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INTRODUCTION: To investigate the relationship between hydrogen sulfide(H2S) and the senescence level of the fetal membranes, and to elucidate how H2S affects the integrity of the fetal membranes. METHODS: The H2S and the senescence levels of fetal membranes, and the expressions of H2S synthase CBS and CSE were detected in the preterm (PT) group and the preterm premature ruptured membranes (pPROM) group. The effects of H2S donors and knockdown of CBS on the senescence level of amniotic epithelial cells, and the expression level of matrix metalloproteinases (MMPs) and epithelial-mesenchymal translation (EMT) were observed. RESULTS: The level of H2S in the fetal membranes in the pPROM group is significantly lower than that in the PT group matched for gestational age. The level of H2S is negatively correlated with the senescence level of fetal membranes. Treatment with H2S donors reduced cell senescence and MMPs expression, but did not affect EMT. CBS siRNA transfection accelerated the senescence of amniotic epithelial cells, and promoted the expression of MMPs and EMT occurrence, but l-cysteine could reverse these effects. DISCUSSION: Our study suggests that H2S, through its anti-aging effect, can influence the expression of MMPs and EMT, thereby contributing to the maintenance of fetal membrane integrity.
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Ruptura Prematura de Membranas Fetais , Sulfeto de Hidrogênio , Recém-Nascido , Feminino , Humanos , Sulfeto de Hidrogênio/farmacologia , Sulfeto de Hidrogênio/metabolismo , Ruptura Prematura de Membranas Fetais/metabolismo , Membranas Extraembrionárias/metabolismo , Senescência Celular , Metaloproteinases da Matriz/metabolismoRESUMO
PURPOSE: To determine the predictive value of maternal White Blood Cells (WBC), neutrophils, and C-Reactive Protein (CRP) for diagnosing Histological Chorioamnionitis (HCA) among women with Preterm Premature Rupture of Membranes (PPROM) who underwent cervical cerclage. METHODS: A retrospective cross-sectional study was conducted among women with singleton pregnancy and PPROM, who underwent cervical cerclage during 2018-2020. RESULTS: A total of 55 eligible women were included in the final analysis, including 36 (61.02%) cases with HCA and 19 (38.98%) without HCA. Women with HCA had higher WBC count (12.31 ± 2.80) × 109/L and neutrophil count (9.67 ± 2.90)×109/L than those without HCA (10.35 ± 2.53) × 109/L and 7.82 ± 2.82 × 109/L, respectively) (both p < 0.05). The cut-off value of WBC count at 10.15×109/L was found to be the most effective in identifying HCA, with an Area Under Curve (AUC) of 0.707 (95% CI: 0.56-0.86; p = 0.012), sensitivity of 86.11%, specificity of 57.90%, Positive Predictive Value (PPV) of 79.49%, Negative Predictive Value (NPV) of 68.75%, and Youden index of 0.44. The combination of WBC + neutrophil had a slightly higher (AUC = 0.711, 95% CI: 0.57-0.86; p = 0.011), specificity (68.42%), and PPV (81.25%), but lower sensitivity (72.22%), than the WBC count alone. A cut-off value of neutrophil at 7.46 × 109/L was effective in identifying HCA, with an AUC of 0.689 (95% CI: 0.53-0.84; p = 0.022). DISCUSSION: Combination use of WBC+neutrophil was found to be the most accurate predictor of HCA among women with PPROM after surgery of cervical cerclage.
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Cerclagem Cervical , Corioamnionite , Nascimento Prematuro , Gravidez , Recém-Nascido , Feminino , Humanos , Corioamnionite/diagnóstico , Estudos Retrospectivos , Estudos Transversais , BiomarcadoresRESUMO
OBJECTIVE: To determine the significance of tumor necrosis factor-α (TNF-α) and matrix metalloproteinase-8 (MMP-8) in vaginally obtained amniotic fluid predicting fetal inflammatory response syndrome (FIRS) after preterm premature rupture of membranes (PPROM). METHODS: In this prospective case-control study, TNF-α and MMP-8 concentrations were evaluated in vaginally obtained amniotic fluid from women with PPROM at 22-34 weeks of pregnancy. Biomarkers' concentrations were determined using an enzyme-linked immunosorbent assay. Patients were divided into two groups: the FIRS group (cord blood interleukin-6 > 11 pg/ml or histological funisitis) and the non-FIRS group (without these findings). The data were analyzed using R package (R-4.0.5). RESULTS: The median TNF-α and MMP-8 concentrations in amniotic fluid from the 145 women included in the study were higher in the FIRS group than in the non-FIRS group. The area under the curve of TNF-α and MMP-8 was 0.77 and 0.75, respectively. The TNF-α concentration cut-off predicting FIRS was 89.20 pg/ml and was 170.76 pg/ml for MMP-8. In regression analysis, MMP-8 concentration was an independent predictor for FIRS. An MMP-8 concentration greater than 170 ng/ml and a TNF-α concentration greater than 89 pg/ml increased the odds of FIRS 7.62 and 14.92 times, respectively. CONCLUSIONS: MMP-8 and TNF-α concentrations in vaginally obtained amniotic fluid may be good predictors for FIRS after PPROM before 34 weeks of pregnancy. The non-invasive amniotic fluid analysis could be an alternative method to invasive amniocentesis.
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Corioamnionite , Ruptura Prematura de Membranas Fetais , Gravidez , Recém-Nascido , Humanos , Feminino , Líquido Amniótico , Fator de Necrose Tumoral alfa , Metaloproteinase 8 da Matriz , Estudos de Casos e Controles , Ruptura Prematura de Membranas Fetais/diagnósticoRESUMO
ABSTRACT Purpose: To determine the predictive value of maternal White Blood Cells (WBC), neutrophils, and C-Reactive Protein (CRP) for diagnosing Histological Chorioamnionitis (HCA) among women with Preterm Premature Rupture of Membranes (PPROM) who underwent cervical cerclage. Methods: A retrospective cross-sectional study was conducted among women with singleton pregnancy and PPROM, who underwent cervical cerclage during 2018-2020. Results: A total of 55 eligible women were included in the final analysis, including 36 (61.02%) cases with HCA and 19 (38.98%) without HCA. Women with HCA had higher WBC count (12.31 ± 2.80) × 109/L and neutrophil count (9.67 ± 2.90)×109/L than those without HCA (10.35 ± 2.53) × 109/L and 7.82 ± 2.82 × 109/L, respectively) (both p < 0.05). The cut-off value of WBC count at 10.15×109/L was found to be the most effective in identifying HCA, with an Area Under Curve (AUC) of 0.707 (95% CI: 0.56-0.86; p = 0.012), sensitivity of 86.11%, specificity of 57.90%, Positive Predictive Value (PPV) of 79.49%, Negative Predictive Value (NPV) of 68.75%, and Youden index of 0.44. The combination of WBC + neutrophil had a slightly higher (AUC = 0.711, 95% CI: 0.57-0.86; p = 0.011), specificity (68.42%), and PPV (81.25%), but lower sensitivity (72.22%), than the WBC count alone. A cut-off value of neutrophil at 7.46 × 109/L was effective in identifying HCA, with an AUC of 0.689 (95% CI: 0.53-0.84; p = 0.022). Discussion: Combination use of WBC+neutrophil was found to be the most accurate predictor of HCA among women with PPROM after surgery of cervical cerclage.
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Background: A prospective cohort was conducted to assess the prevalence of seven RTIs/STIs in adolescent asymptomatic pregnant women to find a significant correlation between infection and pregnancy. Methods: The study was restricted to 18-19 years of asymptomatic adolescent pregnant women attending Ante-Natal Care and the health status of the pregnant women were followed up to parturition. The health status of the infant was followed till 6 months post-delivery. The prevalence of the concerning pathogens and the significance of their association with adverse outcomes of pregnancy were determined. Results: Among 279 subjects, the most significant co-infections were observed for M. hominis with U. parvum (9.31%; p-value-0.0071/OR-2.6421) and U. urealyticum (7.88%; p-value-0.0119/OR-2.6455). Statistically significant associations were found between C. trachomatis [(p-value-0.0439); OR-2.9902] and M. genitalium [(p-value-0.0284); OR-3.442] with PTB, N. gonorrhoeae with LBW <2.5 kg [(p-value-0.0052);OR-4.9017], U. urealyticum with VLBW <2 kg [(p-value-0.0262);OR-3.0207], M. genitalium [(p-value-0.0184); OR-11.7976] and T. vaginalis with PROM [(p-value 0.0063); OR-19.4275] while M. genitalium [(p-value 0.0190); OR-12.9230] and U. urealyticum [(p-value 0.0063); OR-14.5149] with PPROM with 95% CI respectively. Conclusions: Asymptomatic adolescents are at high risk of adverse pregnancy outcomes if infected with the concerned pathogens.
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OBJECTIVE: The aim of this study was to identify the factors and frequencies of induced termination of pregnancies. MATERIALS AND METHODS: This is a retrospective study of 488 terminations of pregnancies (TOPs) between January 2011 and December 2021 to demonstrate the factors affecting the decision to terminate the pregnancy. All cases had been hospitalized to manage the induction of labor. Methods included serial multiple laminaria dilation of the cervix and administration of a cervical misoprostol suppository. After induction of labor, the subject may experience amniotomy, instrumental evacuation of the uterus, and even hysterotomy. Pre-procedure counseling included an agreement to share medical records (paper-based and electronic). We verified the indications for all patients seeking TOPs. All cases were performed according to known diagnostic classifications and divided into seven groups for analysis. RESULTS: The patient ages ranged from 12 to 46 years. The median maternal age was 34 years [interquartile range (IQR) 30, 37]; 52.2% had at least one prior delivery. The pre-procedure diagnosis was divided into seven groups including the following: chromosomal and genetic abnormalities (146/488, 29.9%), no intrauterine heartbeats (126/488, 25.8%), structural anomalies (84/488, 17.2%), elective termination (56/488, 11.5%), preterm premature rupture of membranes (PPROM) (42/488, 8.6%), cervical incompetence (32/488, 6.6%), and other conditions (2/488, 0.4%). After excluding elective terminations, the eleven-year rate of fetal death and stillbirth to births did not show significant changes from 2011 to 2021. CONCLUSIONS: Knowing the factors underlying the decision to induce intrauterine fetal death (IUFD) including reasons for objecting to pregnancy are important for obstetricians-they can offer better planning and medical counseling. It is important to educate all women about family planning to prevent large numbers of unwanted and unsafe pregnancy terminations.
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Aborto Induzido , Misoprostol , Aborto Induzido/métodos , Adolescente , Adulto , Criança , Feminino , Morte Fetal , Humanos , Recém-Nascido , Pessoa de Meia-Idade , Gravidez , Estudos Retrospectivos , Natimorto/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Preterm premature rupture of membranes (PPROM) is one of the most common causes of preterm birth. Antibiotic treatment is recommended to prolong the pregnancy course and reduce fetal morbidity in women with PPROM. However, the guidelines for antibiotic selection are based on studies done years ago, mostly in Western countries, which may not reflect the geographic, temporal, and ethnic variation in microbial colonization and infection in other parts of the world. We aimed to understand whether the antibiotics recommended by the current guidelines were sufficient to eradicate the majority of pathogens involved. METHODS: This is a single-center retrospective study at a tertiary medical center in Taiwan with patients recruited from January 1, 2017, to December 31, 2019. All patient included had a confirmed diagnosis of PPROM. In this study, we aimed to investigate which broad-spectrum antibiotic was most suitable for PPROM cases in Taiwan. RESULTS: 133 women were included, and 121 women had positive culture results. Most of the pregnant women had one positive result (35.5%). The most common pathogen was Lactobacillus species (27.8%), followed by Streptococcus species (12.9%) and Staphylococcus species (12.09%). CONCLUSION: The most appropriate antibiotic therapy for PPROM was a combination of 1 g azithromycin given orally on admission plus a third-generation cephalosporin administered intravenously in the first 48 hours and followed by amoxicillin 500 mg per os for another five days. This recommended antibiotic regimen for women with PPROM needs further study under a randomized clinical trial with a larger study population to evaluate its efficacy.
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Ruptura Prematura de Membranas Fetais , Nascimento Prematuro , Antibacterianos , Feminino , Humanos , Recém-Nascido , Gravidez , Estudos RetrospectivosRESUMO
Objective: Parkinson's disease protein 7 (PARK7/DJ-1) is an important antioxidant multiprotein against inflammation and oxidative stress. We therefore planned this study to demonstrate the association between maternal PARK7 levels and the occurrence of preterm premature rupture of membranes (PPROM). Materials and Methods: We enrolled 80 pregnant women; 50 PPROM patients and 30 healthy controls, into this cross- sectional study between the 24th and 36th gestational weeks. Furthermore, we measured serum PARK 7 levels using enzyme-Linked immunosorbent assay method. Results: Plasma PARK7 levels were higher in PPROM patients compared to those in the healthy controls (p<0.001). With a cutoff value of 2.57 pg/mL; PARK 7 had a 92% sensitivity, 86% specificity, 88% positive predictive value and 83% negative predictive value (p<0.01) for PPROM. PARK7 had positive correlation with blood leukocyte levels (p<0.001), C-reactive protein levels (p<0.001), and negatively correlated with birth weight and birth week. Conclusion: PARK 7 is overexpressed in PPROM patients. Due to its anti-inflammatory and antioxidant properties, PARK7 may be a novel marker in better understanding the pathophysiology and prediction of the prognosis PPROM. Further large-scale studies are needed.
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BACKGROUND: The aim of the present study was to compare the outcomes of pregnancies complicated by preterm premature rupture of membranes (PPROM) in China. METHODS: The present study was a single-center retrospective study of women admitted to Beijing Obstetrics and Gynecology Hospital in 2012, 2014, and 2017. Deliveries at <24 and >37 weeks, fatal deformities, stillbirths, and multiple pregnancies were excluded. Pregnancies were divided into 24-27+6, 28-33+6, and 34-36+6 weeks according to weeks of gestation in each year. In total, 1,178 pregnancies complicated by PPROM were analyzed in terms of incidence rate, risk factors, delivery mode, and neonatal outcomes. RESULTS: The rate of PPROM was 3.11% in 2012, 2.35% in 2014, and 2.4% in 2017; the difference was significant (P<0.001). Age [odds ratio (OR): 1.046, P<0.001], intrauterine infection (OR: 2.087, P=0.007), and vaginitis (OR: 1.812, P=0.039) were risk factors for PPROM. In all 3 years, patients with PPROM tended to choose vaginal delivery rather than cesarean section (CS) delivery (68.9% in 2012, P<0.001; 76.5% in 2014, P<0.001; 69.3% in 2017, P<0.001), and the rate of vaginal deliveries in 2014 was higher than that in 2012 and 2017 (P=0.027). Indications for PPROM at 34-36+6 weeks varied significantly among the 3 years (P<0.001). No significant difference was found in body weight, body length, and Apgar score at 1, 5, and 10 min; however, there was a significant difference in Apgar score after 1 min at 28-33+6 weeks (P=0.012). CONCLUSIONS: The incidence rate of PPROM at our single center varied between 2012, 2014, and 2017. Risk factors for pregnancies complicated by PPROM include age, intrauterine infection, and vaginitis. The rate of CS delivery varied, and breech/transverse presentation was the major indication for patients with PPROM at 34-36+6 weeks.
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OBJECTIVE: Preterm premature rupture of membranes is associated with 30% of all preterm births. The weakening of amniotic membranes is associated with an increase in matrix metallopeptidases (MMPs) along with a decrease in their inhibitors, tissue inhibitor metallopeptidases (TIMPs). Additionally, granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to weaken fetal membranes in-vitro. We hypothesize pregnant mice treated with GM-CSF lead to increased MMPs:TIMPs resulting in membrane rupture and preterm birth. STUDY DESIGN: Pregnant CD-1 mice on gestational day 17 received either an intrauterine injection of GM-CSF or vehicle control. A second series of mice were administered an intrauterine injection of Lipopolysaccharide along with either anti-mouse GM-CSF or control antibody. Mice were evaluated for rupture of membranes and/or preterm birth and the uterus, amniotic fluid, and serum were collected for analysis. RESULTS: 87.5% of GM-CSF mice exhibited evidence of membrane rupture or preterm birth, compared with 0% in control mice (p < .001). Treatment with GM-CSF decreased the expression of TNFα (p < .05) while increasing the ratio of MMP2:TIMP1 (p < .05), MMP2:TIMP2 (p < .05), MMP2:TIMP3 (p < .001), MMP9:TIMP1 (p < .01), MMP9:TIMP2 (p < .05), MMP9:TIMP3 (p < .001), and MMP10:TIMP1 (p < .05). Mice treated with LPS and the GM-CSF antibody resulted in a decrease in the ratio of MMP2:TIMP1 (p < .0001) compared with controls. CONCLUSION: These studies demonstrate GM-CSF will result in membrane rupture and preterm birth by increasing the ratio MMPs:TIMPs in our animal model. By increasing our understanding of the molecular pathways associated with GM-CSF, we may be able to develop future therapies to prevent preterm birth and reduce neonatal morbidity.
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Colagenases/biossíntese , Ruptura Prematura de Membranas Fetais , Fator Estimulador de Colônias de Granulócitos e Macrófagos/efeitos adversos , Nascimento Prematuro , Inibidores Teciduais de Metaloproteinases/biossíntese , Animais , Modelos Animais de Doenças , Feminino , Ruptura Prematura de Membranas Fetais/induzido quimicamente , Ruptura Prematura de Membranas Fetais/metabolismo , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Camundongos , Gravidez , Nascimento Prematuro/induzido quimicamente , Nascimento Prematuro/metabolismoRESUMO
BACKGROUND: The current standard of care in the setting of preterm premature rupture of membranes involves antenatal hospitalization until delivery. The reduced physical activity during this time compounds the heightened risk for venous thromboembolism in pregnancy. Prophylactic anticoagulation can decrease this risk of venous thromboembolism; however, this benefit must be balanced against the risks of precluding neuraxial analgesia or increasing the risk of postpartum hemorrhage. OBJECTIVE: The objective of this study was to determine the optimal modality for venous thromboembolism prophylaxis during hospitalization for preterm premature rupture of membranes using a decision analysis model. STUDY DESIGN: A decision-analytical Markov model was constructed using the TreeAge software comparing the use of unfractionated heparin, low-molecular-weight heparin or no anticoagulation in women with a singleton pregnancy who were hospitalized for preterm premature rupture of membranes after 24 weeks and remained hospitalized until delivery. Maternal outcomes examined included attainment of neuraxial analgesia (vs no analgesia for vaginal delivery or general anesthesia for cesarean delivery), venous thromboembolism, postpartum hemorrhage, and maternal death. Probabilities and utilities were derived from existing literature. Sensitivity analyses were performed to interrogate model assumptions, and a Monte Carlo probabilistic sensitivity analysis was performed to examine the robustness of the model. RESULTS: In this decision-analytical model, no prophylactic anticoagulation maximized maternal utilities. Clinical outcomes among a theoretical cohort of 100,000 women are shown in the Table. The 1- and 2-way sensitivity analyses supported this conclusion. Monte Carlo probabilistic sensitivity analysis indicated that no prophylaxis was the preferred choice in 56% of simulations, unfractionated heparin in 34% of simulations, and low-molecular-weight heparin in 10% of simulations. CONCLUSION: Our results do not support the routine use of prophylactic anticoagulation in women admitted to the hospital for preterm premature rupture of membranes. These findings can be used to inform clinical decisions when admitting low-risk singleton pregnancies to the hospital in the setting of preterm premature rupture of membranes.
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Ruptura Prematura de Membranas Fetais , Nascimento Prematuro , Anticoagulantes , Técnicas de Apoio para a Decisão , Feminino , Ruptura Prematura de Membranas Fetais/epidemiologia , Heparina , Humanos , Recém-Nascido , GravidezRESUMO
Periviable deliveries (less than 26 weeks) are a small percentage of deliveries but account for a disproportionately high number of long-term morbidities. Few studies describe interventions and outcomes for periviable preterm premature rupture of membranes (PPROM). The available reports may include only those neonates who received resuscitation, making interpretation and application difficult. Counseling should consider the impact of oligohydramnios on fetal lung development. This article discusses standard and experimental interventions that may offer neonatal benefit. Antenatal corticosteroids, antibiotics, and magnesium sulfate may improve outcomes but data to support an improvement in outcome are limited. Studies specifically evaluating these interventions are needed.
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Ruptura Prematura de Membranas Fetais/terapia , Viabilidade Fetal , Corticosteroides/uso terapêutico , Líquido Amniótico , Antibacterianos/uso terapêutico , Displasia Broncopulmonar/epidemiologia , Cerclagem Cervical/métodos , Corioamnionite/epidemiologia , Feminino , Ruptura Prematura de Membranas Fetais/diagnóstico , Idade Gestacional , Humanos , Lactente Extremamente Prematuro , Recém-Nascido , Doenças do Prematuro/epidemiologia , Sulfato de Magnésio/uso terapêutico , Gravidez , Resultado da Gravidez , Nascimento PrematuroRESUMO
Preterm premature rupture of membranes (PPROM) is almost uniformly associated with preterm birth and thus sequelae of prematurity explain many of the complications associated with this condition. However, the unique inflammatory environment and oligohydramnios associated with PPROM may impart unique neonatal and childhood morbidity compared with other preterm birth pathways.
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Ruptura Prematura de Membranas Fetais/epidemiologia , Paralisia Cerebral/epidemiologia , Criança , Pré-Escolar , Corioamnionite/epidemiologia , Deficiências do Desenvolvimento/epidemiologia , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Doenças do Recém-Nascido/epidemiologia , Recém-Nascido Prematuro , Morbidade , Oligo-Hidrâmnio/epidemiologia , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Resultado da Gravidez , Nascimento Prematuro/epidemiologiaRESUMO
INTRODUCTION: Home care management offers a suitable alternative to hospitalization for management of preterm premature rupture of membranes (PPROM). Eligibility criteria have not been clearly established. Our aim was to determine predictive factors of complication during home care management of PPROM in order to define optimal eligibility criteria. MATERIAL AND METHODS: Retrospective cohort study of all women with singleton pregnancies with PPROM managed as outpatients between 2009 and 2015. Complications were defined as the occurrence of one of these events: fetal death, placental abruption, umbilical cord prolapse, delivery outside maternity hospital, neonatal death. RESULTS: In all, 187 women with PPROMs were managed as outpatients, of whom 12 had a complication (6.4%). In the "complication" group, gestational age at diagnosis (P = 0.006) and at delivery (P < 0.001) were lower, with no difference in latency between these two events. Three criteria significantly increased the risk for a severe complication: PPROM occurring before 26 weeks (P = 0.008), non-cephalic fetal presentation (P = 0.02) and oligoamnios (P = 0.02). When unfavorable criteria were associated with PPROM, the risk was increased (1 criterion, odds ratio [OR] 1.6; 2 criteria, OR 6.9 and 3 criteria, OR 32.8). CONCLUSIONS: Combination of these three criteria is an indication for conventional hospitalization to limit maternal and fetal morbidity. When two criteria are combined, home care should be discussed for each case. If only one unfavorable criteria is present, outpatient management is suitable. To validate these results, a prospective randomized study should be conducted.
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Assistência Ambulatorial , Contraindicações , Ruptura Prematura de Membranas Fetais/terapia , Serviços de Assistência Domiciliar , Adulto , Feminino , Seguimentos , Idade Gestacional , Humanos , Gravidez , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Uterine and placental pathology can be a major cause of morbidity and mortality in the parturient and infant. When presenting alone, placental abruption, uterine rupture, or placenta accreta can result in significant peripartum hemorrhage, requiring aggressive surgical and anesthetic management; however, the presence of multiple concurrent uterine and placental pathologies can result in significant morbidity and mortality. We present the anesthetic management of a parturient who underwent an urgent cesarean delivery for non-reassuring fetal tracing in the setting of chronic hypertension, preterm premature rupture of membranes, and chorioamnionitis who was subsequently found to have placental abruption, uterine rupture, and placenta accreta.
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Evidence from family and twin-based studies provide strong support for a significant contribution of maternal and fetal genetics to the timing of parturition and spontaneous preterm birth. However, there has been only modest success in the discovery of genes predisposing to preterm birth, despite increasing sophistication of genetic and genomic technology. In contrast, DNA variants associated with other traits/diseases have been identified. For example, there is overwhelming evidence that suggests that the nature and intensity of an inflammatory response in adults and children are under genetic control. Because inflammation is often invoked as an etiologic factor in spontaneous preterm birth, the question of whether spontaneous preterm birth has a genetic predisposition in the case of pathologic inflammation has been of long-standing interest to investigators. Here, we review various genetic approaches used for the discovery of preterm birth genetic variants in the context of inflammation-associated spontaneous preterm birth. Candidate gene studies have sought genetic variants that regulate inflammation in the mother and fetus; however, the promising findings have often not been replicated. Genome-wide association studies, an approach to the identification of chromosomal loci responsible for complex traits, have also not yielded compelling evidence for DNA variants predisposing to preterm birth. A recent genome-wide association study that included a large number of White women (>40,000) revealed that maternal loci contribute to preterm birth. Although none of these loci harbored genes directly related to innate immunity, the results were replicated. Another approach to identify DNA variants predisposing to preterm birth is whole exome sequencing, which examines the DNA sequence of protein-coding regions of the genome. A recent whole exome sequencing study identified rare mutations in genes encoding for proteins involved in the negative regulation (dampening) of the innate immune response (eg, CARD6, CARD8, NLRP10, NLRP12, NOD2, TLR10) and antimicrobial peptide/proteins (eg, DEFB1, MBL2). These findings support the concept that preterm labor, at least in part, has an inflammatory etiology, which can be induced by pathogens (ie, intraamniotic infection) or "danger signals" (alarmins) released during cellular stress or necrosis (ie, sterile intraamniotic inflammation). These findings support the notion that preterm birth has a polygenic basis that involves rare mutations or damaging variants in multiple genes involved in innate immunity and host defense mechanisms against microbes and their noxious products. An overlap among the whole exome sequencing-identified genes and other inflammatory conditions associated with preterm birth, such as periodontal disease and inflammatory bowel disease, was observed, which suggests a shared genetic substrate for these conditions. We propose that whole exome sequencing, as well as whole genome sequencing, is the most promising approach for the identification of functionally significant genetic variants responsible for spontaneous preterm birth, at least in the context of pathologic inflammation. The identification of genes that contribute to preterm birth by whole exome sequencing, or whole genome sequencing, promises to yield valuable population-specific biomarkers to identify the risk for spontaneous preterm birth and potential strategies to mitigate such a risk.
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Sequenciamento do Exoma , Predisposição Genética para Doença , Inflamação/genética , Nascimento Prematuro/genética , Feminino , Estudo de Associação Genômica Ampla , Humanos , Imunidade Inata/genética , Inflamação/complicações , Doenças Inflamatórias Intestinais/genética , Doenças Periodontais/genética , Gravidez , Nascimento Prematuro/etiologiaRESUMO
The incidence of chorioamnionitis varies widely. The highest incidence is reported in preterm deliveries. Among preterm deliveries, chorioamnionitis usually occurs after preterm premature rupture of membranes (PPROM). To date, only five cases of chorioamnionitis due to Serratia marcescens were reported. Here we present a case of a pregnant woman with chorioamnionitis due to Serratia marcescens who delivered a premature neonate at 28 weeks and four days of gestation. We also conducted a review of the literature in order to identify and characterize the clinical presentation and outcomes of this rare infection. A 36 year old female (gravida 9, para 6) was admitted with cervical effacement of 16mm and intact membranes at gestational age of 25 weeks and five days. One week following her admission PPROM was noticed. Treatment with the standard antibiotic regimen for PPROM was initiated. Thirteen days after the diagnosis of PPROM (28 weeks and four days) she developed chills, abdominal pain, sub febrile fever, tachycardia, leukocytosis and fetal tachycardia, and a clinical diagnosis of chorioamnionitis was made. An urgent CS was performed. In the first post-operative day the patient developed surgical sight infection. Cultures obtained from the purulent discharge of the wound, as well as cultures from the placenta and uterine cavity that were obtained during surgery grew Serratia marcescens. The patient was treated with Meropenem for six days, with a good clinical response. We present a rare case of nosocomialy acquired Serratia marcescens chorioamnionitis in a patient with PPROM. This case emphasizes the need for good infection control measures. Our favorable outcome together with the scares reports in the literature, add insight into this type of rare infection.
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Corioamnionite/etiologia , Ruptura Prematura de Membranas Fetais/etiologia , Infecções por Serratia/complicações , Adulto , Antibacterianos/uso terapêutico , Cesárea , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Meropeném , Gravidez , Infecções por Serratia/tratamento farmacológico , Serratia marcescens , Tienamicinas/uso terapêuticoRESUMO
OBJECTIVE: To assess the predictors of outcome in terms of length of stay in the neonatal intensive care unit (NICU) and survival of neonates from women with preterm premature rupture of membranes (PPROM). METHODS: A population-based retrospective study including 331 singleton pregnant women with PPROM at 24-34 gestational weeks between January 2013 and December 2015 was conducted. Gestational age at delivery, birth weight, route of delivery, newborn gender, maternal age, oligohydramnios, premature retinopathy (ROP), necrotising enterocolitis (NEC), sepsis, fetal growth retardation (FGR), intracranial hemorrhagia (ICH), bronchopulmonary dysplasia (BPD), respiratory distress syndrome (RDS), primary pulmonary hypertension (PPH), congenital cardiac disease (CCD), patent ductus arteriosus (PDA), use of cortisol (betamethasone) and maternal complications including gestational diabetes, preeclampsia and chorioamnionitis were used to predict neonatal outcomes in terms of length of stay in the NICU and survival. RESULTS: In linear regression analyses, birth weight, ROP, CCD, BPD, PDA, NEC and preeclampsia were significant confounders for length of stay in the NICU. Among them, birth weight was the most powerful confounder for prolongation of the NICU stay (t: -6.43; p < 0.001). In multivariate logistic regression analyses, birth weight, PDA, ROP and PPH were significantly correlated with neonatal survival. PPH was the most powerful confounder in neonatal survival (ß: 7.22; p = 0.005). CONCLUSION: Prematurity-related complications are the most important problems for which precautions should be taken. Therefore, premature deliveries should be avoided to prevent infection and to prolong the latent period in cases of PPROM in order to decrease prematurity-related outcomes.
Assuntos
Ruptura Prematura de Membranas Fetais , Mortalidade Infantil , Recém-Nascido Prematuro , Unidades de Terapia Intensiva Neonatal/estatística & dados numéricos , Tempo de Internação , Feminino , Humanos , Lactente , Recém-Nascido , Gravidez , Estudos RetrospectivosRESUMO
OBJECTIVE: Our purpose was to determine whether singleton pregnancies complicated by preterm premature rupture of membranes (PPROM) and oligohydramnios are at an increased risk of having maternal and neonatal morbidity. METHODS: We performed a retrospective analysis of 389 women with PPROM between 24 and 34 weeks of gestation in a single tertiary center during 2008-2014. Patients were divided into two groups on the basis of amniotic fluid index (AFI) < 5 cm (n = 188) or AFI ≥ 5 cm (n = 201). Perinatal outcomes were compared according to amniotic fluid volume. The Student's t-test and Mann-Whitney U test were used to compare variables with normal and abnormal distribution, respectively. Categorical variables were examined by the chi-square test. RESULTS: Patients with an AFI < 5 cm demonstrated a significantly shorter latency to delivery (p < 0.001), a higher rate of clinical chorioamnionitis (p = 0.029) and emergency cesarean delivery (p = 0.043) and a lower neonatal Apgar score at first minute (p = 0.004). CONCLUSION: Initial oligohydramnios after PPROM is associated with shorter latency to delivery, higher rate of clinical chorioamnionitis, higher rate of emergency cesarean delivery, and lower 1-min Apgar score.
Assuntos
Índice de Apgar , Cesárea/estatística & dados numéricos , Corioamnionite/etiologia , Ruptura Prematura de Membranas Fetais/fisiopatologia , Oligo-Hidrâmnio/fisiopatologia , Adulto , Feminino , Humanos , Recém-Nascido , Estimativa de Kaplan-Meier , Gravidez , Resultado da Gravidez , Estudos Retrospectivos , Fatores de RiscoRESUMO
OBJECTIVE: To investigate the prevalence of preterm premature rupture of membranes (PPROM) in urban areas in China and examine the associated risk factors. METHODS: A population-based, prospective study was undertaken in 14 cities in China between January 1, 2011, and January 31, 2012. Women were recruited at their first prenatal-care visit, when maternal characteristics were recorded. Risk factors were analyzed by one-way analysis of variance. RESULTS: Of 112 439 women included in analyses, 3077 (2.7%) had PPROM. Univariate analysis showed an increased risk of PPROM before 28weeks of pregnancy in migrant women (odds ratio [OR] 2.25; 95% confidence interval [CI] 1.53-3.30; P<0.001), in those with a history of recurrent induced abortions (OR 2.75; 95% CI 1.66-4.56; P<0.001), and in those with a history of preterm birth (OR 3.90; 95% CI 0.77-19.61; P<0.001). The associations were maintained in multivariate analysis (P<0.001). CONCLUSION: Migration as a result of urbanization, high rates of induced abortion, and preterm birth are potential risk factors for PPROM in Chinese women.