Preterm labor with intact membranes: a simple noninvasive method to identify patients at risk for intra-amniotic infection and/or inflammation.

OBJECTIVE: To develop a noninvasive scoring system to identify patients at high risk for intra-amniotic infection and/or inflammation, which would reduce the need for amniocentesis. METHODS: This prospective cohort study comprised patients admitted with preterm labor and intact membranes (20-34 weeks of gestation) who underwent a transabdominal amniocentesis and for whom concentrations of quantitative cervical fetal fibronectin and of maternal serum C-reactive protein (CRP) were determined. Intra-amniotic infection was defined as a positive amniotic fluid culture for microorganisms. Intra-amniotic inflammation was defined as an amniotic fluid matrix metalloproteinase-8 concentration >23 ng/mL. Multivariate logistic regression analysis was performed to identify intra-amniotic infection/inflammtion with noninvasive parameters that had a significant relationship with univariate analysis. With four parameters identified by multivariate analysis, we generated a noninvasive risk scoring system. RESULTS: Of the study population consisting of 138 singleton pregnant women, (1) the overall rate of intra-amniotic infection/inflammation was 28.3% (39/138); (2) four parameters were used to develop a noninvasive risk scoring system [i.e. cervical fetal fibronectin concentration (score 0-2), maternal serum CRP concentration (score 0-2), cervical dilatation (score 0-2), and gestational age at presentation (score 0-1)]; the total score ranges from 0 to 7; 3) the area under the curve of the risk score was 0.96 (95% confidence interval (CI), 0.92-0.99), significantly higher than that of each predictor in the identification of intra-amniotic infection/inflammation (p < .001, for all); 4) the risk score with a cutoff of 4 had a sensitivity of 94.9% (37/39), a specificity of 90.9% (90/99), a positive predictive value of 80.4% (37/46), a negative predictive value of 97.8% (90/92), a positive likelihood ratio of 10.4 (95% CI, 5.6-19.5), and a negative likelihood ratio of 0.06 (95% CI, 0.15-0.22) in the identification of intra-amniotic infection/inflammation. CONCLUSIONS: (1) The combination of four parameters (concentrations of cervical fetal fibronectin and maternal serum CRP, cervical dilatation, and gestational age) was independently associated with intra-amniotic infection and/or inflammation; and (2) the risk scoring system comprised of the combination of 4 noninvasive parameters was sensitive and specific to identify the patients at risk for intra-amniotic infection and/or inflammation.

Clinical significance of soft markers in second trimester ultrasonography for pregnant Korean women: a multicenter study and literature review.

OBJECTIVE: To evaluate the clinical significance of soft markers for aneuploidy screening in Korean women. METHODS: We retrospectively reviewed the medical records of 5,428 singleton pregnant women who underwent sonography during the second trimester at seven institutions in South Korea. We evaluated the prevalence of the following soft markers: intracardiac echogenic focus, choroid plexus cysts, pyelectasis, echogenic bowel, and mild ventriculomegaly. We developed best-fitted regression equations for the fetal femur and humerus length using our data and defined a short femur and humerus as both long bones below the fifth centile. The results of genetic testing and postnatal outcomes were investigated in patients who had been diagnosed with aforementioned soft markers. RESULTS: The median maternal age of our study population was 33 years, and the median gestational age at the time of ultrasonographic examination was 21 weeks. We detected soft markers in 10.0% (n=540) of fetuses: 9.3% (n=504) were isolated cases and 0.7% (n=36) of cases had two or more markers. We identified only two aneuploides (trisomy 18, 46,XX,t[8;10][q22.1;p13]), of which one was clinically significant. We presented the neonatal outcomes of the fetuses with the respective soft markers. Preterm delivery, low birth weight, and small-for-gestational-age (SGA) were significantly more common in women with a shortened fetal femur (P<0.001, all). However, the presence of a shortened fetal humerus was not associated with those outcomes excluding SGA. CONCLUSION: Soft markers in second-trimester ultrasonography have limited use in screening for fetal aneuploidy in Korean women. However, these markers can be used as a screening tool for adverse outcomes other than chromosomal abnormality.

CT angiography for the management of postpartum hemorrhage refractory to conservative treatment.

INTRODUCTION: Postpartum hemorrhage (PPH) is one of the leading causes of maternal morbidity and mortality. Computerized tomographic (CT) angiography is a useful tool to identify hemorrhage from various conditions. However, the feasibility of CT angiography for the management of PPH has not been well evaluated. OBJECTIVE: To evaluate the clinical usefulness of CT angiography in the management of PPH refractory to the conservative treatment. METHODS: This retrospective cohort study consisted of 528 consecutive patients who were transferred to our institute after delivery at 28 primary maternity hospitals for the management of PPH between 2009 and 2017. Immediate intervention such as arterial embolization and hysterectomy were performed on 278 patients. Of the remaining 250 patients, CT angiography was performed on 61 patients with hemodynamic stability but with sustained hemorrhage refractory to medical treatment. The diagnostic index was assessed using conventional angiography as the reference standard. The clinical outcome was compared between patients with and without contrast extravasation on CT angiography. RESULTS: (1) The prevalence of contrast extravasation was found in 61% of patients (37/61); (2) conventional angiography and arterial embolization were performed in 78% of patients (29/37) with contrast extravasation on CT angiography. Contrast extravasation was confirmed in 83% of patients (24/29) by conventional angiography; (3) among the 24 patients without contrast extravasation on CT angiography, 96% (23/24) were managed conservatively; (4) the patients with contrast extravasation on CT angiography received more packed red blood cell (PRBC) transfusion than those without that condition (7.3 ± 5.2 units vs. 3.8 ± 2.9 units, p = .009). Massive transfusion (defined as transfusion of 10 or more units of PRBC) was more common in patients with contrast extravasation than in those without (27% [10/37] vs. 0% [0/24], p = .004). CONCLUSIONS: Conservative treatment succeeded in 96% of patients without contrast extravasation on CT angiography. CT angiography is useful to identify patients requiring intervention in the management of hemorrhage refractory to medical treatment.

Evaluating outcomes of pulsed dye laser therapy combined with intralesional triamcinolone injection after surgical removal of hypertrophic cesarean section scars.

BACKGROUND: Recently, pulsed dye laser (PDL) combined with triamcinolone intralesional injection (TAILI) has been introduced for surgical scar prevention. However, little is known about this procedure's effectiveness in preventing hypertrophic scar following surgical scar removal. OBJECTIVES: This study aimed to evaluate the outcome of early intervention using PDL combined with TAILI after surgical removal of hypertrophic cesarean section (CS) scars. METHODS: The medical records of 35 patients who underwent early intervention using PDL and TAILI after removal of hypertrophic CS scars were retrospectively reviewed. The scars' average Vancouver Scar Scale (VSS) scores before scar removal and 3 months after the final treatment were compared. RESULTS: The patients received 4.23 treatments on average and were followed up for a mean period of 7.74 months. The mean final VSS was 3.11 ± 1.52 and was significantly lower than that of the previous VSS (9.29 ± 1.74, p = 0.000). VSS of the previous CS scar, and the presence or absence of keloid formation in other areas, was associated with treatment outcome (p = 0.003 and 0.008, respectively). CONCLUSIONS: Early intervention using PDL combined with TAILI could prevent the recurrence or progression of hypertrophic CS scarring after surgical scar removal.

miR-373-3p Regulates Invasion and Migration Abilities of Trophoblast Cells via Targeted CD44 and Radixin.

Preterm labor (PTL) is one of the obstetric complications, and is known to be associated with abnormal maternal inflammatory response and intrauterine inflammation and/or infection. However, the expression of specific miRNAs associated with PTL is not clear. In this study, we performed combination analysis of miRNA array and gene array, and then selected one miRNA (miR-373-3p) and its putative target genes (CD44 and RDX) that exhibited large expression differences in term and PTL placentas with or without inflammation. Using qRT-PCR and luciferase assays, we confirmed that miR-373-3p directly targeted CD44 and RDX. Overexpression of miR-373-3p reduced the migration and invasion of trophoblast cells, while inhibition of miR-373-3p restored the migration and invasion abilities of trophoblast cells. Finally, we validated the expression of miR-373-3p and its target genes in clinical patients' blood. miR-373-3p was increased in PTL patients' blood, and was the most expressed in PTL patients' blood with inflammation. In addition, by targeting the miR-373-3p, CD44 and RDX was decreased in PTL patients' blood, and their expression were the lowest in PTL patients' blood with inflammation. Taken together, these findings suggest that miR-373-3p and its target genes can be potential biomarkers for diagnosis of PTL.

Maternal Hyperglycemia during Pregnancy Increases Adiposity of Offspring.

BACKGROUND: The effect of intrauterine hyperglycemia on fat mass and regional fat proportion of the offspring of mothers with gestational diabetes mellitus (OGDM) remains to be determined. METHODS: The body composition of OGDM (n=25) and offspring of normoglycemic mothers (n=49) was compared using dualenergy X-ray absorptiometry at age 5 years. The relationship between maternal glucose concentration during a 100 g oral glucose tolerance test (OGTT) and regional fat mass or proportion was analyzed after adjusting for maternal prepregnancy body mass index (BMI). RESULTS: BMI was comparable between OGDM and control (median, 16.0 kg/m2 vs. 16.1 kg/m2 ). Total, truncal, and leg fat mass were higher in OGDM compared with control (3,769 g vs. 2,245 g, P=0.004; 1,289 g vs. 870 g, P=0.017; 1,638 g vs. 961 g, P=0.002, respectively), whereas total lean mass was lower in OGDM (15,688 g vs. 16,941 g, P=0.001). Among OGDM, total and truncal fat mass were correlated with fasting and 3-hour glucose concentrations of maternal 100 g OGTT during pregnancy (total fat mass, r=0.49, P=0.018 [fasting], r=0.473, P=0.023 [3-hour]; truncal fat mass, r=0.571, P=0.004 [fasting], r=0.558, P=0.006 [3-hour]), but there was no correlation between OGDM leg fat mass and maternal OGTT during pregnancy. Regional fat indices were not correlated with concurrent maternal 75 g OGTT values. CONCLUSION: Intrauterine hyperglycemia is associated with increased fat mass, especially truncal fat, in OGDM aged 5 years.

Summary of clinically diagnosed amniotic fluid embolism cases in Korea and disagreement with 4 criteria proposed for research purpose.

OBJECTIVE: This study aimed 1) to investigate the clinical characteristics of amniotic fluid embolism (AFE) cases clinically diagnosed by maternal fetal medicine (MFM) specialists in Korea, 2) to check the disagreement with 4 recently proposed criteria by the Society for Maternal-Fetal Medicine (SMFM) for research purpose, and 3) to compare maternal outcomes between cases satisfying all 4 criteria and cases with at least 1 missing criterion. METHODS: This study included 12 patients clinically diagnosed with AFE from 7 referral hospitals in Korea. We collected information, including maternal age, symptoms of AFE, the amount of transfusion, and maternal mortality. RESULTS: The median maternal age was 33 years (range, 28-40 years). Regarding symptoms, cardiovascular arrest, hypotension, respiratory compromise, clinical coagulopathy, and neurologic signs were observed in 41.7%, 83.3%, 83.3%, 100%, and 66.7% of the cases, respectively. Among the 12 cases, 5 women died and 2 suffered severe neurologic disability, showing an intact survival rate of 41.7%. Disagreement with all 4 criteria proposed by the SMFM was found in 66.7% of the cases, due to the lack of criteria for disseminated intravascular coagulation or strict onset time (<30 minutes after delivery). There was no difference in maternal mortality and the amount of transfusion between cases satisfying all 4 criteria and cases with at least 1 missing criterion. CONCLUSION: Two-thirds of clinically confirmed AFE cases did not satisfy all 4 criteria proposed by the SMFM, despite similar rates of maternal mortality with cases satisfying all 4 criteria. Our study suggests that there may be some discrepancy between the clinical diagnosis of AFE and the recent diagnostic criteria proposed by the SMFM for research purpose.

The effect of postoperative vaginal progesterone in ultrasound-indicated cerclage to prevent preterm birth.

OBJECTIVES: To compare pregnancy outcomes according to the use of postoperative vaginal progesterone in patients who underwent ultrasound-indicated cerclage. METHODS: This was a retrospective cohort study of 86 consecutive asymptomatic singleton pregnancies who had undergone cerclage because of incidentally found short cervical length under 20 mm through transvaginal ultrasound between 16°/7 and 246/7 weeks' gestational age. Outcomes were compared according to the use of vaginal progesterone after cerclage. Primary outcome measure was preterm delivery < 34 weeks of gestation. RESULTS: (1) The frequency of preterm delivery < 34 weeks of gestation was significantly lower in patients with postoperative vaginal progesterone than those without (2.2 versus 18.4%, p = .021); (2) the median gestational age at delivery in the postoperative vaginal progesterone group was significantly longer than the control group (38.3 weeks (interquartile range, 37.5-39.1 weeks) versus 37.3 weeks (interquartile range 33.9-38.6 weeks), p = .020); (3) Multivariable logistic regression analysis demonstrated the use of vaginal progesterone after cerclage was found to be independently associated with decrease in preterm delivery before 34 weeks (Odds ratio 0.10; 95% confidence interval, 0.01-0.93) and 37 weeks (Odds ratio 0.24; 95% confidence interval, 0.07-0.85). CONCLUSIONS: The use of vaginal progesterone was associated with lower rates of preterm birth before 34 and 37 weeks of gestation in women who underwent ultrasound-indicated cerclage placement.

A new quantification system for assessing the degree of acute cervical insufficiency based on physical and sonographic examination.

OBJECTIVES: Acute cervical insufficiency accounts for 10-25 % of all mid-trimester pregnancy losses. However, the definition and description for the degree of acute cervical insufficiency were obscure and different among the many studies. The aim of this study was to suggest a new 4-digit quantification system and to evaluate the outcome according to the new system in women with acute cervical insufficiency. STUDY DESIGN: A retrospective cohort study was conducted in patients with acute cervical insufficiency who underwent physical examination indicated cervical cerclage. Acute cervical insufficiency was defined as painless external os dilation with prolapsed and/or visible membranes on speculum examination. The status of fetal membranes was described using two values: 1) size of the prolapsed membrane (P, measured using ultrasound); and 2) size of visible fetal membranes (M, evaluated by speculum examination). The status of cervix was described using two values: 1) dilatation of the narrowest os (O, measured by ultrasound); and 2) functional cervical length (C, measured by ultrasound). The patients were divided into 3 groups as follows: Stage I, patients with visible fetal membranes (M > 0) but with a remaining functional cervix (C > 0) (N = 7); stage II, those with visible fetal membranes (M > 0) and a functional cervical length of 0 but without prolapsed membranes (P = 0) (N = 33); and stage III, those with prolapsed membranes (P > 0) (N = 40). RESULTS: 1) Patients who delivered before 34 weeks of gestation had a significantly lower median gestational age at cerclage operation and a significantly higher median P, M, C values than those who delivered at or beyond 34 weeks of gestation(P < 0.01 for gestational age at operation, P and M values; P < 0.05 for C value); 2) The higher the stage based on PMOC quantification system, the greater the risk of preterm delivery before <24, <32, <34, and <37 weeks of gestation (P < 0.001 for all); 3) The neonatal survival rate was 100 % (7/7) for stage I, 93.9 % (31/33) for stage II, and 60 % (24/40) for stage III. CONCLUSION: The PMOC system was a simple method to describe the individualized conditions and to predict the risk of preterm births in all spectrums of acute cervical insufficiency.

Longitudinal change in arterial stiffness after delivery in women with preeclampsia and normotension: a prospective cohort study.

BACKGROUND: Preeclampsia is associated with increased arterial stiffness during pregnancy. However, data on the longitudinal change in arterial stiffness after delivery in women with preeclampsia are lacking. In this pilot study, we aimed to examine the longitudinal change in arterial stiffness using the cardio-ankle vascular index after delivery in women with preeclamptic and normotensive pregnancies. METHODS: We enrolled pregnant women with preeclampsia (n = 37) and normotension (n = 36) who gave birth at Seoul National University Bundang Hospital between March 2013 and May 2016, and followed-up at day 1, 6 months, and 12 months after delivery. The longitudinal change in the cardio-ankle vascular index and other variables (blood pressure, lipid profiles, serum creatinine, and liver enzymes) were compared between the two groups using the mixed-effects model, and interactions among the main predictors were examined. RESULTS: The longitudinal change in the cardio-ankle vascular index did not significantly differ between the two groups (ß = 0.11, 95% CI: - 0.31-0.54, p = 0.60). Predictors of the longitudinal change in the cardio-ankle vascular index included age, time since delivery, body mass index, and diabetes mellitus. Women with preeclampsia showed significantly elevated blood pressure, lipid profiles, serum creatinine, and liver enzymes compared to women with normotension over the course of 1 year of follow-up. CONCLUSIONS: Preeclampsia is associated with unfavorable blood pressure and metabolic indices after delivery. However, we found no difference in the longitudinal change in arterial stiffness between women with preeclampsia and normotension over the course of 1 year after delivery. TRIAL REGISTRATION: Retrospectively registered at ClinicalTrials.gov on October 29, 2019 ( NCT04142268 ).

Gestational weight gain in twin pregnancies in Korea: application of the 2009 Institute of Medicine recommendations.

OBJECTIVE: To investigate the effect of gestational weight gain (GWG) on maternal and neonatal outcomes based on the Institute of Medicine (IOM) guidelines for twin pregnancies. METHODS: This study included women with twin pregnancies who delivered at Seoul National University Bundang Hospital. Based on the weight gain per gestational week according to the 2009 IOM guidelines, the subjects were divided into the following 3 groups: inadequate, adequate, and excessive GWG. We compared the maternal and neonatal outcomes of each group. RESULTS: A total of 1,738 twin pregnancies were included in our study. Of these cases, 881, 694, and 163 (50.7%, 39.9%, and 9.4%, respectively) twin pregnancies were categorized into the inadequate, adequate, and excessive GWG groups, respectively. In the inadequate GWG group, the risks of preterm birth <34 weeks (aOR, 2.33, 95% confidence interval [CI], 1.63-3.34) and delivering neonates who were small for gestational age (aOR, 1.92, 95% CI, 1.42-2.60) were increased, and the risk of preeclampsia (aOR, 0.49, 95% CI, 0.32-0.76) was decreased. The excessive GWG group had an increased risk of the neonates being large for gestational age (aOR, 1.79, 95% CI, 1.15-2.81). CONCLUSION: The 2009 IOM recommendations for GWG can be applied to Korean women with twin pregnancies to help achieve optimal maternal and neonatal outcomes. However, more than half of the women were categorized as having inadequate weight gain according to the guidelines. Further studies should be performed to obtain Korean national references for GWG in twin pregnancies.

High-risk human papillomavirus testing as a primary screening for cervical cancer: position statement by the Korean Society of Obstetrics and Gynecology and the Korean Society of Gynecologic Oncology.

Based on emerging data and current knowledge regarding high-risk human papillomavirus (hrHPV) testing as a primary screening for cervical cancer, the Korean Society of Obstetrics and Gynecology and the Korean Society of Gynecologic Oncology support the following scientific facts: • Compared to cytology, hrHPV screening has higher sensitivity and detects more cases of high-grade cervical intraepithelial neoplasia. • Qualified hrHPV testing can be considered as an alternative primary screening for cervical cancer to the current cytology method. • The starting age of primary hrHPV screening should not be before 25 years because of possible overtreatment in this age, which has a high human papillomavirus (HPV) prevalence but rarely progresses to cancer. The screening interval should be no sooner than every 3 years and no longer than every 5 years. • Before the introduction of hrHPV screening in Korea, research into comparative effectiveness of primary hrHPV screening for cervical cancer should be conducted to determine the appropriate HPV assay, starting age, and screening interval.

Subsequent pregnancy outcomes according to the presence of acute histologic chorioamnionitis in women with spontaneous preterm delivery.

OBJECTIVE: To compare subsequent pregnancy outcomes according to the presence of acute histologic chorioamnionitis (HCA) in women with spontaneous preterm delivery (SPTD). METHODS: Among 1,706 women who gave birth twice or more at our institution, 138 women delivered spontaneously at preterm (<37.0 weeks). Subsequent deliveries occurred at our institution and placental biopsy results were available. The study population was categorized into 2 groups based on the presence of acute HCA at the time of SPTD: HCA group (n=52) and non-HCA group (n=86). The primary outcome measures were gestational age at delivery, birthweight, and frequency of preterm delivery in subsequent pregnancies. RESULTS: The median gestational age at the time of SPTD was 34.0 weeks (interquartile range [IQR], 28.9-35.3 weeks), and the frequency of acute HCA was 52/138 (38%). There were no differences in gestational age at delivery, birthweight, and frequency of preterm delivery between the HCA group and non-HCA group (median gestational age at delivery, 38.0 weeks (IQR, 36.7-38.8 weeks) in the HCA group vs. 37.9 weeks (IQR, 35.7-39.0 weeks) in the non-HCA group; frequency of preterm delivery, 14/52 (27%) in the HCA group vs. 33/86 (38%) in the non-HCA group; and median birthweight, 3.14 kg (IQR, 2.64-3.45 kg) in the HCA group vs. 2.95 kg (IQR, 2.44-3.36 kg) in the non-HCA group; P>0.1 for all. CONCLUSION: The presence of acute HCA in women at prior SPTD did not significantly affect their subsequent pregnancy outcomes.

A new rapid bedside test to diagnose and monitor intraamniotic inflammation in preterm PROM using transcervically collected fluid.

BACKGROUND: Microbial invasion of the amniotic cavity, a clinical condition present in approximately 50% of patients with preterm prelabor rupture of membranes, is often associated with intraamniotic inflammation, a risk factor for a short admission-to-delivery interval, early preterm delivery, and neonatal complications. We previously developed a transcervical amniotic fluid collector, the device that allows the collection of fluid noninvasively from the cervical canal when membrane rupture occurs. OBJECTIVE: This study was designed to determine whether rapid analysis of an interleukin-8 concentration in fluid obtained noninvasively by the transcervical amniotic fluid collector can be used to assess the risk of intraamniotic inflammation. We also compared the diagnostic performance of this point-of-care test for interleukin-8 in transcervically obtained fluid to that of a white blood cell count determined in amniotic fluid retrieved by transabdominal amniocentesis. STUDY DESIGN: This prospective cohort study was conducted between October 2011 and April 2017. Fluid was retrieved through both transabdominal amniocentesis and the use of a transcervical amniotic fluid collector within 24 hours of amniocentesis in patients with a singleton pregnancy and preterm prelabor rupture of the membranes (16-35 weeks of gestation). Amniotic fluid obtained via amniocentesis was cultured for aerobic and anaerobic bacteria and genital mycoplasmas; a white blood cell count was also measured in amniotic fluid. Intraamniotic infection was diagnosed when microorganisms were identified by the cultivation of amniotic fluid. Intraamniotic inflammation was defined as an elevated amniotic fluid matrix metalloproteinase-8 concentration (>23 ng/mL) assayed by enzyme-linked immunosorbent assay. Interleukin-8 in cervical fluid obtained by the collector was measured by the point-of-care test that used a test strip and scanner based on the fluorescence immunochromatographic analysis in 2019. The diagnostic indices, predictive values, and likelihood ratios of the 2 different tests were calculated. RESULTS: First, interleukin-8 concentration ≥9.5 ng/mL in cervical fluid, determined by the point-of-care test, was at the knee of the receiver operating characteristic curve analysis and had a sensitivity of 98% (56/57; 95% confidence interval, 91-99.96%), specificity of 74% (40/54; 95% confidence interval, 60-85%), positive predictive value of 80% (56/70; 95% confidence interval, 72-86%), negative predictive value of 98% (40/41; 95% confidence interval, 85-99.6%), positive likelihood ratio of 3.79 (95% confidence interval, 2.41-5.96), and negative likelihood ratio of 0.02 (95% confidence interval, 0.003-0.17) in the identification of intraamniotic inflammation; a concentration of matrix metalloproteinase-8 >23 ng/mL by enzyme-linked immunosorbent assay had a prevalence of 51% (57/111). Second, a cervical fluid interleukin-8 concentration ≥9.5 ng/mL had significantly higher sensitivity than a transabdominally obtained amniotic fluid white blood cell count (≥19 cells/mm3) in the identification of intraamniotic inflammation (sensitivity: 98% [95% confidence interval, 91-99.96%] vs 84% [95% confidence interval, 72-93%]; P<.05; specificity: 74% [95% confidence interval, 60-85%] vs 76% [95% confidence interval, 62-87%); positive and negative predictive values: 80% [95% confidence interval, 72-86%] and 98% [95% confidence interval, 85-99.6%] vs 79% [95% confidence interval, 69-86%] and 82% [95% confidence interval, 71-89%]) and in the identification of intraamniotic inflammation/infection (gold standard: positive culture for bacteria or a matrix metalloproteinase-8 >23 ng/mL; sensitivity: 91% [95% confidence interval, 82-97%] vs 75% [95% confidence interval, 63-85%]; P<.05). CONCLUSION: The point-of-care test was predictive of intraamniotic inflammation, based on the determination of interleukin-8 in fluid retrieved by a transcervical amniotic fluid collector. Therefore, the analysis of cervically obtained fluid by such point-of-care test may be used to noninvasively monitor intraamniotic inflammation in patients with preterm prelabor rupture of membranes.

Identification of microRNAs and their target genes in the placenta as biomarkers of inflammation.

OBJECTIVE: Recently, microRNA (miRNA) has been identified both as a powerful regulator involved in various biological processes through the regulation of numerous genes and as an effective biomarker for the prediction and diagnosis of various disease states. The objective of this study was to identify and validate miRNAs and their target genes involved in inflammation in placental tissue. METHODS: Microarrays were utilized to obtain miRNA and gene expression profiles from placentas with or without inflammation obtained from nine normal pregnant women and 10 preterm labor patients. Quantitative real-time polymerase chain reaction and Western blots were performed to validate the miRNAs and differentially-expressed genes in the placentas with inflammation. Correlations between miRNA and target gene expression were confirmed by luciferase assays in HTR-8/SVneo cells. RESULTS: We identified and validated miRNAs and their target genes that were differentially expressed in placentas with inflammation. We also demonstrated that several miRNAs (miR-371a-5p, miR-3065-3p, miR-519b-3p, and miR-373-3p) directly targeted their target genes (LEF1, LOX, ITGB4, and CD44). However, some miRNAs and their direct target genes showed no correlation in tissue samples. Interestingly, miR-373-3p and miR-3065-3p were markedly regulated by lipopolysaccharide (LPS) treatment, although the expression of their direct targets CD44 and LOX was not altered by LPS treatment. CONCLUSION: These results provide candidate miRNAs and their target genes that could be used as placental biomarkers of inflammation. These candidates may be useful for further miRNA-based biomarker development.

High-risk human papillomavirus testing as a primary screening for cervical cancer: position statement by the Korean Society of Obstetrics and Gynecology and the Korean Society of Gynecologic Oncology.

Based on emerging data and current knowledge regarding high-risk human papillomavirus (hrHPV) testing as a primary screening for cervical cancer, the Korean Society of Obstetrics and Gynecology and the Korean Society of Gynecologic Oncology support the following scientific facts: • Compared to cytology, hrHPV screening has higher sensitivity and detects more cases of high-grade cervical intraepithelial neoplasia. • Qualified hrHPV testing can be considered as an alternative primary screening for cervical cancer to the current cytology method. • The starting age of primary hrHPV screening should not be before 25 years because of possible overtreatment in this age, which has a high human papillomavirus (HPV) prevalence but rarely progresses to cancer. The screening interval should be no sooner than every 3 years and no longer than every 5 years. • Before the introduction of hrHPV screening in Korea, research into comparative effectiveness of primary hrHPV screening for cervical cancer should be conducted to determine the appropriate HPV assay, starting age, and screening interval.

Umbilical cord-derived mesenchymal stem cell extracts ameliorate atopic dermatitis in mice by reducing the T cell responses.

Mesenchymal stem cells derived from Wharton's jelly of the umbilical cord (UC-MSCs) have immunomodulatory properties. The aim of this study was to explore whether extracts of MSCs (MSC-Ex) could augment the low therapeutic efficacy of the whole cells in an Aspergillus fumigatus (Af)-induced atopic dermatitis (AD) model. LPS- or TNF-α/IFN-γ-stimulated keratinocytes (HaCaT cells) were treated with MSC-Ex, and the Af-induced AD model was established in BALB/c mice. In HaCaT cells, MSC-Ex treatment significantly reduced the inflammatory cytokine (IL-6, IL-1ß, IL-4, IL-5 and TNF-α), iNOS and NF-κB levels, and upregulated the anti-inflammatory cytokines (IL-10 and TGF-ß1). In the AD mice, the MSC-Ex group showed greatly reduced dermatitis, and lower clinical symptom scores and IgE levels. The histological dermatitis scores were also markedly lower in the MSC-Ex-treated animals compared with the MSC-treated group. Decreased levels of IFN-γ (Th1) and IL-17 (Th17), IL-4 and IL-13 (Th2) were detected in T cells and the skin tissue from the MSC-Ex treated AD mice. The therapeutic capacity of MSC-Ex was preserved after lyophilization and reconstitution. MSC-Ex treatment reproducibly suppresses dermatitis and inhibits the induction of inflammatory cytokines in the skin of AD mice. MSC-Ex is therefore a potential new treatment agent for AD.

The earlier the gestational age, the greater the intensity of the intra-amniotic inflammatory response in women with preterm premature rupture of membranes and amniotic fluid infection by Ureaplasma species.

Objectives To determine the relationship between the intensity of the intra-amniotic inflammatory response and the gestational age at the time of diagnosis in cases with preterm premature rupture of membranes (PROM) and intra-amniotic infection caused by Ureaplasma spp. Methods A retrospective cohort study was conducted which included 71 women with preterm PROM and a positive amniotic fluid culture with Ureaplasma spp. Women with mixed intra-amniotic infections were excluded. The study population was classified into three groups according to gestational age: group 1, <26 weeks (extreme preterm PROM, n = 17); group 2, 26.0-33.9 weeks (moderate preterm PROM, n = 39); group 3, 34.0-36.9 weeks (late preterm PROM, n = 15). The intensity of the intra-amniotic and maternal inflammatory response was compared among the three groups. The intensity of the intra-amniotic inflammatory response was assessed by the concentration of amniotic fluid matrix metalloproteinase-8 (MMP-8) and white blood cell (WBC) count. The maternal inflammatory response was assessed by the concentration of C-reactive protein (CRP) and WBC count in maternal blood at the time of amniocentesis. Results (1) The median values of amniotic fluid MMP-8 concentration and WBC count were the highest in the extreme preterm PROM group and the lowest in the late preterm PROM group (P < 0.001 and P = 0.01, respectively); (2) the intensity of the maternal inflammatory response measured by maternal blood WBC count and CRP concentration was not significantly associated with gestational age at the time of diagnosis. Conclusion The earlier the gestational age at the time of PROM, the higher the intensity of the intra-amniotic inflammatory response in women with preterm PROM and intra-amniotic infection caused by Ureaplasma spp.

Evidence that antibiotic administration is effective in the treatment of a subset of patients with intra-amniotic infection/inflammation presenting with cervical insufficiency.

BACKGROUND: Cervical insufficiency is a risk factor for spontaneous midtrimester abortion or early preterm birth. Intra-amniotic infection has been reported in 8-52% of such patients and intra-amniotic inflammation in 81%. Some professional organizations have recommended perioperative antibiotic treatment when emergency cervical cerclage is performed. The use of prophylactic antibiotics is predicated largely on the basis that they reduce the rate of complications during the course of vaginal surgery. However, it is possible that antibiotic administration can also eradicate intra-amniotic infection/inflammation and improve pregnancy outcome. OBJECTIVE: To describe the outcome of antibiotic treatment in patients with cervical insufficiency and intra-amniotic infection/inflammation. STUDY DESIGN: The study population consisted of 22 women who met the following criteria: (1) singleton pregnancy; (2) painless cervical dilatation of >1 cm between 16.0 and 27.9 weeks of gestation; (3) intact membranes and absence of uterine contractions; (4) transabdominal amniocentesis performed for the evaluation of the microbiologic and inflammatory status of the amniotic cavity; (5) presence of intra-amniotic infection/inflammation; and (6) antibiotic treatment (regimen consisted of ceftriaxone, clarithromycin, and metronidazole). Amniotic fluid was cultured for aerobic and anaerobic bacteria and genital mycoplasmas, and polymerase chain reaction for Ureaplasma spp. was performed. Intra-amniotic infection was defined as a positive amniotic fluid culture for microorganisms or a positive polymerase chain reaction for Ureaplasma spp., and intra-amniotic inflammation was suspected when there was an elevated amniotic fluid white blood cell count (≥19 cells/mm3) or a positive rapid test for metalloproteinase-8 (sensitivity 10 ng/mL). For the purpose of this study, the "gold standard" for diagnosis of intra-amniotic inflammation was an elevated interleukin-6 concentration (>2.6 ng/mL) using an enzyme-linked immunosorbent assay. The results of amniotic fluid interleukin-6 were not available to managing clinicians. Follow-up amniocentesis was routinely offered to monitor the microbiologic and inflammatory status of the amniotic cavity and fetal lung maturity. Treatment success was defined as resolution of intra-amniotic infection/inflammation or delivery ≥34 weeks of gestation. RESULTS: Of 22 patients with cervical insufficiency and intra-amniotic infection/inflammation, 3 (14%) had microorganisms in the amniotic fluid. Of the 22 patients, 6 (27%) delivered within 1 week of amniocentesis and the remaining 16 (73%) delivered more than 1 week after the diagnostic procedure. Among these, 12 had a repeat amniocentesis to assess the microbial and inflammatory status of the amniotic cavity; in 75% (9/12), there was objective evidence of resolution of intra-amniotic inflammation or intra-amniotic infection demonstrated by analysis of amniotic fluid at the time of the repeat amniocentesis. Of the 4 patients who did not have a follow-up amniocentesis, all delivered ≥34 weeks, 2 of them at term; thus, treatment success occurred in 59% (13/22) of cases. CONCLUSION: In patients with cervical insufficiency and intra-amniotic infection/inflammation, administration of antibiotics (ceftriaxone, clarithromycin, and metronidazole) was followed by resolution of the intra-amniotic inflammatory process or intra-amniotic infection in 75% of patients and was associated with treatment success in about 60% of cases.

Antibiotic administration can eradicate intra-amniotic infection or intra-amniotic inflammation in a subset of patients with preterm labor and intact membranes.

BACKGROUND: Intra-amniotic infection is present in 10% of patients with an episode of preterm labor, and is a risk factor for impending preterm delivery and neonatal morbidity/mortality. Intra-amniotic inflammation is often associated with intra-amniotic infection, but is sometimes present in the absence of detectable microorganisms. Antibiotic treatment of intra-amniotic infection has traditionally been considered to be ineffective. Intra-amniotic inflammation without microorganisms has a prognosis similar to that of intra-amniotic infection. OBJECTIVE: To determine whether antibiotics can eradicate intra-amniotic infection or intra-amniotic inflammation in a subset of patients with preterm labor and intact membranes. MATERIALS AND METHODS: The study population consisted of women who met the following criteria: 1) singleton gestation between 20 and 34 weeks; 2) preterm labor and intact membranes; 3) transabdominal amniocentesis performed for the evaluation of the microbiologic/inflammatory status of the amniotic cavity; 4) intra-amniotic infection and/or intra-amniotic inflammation; and 5) received antibiotic treatment that consisted of ceftriaxone, clarithromycin, and metronidazole. Follow-up amniocentesis was performed in a subset of patients. Amniotic fluid was cultured for aerobic and anaerobic bacteria and genital mycoplasmas, and polymerase chain reaction was performed for Ureaplasma spp. Intra-amniotic infection was defined as a positive amniotic fluid culture or positive polymerase chain reaction, and intra-amniotic inflammation was suspected when there was an elevated amniotic fluid white blood cell count or a positive result of a rapid test for matrix metalloproteinase-8. For this study, the final diagnosis of intra-amniotic inflammation was made by measuring the interleukin-6 concentration in stored amniotic fluid (>2.6 ng/mL). These results were not available to managing clinicians. Treatment success was defined as eradication of intra-amniotic infection and/or intra-amniotic inflammation or delivery ≥37 weeks. RESULTS: Of 62 patients with intra-amniotic infection and/or intra-amniotic inflammation, 50 received the antibiotic regimen. Of those patients, 29 were undelivered for ≥7 days and 19 underwent a follow-up amniocentesis. Microorganisms were identified by culture or polymerase chain reaction of amniotic fluid obtained at admission in 21% of patients (4/19) who had a follow-up amniocentesis, and were eradicated in 3 of the 4 patients. Resolution of intra-amniotic infection/inflammation was confirmed in 79% of patients (15/19), and 1 other patient delivered at term, although resolution of intra-amniotic inflammation could not be confirmed after a follow-up amniocentesis. Thus, resolution of intra-amniotic inflammation/infection or term delivery (treatment success) occurred in 84% of patients (16/19) who had a follow-up amniocentesis. Treatment success occurred in 32% of patients (16/50) with intra-amniotic infection/inflammation who received antibiotics. The median amniocentesis-to-delivery interval was significantly longer among women who received the combination of antibiotics than among those who did not (11.4 days vs 3.1 days: P = .04). CONCLUSION: Eradication of intra-amniotic infection/inflammation after treatment with antibiotics was confirmed in 79% of patients with preterm labor, intact membranes, and intra-amniotic infection/inflammation who had a follow-up amniocentesis. Treatment success occurred in 84% of patients who underwent a follow-up amniocentesis and in 32% of women who received the antibiotic regimen.