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.

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.

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 ).

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.

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.

A high concentration of fetal fibronectin in cervical secretions increases the risk of intra-amniotic infection and inflammation in patients with preterm labor and intact membranes.

Objective To determine whether the risk of intra-amniotic infection/inflammation and spontaneous preterm delivery (SPTD) varies as a function of the concentration of cervical fetal fibronectin (fFN) in patients with preterm labor and intact membranes. Methods This prospective study included 180 patients with preterm labor and intact membranes who had a sample collected for quantitative fFN measurement and underwent amniocentesis. Amniotic fluid was cultured for aerobic and anaerobic bacteria and genital mycoplasmas. Intra-amniotic inflammation was defined as an amniotic fluid matrix metalloproteinase-8 concentration >23 ng/mL. Results (1) The prevalence of intra-amniotic infection/inflammation and SPTD within 7 days was 32.2% (58/180) and 33.9% (61/178), respectively; (2) The higher the fFN concentration, the greater the risk of intra-amniotic infection/inflammation and SPTD within 7 days (P<0.001, respectively); (3) An fFN concentration 150 ng/mL had a better diagnostic performance than an fFN 50 ng/mL in the identification of intra-amniotic infection/inflammation and SPTD within 7 days; (4) Among the patients with an fFN <50 ng/mL, intra-amniotic infection/inflammation was identified in 7.6% (6/79) of patients and 66.7% (4/6) delivered within 7 days. Conclusion The higher the concentration of fFN, the greater the risk of intra-amniotic infection/inflammation and SPTD in patients with preterm labor and intact membranes.

Addition of Cervical Elastography May Increase Preterm Delivery Prediction Performance in Pregnant Women with Short Cervix: a Prospective Study.

BACKGROUND: We investigated whether there is a difference in elastographic parameters between pregnancies with and without spontaneous preterm delivery (sPTD) in women with a short cervix (≤ 25 mm), and examined the ability of elastographic parameters to predict sPTD in those women. METHODS: E-CervixTM (WS80A; Samsung Medison, Seoul, Korea) elastography was used to examine the cervical strain. Elastographic parameters were compared between pregnancies with and without sPTD. Diagnostic performance of elastographic parameters to predict sPTD ≤ 37 weeks, both alone and in combination with other parameters, was compared with that of cervical length (CL) using area under receiver operating characteristic curve (AUC) analysis. RESULTS: A total of 130 women were included. Median gestational age (GA) at examination was 24.4 weeks (interquartile range, 21.4-28.9), and the prevalence of sPTD was 20.0% (26/130). Both the elastographic parameters and CL did not show statistical difference between those with and without sPTD. However, when only patients with CL ≥ 1.5 cm (n = 110) were included in the analysis, there was a significant difference between two groups in elasticity contrast index (ECI) within 0.5/1.0/1.5 cm from the cervical canal (P < 0.05) which is one of elastographic parameters generated by E-Cervix. When AUC analysis was performed in women with CL ≥ 1.5 cm, the combination of parameters (CL + pre-pregnancy body mass index + GA at exam + ECI within 0.5/1.0/1.5 cm) showed a significantly higher AUC than CL alone (P < 0.05). CONCLUSION: An addition of cervical elastography may improve the ability to predict sPTD in women with a short CL between 1.5 and 2.5 cm.

Pregnancy in women with immunoglobulin A nephropathy: are obstetrical complications associated with renal prognosis?

Background: Recent studies regarding immunoglobulin A nephropathy (IgAN) suggest no relationship between pregnancy and disease progression, although complicated pregnancies and impaired renal function are closely related. Methods: This study used a propensity-score-matched cohort analysis. Among biopsy-confirmed IgAN women in three hospitals in Korea, those who experienced pregnancy after their diagnosis were included in the study group. Renal outcome was the composite of serum creatinine doubling, estimated glomerular filtration rate (eGFR) halving and events of end-stage renal disease. Pregnancies with preterm birth, low birth weight and pre-eclampsia were defined as complicated. Results: Overall, 59 IgAN women who became pregnant after their diagnosis, and the same number of IgAN women who did not experience pregnancy were included in the control group. Although pregnancy itself did not worsen renal outcomes [adjusted hazard ratio (HR): 1.51; 95% confidence interval (CI) 0.57-4.01; P = 0.41], mothers with complicated pregnancies experienced worse renal prognosis, even after adjustment for baseline and pre-gestational characteristics (adjusted HR: 5.07; 95% CI 1.81-14.22; P = 0.002). Moreover, this relationship was only significant in mothers with decreased renal function (eGFR <60 mL/min/1.73 m2) (adjusted HR: 18.70; 95% CI 1.63-214.40; P = 0.02), baseline hypertension (adjusted HR: 4.17; 95% CI 1.13-15.33; P = 0.03) and overt proteinuria (≥1 g/day) (adjusted HR: 4.21; 95% CI 1.24-14.27; P = 0.02). In contrast, patients who experienced pregnancies without complications showed better renal outcomes than did those without post-biopsy pregnancy (P = 0.01). Conclusion: Obstetric complications in patients with high renal risk, rather than pregnancy itself, are associated with renal progression of IgAN women.

Gestational Estimated Glomerular Filtration Rate and Adverse Maternofetal Outcomes.

BACKGROUND/AIMS: The association between gestational estimated glomerular filtration rate (eGFR) and adverse pregnancy outcomes has not been fully investigated. METHODS: This observational cohort study included pregnancy cases of singleton mothers whose serum creatinine levels were measured during pregnancy at two tertiary hospitals in Korea from 2000 to 2015. Those with identified substantial renal function impairment (eGFR < 60 mL/min/1.73 m2 at baseline, during, or after pregnancy) were excluded. The Chronic Kidney Disease Epidemiology Collaboration equation was used for the eGFR calculation. We computed the time-averaged eGFR during gestation to determine representative values when there were multiple measurements. We studied the following three gestational complications: preterm birth (< 37 weeks' gestational age), low birth weight (< 2.5 kg), and preeclampsia. RESULTS: Among the 12,899 studied pregnancies, 4,360 cases experienced one or more gestational complications. The adjusted odds ratio (aOR) and 95% confidence interval of composite gestational complications for eGFR ranges other than the reference range of 120-150 mL/ min/1.73m2 were: ≥150 mL/min/1.73m2, aOR 1.64 (1.38-1.95), P< 0.001; 90-120 mL/min/1.73m2, aOR 1.41 (1.28-1.56), P< 0.001; and 60-90 mL/min/1.73m2, aOR 2.56 (1.70-3.84), P< 0.001. Incidence of preterm birth or low birth weight showed similar U-shaped association with eGFR values; otherwise, preeclampsia or small for gestational age occurred more often in mothers with a lower gestational eGFR than in those with a higher value. CONCLUSION: Considering the unique association between gestational eGFR and pregnancy outcomes, carefully interpreting these results may help predict obstetric complications.

Outcomes of physical examination-indicated cerclage in twin pregnancies with acute cervical insufficiency compared to singleton pregnancies.

Objectives To compare pregnancy outcomes of physical examination-indicated cerclage in twin pregnancies with acute cervical insufficiency with that of singletons. Methods This retrospective cohort study included 88 consecutive women (17 twins and 71 singletons) who had undergone physical examination-indicated cerclage because of acute cervical insufficiency (defined as painless cervical dilation with (1) prolapsed and/or visible membranes at the external cervical os on speculum examination and (2) a functional cervical length of zero on transvaginal ultrasound) between 160/7 and 236/7 weeks. The primary outcome measure was preterm delivery <34 weeks. Results (1) The frequency of preterm delivery <34 weeks was not significantly different between the two groups [twins, 56% (9/16) vs. singleton, 53% (37/70), P>0.999]. (2) The perinatal mortality was 21% (7/34) in twins and 32% (23/71) in singletons. (3) The median gestational age at delivery for twin pregnancies was 31.0 weeks (IQR, 22.6-36.5 weeks), which was similar to that of singleton pregnancies (median 32.4 weeks; IQR 22.3-38.3 weeks). (4) There were no significant differences in preterm delivery before 28 and 32 weeks, interval from cerclage to delivery within 1, 2, 4 and 8 weeks and neonatal morbidities between the two groups. Conclusion The obstetric and neonatal outcomes of physical examination-indicated cerclage in twin pregnancies were comparable to those in singleton pregnancies.

The combined exposure to intra-amniotic inflammation and neonatal respiratory distress syndrome increases the risk of intraventricular hemorrhage in preterm neonates.

OBJECTIVE: To evaluate the impact of combined exposure to intra-amniotic inflammation and neonatal respiratory distress syndrome (RDS) on the development of intraventricular hemorrhage (IVH) in preterm neonates. METHODS: This retrospective cohort study includes 207 consecutive preterm births (24.0-33.0 weeks of gestation). Intra-amniotic inflammation was defined as an amniotic fluid matrix metalloproteinase-8 concentration >23 ng/mL. According to McMenamin's classification, IVH was defined as grade II or higher when detected by neurosonography within the first weeks of life. RESULTS: (1) IVH was diagnosed in 6.8% (14/207) of neonates in the study population; (2) IVH was frequent among newborns exposed to intra-amniotic inflammation when followed by postnatal RDS [33% (6/18)]. The frequency of IVH was 7% (8/115) among neonates exposed to either of these conditions - intra-amniotic inflammation or RDS - and 0% (0/64) among those who were not exposed to these conditions; and (3) Neonates exposed to intra-amniotic inflammation and postnatal RDS had a significantly higher risk of IVH than those with only intra-amniotic inflammation [odds ratio (OR) 4.6, 95% confidence interval (CI) 1.1-19.3] and those with RDS alone (OR 5.6, 95% CI 1.0-30.9), after adjusting for gestational age. CONCLUSION: The combined exposure to intra-amniotic inflammation and postnatal RDS markedly increased the risk of IVH in preterm neonates.

Twenty-four percent of patients with clinical chorioamnionitis in preterm gestations have no evidence of either culture-proven intraamniotic infection or intraamniotic inflammation.

BACKGROUND: Recent studies on clinical chorioamnionitis at term suggest that some patients with this diagnosis have neither intraamniotic infection nor intraamniotic inflammation. A false-positive diagnosis of clinical chorioamnionitis in preterm gestation may lead to unwarranted preterm delivery. OBJECTIVE: We sought to determine the frequency of intraamniotic inflammation and microbiologically proven amniotic fluid infection in patients with preterm clinical chorioamnionitis. STUDY DESIGN: Amniocentesis was performed in singleton pregnant women with preterm clinical chorioamnionitis (<36 weeks of gestation). Amniotic fluid was cultured for aerobic and anaerobic bacteria and genital mycoplasmas and assayed for matrix metalloproteinase-8 concentration. Microbial invasion of the amniotic cavity was defined as a positive amniotic fluid culture; intraamniotic inflammation was defined as an elevated amniotic fluid matrix metalloproteinase-8 concentration of >23 ng/mL. Nonparametric and survival techniques were used for analysis. RESULTS: Among patients with preterm clinical chorioamnionitis, 24% (12/50) had neither microbiologic evidence of intraamniotic infection nor intraamniotic inflammation. Microbial invasion of the amniotic cavity was present in 34% (18/53) and intraamniotic inflammation in 76% (38/50) of patients. The most common microorganisms isolated from the amniotic cavity were the Ureaplasma species. Finally, patients without microbial invasion of the amniotic cavity or intraamniotic inflammation had significantly lower rates of adverse outcomes (including lower gestational age at delivery, a shorter amniocentesis-to-delivery interval, acute histologic chorioamnionitis, acute funisitis, and significant neonatal morbidity) than those with microbial invasion of the amniotic cavity and/or intraamniotic inflammation. CONCLUSION: Among patients with preterm clinical chorioamnionitis, 24% had no evidence of either intraamniotic infection or intraamniotic inflammation, and 66% had negative amniotic fluid cultures, using standard microbiologic techniques. These observations call for a reexamination of the criteria used to diagnose preterm clinical chorioamnionitis.

Differential immunophenotype of macrophages in acute and chronic chorioamnionitis.

AIM: The aim of this study was to investigate the involvement and immunophenotype of macrophages in acute chorioamnionitis (ACA) and chronic chorioamnionitis (CCA), marking amniotic fluid infection and anti-fetal rejection, respectively. METHODS: Chorioamniotic membranes from (1) gestational age-matched cases without chorioamnionitis, (2) cases with ACA, and (3) cases with CCA were studied after immunohistochemical staining using antibodies against CD14, CD68, CD163, and DC-SIGN. RESULTS: Macrophages increased prominently in the chorionic trophoblastic layer of both ACA and CCA cases in contrast to non-inflammatory cases. Macrophages in the decidua and the chorioamniotic membranes of ACA cases expressed CD14. Macrophages in the chorionic trophoblastic layer of CCA cases were characterized by CD68 positivity. DC-SIGN-positive cells were increased in the chorioamniotic mesodermal layer of CCA cases. CONCLUSIONS: Macrophages participate in the inflammatory response in ACA and CCA. The differential immunophenotypes of macrophages in the decidua and chorioamniotic membranes of ACA and CCA cases suggest their disease-specific and region-specific roles at the feto-maternal interface.

Can coagulopathy in post-partum hemorrhage predict maternal morbidity?

AIM: The purpose of this study was to evaluate the clinical implications of coagulopathy in women with post-partum hemorrhage (PPH). METHODS: This retrospective cohort study included 262 consecutive women referred for management of PPH at a single tertiary hospital between 2009 and 2012. We reviewed medical records, including vital signs at arrival, laboratory values (hemoglobin, prothrombin time international normalized ratio [PT-INR], platelet, fibrinogen), and total amount of transfused blood product. Results of arterial embolization, need for hysterectomy, and significant morbidity such as pulmonary edema, endometritis or brain lesions were reviewed. Multivariate logistic analysis was used to identify risk of massive transfusion and significant morbidity. RESULTS: The prevalence of coagulopathy (PT-INR > 1.5) was 29.3% (77/262). Of the 262 women, pelvic arterial embolization was performed in 153 women, and was successful in 146 (95.4%). Hysterectomy was performed in 18 women (6.2%). The presence of coagulopathy led to increased risk for massive transfusion (odds ratio [OR], 23.96; 95%CI: 11.65-49.27), hysterectomy (OR, 9.94; 95%CI: 3.16-31.33), and significant morbidity (OR, 9.37; 95%CI: 4.95-17.75). Even after adjusting for other confounding factors, coagulopathy was independently associated with massive transfusion (adjusted OR, 12.24; 95%CI: 4.49-14.28), hysterectomy (adjusted OR, 4.66; 95%CI: 1.12-19.48), and significant morbidity (adjusted OR, 4.67; 95%CI: 2.05-10.64). CONCLUSION: Coagulopathy in PPH is the single most important predictor for massive transfusion and hysterectomy, and is related to maternal morbidity.

Addition of adjuvant progesterone to physical-exam-indicated cervical cerclage to prevent preterm birth.

AIM: The aim of this study was to assess the effect of vaginal progesterone as an adjuvant therapy to physical-exam-indicated cervical cerclage (PEICC). METHODS: This retrospective cohort study included 53 consecutive singleton women who underwent PEICC because of acute cervical insufficiency at 17-24 gestational weeks. The study population was divided into two groups: the adjuvant progesterone group (n = 18) and the non-adjuvant group (n = 35). A 200-mg dose of vaginal micronized natural progesterone was administered after cerclage in the adjuvant progesterone group. Primary outcome measure was spontaneous preterm birth (SPTB) at <36 weeks. RESULTS: The SPTB rate at <36 weeks in the adjuvant group was significantly lower than in the non-adjuvant group (17% vs 51%, P < 0.05). Adjuvant progesterone therapy was significantly associated with a reduction in SPTB at <36 weeks (adjusted odds ratio, 0.12; 95% confidence interval, 0.02-0.69, P < 0.05) even after adjusting for known covariates, including a visible membrane size of ≥4 cm, gestational age, prior SPTB, and use of amnioreduction. The frequency of SPTB at <32 weeks, birthweight < 2500 g, and neonatal intensive care unit admission was significantly lower in the adjuvant progesterone group than in the non-adjuvant group (P < 0.05 for all). CONCLUSION: Adjuvant vaginal progesterone therapy with PEICC was associated with reductions in SPTB, low birthweight, and neonatal intensive care unit admission.

Ultrasonographic severity scoring of non-immune hydrops: a predictor of perinatal mortality.

AIM: To develop an ultrasonographic severity scoring of non-immune hydrops in order to predict perinatal outcomes in women with non-immune hydrops. METHODS: The study population consisted of pregnant women who were admitted and delivered with the diagnosis of fetal non-immune hydrops and singleton gestation. Cases were divided into "perinatal survivor" and "perinatal non-survivor" groups. Perinatal non-survivor cases were defined as those with stillbirth or neonatal death ≤28 completed days after birth. The presence of an abnormal fluid collection in each body compartment, such as subcutaneous edema, pleural effusion, pericardial effusion, or ascites was assigned a score of 1 point per each body compartment, and the absence of abnormal fluid collection was scored as 0 point. The total number of abnormal fluid collections was converted to a numeric score, which was called the ultrasonographic severity scoring of non-immune hydrops (USNIH). RESULTS: Perinatal death occurred in 46.5% (20/43) of the cases of non-immune hydrops. USNIH in patients of the non-survivor group was significantly higher than that in those of the survivor group [non-survivor group 3 (2-4) vs. survivor 2 (2-3); median (range); P<0.05]. Perinatal mortality rates were higher in patients with USNIH ≥3 points than in those with USNIH of 2 points (67% vs. 13%, P<0.005). This difference remained significant after adjustment for confounding variables. When confining analysis to those with idiopathic non-immune hydrops, women in the perinatal non-survivor group had significantly higher USNIH score than those in the perinatal survivor group, and this difference remained significant after adjustment. CONCLUSIONS: Our USNIH system may be a reliable predictive marker for perinatal outcomes in cases of non-immune hydrops, especially in idiopathic hydrops during the antenatal period.

Incidence and risk factors of symptomatic peripartum diastasis of pubic symphysis.

This study was undertaken to determine incidence, associated risk factors, and clinical outcomes of a diastasis of pubic symphysis. Among 4,151 women, who delivered 4,554 babies at the Department of Obstetrics of Seoul National University Bundang hospital from January 2004 to December 2006, eleven women were diagnosed as having a symptomatic diastasis of pubic symphysis. We estimated the incidence of the diastasis and identified the associated risk factors. To evaluate the pain relief and reduction of diastasis we followed up the 11 diastatic patients. The incidence of the diastasis was 1/385. Primiparity (P = 0.010) and twin gestation (P = 0.016) appeared as risk factors for diastasis by univairable analysis; and twin gestation appeared to be the only risk factor (P = 0.006) by logistic analysis. Two patients were operated due to intractable pain; and the remaining nine patients were treated conservatively. The diastatic gap decreased to less than 1.5 cm by 2 to 6 weeks after the diagnosis and then remained stationary. At a mean follow-up of 22.1 months (range, 12 to 47 months), five of 11 patients had persistent symphysis pubis dysfunction. Diastasis is more frequent than generally acknowledged. Pregnant women with multiple gestations should be informed about the potential risk of pubic symphysis diastasis.

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.

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.