Chorioamnionitis (CAM), an inflammation of the foetal membranes due to infection, is associated with preterm birth and poor perinatal prognosis. The present study aimed to determine whether CAM can ...be diagnosed prior to delivery based on the bacterial composition of the amniotic fluid (AF). AF samples from 79 patients were classified according to placental inflammation: Stage III (n = 32), CAM; Stage II (n = 27), chorionitis; Stage 0-I (n = 20), sub-chorionitis or no neutrophil infiltration; and normal AF in early pregnancy (n = 18). Absolute quantification and sequencing of 16S rDNA showed that in Stage III, the 16S rDNA copy number was significantly higher and the α-diversity index lower than those in the other groups. In principal coordinate analysis, Stage III formed a separate cluster from Stage 0-I, normal AF, and blank. Forty samples were classified as positive for microbiomic CAM (miCAM) defined by the presence of 11 bacterial species that were found to be significantly associated with CAM and some parameters of perinatal prognosis. The diagnostic accuracy for CAM according to miCAM was: sensitivity, approximately 94%, and specificity, 79-87%. Our findings indicate the possibility of predicting CAM prior to delivery based on the AF microbiome profile.
This study was performed to determine whether the combination of maternal blood and amniotic fluid biomarkers can improve the predictive accuracy of histologic chorioamnionitis (HC).
This ...retrospective study included 80 singleton pregnant women who were suspected to have intrauterine infection and underwent measurement of two maternal blood biomarkers maternal white blood cell count (mWBC) and maternal C-reactive protein level (mCRP) and three amniotic fluid biomarkers amniotic white blood cell count (aCell), amniotic glucose level (aGlucose), and amniotic lactate dehydrogenase level (aLDH). We divided the patients into two groups based on the presence or absence of HC and assessed the predictors of HC using logistic regression models: Model 1, combination of mWBC and mCRP; Model 2, combination of Model 1 and aGlucose; and Model 3, combination of Model 2, aCell, and aLDH.
The multivariable analysis showed that aCell was the only significant predictor of HC odds ratio, 1.24; 95% confidence interval (CI), 1.06–1.68 independent of mWBC, mCRP, aGlucose, and aLDH. The c-statistics were higher in Model 3 (0.803; 95% CI, 0.701–0.905) than Model 1 (0.634; 95% CI, 0.511–0.758) and Model 2 (0.785; 95% CI, 0.684–0.887).
We found that the combination of maternal blood and amniotic fluid biomarkers can improve the predictive accuracy of HC. Therefore, our data provide relevant information to support counseling with regard to improving the predictive accuracy of HC in patients with suspected intrauterine infection.
•Chorioamnionitis (CAM) is difficult to diagnose during pregnancy.•Eighty singleton pregnant women with suspected CAM underwent amniocentesis.•The combination of maternal blood and amniotic fluid biomarkers can predict CAM.•Amniocentesis should be performed for early diagnosis of CAM.
A 39-year-old woman with a 9-week abdominal pregnancy noted pain in her lower abdomen and left leg. Since successive thrombi were observed extending from the left common iliac vein to the popliteal ...vein along with a thrombus in the left pulmonary artery, we diagnosed her with pulmonary thromboembolism with deep venous thrombosis (DVT). May-Thurner syndrome may have contributed to DVT in the left leg when the left iliac vein was compressed by the right iliac artery. She underwent anticoagulant therapy with heparin, followed by the subcutaneous injection of heparin at home after discharge. We herein report the case of a pregnant woman with May-Thurner syndrome who safely gave birth.
The purpose of this study was to report the 3-year experience of a nationwide demonstration project to introduce non-invasive prenatal testing (NIPT) of maternal plasma for aneuploidy, and review the ...current status of NIPT in Japan.
Tests were conducted to detect aneuploidy in high-risk pregnant women, and adequate genetic counseling was provided. The clinical data, test results, and pregnancy outcomes were recorded. We discuss the problems of NIPT on the basis of published reports and meta-analyses.
From April 2013 to March 2016, 30 613 tests were conducted at 55 medical sites participating in a multicenter clinical study. Among the 30 613 women tested, 554 were positive (1.81%) and 30 021 were negative (98.1%) for aneuploidy. Of the 289, 128, and 44 women who tested positive for trisomies 21, 18, and 13, respectively, and underwent definitive testing, 279 (96.5%), 106 (82.8%), and 28 (63.6%) were determined to have a true-positive result. For the 13 481 women with negative result and whose progress could be traced, two had a false-negative result (0.02%). The tests were performed on the condition that a standard level of genetic counseling be provided at hospitals.
Here, we report on the 3-year nationwide experience with NIPT in Japan. It is important to establish a genetic counseling system to enable women to make informed decisions regarding prenatal testing. Moreover, a welfare system is warranted to support women who decide to give birth to and raise children with chromosomal diseases.
Abstract Objective Pulmonary embolism (PE) is the leading cause of maternal death in developed countries, and the prevention of venous thromboembolism (VTE) is a pivotal part of current obstetric ...care. This study evaluated the safety and efficacy of enoxaparin sodium for thromboprophylaxis after cesarean section (C/S), and analyzed the risk factors associated with VTE. Materials and methods One hundred and forty-three women deemed to be at high risk of postoperative deep vein thrombosis (DVT) were enrolled between January 2011 and May 2012 in seven institutions in Japan. Subcutaneous administration of enoxaparin 4000 units/d was initiated 24–36 hours after C/S for 5 days. Adverse events, based on the Common Terminology Criteria for Adverse Events, Version 4, were recorded. The diagnoses of PE and DVT were made on clinical signs. Venous ultrasonography in the lower extremities was performed in 102 patients. The association between VTE and various risk factors was evaluated using univariate analysis. Results There were 10 (7.0%) Grade 1 adverse events: elevated aspartate aminotransferase or alanine aminotransferase levels in eight patients, chest pain in one patient, and subcutaneous hematoma in one patient. No patients showed clinical signs of PE and/or DVT. Among 102 patients who underwent venous ultrasonography, thrombus was detected in unilateral soleus veins in four (3.9%) patients. A body mass index (BMI) ≥ 25 kg/m2 before pregnancy was associated with asymptomatic DVT. Conclusion The current study demonstrates the safety and efficacy of enoxaparin for thromboprophylaxis after C/S. Further studies are required to determine the best method of preventing asymptomatic DVT.
Purpose
To observe age-related changes in the anterior lower uterine segment (LUS) thickness in normal pregnancy from 20 to 35 weeks’ gestation.
Methods
Subjects were 235 uncomplicated singleton ...cases that underwent single ultrasound examination at 4-week intervals during 20–35 weeks’ gestation. Sagittal LUS sections were evaluated with transvaginal ultrasonography. Anterior LUS thickness (Th) was measured every centimeter from the lowest bladder point (Th
0cm
) to 4 cm from that point (Th
4cm
). Th values were standardized by dividing by the Th
0cm
value. Intragroup comparisons of standardized Th values and intergroup comparisons of actual Th values were made according to gestational age. Statistical analyses were performed with the Kruskal–Wallis and Tukey honest standard deviation tests; significance was set at
p
< 0.05.
Results
In the 20–23-, 24–27- and 32–35-week groups, standardized Th decreased from Th
0cm
to Th
2cm
; in the 28–31-week group standardized Th decreased from Th
0cm
to Th
3cm
. Median Th
3cm
values decreased from 5.0 mm at 20–23 weeks to 3.0 mm at 28–31 weeks, but remained unchanged thereafter.
Conclusions
The anterior LUS gradually thinned from Th
0cm
to Th
3cm
at 20–35 weeks’ gestation. Th
3cm
became increasingly thin between 20–23 and 28–31 weeks’ gestation.
Although drugs inhibiting ErbB receptors such as epidermal growth factor receptor (EGFR) and HER2 have been developed as anticancer agents targeting the EGF family, they are not effective for all ...types of cancer and instead target only certain types. We propose the following four main reasons for these observations: (i) although seven EGFR ligands exist, effective inhibition of specific EGFR ligands may occur because their expression levels differ in different malignancies; (ii) suppressing EGFR ligands inhibits aggregation of EGFR and other ErbB receptors and activation of ERK and Akt signals; (iii) EGFR ligands may have various combinations for signal transduction through the EGFR pathway and other receptor signals; and (iv) the intracellular C-terminals of EGFR ligands move into the nucleus and strongly regulate cell proliferation. In this review, we describe important implications for targeted cancer therapy against EGFR ligands and describe the current situation in the development of ligand-based therapies for cancer.
Abstract Objective To validate a new parameter of the distance between the external os (EO) and placental edge (PE) to diagnose a low-lying placenta in the third trimester. Materials and methods The ...study participants included 94 uncomplicated singleton pregnant women with cephalic presentation. These women were cared for in our hospital in 1998–2011, with a posterior low-lying placenta, which was diagnosed as the distance between the internal os (IO) and a PE of 0–3.0 cm at 34–36 weeks' gestation. Measurements of cervical length (CL) and the distances of IO–PE and EO–PE were performed using transvaginal ultrasonography at least twice at 28–30 weeks, 31–33 weeks, and 34–36 weeks. Changes in CL, and the IO–PE and EO–PE distances were analyzed. Results CL and the IO–PE and EO–PE distances did not change prior to 31–33 weeks. CL was shortened and the IO–PE distance was increased after 31–33 weeks ( p = 0.0001), but the EO–PE distance was unchanged. Conclusion The EO–PE distance is a promising parameter for diagnosis of low-lying placenta in the third trimester up to 36 weeks' gestation.
Aim: To describe the longitudinal changes in canal length at 16–35 weeks' gestation in cases of twin pregnancy with preterm labor and delivery.
Methods: We studied 22 cases of twin pregnancy that ...were delivered at <36 weeks and/or that underwent preterm labor requiring tocolysis. We also studied 44 cases of twin pregnancy delivered at ≥36 weeks without tocolysis (non‐tocolysis twin pregnancy). Controls were 82 cases of normal singleton pregnancy. Canal length was longitudinally measured using transvaginal ultrasonography. The observational period of 16–35 weeks was divided into 4‐week periods for analysis.
Results: From 28 to 31 weeks onwards the canal length of non‐tocolysis twin pregnancies was shorter than that of normal singleton pregnancies (P < 0.05). The canal length of twin pregnancies with preterm labor and delivery was shorter than that of non‐tocolysis twin pregnancies at 16–19 weeks and decreased rapidly until 24–27 weeks (P < 0.01).
Conclusions: A short canal length at 16–19 weeks followed by rapid canal length shortening in the second trimester are specific characteristics in preterm labor and delivery of twin pregnancies. Sequential measurements of canal length in the second trimester starting at <20 weeks may be a suitable parameter to predict preterm labor and delivery in twin pregnancies.
Clinical prediction of foetal inflammatory response syndrome (FIRS) is highly necessary. We have previously reported that miR-4535 and miR-1915–5p are potential biomarkers for severe chorioamnionitis ...based on the results of microRNA array analysis. Therefore, we evaluated the relationship between foetal morbidity of infection and miR-4535, miR-1915–5p, interleukin (IL)-6, or 16S rDNA copy number levels in amniotic fluid from pregnant women with chorioamnionitis.
Amniotic fluid from 57 pregnant women with preterm premature membrane rupture or threatened premature labour were collected. Infants with WBC counts <5000/μL or >20,000/μL, CRP >0.5 mg/mL, or IgM >20 mg/mL at birth received a diagnosis of suspicious foetal infection, and those requiring antibiotic administration for >5 days were considered infected newborns. miR-4535, miR-1915–5p, and IL-6 levels and 16S rDNA copy number were evaluated. Mann-Whitney U test and Dunn's test were used for comparison. The area under the curve (AUC) and Youden index were calculated to examine the diagnostic accuracy of foetal morbidity of infection.
miR-4535, miR-1915–5p, 16S rDNA, and IL-6 were significantly higher in patients with severe chorioamnionitis than in patients with chorionitis or sub-chorionitis (P < 0.05). miR-4535 and miR-1915–5p levels were significantly associated with WBC counts <5000/μL or >20,000/μL, CRP >0.5 mg/mL, or IgM >20 mg/mL (P < 0.05). AUC values of miR-4535 and miR-1915–5p indicated moderate or low accuracy for foetal morbidity of infection, while those of IL-6 and 16S rDNA seemed unreliable.
MiR-4535 and miR-1915–5p levels in amniotic fluid may be considered clinically predictive for foetal morbidity of infection.
•Specific miRNA levels were elevated in amniotic fluid in severe chorioamnionitis.•Inflammatory biomarkers and infectious index were significantly correlated.•An association was observed between specific miRNAs and sustained neonatal sepsis.•Specific miRNAs could be accurate markers for foetal morbidity of infection.