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1.
Article in English | MEDLINE | ID: mdl-39287057

ABSTRACT

INTRODUCTION: Intra-amniotic inflammation is causally linked to spontaneous preterm labor. The gold standard for the diagnosis of intra-amniotic inflammation is the determination of an amniotic fluid profile obtained from transabdominal amniocentesis, which is invasive. Cervicovaginal fluid fetal fibronectin (fFN) is a widely-used predictive biomarker for spontaneous preterm labor. The aims of this study are to determine (1) whether a quantitative cervicovaginal fluid fFN test can be used to identify the presence of intra-amniotic inflammation; and (2) an appropriate cut-off value of a cervicovaginal fluid fFN concentration for the identification of intra-amniotic inflammation. MATERIAL AND METHODS: This prospective cohort study included 78 patients with preterm labor and intact membranes who had a sample collected for quantitative cervicovaginal fluid fFN measurement and underwent transabdominal amniocentesis. Intra-amniotic inflammation was defined as an amniotic fluid interleukin-6 concentration ≥2.6 ng/mL. Clinicians were masked from the results of cervicovaginal fluid fFN and amniotic fluid interleukin-6 concentrations. Logistic regression analysis was used to determine which factors were significant predictors of intra-amniotic inflammation. The diagnostic indices of the cervicovaginal fluid fFN test for the identification of intra-amniotic inflammation were calculated. RESULTS: (1) Frequency of intra-amniotic inflammation was 26.9% (21/78); (2) the higher the cervicovaginal fluid fFN concentration, the greater the risk of intra-amniotic inflammation (p < 0.001); (3) cervicovaginal fluid fFN concentration ≥125 ng/mL had an area under the curve of 0.91 (95% confidence interval: 0.83-0.96) for the identification of intra-amniotic inflammation with 100% sensitivity, 100% negative predictive value, 82.46% specificity and a positive likelihood ratio of 5.7; and (4) cervicovaginal fluid fFN cut-off of 125 ng/mL had a significant higher predictive performance than the traditional cut-off (50 ng/mL) for the identification of intra-amniotic inflammation. CONCLUSIONS: Quantitative cervicovaginal fluid fFN with a cut-off of 125 ng/mL had a high sensitivity and a negative predictive value as well as a positive likelihood ratio for the identification of intra-amniotic inflammation. Its high sensitivity and negative predictive value can be used to decrease an index of suspicion of intra-amniotic inflammation. This test may be useful as an initial assessment test to select appropriate patients for amniocentesis to determine intra-amniotic inflammation.

2.
J Clin Ultrasound ; 2024 Sep 16.
Article in English | MEDLINE | ID: mdl-39283060

ABSTRACT

OBJECTIVE: To compare the effects of nifedipine and indomethacin, used for tocolytic purposes in the treatment of preterm labor (PTL), on fetal-maternal Doppler blood flows and perinatal outcomes. MATERIALS AND METHODS: Eighty pregnant women between weeks 24 and 32 of gestation who used nifedipine (n = 40) and indomethacin (n = 40) as tocolytic treatments due to PTL were prospectively and consecutively included in the study. Sociodemographic, obstetric, and laboratory and Doppler flow parameters were compared between the groups. RESULTS: Statistically significant differences were observed between the groups in terms of gestational age at delivery and birth weight, Doppler flows (umbilical artery (UA) Pulsatility Index (PI), and UA Resistance Index (RI)) at 12, 24, and 48 h, middle cerebral artery RI at 12 h, and ductus venosus (DV) PI and DV-RI at 12, 24, and 48 h (p < 0.05). CONCLUSIONS: The findings of this study showed that nifedipine and indomethacin used in the treatment of PTL had significant effects on UA-PI and UA-RI Doppler flows at 12, 24, and 24 h, MCA-RI Doppler flows at 12 h, and DV-PI and DV-RI Doppler flows at 12, 24, and 48 h. Further studies involving larger numbers of participants are now needed to support these results.

3.
Eur J Obstet Gynecol Reprod Biol ; 302: 56-60, 2024 Aug 28.
Article in English | MEDLINE | ID: mdl-39217760

ABSTRACT

OBJECTIVE: To investigate the contribution of the cervical sliding sign to conventional cervical length measurement in patients at risk of preterm labor. METHODS: The study, performed as a prospective cohort study, included patients admitted to a tertiary research hospital with a diagnosis of threatened preterm labor. The participants were divided into two groups: those who gave birth before and after 37 weeks of gestation. The clinical and demographic characteristics, cervical length, presence of a short cervix (SC), and cervical sliding sign (CSS) were compared between the groups. Furthermore, correlation and regression analyses were conducted to investigate the relationship between the presence of a SC, the presence of CSS, and the coexistence of these two findings with preterm delivery, as well as the interval between the symptoms and delivery being less than four weeks. RESULTS: The study included 77 patients who delivered prematurely and 65 patients who delivered at term. The following variables were significantly lower in the preterm delivery group: cervical length, gestational age at delivery, neonatal weight, and time between the first examination and delivery (p = 0.003, <0.001, <0.001 and < 0.001, respectively). A higher percentage of women in the preterm delivery group exhibited a diagnosis of a SC, the presence of CSS, and the coexistence of both conditions (p = 0.002, 0.012 and 0.018, respectively). The results of the logistic regression analysis indicated that the odds ratios for preterm delivery were 3.3 in the presence of a SC alone, 2.67 in the presence of CSS alone, and 2.85 in the association of both findings (p = 0.003, 0.013 and 0.021 respectively). The odds ratios for delivery in less than four weeks were 3.08 in the presence of a SC alone, 3.4 in the presence of CSS alone, and 3.54 in the association of both findings (p = 0.004, 0.002 and 0.005 respectively). CONCLUSION: In singleton pregnant women presenting with threatened preterm labor, the presence of CSS is associated with an increased risk of preterm delivery and a decreased presentation-to-delivery interval. However, its contribution to conventional cervical length measurement appears to be relatively limited.

4.
J Clin Med ; 13(15)2024 Jul 25.
Article in English | MEDLINE | ID: mdl-39124610

ABSTRACT

Prevention of pregnancy complications related to the "great obstetrical syndromes" (preeclampsia, fetal growth restriction, spontaneous preterm labor, and stillbirth) is a global research and clinical management priority. These syndromes share many common pathophysiological mechanisms that may contribute to altered placental development and function. The resulting adverse pregnancy outcomes are associated with increased maternal and perinatal morbidity and mortality and increased post-partum risk of cardiometabolic disease. Maternal nutritional and environmental factors are known to play a significant role in altering bidirectional communication between fetal-derived trophoblast cells and maternal decidual cells and contribute to abnormal placentation. As a result, lifestyle-based interventions have increasingly been recommended before, during, and after pregnancy, in order to reduce maternal and perinatal morbidity and mortality and decrease long-term risk. Antenatal screening strategies have been developed following extensive studies in diverse populations. Multivariate preeclampsia screening using a combination of maternal, biophysical, and serum biochemical markers is recommended at 11-14 weeks' gestation and can be performed at the same time as the first-trimester ultrasound and blood tests. Women identified as high-risk can be offered prophylactic low dose aspirin and monitored with angiogenic factor assessment from 22 weeks' gestation, in combination with clinical assessment, serum biochemistry, and ultrasound. Lifestyle factors can be reassessed during counseling related to antenatal screening interventions. The integration of lifestyle interventions, pregnancy screening, and medical management represents a conceptual advance in pregnancy care that has the potential to significantly reduce pregnancy complications and associated later life cardiometabolic adverse outcomes.

5.
Cureus ; 16(7): e64784, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39156454

ABSTRACT

Background This study aimed to investigate the obstetric outcomes in antenatal women with first-trimester vaginal bleeding. Methodology This single-centered, prospective, observational study was conducted in a tertiary healthcare institution. Antenatal women with first-trimester vaginal bleeding who visited the hospital were screened for eligibility and included in the study. They were followed up until the termination of pregnancy or delivery based on the etiology of vaginal bleeding. Various fetomaternal outcomes such as pregnancy outcomes, obstetric complications, mode of delivery, and neonatal outcomes were analyzed. Results This study included 120 antenatal women who experienced first-trimester vaginal bleeding during the study period. Vaginal bleeding was more prevalent in the age group of 25-34 years and primigravidas. Out of 120 women, 14 (11.6%) either aborted or the pregnancy was terminated as a result of a nonviable gestation, and 106 (88.4%) delivered after the period of viability. Out of 106 women, 56 (52.8%) had full-term pregnancies without any obstetric complications. We analyzed the obstetric complications developed in all the study participants and found that 23 (21.7%) had preterm labor, 12 (11.3%) had placental abruption, 6 (5.7%) had premature rupture of membrane, 4 (3.9%) had anemia, and 2 (1.9%) developed hypertensive disorder of pregnancy. Of all deliveries, 54 (50.9%) delivered vaginally and 52 (49.1%) had cesarean delivery. There were no major adverse neonatal outcomes in terms of birthweight, APGAR score at one minute, and APGAR score at five minutes. Conclusions A large proportion of antenatal women with first-trimester vaginal bleeding can have favorable perinatal outcomes. However, as a few may develop obstetric complications, regular follow-up of such cases is mandated to prevent adverse outcomes.

6.
Am J Reprod Immunol ; 92(1): e13899, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39042514

ABSTRACT

OBJECTIVE: To investigate the role of inflammatory markers, including neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and monocyte to lymphocyte ratio (MLR), c-reactive protein (CRP) to albumin ratio (CAR), fibrinogen to albumin ratio (FAR), and fibrinogen to CRP ratio (FCR) in predicting the latency period (≤72 vs. >72 hours) before preterm birth. MATERIALS AND METHODS: In a retrospective study, we assessed 135 patients meeting the specified criteria with signs of preterm labor (<34 weeks). The patients were categorized into two groups: 71 patients giving birth within 72 h (latency ≤ 72 h) and 64 patients giving birth after 72 h (latency > 72 h). We examined the demographic and medical characteristics and perinatal outcomes of all participants. Categorical variables between groups were compared using the Chi-square test. The Student's t-test was utilized for normally distributed continuous variables, and the Mann-Whitney U test was applied for non-normally distributed data. Receiver operating characteristic (ROC) curve analysis was conducted to identify the optimal cut-off levels for inflammatory markers in predicting the latency period before birth. RESULTS: Among the parameters examined, significant differences were observed between the groups only in terms of CAR and FCR. While CAR showed a significantly higher value in the group with latency period ≤72 h (0.537 ± 1.239 vs. 0.247 ± 0.325, p = 0.022), FCR showed a significantly lower value in the group with latency period ≤72 h (63.58 (2.99-1165) vs. 88.93 (9.35-1165), p = 0.013). The identified cut-off value for CAR was 0.190, providing a sensitivity of 57.7% and a specificity of 56.3% (p = 0.022). The cut-off value for FCR was 71.67, with a sensitivity of 42.3% and a specificity of 42.2% (p = 0.013). CONCLUSIONS: The CAR and the FCR, serving as predictive markers for preterm labor, may offer a simple, cost-effective, and easily accessible approach, particularly in resource-limited settings.


Subject(s)
Biomarkers , C-Reactive Protein , Fibrinogen , Obstetric Labor, Premature , Humans , Female , C-Reactive Protein/analysis , C-Reactive Protein/metabolism , Pregnancy , Fibrinogen/metabolism , Fibrinogen/analysis , Adult , Retrospective Studies , Obstetric Labor, Premature/diagnosis , Obstetric Labor, Premature/blood , Biomarkers/blood , ROC Curve , Predictive Value of Tests
7.
Cytokine Growth Factor Rev ; 78: 50-63, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39048393

ABSTRACT

Preterm birth is a major public health concern, requiring a deeper understanding of its underlying inflammatory mechanisms and to develop effective therapeutic strategies. This review explores the complex interaction between inflammation and preterm labor, highlighting the pivotal role of the dysregulation of inflammation in triggering premature delivery. The immunological environment of pregnancy, characterized by a fragile balance of immune tolerance and resistance, is disrupted in preterm labor, leading to a pathological inflammatory response. Feto-maternal infections, among other pro-inflammatory stimuli, trigger the activation of toll-like receptors and the production of pro-inflammatory mediators, promoting uterine contractility and cervical ripening. Emerging anti-inflammatory therapeutics offer promising approaches for the prevention of preterm birth by targeting key inflammatory pathways. From TLR-4 antagonists to chemokine and interleukin receptor antagonists, these interventions aim to modulate the inflammatory environment and prevent adverse pregnancy outcomes. In conclusion, a comprehensive understanding of the inflammatory mechanisms leading to preterm labor is crucial for the development of targeted interventions in hope of reducing the incidence of preterm birth and improving neonatal health outcomes.


Subject(s)
Anti-Inflammatory Agents , Inflammation , Obstetric Labor, Premature , Humans , Pregnancy , Female , Obstetric Labor, Premature/immunology , Inflammation/immunology , Anti-Inflammatory Agents/therapeutic use , Premature Birth/immunology , Premature Birth/prevention & control , Animals , Infant, Newborn
8.
Fetal Diagn Ther ; : 1-11, 2024 Jul 22.
Article in English | MEDLINE | ID: mdl-38964308

ABSTRACT

INTRODUCTION: The aim of the study was to identify predictive values of the soluble fms-like tyrosine kinase/placental growth factor (sFlt-1/PlGF) ratio and interleukin (IL)-6, assessed with a clinically available method in a large-volume biochemistry laboratory, in maternal blood, amniotic fluid, and umbilical cord blood for the presence of the placental lesions consistent with maternal vascular malperfusion (MVM) and acute histological chorioamnionitis (HCA), respectively. METHODS: This retrospective study included 92 women with preterm labor with intact membranes (PTL) delivered within 7 days of admission with gestational ages between 22+0 and 34+6 weeks. The sFlt-1/PlGF ratio and IL-6 were assessed in stored samples of maternal serum, amniotic fluid, and umbilical cord serum using Elecsys® sFlt-1, PlGF, and IL-6 immunoassays. RESULTS: Women with MVM had a higher sFlt-1/PlGF ratio in the maternal serum, compared to those without MVM (19.9 vs. 4.6; p < 0.0001), but not in the amniotic fluid or umbilical cord blood. A cut-off value of 8 for the sFlt-1/PlGF ratio in maternal serum was identified as optimal for predicting MVM in patients with PTL. Women with HCA had higher concentrations of IL-6 in maternal serum, compared to those without HCA (11.1 pg/mL vs. 8.4 pg/mL; p = 0.03), amniotic fluid (9,216 pg/mL vs. 1,423 pg/mL; p < 0.0001), and umbilical cord blood (20.7 pg/mL vs. 10.7 pg/mL, p = 0.002). Amniotic-fluid IL-6 showed the highest predictive value. A cut-off value of IL-6 concentration in the amniotic fluid of 5,000 pg/mL was found to be optimal for predicting HCA in PTL. CONCLUSION: Maternal serum sFlt-1/PlGF and amniotic fluid IL-6 concentrations can be used for liquid biopsy to predict placental lesions in women with PTL who deliver within 7 days.

9.
Am J Reprod Immunol ; 91(6): e13889, 2024 Jun.
Article in English | MEDLINE | ID: mdl-39031744

ABSTRACT

PROBLEM: 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. METHODS OF THE STUDY: 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. RESULTS: 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. CONCLUSIONS: 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.


Subject(s)
Arginine , Premature Birth , Humans , Female , Arginine/analogs & derivatives , Arginine/blood , Pregnancy , Prospective Studies , Adult , Premature Birth/blood , Sweden , Labor, Obstetric/blood , Biomarkers/blood , Cohort Studies , Infant, Newborn , Inflammation/blood
10.
AJP Rep ; 14(2): e188-e192, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38860132

ABSTRACT

Cancer in pregnancy is rare, with incidence less than 1%, and the most common cancers being melanoma, breast, and cervical cancers. Fibromyxoid sarcoma is a soft tissue tumor involving deep soft tissues of the extremities and trunk, rarely located in the abdomen. A low-grade fibromyxoid sarcoma (LGFMS) falls in the family of fibrosarcoma. Only two cases of LGFMS in pregnancy have been reported. We report a case of abdominal LGFMS in pregnancy leading to preterm labor, sepsis, and an acute abdomen requiring surgery in the third trimester. A 19-year-old woman, gravida 1 at 32 weeks and 5 days presented to an outside hospital with preterm contractions and cervical effacement. She had a known abdominal mass, suspected to be accessory liver lobe, measuring 9.0 × 6.4 × 7.7 cm in the right upper quadrant. At 33 weeks of gestation, she developed fever and hypotension. Magnetic resonance imaging confirmed the presence of the mass, which was now on the left side of the abdomen and associated with a suspected abscess. She underwent cesarean delivery, and complete surgical resection of the mass along with a small bowel resection. Final pathology of the mass revealed a LGFMS. This case also highlights the need for a multidisciplinary approach to manage a rare presentation of sepsis and preterm labor in pregnancy.

11.
Cureus ; 16(5): e59982, 2024 May.
Article in English | MEDLINE | ID: mdl-38854168

ABSTRACT

Background Transdermal nitroglycerin (NTG) is a potent smooth muscle relaxant acting as a tocolytic agent by acting on the uterine muscles. The transdermal patch allows for continuous and controlled release of NTG through the skin into the bloodstream. This method offers the advantage of sustained drug delivery over a prolonged period. Objective of the study The study aimed to evaluate the efficacy of NTG patches for the arrest of preterm labor. Materials and methods This retrospective study comprised 100 patients admitted to our tertiary care center, ranging from 27 to 35 weeks of gestation, exhibiting preterm labor, uterine contractions, effacement, and dilatation of the cervix, without comorbidities and complications. Results In this study, it was observed that the incidence of preterm labor was higher among women aged 21-25 years. Pregnancy duration was extended by an average of approximately 28.63 days in our study cohort, with 90% of patients experiencing a prolongation of pregnancy to 48 hours after the application of a transdermal NTG patch. Parity distribution showed 50% of patients having a parity of G2-G4 and 30% being primigravida. However, 40% of the participants reported experiencing side effects, including headaches (15%) and local reactions (25%), while 60% did not experience any adverse effects. Conclusion In this study we found that the application of transdermal NTG patches led to a mean prolongation of pregnancy by 28.63 days, allowing time for the administration of steroids and fetal maturation. The inhibition of preterm contractions was successful, with an efficacy rate of 92%. These findings suggest the potential effectiveness of transdermal NTG patches as a tocolytic agent in managing preterm labor. However, the occurrence of side effects highlights the importance of careful monitoring and management during treatment.

13.
J Perinat Med ; 52(7): 706-711, 2024 Sep 25.
Article in English | MEDLINE | ID: mdl-38890768

ABSTRACT

OBJECTIVES: The aim of this study was to compare the efficacy of cervical cerclage with spontaneous follow-up strategy on pregnancy duration and neonatal outcomes in women with visible or prolapsed fetal membranes. METHODS: Patients who were referred to a single tertiary care centre between 1st January 2017 and 31st December 2022 were included in this comparative, retrospective cohort study. Patients were divided into two groups, those undergoing cerclage and those followed with no-cerclage. The range of pregnancy weeks for cerclage is between 18th and 27+6 weeks. RESULTS: A total of 106 cases were reviewed and nine were excluded. Based on shared decision making, cervical cerclage was performed in 76 patients (78.3 %) and 21 patients (21.6 %) were medically treated in no-cerclage group if there was no early rupture of the fetal membranes. The gestational age at delivery was 29.8 ± 6 [median=30 (19-38)] weeks in the cerclage group and 25.8 ± 2.9 [median=25 (19-32)] weeks in the no-cerclage group (p=0.004). Pregnancy prolongation was significantly longer in the cerclage group compared to the no-cerclage group (55 ± 48.6 days [median=28 (3-138)] vs. 12 ± 17.9 days [median=9 (1-52)]; p<0.001). Take home baby rate was 58/76 (76.3 %) in cerclage group vs. 8/21 (38 %) in no-cerclage group. In the post-24 week cerclage group the absolute risk reduction for pregnancy loss was 50 % (95 % CI=21.7-78.2). CONCLUSIONS: Cervical cerclage applied before and after 24 weeks (until 27+6 weeks) increased take home baby rate in women with visible or prolapsed fetal membranes without increasing adverse maternal outcome when compared with no-cerclage group.


Subject(s)
Cerclage, Cervical , Fetal Membranes, Premature Rupture , Pregnancy Trimester, Second , Watchful Waiting , Humans , Female , Pregnancy , Cerclage, Cervical/methods , Adult , Retrospective Studies , Watchful Waiting/methods , Pregnancy Outcome , Gestational Age , Prolapse
14.
J Reprod Immunol ; 164: 104278, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38901109

ABSTRACT

The objective of this study was to investigate the immune mechanisms involved in preterm labor (PTL), preterm prelabor rupture of the membranes (PPROM), and normal pregnancies. The second objective was to explore immune profiles in PTL for association with early ( < 34 gestational weeks (gw)) or instant ( < 48 h) delivery. This prospective observational multi-center study included women with singleton pregnancies with PTL (n = 80) or PPROM (n = 40) before 34 gw, women with normal pregnancies scheduled for antenatal visits (n = 44), and women with normal pregnancies in active labor at term (n = 40). Plasma samples obtained at admission were analyzed for cytokine and chemokine quantification using a multiplex bead assay in order to compare the immune profiles between PTL, PPROM, and normal pregnancies. In PTL, CXCL1 and CCL17 were significantly higher compared to gestational age-matched women at antenatal visits, whereas for PPROM, CXCL1 and IL-6 were increased. Women in term labor had a more pronounced inflammatory pattern with higher levels of CXCL1, CXCL8, and IL-6 compared with PTL (p = 0.007, 0.003, and 0.013, respectively), as well as higher levels of CCL17, CXCL1 and IL-6 (all p < 0.001) compared with the women at antenatal visits. In PTL, CXCL8 was higher in women with delivery before 34 gw, whereas CXCL8, GM-CSF, and IL-6 were significantly higher in women with delivery within 48 h. To conclude, PTL and PPROM were associated with a complex pattern of inflammation, both involving Th17 (CXCL1) responses. Although further studies are needed, CXCL8, GM-CSF, and IL-6 may be potential candidates for predicting preterm birth in PTL.


Subject(s)
Fetal Membranes, Premature Rupture , Obstetric Labor, Premature , Humans , Female , Pregnancy , Fetal Membranes, Premature Rupture/blood , Fetal Membranes, Premature Rupture/immunology , Adult , Obstetric Labor, Premature/immunology , Obstetric Labor, Premature/blood , Obstetric Labor, Premature/diagnosis , Prospective Studies , Cytokines/blood , Chemokines/blood , Interleukin-6/blood , Gestational Age , Chemokine CXCL1/blood , Chemokine CXCL1/metabolism , Chemokine CCL17
15.
Clin Perinatol ; 51(2): 441-459, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38705651

ABSTRACT

Throughout pregnancy, the maternal peripheral circulation contains valuable information reflecting pregnancy progression, detectable as tightly regulated immune dynamics. Local immune processes at the maternal-fetal interface and other reproductive and non-reproductive tissues are likely to be the pacemakers for this peripheral immune "clock." This cellular immune status of pregnancy can be leveraged for the early risk assessment and prediction of spontaneous preterm birth (sPTB). Systems immunology approaches to sPTB subtypes and cross-tissue (local and peripheral) interactions, as well as integration of multiple biological data modalities promise to improve our understanding of preterm birth pathobiology and identify potential clinically actionable biomarkers.


Subject(s)
Premature Birth , Humans , Pregnancy , Female , Premature Birth/immunology , Biomarkers , Risk Assessment , Infant, Newborn
16.
Clin Perinatol ; 51(2): 475-495, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38705653

ABSTRACT

Preterm birth (PTB) is a complex syndrome traditionally defined by a single parameter, namely, gestational age at birth (ie, ˂37 weeks). This approach has limitations for clinical usefulness and may explain the lack of progress in identifying cause-specific effective interventions. The authors offer a framework for a functional taxonomy of PTB based on (1) conceptual principles established a priori; (2) known etiologic factors; (3) specific, prospectively identified obstetric and neonatal clinical phenotypes; and (4) postnatal follow-up of growth and development up to 2 years of age. This taxonomy includes maternal, placental, and fetal conditions routinely recorded in data collection systems.


Subject(s)
Premature Birth , Humans , Female , Pregnancy , Infant, Newborn , Gestational Age , Infant, Premature , Syndrome , Risk Factors , Fetal Membranes, Premature Rupture
17.
Mol Hum Reprod ; 30(6)2024 May 30.
Article in English | MEDLINE | ID: mdl-38704863

ABSTRACT

Persistent and intense uterine contraction is a risk factor for preterm labor. We previously found that methyl-CpG-binding protein 2 (MeCP2), as a target of infection-related microRNA miR-212-3p, may play an inhibitory role in regulating myometrium contraction. However, the molecular mechanisms by which MeCP2 regulates myometrial contraction are still unknown. In this study, we found that MeCP2 protein expression was lower in myometrial specimens obtained from preterm labor cases, compared to those obtained from term labor cases. Herein, using RNA sequence analysis of global gene expression in human uterine smooth muscle cells (HUSMCs) following siMeCP2, we show that MeCP2 silencing caused dysregulation of the cholesterol metabolism pathway. Notably, MeCP2 silencing resulted in the upregulation of CYP27A1, the key enzyme involved in regulating cholesterol homeostasis, in HUSMCs. Methylation-specific PCR, chromatin immunoprecipitation, and dual luciferase reporter gene technology indicated that MeCP2 could bind to the methylated CYP27A1 promoter region and repress its transcription. Administration of siCYP27A1 in a lipopolysaccharide (LPS)-induced preterm labor mouse model delayed the onset of preterm labor. Human preterm myometrium and the LPS-induced preterm labor mouse model both showed lower expression of MeCP2 and increased expression of CYP27A1. These results demonstrated that aberrant upregulation of CYP27A1 induced by MeCP2 silencing is one of the mechanisms facilitating inappropriate myometrial contraction. CYP27A1 could be exploited as a novel therapeutic target for preterm birth.


Subject(s)
Methyl-CpG-Binding Protein 2 , Myometrium , Obstetric Labor, Premature , Uterine Contraction , Adult , Animals , Female , Humans , Mice , Pregnancy , Cholestanetriol 26-Monooxygenase/genetics , Cholestanetriol 26-Monooxygenase/metabolism , Cholesterol/metabolism , Lipopolysaccharides/pharmacology , Methyl-CpG-Binding Protein 2/metabolism , Methyl-CpG-Binding Protein 2/genetics , Myocytes, Smooth Muscle/metabolism , Myometrium/metabolism , Obstetric Labor, Premature/metabolism , Obstetric Labor, Premature/genetics , Promoter Regions, Genetic , Uterine Contraction/drug effects
18.
Clin Perinatol ; 51(2): 497-510, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38705654

ABSTRACT

This review examines the complexities of preterm birth (PTB), emphasizes the pivotal role of inflammation in the pathogenesis of preterm labor, and assesses current available interventions. Antibiotics, progesterone analogs, mechanical approaches, nonsteroidal anti-inflammatory drugs, and nutritional supplementation demonstrate a limited efficacy. Tocolytic agents, targeting uterine activity and contractility, inadequately prevent PTB by neglecting to act on uteroplacental inflammation. Emerging therapies targeting toll-like receptors, chemokines, and interleukin receptors exhibit promise in mitigating inflammation and preventing PTB.


Subject(s)
Premature Birth , Tocolytic Agents , Humans , Pregnancy , Female , Premature Birth/prevention & control , Tocolytic Agents/therapeutic use , Infant, Newborn , Inflammation/drug therapy , Inflammation/prevention & control , Obstetric Labor, Premature/prevention & control
19.
Ginekol Pol ; 2024 May 08.
Article in English | MEDLINE | ID: mdl-38717222

ABSTRACT

OBJECTIVES: Genitourinary tract infections in pregnant women are one of the causes of abnormal pregnancy development including miscarriages, premature labor or premature rupture of membranes (PPROM). Atypical bacteria responsible for reproductive tract infections include Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma urealyticum and Ureaplasma parvum. Identification of pathogens and appropriately selected therapy can improve obstetric outcomes in patients with symptoms of threatened miscarriage or threatened preterm labor. The purpose of our study is to analyze the impact of reproductive tract infections with ureaplasma and mycoplasma bacteria during pregnancy. MATERIAL AND METHODS: In the presented study, we retrospectively analyzed the cases of 201 pregnant patients hospitalized in the Obstetrics and Gynecology Department of Poznan Regional Hospital in 2019-2022, who had a swab taken from external os area of the cervix for atypical bacteria - Ureaplasma and Mycoplasma. Only patients with symptoms of threatened miscarriage or threatened preterm labor were included in the study group. Microbiological tests were performed in the hospital laboratory with the Mycoplasma IST 3 test from Biomerieux. RESULTS: We found a higher incidence of preterm labor in patients with symptoms of threatened preterm labor and a genital tract infection with Ureaplasma/Mycoplasma bacteria, compared to patients not infected with Mycoplasma/Ureaplasma - 31.1% vs 20% (p = 0.098). This observation in the case of Ureaplasma/Mycoplasma monoinfection group applied to 6 patients. - 75% of the group. Pregnant patients who had co-infection with other types of bacteria (48 patients in total) gave birth before 37 weeks of pregnancy in 27.1% of cases. We obtained a significant difference (p = 0.007) when comparing groups with positive and negative cultures for Ureaplasma/Mycoplasma by the presence of monoinfection/coinfection and the week of pregnancy in which delivery occurred. We also noted the effect of atypical bacterial infection for PPROM - this complication preceded preterm delivery in 40% of ureaplasma-positive patients, compared to 20% of PPROM without infection. We found a similar rate of preterm labor and pregnancy loss in Ureaplasma/Mycoplasma-positive patients who received antibiotic therapy (35.7%) compared to a group of pregnant women who did not receive treatment (31.6%). CONCLUSIONS: Infection of the genital tract with atypical bacteria Ureaplasma and Mycoplasma has a negative impact on the course of pregnancy. Identification of the type of microorganisms in cervical canal secretions of pregnant patients with symptoms of threatened miscarriage or preterm labor seems crucial. The impact of antibiotic therapy though, requires further analysis.

20.
JBRA Assist Reprod ; 28(3): 418-423, 2024 Aug 26.
Article in English | MEDLINE | ID: mdl-38712834

ABSTRACT

OBJECTIVE: The safety of assisted reproductive technology can be assessed by examining birth weight as an outcome measure. The objective of this study was to evaluate the effect of endometrial thickness during embryo transfer on newborn birth weight and preterm labor. METHODS: We conducted a retrospective cohort study at the infertility department of a teaching hospital affiliated with a university of medical sciences. Eligible women were ≥18 years old and conceived a singleton pregnancy with embryo transfer and an endometrial thickness of ≥7 mm. None of the patients had diabetes, blood hypertension, and polycystic ovarian syndrome. We assessed maternal and newborn characteristics and perinatal pregnancy outcomes. RESULTS: In total, 100 eligible patients with a mean (SD) age of 32.8 (6.2) years were included. The mean endometrial thickness during embryo transfer was 9.1 (1.2) mm, and the mean birth weight was 3040.7 (565.3)g. There were no statistically significant associations between endometrial thickness and preterm labor (p=0.215) and between endometrial thickness and stillbirth or intra-uterine fetal death (p=0.880). However, after adjusting for confounding factors, the association of endometrial thickness with birth weight was statistically significant [b=124.6 (51.6), p=0.018]. CONCLUSIONS: Within the range of ≥7mm, endometrial thickness during embryo transfer is a predictor of newborn weight; however, it is not related to the risk of preterm labor, stillbirth, or intra-uterine fetal death.


Subject(s)
Embryo Transfer , Endometrium , Pregnancy Outcome , Humans , Female , Pregnancy , Embryo Transfer/methods , Embryo Transfer/statistics & numerical data , Retrospective Studies , Adult , Pregnancy Outcome/epidemiology , Birth Weight , Infant, Newborn
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