarean sections due to breech presentation. Overall, for the rudimentary horn solidly attached to the unicornuate uterus, the laparoscopic resection of the horn site of hematometra seems to be safe and effective.

Artificial Neural Network Modeling to Predict Neonatal Metabolic Bone Disease in the Prenatal and Postnatal Periods

Early recognition of metabolic bone disease (MBD) in infants is necessary but difficult; an appropriate tool to screen infants at risk of developing MBD is needed. To develop a predictive model for neonates at risk for MBD in the prenatal and postnatal periods and detect the pivotal exposed factors in each period. A diagnostic study was conducted from January 1, 2012, to December 31, 2021, in Shanghai, China. A total of 10 801 pregnant women (singleton pregnancy, followed up until 1 month after parturition) and their infants (n = 10 801) were included. An artificial neural network (ANN) framework was used to build 5 predictive models with different exposures from prenatal to postnatal periods. The receiver operating characteristic curve was used to evaluate the model performance. The importance of each feature was examined and ranked. Of the 10 801 Chinese women who participated in the study (mean [SD] age, 29.7 [3.9] years), 7104 (65.8%) were local residents, 1001 (9.3%) had uterine scarring, and 138 (1.3%) gave birth to an infant with MBD. Among the 5 ANN models, model 1 (significant prenatal and postnatal factors) showed the highest AUC of 0.981 (95% CI, 0.970-0.992), followed by model 5 (postnatal factors; AUC, 0.977; 95% CI, 0.966-0.988), model 4 (all prenatal factors; AUC, 0.850; 95% CI, 0.785-0.915), model 3 (gestational complications or comorbidities and medication use; AUC, 0.808; 95% CI, 0.726-0.891), and model 2 (maternal nutritional conditions; AUC, 0.647; 95% CI, 0.571-0.723). Birth weight, maternal age at pregnancy, and neonatal disorders (anemia, respiratory distress syndrome, and septicemia) were the most important model 1 characteristics for predicting infants at risk of MBD; among these characteristics, extremely low birth weight (importance, 50.5%) was the most powerful factor. The use of magnesium sulfate during pregnancy (model 4: importance, 21.2%) was the most significant predictor of MBD risk in the prenatal period. In this diagnostic study, ANN appeared to be a simple and efficient tool for identifying neonates at risk for MBD. Combining prenatal and postnatal factors or using postnatal exposures alone provided the most precise prediction. Extremely low birth weight was the most significant predictive factor, whereas magnesium sulfate use during pregnancy could be an important bellwether for MBD before delivery.

Analysis of Risk Factors for Low Birth Weight (LBW) in the Work Area of the Setu II Bekasi Health Center

The aim of the study was to analyze the risk factors for LBW events in the working area of the Setu II Bekasi Health Center in 2022. This research was an analytic survey study using a cross-sectional study design with a population of 521 people and a sample of 84 people who were selected using a random sampling technique. Data was taken using a questionnaire which was then processed using a statistical program. Results: The study found that 22.6% of babies were born with a weight &lt; 2500 grams, 27.4% of mothers aged &lt; 20 and &gt; 35 years, 20.2% of mothers with gestational age &lt; 37 weeks, 28.6% of mothers with parity ≥ 3 children, 14.3% of mothers had LILA &lt;23.5 cm, 7.1% of mothers had HB levels &lt;10 g/dl, 10.7% of mothers experienced pregnancy complications. The results of statistical analysis using the chi square test found that the risk factors associated with the incidence of LBW were gestational age (p value = 0.000), parity (p value = 0.019) and pregnancy complications (p value = 0.025). While the risk factors that were not related to the incidence of LBW were mother's age (p value = 0.179), upper arm circumference (p value = 0.455) and HB levels (p value = 0.126). Conclusion: the risk factors associated with the incidence of LBW are gestational age, parity and complications of pregnancy. Therefore, it is hoped that parents will always take care of their pregnancies by checking their pregnancies to health services, so as to minimize risk factors during pregnancy

Obesity and pregnancy: possible ways to overcome complications and improve reproductive outcomes

Introduction. Obesity, due to its high prevalence and relevance, can be considered an epidemic of modern society. Obesity-related microcirculatory vascular disease and chronic inflammation with endothelial dysfunction are associated with adverse effects on reproductive potential. Sulodexide reduces the risk of hemostatic complications in patients planning pregnancy due to its polypotent effect, which is especially important in metabolic disorders and comorbidities. Therefore, it is promising to assess the effectiveness of integrated management of obese patients as part of pregnancy planning.&#x0D; Aim. To modify the complex treatment of obesity in patients planning pregnancy to reduce the risk of reproductive losses and gestational complications.&#x0D; Materials and methods. The prospective analysis included 92 patients with grade 1 obesity. According to the clinical protocols and guidelines of the Reproductive Health Professional Medical Association, 46 patients in the control group (group 1) were prescribed treatment to reduce the body mass index, including lifestyle correction, folic acid, and vitamin D. Patients in the comparison group (Group 2, n=46) also received endotheliotropic agent sulodexide. The treatment efficacy was analyzed based on the frequency of pregnancy, the change of laboratory markers of endothelial dysfunction, the incidence of gestational complications, and reproductive losses.&#x0D; Results. The study showed that in comparison group patients, the frequency of pregnancy (58.7% of cases in Group 1, 71.7% in Group 1), favorable course of the first trimester (39.1% in Group 1, 63.0% in Group 2), and delivery at term (30.4% in Group 1, 56.5% in Group 2) were higher compared to the control group. There was also a more significant decrease in the body mass index and endothelial dysfunction factors (homocysteine level in group 1 before treatment was 172.4 mol/L, and 141.8 mol/L after treatment; 191.7 mol/L before treatment and 91.4 mol/L after treatment in Group 2, respectively) in patients receiving complex treatment with sulodexide. Analysis of the pregnancy course showed a lower risk of gestational diabetes (33.3% in Group 1 and 13.8% in Group 2).&#x0D; Conclusion. Treatment of obesity in patients planning pregnancy requires a complex effect aimed at correcting lifestyle, reducing body weight, restoring the endothelial layer, and reducing the severity of chronic inflammation, thus improving reproductive outcomes and minimizing the risk of gestational complications.

Raised Thyroid-Stimulating Hormone in Girls with Polycystic Ovary Syndrome: Effects of Randomized Interventions

Introduction: Polycystic ovary syndrome (PCOS) in women associates with raised levels of circulating thyroid-stimulating hormone (TSH) and with high rates of gestational complications. A low range of preconception TSH is followed by low rates of gestational complications. It is unknown whether TSH levels are elevated in adolescents with PCOS and, if so, whether traditional or exploratory treatments can lower them into safe preconception range. We investigated TSH in nonobese adolescents with PCOS, including the effects of randomized interventions. Methods: Morning TSH was a safety marker in randomized pilot studies comparing the effects of an oral contraceptive (OC) versus those of a low-dose combination of spironolactone-pioglitazone-metformin (SPIOMET) in nonobese adolescents with PCOS. A post hoc analysis compared TSH levels in PCOS (N = 62) versus controls, TSH changes on treatment (for 1 year), and TSH levels posttreatment (for 1 year). Results: Mean TSH levels were higher in PCOS patients than in control girls (p < 0.01). On-treatment TSH levels diverged (p < 0.001), remaining elevated on OC, and descending swiftly on SPIOMET, well into safe preconception range. Posttreatment TSH levels were stable in both subgroups. On-treatment changes of circulating TSH associated to those of liver fat (R = 0.307, p = 0.017). Conclusion: The endocrine signature of early PCOS is herewith extended to include modestly raised levels of circulating TSH; the normalizing effects of SPIOMET intervention in nonobese adolescents with PCOS are herewith extended to include on- and posttreatment TSH.

LEVEL OF KNOWLEDGE OF WOMEN ABOUT THE RISKS ASSOCIATED WITH OVERWEIGHT DURING PREGNANCY

Worldwide half of women start pregnancy with overweight/obese, which greatly increases the risk of pregnancy and birth complications. Recommendations to improve preconception care emphasize the need to ensure that women of reproductive age understand factors that increase the obstetric and perinatal risks connected with high body mass index (BMI).&#x0D; Aim. Study whether women who start pregnancy with overweight were known of the increased risks of the gestational complications associated with a high (BMI) and the barriers and limitations that women had to optimize their body weight before conception.&#x0D; Materials and methods. total of 117 pregnant were enrolled in the research. The first group included 68 overweight women (BMI 25.0-29.9 kg/m2), the second - 49 normal body weight women (BMI 18.5-24.9 kg/m2) before pregnancy. Two questionnaires were used: "Questionnaire on the assessment of the level of knowledge of women about the risks associated with overweight during pregnancy" and "Barriers and limitations that women had to optimize body weight before conception". Patients filled out the presented questionnaires individually during the first antenatal visit (9-12 weeks). The results were statistically analyzed using Statistica 10.0 program pack (StatSoft Inc., USA) and Microsoft Excel statistical analysis package. The differences between the groups were considered statistically significant at p&lt;0.05.&#x0D; Results. It was shown that the majority of women knew that overweight increased the general risk of pregnancy complications regardless of the woman's BMI. However, the chances of underestimating the high risk of operative delivery in overweight patients were (OR=3.80; 95% CI: 1.83-7.87; p&lt;0.001 and OR=3.69; 95% CI: 1.58 -8.64; p=0.004), premature birth (OR=2.96; 95% CI: 1.47-5.95; p=0.003 and OR=2.99; 95% CI: 1.31-6 .83; p=0.015), adverse neonatal outcomes (OR=2.96; 95% CI: 1.47-5.95; p=0.0031), and especially fetal congenital anomalies of development (OR=5.50; 95 % CI: 2.62-11.54; p&lt;0.001 and OR=12.38; 95% CI: 4.56-33.58; p&lt;0.001) among patients of the first and second groups, respectively. An underestimation of the risk of diabetes, caesarean section, premature birth, and negative perinatal outcomes, and especially congenital fetal abnormalities, has been confirmed if weight loss occurs before conception. The main barriers and limitations for women to optimize their weight before pregnancy were insufficient basic knowledge about the risk of gestational, especially perinatal complications during pregnancy and childbirth associated with overweight, family culture and habits, unsuccessful repeated irregular attempts to weight lose, lack of information and consulting medical professionals on this issue. Only 14.7 % of women reported that they were satisfied with their appearance and health and did not need to lose weight.&#x0D; Conclusions. Being overweight, usually caused by incorrect lifestyle, including dietary choices and lack of physical activity, has long-term negative health consequences for women and their children. The preconception, pregnancy, and postpartum periods are unique opportunities for intervention to establish sustainable healthy lifestyles. It remains relevant to develop programs aimed at improving women's knowledge about overweight as a factor of high obstetric and perinatal risks, and lifestyle modeling with the aim of optimizing body weight at the preconceptional stage.