Pathogenesis Of Preterm Birth Research Articles

Elevated Plasma Levels of Arginines During Labor Among Women with Spontaneous Preterm Birth: A Prospective Cohort Study.

Preterm birth (PTB) is a leading cause of infant mortality and morbidity. The pathogenesis of PTB is complex and involves many factors, including socioeconomy, inflammation and infection. Asymmetric dimethylarginine, ADMA and symmetric dimethylarginine, SDMA are involved in labor as inhibitors of nitric oxide, a known relaxant of the uterine smooth muscles. Arginines are scarcely studied in relation to PTB and we aimed to investigate arginines (ADMA, SDMA and L-arginine) in women with spontaneous PTB and term birth. The study was based on data from the population-based, prospective cohort BASIC study conducted in Uppsala County, Sweden, between September 2009 and November 2018. Arginines were analyzed by Ultra-High Performance Liquid Chromatography using plasma samples taken at the onset of labor from women with spontaneous PTB (n = 34) and term birth (n = 45). We also analyzed the inflammation markers CRP, TNF-R1 and TNF-R2 and GDF-15. Women with spontaneous PTB had higher plasma levels of ADMA (p<0.001), and L-Arginine (p = 0.03). In addition, inflammation marker, TNF-R1 (p = 0.01) was higher in spontaneous PTB compared to term birth. Further, in spontaneous PTB, no significant correlations could be observed when comparing levels of arginines with inflammation markers, except ADMA versus CRP. These findings provide novel evidence for the potential involvement of arginines in the pathogenesis of spontaneous PTB and it seems that arginine levels at labor vary independently of several inflammatory markers. Further research is warranted to investigate the potential of arginines as therapeutic targets in the prevention and management of spontaneous PTB.

B Cells Induce Early-Onset Maternal Inflammation to Protect against LPS-Induced Fetal Rejection.

The maternal balance between B regulatory (Breg) cells and inflammatory B cells is of central importance for protection against preterm birth (PTB). However, the impact of B cell signaling in early maternal and fetal immune responses on inflammatory insults remains underinvestigated. To understand which role B cells and B-cell-specific signaling play in the pathogenesis of PTB, the later was induced by an injection of LPS in B cell-sufficient WT mice, CD19-/-, BMyD88-/- and µMT murine dams at gestational day 16 (gd 16). WT dams developed a strong inflammatory response in their peritoneal cavity (PC), with an increased infiltration of granulocytes and enhanced IL-6, TNF-α, IL-17 and MCP-1 levels. However, they demonstrated a reduced NOS2 expression of PC macrophages 4 h after the LPS injection. Simultaneously, LPS-challenged WT dams upregulated pregnancy-protective factors like IL-10 and TARC. The concentrations of inflammatory mediators in the placental supernatants, amniotic fluids, fetal serums and gestational tissues were lower in LPS-challenged WT dams compared to CD19-/-, BMyD88-/- and µMT dams, thereby protecting WT fetuses from being born preterm. B cell deficiency, or the loss of B-cell-specific CD19 or MyD88 expression, resulted in an early shift from immune regulation towards inflammation at the fetomaternal interface and fetuses, resulting in PTB.

Lack of association between the VEGFA gene polymorphisms and preterm birth in Korean women.

Preterm birth (PTB), a pregnancy-related disease, is defined as a birth before 37 weeks of gestation. It is a major cause of maternal mortality and morbidity worldwide, and its incidence rate is steadily increasing. Various genetic factors can contribute to the etiology of PTB. Vascular endothelial growth factor A (VEGFA) gene is an important angiogenic gene and its polymorphisms have been reported to be associated with PTB development. Therefore, we conducted a case-control study to evaluate the association between VEGFA rs699947, rs2010963, and rs3025039 polymorphisms and PTB in Korean women. A total of 271 subjects (116 patients with PTB and 155 women at ≥38 weeks of gestation) were analyzed in this study. The genotyping of VEGFA gene polymorphisms was performed using polymerase chain reaction- restriction fragment length polymorphism. No significant association between the patients with PTB and the control groups was confirmed. In the combination analysis, we found a significant association between PTB and VEGFA rs699947 CC-rs2010963 GG-rs3025039 CC combination (odds ratio, 3.77; 95% confidence interval, 1.091 to 13.032; p = 0.031). The VEGFA rs699947, rs2010963, and rs3025039 polymorphisms might have no genetic association with the pathogenesis of PTB in Korean women. However, the combination analysis indicates the possibility that VEGFA acts in PTB pathophysiology. Therefore, larger sample sets and replication studies are required to further elucidate our findings.

The Association of Prenatal C-Reactive Protein and Interleukin-8 Levels with Maternal Characteristics and Preterm Birth.

The determinants of preterm birth remain unknown. Excessive maternal inflammation during pregnancy may play an important role in the pathogenesis of preterm birth. Our objective was to describe the association of prenatal levels of proinflammatory C-reactive protein (CRP) and interleukin-8 (IL-8) with preterm birth in participants of the Vitamin D Antenatal Asthma Reduction Trial. Five hundred and twenty-eight patients with available samples of both first- and third-trimester plasma were included in this analysis. CRP and IL-8 were measured from maternal prenatal samples. We examined the association between prenatal CRP and IL-8 with maternal health characteristics and the outcome of preterm birth. We also described the patterns of change in CRP and IL-8 from first to third trimester and their association with preterm birth. A subgroup analysis comparing only those with a spontaneous preterm birth phenotype to those with term birth was also performed. Maternal characteristics including lower educational attainment, higher prepregnancy body mass index, gestational diabetes, lower vitamin D, and an unhealthy diet were associated with elevated levels of prenatal CRP and IL-8. Higher third trimester CRP and an increase in CRP from first to third trimester were associated with an increased odds of preterm birth when compared to lower levels of CRP (adjusted odds ratio [aOR] = 1.49, 95% confidence interval: 1.02, 2.23, p = 0.04) or a decrease in CRP over pregnancy (aOR = 3.06, 95% CI = 1.31,7.55, p = 0.01), after adjusting for potential confounders. These associations were strengthened when comparing only patients with spontaneous preterm birth (n = 22) to those with term births. Higher levels of the proinflammatory markers CRP and IL-8 are associated with indicators of poor maternal health and preterm birth. Prenatal CRP levels may reflect maternal prenatal health status and serve as a predictor of preterm birth, especially among those with spontaneous preterm birth. · Elevated prenatal CRP is associated with poor maternal health.. · High prenatal CRP may predict premature birth, especially spontaneous premature birth phenotypes.. · Vitamin D insufficiency may be a modifiable risk factor for prenatal inflammation..

Transcriptomic analysis of the human placenta reveals trophoblast dysfunction and augmented Wnt signalling associated with spontaneous preterm birth.

Preterm birth (PTB) is the leading cause of death in under-five children. Worldwide, annually, over 15million babies are born preterm and 1million of them die. The triggers and mechanisms of spontaneous PTB remain largely unknown. Most current therapies are ineffective and there is a paucity of reliable predictive biomarkers. Understanding the molecular mechanisms of spontaneous PTB is crucial for developing better diagnostics and therapeutics. To address this need, we conducted RNA-seq transcriptomic analysis, qRT-PCR and ELISA on fresh placental villous tissue from 20 spontaneous preterm and 20 spontaneous term deliveries, to identify genes and signalling pathways involved in the pathogenesis of PTB. Our differential gene expression, gene ontology and pathway analysis revealed several dysregulated genes (including OCLN, OPTN, KRT7, WNT7A, RSPO4, BAMBI, NFATC4, SLC6A13, SLC6A17, SLC26A8 and KLF8) associated with altered trophoblast functions. We identified dysregulated Wnt, oxytocin and cellular senescence signalling pathways in preterm placentas, where augmented Wnt signalling could play a pivotal role in the pathogenesis of PTB due to its diverse biological functions. We also reported two novel targets (ITPR2 and MYLK2) in the oxytocin signalling pathways for further study. Through bioinformatics analysis on DEGs, we identified four key miRNAs, - miR-524-5p, miR-520d-5p, miR-15a-5p and miR-424-5p - which were significantly downregulated in preterm placentas. These miRNAs may have regulatory roles in the aberrant gene expressions that we have observed in preterm placentas. We provide fresh molecular insight into the pathogenesis of spontaneous PTB which may drive further studies to develop new predictive biomarkers and therapeutics.

Uterine Fibroids Causing Preterm Birth: A New Pathophysiological Hypothesis on the Role of Fibroid Necrosis and Inflammation.

According to recent studies and observations in clinical practice, uterine fibroids increase the risk of preterm birth. There are several theories on the pathogenesis of preterm birth in the presence of fibroids. One theory proclaims that fibroid necrosis leads to preterm birth, though pathophysiological mechanisms have not been described. Necrotic tissue secretes specific cytokines and proteins and we suggest these to be comparable to the inflammatory response leading to spontaneous preterm birth. We hypothesize that fibroid necrosis could induce preterm parturition through a similar inflammatory response. This new hypothesis generates novel perspectives for future research and the development of preventative strategies for preterm birth. Moreover, we emphasize the importance of the recognition of fibroids and especially fibroid necrosis by clinicians during pregnancy.

MODERN ASPECTS OF THE ETIOPATHOGENESIS OF ISTMIC-CERVICAL INSUFFICIENCY

Isthmic-cervical insufficiency (ICI), which results in the failure of the circular muscles of the internal os, isthmus and cervix of the uterus is important in the pathogenesis of preterm birth. The existing types are anatomical, functional and congenital ICI. ICI is a pathological condition of the cervix and the isthmus, in which they are unable to withstand the intrauterine pressure and keep a fertilized egg in the uterine cavity until birth. ICI is a serious complication of pregnancy. Genetic, hormonal, inflammatory-infectious, immunological, traumatic factors play a role in the occurrence of ICI. The aim of the study is to study the peculiarities of reproductive health and gestational process of pregnant women with ICI, according to the literature. For the study, we analyzed domestic and foreign publications on this topic in professional journals, as well as data from Internet resources. Results of the research show that ICI plays a special role among many causes that lead to preterm termination of pregnancy and premature birth in the II-III trimesters. The properties of the cervix depend on the ratio of connective and muscle tissue. Today, most authors distinguish between congenital, acquired, organic and functional isthmic-cervical insufficiency.Organic (post-traumatic, secondary) ICI occurs due to mechanical damage to the cervix. Functional ICI is the result of a violation of the relationship between the muscular and connective tissues of the cervix, as well as the result of changes in the response of its structural elements to neurohumoral stimuli. Functional ICI most often occurs as a consequence of a violation of the hormonal background of women (ovarian hypofunction, hyperandrogenism). Congenital ICI occurs in malformations of the uterus, genital infantilism. Histological examination of cervical tissue in women with ICI reveals an increase in muscle tissue up to 50%, which leads to early softening of the cervix of the uterus and development of its functional insufficiency. According to Kaufman KP (2021), the role of connective tissue in the development of ICI is confirmed by the fact, that this pathological condition of the cervix is found in women with Marfan syndrome and Ehlers-Danlos syndrome. The role of undifferentiated connective tissue dysplasia (UCTD) as a risk factor for complicated pregnancy, including ICI.Research of Huang J and co-authors (2021) found the presence of nutritional imbalance in patients with UCTD, which was manifested by changes in serum concentrations of magnesium, calcium, zinc, iron, copper, selenium, inorganic phosphorus. The relationship between changes in the microcirculation system, tissue perfusion and cervical condition is currently being actively discussed and confirmed in numerous studies.Fettweis JM (2019) believes that the mechanism of abortion at different stages of gestation is not the same in pregnant women with ICI. At the same time, all pregnant women with ICI at all stages of gestation have increased cytokine levels. However, an important factor in the premature termination of pregnancy in ICI is assigned to the infectious factor. The results of the study of the pathogenetic role of local immune responses in women with habitual miscarriage are often contradictory and dictate the need for further researches.Eventually, isthmic-cervical insufficiency is a multifactorial complication of pregnancy, in which genetic, hormonal, inflammatory-infectious, immunological or traumatic factors play a role.

Maternal plasma lipids are involved in the pathogenesis of preterm birth.

BackgroundPreterm birth is defined by the onset of labor at a gestational age shorter than 37 weeks, and it can lead to premature birth and impose a threat to newborns’ health. The Puerto Rico PROTECT cohort is a well-characterized prospective birth cohort that was designed to investigate environmental and social contributors to preterm birth in Puerto Rico, where preterm birth rates have been elevated in recent decades. To elucidate possible relationships between metabolites and preterm birth in this cohort, we conducted a nested case-control study to conduct untargeted metabolomic characterization of maternal plasma of 31 women who experienced preterm birth and 69 controls who underwent full-term labor at 24–28 gestational weeks.ResultsA total of 333 metabolites were identified and annotated with liquid chromatography/mass spectrometry. Subsequent weighted gene correlation network analysis shows that the fatty acid and carene-enriched module has a significant positive association (P = 8e−04, FDR = 0.006) with preterm birth. After controlling for potential clinical confounders, a total of 38 metabolites demonstrated significant changes uniquely associated with preterm birth, where 17 of them were preterm biomarkers. Among 7 machine-learning classifiers, the application of random forest achieved a highly accurate and specific prediction (AUC = 0.92) for preterm birth in testing data, demonstrating their strong potential as biomarkers for preterm births. The 17 preterm biomarkers are involved in cell signaling, lipid metabolism, and lipid peroxidation functions. Additional modeling using only the 19 spontaneous preterm births (sPTB) and controls identifies 16 sPTB markers, with an AUC of 0.89 in testing data. Half of the sPTB overlap with those markers for preterm births. Further causality analysis infers that suberic acid upregulates several fatty acids to promote preterm birth.ConclusionsAltogether, this study demonstrates the involvement of lipids, particularly fatty acids, in the pathogenesis of preterm birth.

Preterm Labor, a Syndrome Attributed to the Combination of External and Internal Factors

Abstract Preterm labor (before 37 weeks’ gestation) is the leading cause of neonatal mortality and morbidity, which can be divided into iatrogenic preterm labor, infectious preterm labor, and spontaneous preterm labor (sPTL). Up to now, there continue to be great difficulties in prediction and prevention of sPTL, owing to multiple risk factors, pathogenesis, and pathologic processes contributing to the event, which have not been fully clarified. Pregnancy maintenance and parturition is a complicated process with continuous maternal-fetal dialogue, in which both maternal and fetal factors participate and affect the outcome of pregnancy, including sPTL. Besides, external factors can also participate in sPTL, individually or through the interaction with internal factors. In this article, we summarize recent studies regarding sPTL from our and other groups, and discuss the risk factors and pathogenesis of preterm birth from both external and internal (maternal and fetal) aspects, so as to provide theoretical evidences for the diagnosis, prevention, and treatment of sPTL in the future.

Association of Maternal Sexually Transmitted Infections With Risk of Preterm Birth in the United States

Maternal infection has been implicated in the pathogenesis of preterm birth through intrauterine inflammatory response. Chlamydia, gonorrhea, and syphilis are among the most common sexually transmitted infections worldwide, but studies on their association with preterm birth are sparse. To examine the association between maternal chlamydia, gonorrhea, and syphilis infections in pregnancy and the risk of preterm birth in a large population-based study in the US. This population-based retrospective cohort study examined nationwide birth certificate data from the US National Vital Statistics System between 2016 and 2019. All mothers who had a singleton live birth and available data on chlamydia, gonorrhea, or syphilis infection before or during pregnancy and gestational age at birth were included in analysis. Sexually transmitted infection (chlamydia, gonorrhea, or syphilis) occurring before or during pregnancy. Preterm birth, defined as gestational age less than 37 weeks. This study included 14 373 023 mothers (mean [SD] age 29 [5.8] years; Hispanic, 3 435 333 [23.9%]; non-Hispanic Asian, 912 425 [6.3%]; non-Hispanic Black, 2 058 006 [14.3%]; and non-Hispanic White, 7 386 568 [51.4%]). Among the mothers, 267 260 (1.9%) had chlamydia, 43 147 (0.3%) had gonorrhea, and 16 321 (0.1%) had syphilis. Among the newborns, 1 146 800 (8.0%) were preterm births. The rate of preterm birth was 9.9%, 12.2%, and 13.3% among women with chlamydia, gonorrhea, and syphilis infection, respectively. After adjustment for sociodemographic and medical and/or health factors, the adjusted odds ratio of preterm birth was 1.03 (95% CI, 1.02-1.04) for chlamydia, 1.11 (95% CI, 1.08-1.15) for gonorrhea, 1.17 (95% CI, 1.11-1.22) for syphilis, and 1.06 (95% CI, 1.05-1.07) for any of these sexually transmitted infections comparing mothers with these conditions and those without. Maternal sexually transmitted infections (gonorrhea, syphilis, or chlamydia) were associated with an increased risk of preterm birth. Pregnant women with sexually transmitted infections before or during pregnancy might benefit from targeted prevention for preterm birth.

Identification of Key Candidate Genes and Pathways in Preterm Birth by Integrated Bioinformatical Analysis

Background: Preterm birth（PTB） is a primary cause of neonatal morbidity and mortality, the pathogenic mechanisms of PTB still remain largely unexplored. In the present study, we aimed to identify potential key genes and pathway associated with PTB by bioinformatics analysis. Methods: The GSE46510 dataset was obtained from GEO database. Differentially expressed genes (DEGs) were identified using the limma package in R software, the functional enrichment analysis was performed, and the protein-protein interaction (PPI) network was constructed by Cytoscape software. The network topology was analyzed using MCODE. Results: A total of 335 DEGs were identified from the dataset. The majority of up-regulated DEGs were significantly enriched in inflammatory response, while down-regulated DEGs were mainly enriched in mitotic nuclear division. The top 5 hub up regulated genes were ITGAM, IL1B, ITGAX, NFKB1, and SOCS3. Pathway analysis indicated enrichment in Cytokine-cytokine receptor interaction, signaling by Interleukins. The top 5 hub down regulated genes were CXCR4, ANAPC10, ANAPC4, UBE2V2, UBA3, Pathway analysis indicated enrichment in Ubiquitin mediated proteolysis, Phosphorylation of the APC/C. Conclusion: Our study indicated genes and pathways in PTB by bioinformatics analysis, which may provide novel insights for unraveling pathogenesis of PTB.

Модификация метаболических нарушений в патогенезе спонтанных преждевременных родов

Objective. To determine the levels of interleukins, neopterin, S100β protein in amniotic fluid and cord blood, show their role in the pathogenesis of preterm birth and perinatal injury of the central nervous system (CNS) in newborns. Patients and methods. The study included 77 women randomly selected by simple randomization. A single-center, singlestage, controlled, randomized trial was conducted, which included 77 women comprising two groups: the main group – 33 patients with spontaneous preterm birth (35–37 weeks) and the control group – 44 women with the physiological course of pregnancy and childbirth (38–40 weeks). All newborns were also examined. The levels of interleukins IL-33 and IL-4, as well as neopterin and S100β protein were determined in amniotic fluid and cord blood by a solid-phase enzyme-linked immunosorbent assay (ELISA). Results. It was found that the increased production of interleukins and neurospecific proteins under study have a negative effect on the body of the pregnant woman and the fetus, which leads to serious pregnancy complications such as premature birth and perinatal CNS injury. Conclusion. The identified patterns provide a basis for the development of schemes for predicting preterm birth, which will improve perinatal outcomes and the health status of newborns. Key words: S100β protein, interleukins, neopterin, amniotic fluid, spontaneous preterm birth

Perinatal Gram-Positive Bacteria Exposure Elicits Distinct Cytokine Responses In Vitro.

During pregnancy, infections caused by the gram-positive bacteria Enterococcus faecalis (E. faecalis), Streptococcus agalacticae (S. agalacticae), and Staphylococcus aureus (S. aureus) are major reasons for preterm labor, neonatal prematurity, meningitis, or sepsis. Here, we propose cytokine responses to bacterial infections by the immature perinatal immune system as central players in the pathogenesis of preterm birth and neonatal sepsis. We aimed to close the gap in knowledge about such cytokine responses by stimulating freshly isolated umbilical blood mononuclear cells (UBMC) with lysates of E. faecalis, S. agalacticae, and S. aureus collected from pregnant women in preterm labor. Bacterial lysates and, principally, S. aureus and S. agalacticae distinctly triggered most of the eleven inflammatory, anti-inflammatory, TH1/TH2 cytokines, and chemokines quantified in UBMC culture media. Chemokines depicted the most robust induction. Among them, MIP-1β was further enhanced in UBMC from female compered to male newborn infants. Due to its stability and high levels, we investigated the diagnostic value of IL-8. IL-8 was critically upregulated in cord blood of preterm neonates suffering from infections compared to gestational age-matched controls. Our results provide novel clues about perinatal immunity, underscoring a potential value of IL-8 for the timely detection of infections and suggesting that MIP-1β constitutes an early determinant of sex-specific immunity, which may contribute, e.g., to male’s vulnerability to preterm birth.

Cytokine profiling: variation in immune modulation with preterm birth vs. uncomplicated term birth identifies pivotal signals in pathogenesis of preterm birth.

To assess deviations in longitudinally measured cytokines with preterm birth (PTB). Prospective longitudinal study targeting 80 subjects. Phlebotomy specimens for broad panel of cytokine analysis were obtained at three time (T)intervals: first trimester (T1: 8-14weeks' gestation), second trimester (T2: 18-22weeks' gestation), and third trimester (T3: 28-32weeks' gestation). Important demographics and outcomes were tracked. Data were stratified and the target groups were analyzed as follows: "Uncomplicated" (delivered≥37weeks) or "Preterm Birth" (<37weeks). Generalized Linear Modeling determined rate of change T1-T3 by outcome. Complete data replete with phlebotomy at all three visits were obtained on 80 women. Birth outcomes were as follows: 11 Uncomplicated Term Birth (UTB), 28 PTB, 4 low birth weight (LBW), 16 OB complications (OBC), 11 current infections (IFN), and 10 mixed complications (MC=2 or more of the above). 28 PTB were compared to 11 uncomplicated term deliveries. In both groups, T helper type 1 (TH1) cytokine (IL-1β), pleiotrophic pro-inflammatory cytokine (IL-6), and counter-regulatory cytokine (IL-10) responses decreased over gestation, but rates of change in IL-1β, IL-6, and IL-10 were significantly different. Stratification of women by smoking status additionally demonstrated significant variance in immune status over the course of pregnancy. Women delivering PTB demonstrated significant differences in cytokine trajectory over pregnancy; these data further validate key role played by immune regulation in directing pregnancy outcome. Likewise, smoking impacts longitudinal trajectory of cytokines over pregnancy.

Chronic HPA activity in mothers with preterm delivery: A pilot nested case-control study.

Chronic hypothalamic-pituitary-adrenal (HPA) axis activity role in the pathogenesis of preterm birth (PTB) remains unclear due to inconsistent measures with limited ability to monitor long-term cortisol concentrations. We explored this relationship using the novel method of assessing cortisol in hair, which is a valid and reliable measure of chronic HPA axis activity. 137 participants (40 PTB cases and 97 controls from a birth cohort of pregnant women in Peru) were interviewed and invited to provide a 9-cm hair sample from the posterior vertex position of the scalp (mean = 13 weeks gestation). Hair cortisol concentration (HCC) was determined using luminescence immunoassay and values were natural-log transformed. PTB cases were defined as women who delivered before 37 gestational weeks. Case-control differences were assessed using multivariable linear and logistic regressions. Overall, combined pre-conception and first-trimester HCC was 13% lower among cases as compared with controls (p-value = 0.01). Compared with controls, maternal HCC among PTB cases were 14% (p = 0.11), 10% (p = 0.22) and 14% (p = 0.08) lower for 3-6 months pre-conception, 0-3 months pre-conception, and first trimester, respectively. After adjusting for putative confounders, a 1-unit increase in HCC was associated with 55% reduced odds of PTB (aOR = 0.45; 95% CI: 0.17-1.17). For a 1-unit increase in HCC in the scalp-intermediate and scalp-distal segments (representing HCC concentrations in 0-3 months pre-conception and first trimester), the corresponding odds for PTB were 0.53 (95% CI: 0.19-1.48) and 0.39 (95% CI: 0.13-1.13), respectively. Women who deliver preterm, as compared with those who deliver at term, have lower preconception and first trimester HCC. Our findings suggest that HPA axis activation, integral to the adaptive stress-response system, may be chronically dysregulated in women at increased risk of PTB.

Профілактика порушень фетоплацентарного комплексу у жінок із ризиком і загрозою передчасних пологів (Огляд літератури)

The obstetrician-gynaecologist practitioners consider a woman’s health from her reproductive potential support standpoint, and the problem of miscarriage is considered as one of the most important health problems in the world. The difficulty in solving the premature birth problem is the presence of many factors and preconditions that determine the risks of miscarriage. The article provides an overview of current international guidelines for assessing the root causes and preconditions for preterm birth. The problem of preterm birth risks is discussed, taking into account both the socio-economic living conditions of pregnant women and the factors that accompany the formation of the pathogenesis of preterm birth (placental dysfunction). Attention is paid to the hemodynamic disorders assessment (vascularization of the lower uterus) in pregnant women and determination of their role in the fetoplacental dysfunction development. The role of the hemodynamic disorders in the placenta is considered as the morphological and biochemical adaptive reactions abnormality. Keywords: miscarriage, premature birth, fetoplacental complex, placental dysfunction.

Значение оксида азота и кахектина в патогенезе преждевременных родов

Значение оксида азота и кахектина в патогенезе преждевременных родов

Racial disparities in prematurity persist among women of high socioeconomic status

Despite persistent racial disparities in preterm birth (PTB) in the US among non-Hispanic (NH) black women compared to NH white women, it remains controversial whether sociodemographic factors can explain these differences. We sought to evaluate whether disparities in PTB persist among NH black women with high socioeconomic status (SES). We conducted a population-based cohort study of all live births in the US from 2015-2017 using birth certificate data from the National Vital Statistics System. We included singleton, non-anomalous live births among women who were of high SES (defined as having ≥ 16 years of education, private insurance, and not receiving Women, Infants and Children [WIC] benefits) and who identified as NH white, NH black, or 'mixed' NH black and white race. The primary outcome was PTB <37 weeks; secondary outcomes included PTB <34 and <28 weeks. In addition, analyses were repeated considering birthweight <2500g as a surrogate for preterm birth <37 weeks, birthweight <1500g as a surrogate for preterm birth <34 weeks, and birthweight <750g as a surrogate for preterm birth <28 weeks' gestation. Data were analyzed with chi-square, t-test, and logistic regression. 2,170,686 live births met inclusion criteria, with 92.9% NH white, 6.7% NH black, and 0.4% both NH white and black race. Overall, 5.9% delivered <37, 1.3% <34, and 0.3 % <28 weeks. In unadjusted analyses of women with high SES, the PTB rate at each gestational age cutoff was higher for women of 'mixed' NH white and black race, and highest for women who were NH black only compared to women who were NH white only. In regression models we further adjusted for women with insurance and prenatal care their entire pregnancy, maternal race was associated with higher odds of PTB at each GA cutoff, with the highest odds observed at <28 weeks. Finally, in further adjustement analysis including only the 1,934,912 women who received prenatal care in the first trimester, findings were similar. Rates of preterm birth at each gestational age cutoff remained highest for women who identified as non-Hispanic black, intermediate for women identifying as both non-Hispanic black and white race, and lowest for non-Hispanic white women at <37 weeks (9.9% vs. 6.1% vs. 5.5%, respectively; p<0.001), <34 weeks (3.5% vs. 1.5% vs. 1.1%, respectively; p<0.001), and <28 weeks' gestation (1.2% vs. 0.4% vs. 0.2%, respectively, p<0.001). Even among college-educated women with private insurance who are not receiving WIC, racial disparities in prematurity persist. These national findings are consistent with prior studies that suggest factors other than socio-demographics are important in the underlying pathogenesis of PTB.

Актуальні питання прогнозування і профілактики передчасних пологів

Premature birth is a significant problem in modern medicine. The main aspects of its solution are the prediction and prevention of premature birth. Nowadays, among a large number of biophysical and biochemical markers of preterm birth, ultrasonic cevicometry is the most popular one. It is known that «short cervix syndrome» is not the equivalent of cervical insufficiency. The known strategies of preventive combinations are used in case of an increased risk of preterm birth. Therefore, the issue of developing a differentiated approach to the combined or separate use of progesterone, pessary, or cerclage has not been answered yet. It should be added that in most practical recommendations based on the principles of evidence-based medicine, there are no differences according to the possible pathogenesis of preterm birth. A therapeutic strategy should be set based on the possible use or misuse of any preventive combination, taking into account maternal and fetal contraindications. The combined testing on ultrasound cervicometry and biochemical markers could ameliorate the identification of patients at risk of preterm birth. The fetal fibronectin is known to be the best among all biochemical markers of preterm birth. However, the prognostic value of this test, as well as the phosphorylated transport protein insulin-like growth factor, when used separately, is limited. In pregnant women with a length of the cervix between 1.5 cm and 3 cm, it is recommended to use the analysis for placental alpha-microglobulin-1. The administration of corticosteroids should only be performed when the risk of preterm delivery is confirmed by decreased cervical length and a positive test for placental alpha-microglobulin-1 (there is a high risk of preterm delivery within 7 days). The cerclage is indicated in patients with cervical insufficiency before 16 weeks of gestation. In the presence of a «short cervix» and the lack of anamnestic data, the strategy should be individualized. The efficacy of cerclage or pessary application has not been proven. It is necessary to start with vaginal progesterone administration. In the process of the patient observation (cervicometry in dynamics) will allow you to find out an effective method: cerclage or pessary and vaginal progesterone. In the case of progredient cervical effacement in the second trimester, it is advisable to perform an urgent cerclage. In the case of incompetent cervical stitch, the additional application of a pessary is possible. In women with multiple pregnancies, there is no evidence of elective cerclage or pessary efficacy. However, it is possible to use heroic cerclage, pessary in combination with vaginal progesterone or vaginal progesterone monotherapy. Key words: preterm delivery, prediction, prevention.

Membranous rupture in relation to c-reactive protein

The aim of the study was to prediction of sub rupture of membranes (PPROM) and preterm labour. Maternal and cord blood for C (CRP) sensitivity as a confirmative test for sub with PPROM as study group and 30 pregnant of same gestat in labour. All submitted to CRP test, high vaginal swab, placental swab for C/S and cord blood for CRP. CRP positive in study group 18 cases (60%) and control group 8 cases (36.6%) for urine C/S in study group was 11 positive in study group 8 cases (27.3%) and in control group 3 cases (10%), CRP test, urine for C/S and high the vag. for C/S were statistically not significant CRP test sensitivity was 78% and specificity was 62.5% So CRP test can used as screening test for infection. Introduction: Preterm pre labour rupture of membranes (PPROM) mean rupture of fetal membranes after 24 weeks gestation and before 37 completed weeks or 259 completed days of gestation. Preterm birth: mean birth occurs before 37 completed weeks or 259 completed days of gestation. It is a leading cause of infant death and several contributing mechanisms to this morbidity have been identified over the past 10 years Macdonald Gant, 2000). It is obvious that seve involved in the pathogenesis of preterm birth, which may explain why it has proved so difficult to predict and prevent, the too early activation of the fetal hypothalamic adrenal axis may result from maternal psychosocial or fet physiological stress. Such physiological fetal stress may in turn be a consequence of microbial invasion of fetal membranes, amniotic fluid and the fetus itself. The critical mediator of stress-induced preterm birth appear to be corticotrophin releasing hormone. It stimulates the production of prostaglandins by cells in the amnion, placenta, chorion and utrine deciduas (Staffan Bergstrom, 2003). membranes