Identifying the associated factors with onset of preterm PROM compared with term PROM - A retrospective cross-sectional study.

OBJECTIVE: To determine the risk factors associated with the preterm premature rupture of membranes (p-PROM). MATERIALS AND METHODS: This retrospective cross-sectional study assessed 110 p-PROM cases from among 6642 deliveries at a Japanese perinatal medical center, from June 2016 to September 2018. The control group comprised 220 term PROM (t-PROM) cases. We excluded cases with artificial PROM or rupture of membranes after labor, those with multiple pregnancies, those with p-PROM at 36 weeks and those with t-PROM at 37 weeks. In order to compare p-PROM with t-PROM, univariate and multivariate analysis were performed using several clinical factors at the time of PROM onset. RESULTS: The p-PROM group included 110 cases with 14-35 weeks PROM, and the t-PROM group included 220 cases with 38-41 weeks PROM. Eleven factors were identified as significant factors on the univariate analysis. A history of cervical conization (OR 37.5, 95% CI: 2.31-607.1), cervical length <25 mm at 28 weeks (OR 9.31, 95% CI: 1.76-49.3), negative Lactobacillus (OR 4.01, 95% CI: 1.18-13.7), and bleeding during the second trimester (OR 3.35, 95% CI: 1.18-9.53) were identified as significant factors by the multivariate analysis. Based on the risk factors identified during the multivariate analysis, we divided the 330 cases in the following three groups: 0 group (n = 244), 1 group (n = 60), and 2-4 group (n = 26). The ratio of p-PROM:t-PROM was calculated and compared for each group. The ratios were 21% (0 group), 57% (1 group), and 100% (2-4 group), indicating statistically significant differences between the groups (p < 0.001). CONCLUSION: We found that the following four factors were associated with p-PROM: history of cervical conization, cervical length <25 mm at 28 weeks, negative Lactobacillus, and bleeding during the second trimester. Our results suggest that we can identify patients who are at increased risk for p-PROM, based on these factors. Further research is necessary to determine the optimal treatment approach for these patients to prevent p-PROM.

Low antithrombin levels accompanied by high urine protein/creatinine ratios are predictive of acute kidney injury among CS patients with preeclampsia.

OBJECTIVES: Previous acute kidney injury (AKI) is reportedly a risk factor for future preeclampsia (PE), and PE in current pregnancies may trigger the onset of AKI. In this study, we identified risk factors for AKI among Cesarean section (CS) patients with PE. METHODS: We performed a retrospective study at a single center. Among 4602 deliveries between January 2017 and July 2018, 944 women underwent CS. Of these, 90 women had hypertensive disorders during their pregnancies, with 53 diagnoses of PE and 37 diagnoses of gestational hypertension. Medical records of the 90 women were reviewed retrospectively. RESULTS: The rate of AKI was significantly higher in the PE group than in the GH group (17 versus 3%, p < .05). Univariate analyses of the PE group identified low preoperative serum albumin levels, low antithrombin III (ATIII) activities, and urine protein/creatinine ratios (U-P/Cr) as significant predictors of AKI. Cutoff values for these factors were calculated using ROC analyses, and the combination of ATIII and U-P/Cr, which were poorly correlated, was predictive of AKI. Specifically, the proportion of AKI in patients with low ATIII-high U-P/Cr was 50% (7/14), higher than that among patients with high ATIII-low U-P/Cr (0%, 0/19, p < .05), low ATIII-low U-P/Cr (10%, 1/10, p < .05), and high ATIII-high U-P/Cr (10%, 1/10, p < .05). CONCLUSIONS: These data demonstrate that lower preoperative serum albumin levels, ATIII activities, and heavy proteinuria among CS patients with PE are risk factors for AKI.

Secretory leukocyte protease inhibitor and progranulin as possible regulators of cervical remodeling in pregnancy.

Secretory leukocyte protease inhibitor (SLPI) and progranulin (PGRN) are secretory proteins with an anti-inflammatory property. Their involvement in cervical remodeling in pregnant uterus is not yet elucidated. Thus, this study aimed to explore the significance of SLPI and PGRN in the maintenance of pregnancy by investigating the factors associated with their expression levels at the cervix. Concentrations of SLPI and PGRN proteins were measured in cervical mucus samples collected from asymptomatic pregnant women at 24-26 weeks of gestation (n = 166). The concentrations of those molecules were analyzed with clinical parameters related to risk for preterm delivery (PD). In pregnant mice, we evaluated the effect of lipopolysaccharide-induced inflammation and progesterone effect modulation on cervical mRNA expression of SLPI and PGRN. The cervical PGRN level was significantly lower in women with short cervix (<35 mm) and with a history of threatened PD. In women with short cervix, cervical SLPI concentrations were positively correlated with inflammatory cytokines, interleukin-6 (R2 = 0.75) and interleukin-8 (R2 = 0.71). In pregnant mice, cervical mRNA expressions of PGRN and SLPI were increased in response to progesterone supplementation and were suppressed by a progesterone antagonist, mifepristone. Lipopolysaccharide-induced inflammation caused remarkable upregulation in cervical SLPI mRNA level but not in PGRN. Progesterone and local inflammation are the factors controlling expression levels of PGRN and SLPI at the cervix. The observed relationship of PGRN and SLPI levels in the cervical mucus with PD-related clinical parameters supports that those anti-inflammatory molecules possibly play a significant role in appropriate regulation of cervical remodeling.

Impact of additional risk factors on the incidence of preterm delivery among pregnant women diagnosed with short cervix.

OBJECTIVE: Additional risk factors for preterm delivery in pregnant women with cervical shortening are not fully understood; however, mid-trimester cervical shortening is accepted as a risk factor for preterm delivery. This study aimed to identify risk factors associated with subsequent preterm delivery among patients with short cervix detected after late mid-trimester. MATERIALS AND METHODS: This was a retrospective study of medical data from a single perinatal tertiary facility. We identified 134 asymptomatic women with singleton pregnancies where cervical shortening (≤25 mm) was detected during routine universal screening at 22-33 weeks. Statistical analyses were conducted to identify causal relationships between the incidence of preterm delivery and known risk factors for preterm delivery. RESULTS: Incidence of preterm delivery was 27.6% (37/134) and preterm premature rupture of membrane was preceded in 46.0% (17/37) of the women with preterm delivery. Using logistic regression analysis, we identified uterine contractions [aOR 4.25, 95% confidence intervals (CI):1.68-12.1] and increased C-reactive protein (CRP) and increased white blood cell (WBC) in blood test (CRP: aOR 3.45, 95% CI:1.50-9.71; WBC: aOR 1.28, 95% CI: 1.08-1.55) as risk factors which significantly increased the risk of preterm delivery among women diagnosed with short cervix. Preterm delivery occurred in 91% of women positive for both uterine contractions and CRP >0.5 mg/dl. CONCLUSIONS: Uterine contraction and elevated CRP were additional risk factors for preterm delivery among women with short cervix. These results might be clinically useful to evaluate subsequent risk for preterm delivery in asymptomatic pregnant women presenting with short cervix in mid-pregnancy.

Recurrence of Ovarian Cancer with Placental Metastasis: A Case Report.

A 39-year-old primiparous Japanese female was admitted to the obstetrical emergency department of our hospital because of respiratory distress resulting from a large amount of pleural effusion, soon after a caesarean delivery (CD) at another hospital. While she was undergoing the CD, a giant ovarian tumour was identified. However, the tumour could not be removed at that facility and she was transferred to our hospital. Three days after the CD, a left salpingo-oophorectomy was performed with the purpose of controlling pleural and peritoneal effusions. Based on her past treatment history and the information gathered from this surgery, recurrence of ovarian cancer was considered the final diagnosis. Earlier, at the age of 37 years, she had been diagnosed with stage IC ovarian adenocarcinoma arising from a mature cystic teratoma detected after a right salpingo-oophorectomy. These kinds of situations of accidental detection of recurrent advanced ovarian cancer in a newly pregnant patient in the emergency department are rare. Amongst them, we have identified an extremely rare case showing placental metastasis. The important lesson learnt from this case report is that detailed medical interviews and physical examinations are crucial when a pregnant woman visits a hospital without a letter of referral, especially in the third trimester of pregnancy.

Labor prediction based on the expression patterns of multiple genes related to cervical maturation in human term pregnancy.

PROBLEM: This study explored the possibility of evaluating cervical maturation using swabbed cervical cell samples at term pregnancy, and aimed to develop a novel approach to predict labor onset. METHOD OF STUDY: Women with uncomplicated pregnancies (n=117 from 62 women at term pregnancy) were recruited. Messenger RNA expression levels of cervical cells for ten genes were quantified by qPCR. Principal component analysis (PCA) was conducted, and principal components that significantly contributed to the prediction of days to delivery were determined. RESULTS: PCA demonstrated that 76% of the expression information from the ten genes can be represented by three principal components (PC1-3). By the multiple regression analysis, PC2 and Bishop score but not PC1 or PC3 were significant variables in the prediction of days to delivery. CONCLUSION: These findings support the concurrent assessment of multiple gene activities in cervical cells as a promising approach to predict the initiation of labor.

Elevated C-reactive protein levels in histological chorioamnionitis at term: impact of funisitis on term neonates.

OBJECTIVE: To compare clinical features and inflammatory effects for mothers and newborns between cases with or without funisitis among histlogical chorioamnionitis (HCA) at term. METHODS: We recruited 42 patients who were diagnosed with HCA at term. The women were classified into group HCA1/2 (HCA without funisitis, n = 22) and group HCA3 (HCA with funisitis, n = 20). Medical records and cardiotocograms were retrospectively reviewed to analyze predelivery maternal signs, abnormal FHR patterns, and neonatal outcomes. Differences between the two groups were evaluated using the Mann-Whitney U-test. RESULTS: The maternal CRP and WBC level of group HCA3 was observed to be significantly greater than that of group HCA1/2. Moreover, neonatal CRP levels at days 0, 1 and 2 of group HCA3 were significantly greater than of group HCA1/2. The ratios of abnormal FHR patterns of the two groups for recurrent late deceleration and prolonged deceleration were 26% and 43%, respectively, which was not statistically significant between the two groups. CONCLUSION: We showed that HCA at term, particularly for funisitis, elevates the levels of maternal and neonatal CRP. Neonatal inflammatory signs, including elevated CRP levels, should be considered when managing cases of abnormal elevated CRP levels during labor at term.

Elevated concentration of secretory leukocyte protease inhibitor in the cervical mucus before delivery.

BACKGROUND: Cervical remodeling during parturition progresses under exquisite regulation by immunologic mediators and proteases. Secretory leukocyte protease inhibitor is a secretory protein that can function as an antimicrobial peptide, an antiinflammatory molecule, and a protease inhibitor. The involvement of secretory leukocyte protease inhibitor in cervical remodeling before and during parturition is understood poorly. OBJECTIVE: We aimed to reveal the role of secretory leukocyte protease inhibitor in the cervical remodeling process before normal term delivery and to evaluate its utility as a predictive biomarker for timing of delivery. STUDY DESIGN: Cervical mucus samples were collected prospectively at weekly prenatal visits from a cohort of pregnant women at term. The secretory leukocyte protease inhibitor concentrations in 95 mucus samples that were obtained from 49 women with uncomplicated pregnancy who subsequently underwent normal vaginal delivery were assessed. Alterations in secretory leukocyte protease inhibitor concentrations at term and the association of secretory leukocyte protease inhibitor levels with the time to delivery were analyzed. RESULTS: A moderate positive correlation with significance was detected between cervical mucus secretory leukocyte protease inhibitor concentrations and days to delivery (r = 0.38; P = .0001). The secretory leukocyte protease inhibitor concentration was significantly higher in samples that were collected within 7 days of delivery when compared with samples that were collected >7 days before delivery (P = .001). Secretory leukocyte protease inhibitor concentrations were also significantly higher in samples from women with premature rupture of membranes when compared with those without premature rupture of membranes (P = .01), all of whom delivered within 7 days. A logistic regression analysis revealed that the cervical secretory leukocyte protease inhibitor level was a significant parameter for the prediction of the onset of delivery. (P = .017; unit odds ratio, 1.28; 95% confidence interval, 1.07-1.61). A cut-off value of cervical secretory leukocyte protease inhibitor/total protein to predict delivery within 7 days was determined to be 1.62 µg/mg (sensitivity, 0.69; specificity, 0.72) using receiver operating characteristic curve-analysis. CONCLUSION: Secretory leukocyte protease inhibitor concentrations in the cervical mucus elevate progressively before delivery in uncomplicated term pregnancies. Our findings suggest that cervical secretory leukocyte protease inhibitor is a candidate biomarker for delivery prediction.

Identifying patients who can improve fertility with myomectomy.

OBJECTIVE: To identify the characteristics of cases and fibroids that will indicate which patients should undergo myomectomy to improve fertility. MATERIALS AND METHODS: We recruited patients (n=101) who had undergone myomectomy to improve fertility and received follow-up care for at least six months by the hospital. Medical records were retrospectively reviewed to analyze the pregnancy rates after myomectomy and to identify clinical factors that correlate with pregnancy rates. Cumulative pregnancy rates were analyzed using the Kaplan-Meier method and the Log rank test. The patients were then divided into three groups according to the timing of the myomectomy. The analysis was performed for all patients, for patients in the post-superovulation and/or intrauterine insemination (post-SO/IUI) group and the post-assisted reproductive technology (post-ART) group combined, and for patients in the post-ART group. RESULTS: Sixty-three pregnancies were achieved by 58 patients (57.4%) who underwent myomectomy. The mean time period between surgery and conception was 9.8 months. Most pregnancies (91.5%) were achieved within two years after surgery. Pregnancy rates were higher in patients aged less than 36 years, with no male factors, and without severe endometriosis, in comparison with patients 36 years of age or older (p<0.05), with male factor (p<0.05), and severe endometriosis (p<0.05). In the analysis of the post-ART group, pregnancy rates were higher (p<0.05) in cases where enucleation had penetrated the endometrial cavity in comparison with patients where the cavity was not penetrated; however, fibroid characteristics did not correlate with the post-myomectomy pregnancy rate in the post-SO/IUI plus post-ART group. CONCLUSION: Post-myomectomy pregnancy rates were higher in women who did not have additional infertility factors. These results suggest that the removal of fibroids benefits especially patients who suffer from infertility of an otherwise unknown cause: surgery should be strongly recommended for these patients. Our study also shows the difficulty in identifying fibroids for removal to improve fertility. Further studies are needed to develop new diagnostic techniques for identifying patients who can improve fertility with myomectomy.

Xanthogranulomatous inflammation of the perimetrium with infiltration into the uterine myometrium in a postmenopausal woman: a case report.

BACKGROUND: Xanthogranulomatous inflammation is an uncommon form of chronic inflammation that is destructive to the normal tissue of affected organs. Although xanthogranulomatous endometritis and xanthogranulomatous salpingitis of the female genital tract has been described previously, to the best of our knowledge, this is the first report of xanthogranulomatous inflammation with infiltration into the uterine myometrium from the perimetrium without endometritis. CASE PRESENTATION: A 68-year-old Japanese woman with intermittent lower abdominal pain and low-grade fever who was initially treated with antibiotics underwent hysterectomy due to abscess formation in the posterior wall of the myometrium and perimetrium (the outer serosal layer of the uterus). Histopathological findings revealed that the abscess was caused by xanthogranulomatous inflammation with the granulation tissue and chronic inflammatory cells that consisted of focal and sheets of foam cells. The inflammation destroyed the perimetrial elastic lamina, and the myometrium was deeply infiltrated by the xanthoma cells. Neither endometritis nor salpingitis was coexistent with the xanthogranulomatous inflammation. CONCLUSION: The patient was diagnosed as xanthogranulomatous inflammation, most likely arising from the perimetrium. Our findings suggest that the perimetrium, as well as the endometrium and adnexae, is one of the origins of xanthogranulomatous inflammation in female genital tract.