Impaired Angiogenic Function of Fetal Endothelial Progenitor Cells via PCDH10 in Gestational Diabetes Mellitus.

Maternal hyperglycemia, induced by gestational diabetes mellitus (GDM), has detrimental effects on fetal vascular development, ultimately increasing the risk of cardiovascular diseases in offspring. The potential underlying mechanisms through which these complications occur are due to functional impairment and epigenetic changes in fetal endothelial progenitor cells (EPCs), which remain less defined. We confirm that intrauterine hyperglycemia leads to the impaired angiogenic function of fetal EPCs, as observed through functional assays of outgrowth endothelial cells (OECs) derived from fetal EPCs of GDM pregnancies (GDM-EPCs). Notably, PCDH10 expression is increased in OECs derived from GDM-EPCs, which is associated with the inhibition of angiogenic function in fetal EPCs. Additionally, increased PCDH10 expression is correlated with the hypomethylation of the PCDH10 promoter. Our findings demonstrate that in utero exposure to GDM can induce angiogenic dysfunction in fetal EPCs through altered gene expression and epigenetic changes, consequently increasing the susceptibility to cardiovascular diseases in the offspring of GDM mothers.

Whole blood RNA sequencing reveals a differential transcriptomic profile associated with cervical insufficiency: a pilot study.

BACKGROUND: The uterine cervix is a mechanical and immunological barrier against ascending infection during pregnancy. Cervical insufficiency (CI), a painless cervical dilation that occurs in the mid-trimester, is an important cause of extremely preterm birth. We hypothesized that women with CI have a differential transcriptomic profile. Therefore, we compared the transcriptomic profile of peripheral blood in women with CI and that of controls. METHODS: RNA sequencing was used to generate the global gene expression profiles of 11 women with CI and 4 controls, and differential expression analysis was performed to identify genes showing significant expression changes between the CI (n = 11) and control (n = 4) groups as well as between the CI-preterm (n = 7) and CI-term (n = 4) groups. Gene set enrichment was assessed in terms of Gene Ontology processes, and a subset of differentially expressed genes in CI was validated in a different sample-set by qRT-PCR and ELISA. RESULTS: Thirty genes were differentially expressed between the CI and control groups. Differentially upregulated genes in the CI group included neutrophil-mediated immunity-associated (DEFA3 and ELANE) and bicarbonate transport-related genes. The serum concentration of alpha defensin 3 was significantly higher in women with CI than in controls (P = 0.014). Analysis of differential gene expression according to pregnancy outcomes revealed 338 differentially expressed genes between the CI-term and CI-preterm groups. Immune and defense response to organism-associated genes and influenza A and NOD-like receptor signaling pathways were upregulated in the CI-term group. CONCLUSIONS: Our results revealed significant differences in the whole blood transcriptomic profiles of women with CI compared to those of controls. Different immune responses in women with CI may affect pregnancy outcomes.

Content Analysis and Quality Evaluation of Cesarean Delivery-Related Videos on YouTube: Cross-sectional Study.

BACKGROUND: YouTube is one of the most popular open-access video-sharing websites, and it is also used to obtain health care information. Cesarean delivery is the most common major surgical intervention in many countries. Videos related to cesarean delivery have also been uploaded to YouTube. However, no study has explored the overall quality of cesarean delivery videos on the platform. OBJECTIVE: The objective of this study was to analyze the content and evaluate the quality of the most frequently viewed videos related to cesarean delivery that are accessible on YouTube. METHODS: We searched for a total of 18 terms by combining the 6 terms retrieved from Google AdWords and the 3 terms c section, cesarean section, and cesarean delivery, which are used interchangeably. Videos were sorted by view count, and the 100 videos with the highest view counts were chosen. The number of views, duration, likes and dislikes, content type, and source of each video were recorded. In evaluating the quality of the videos, we referred to a previous study. Additionally, we developed a detailed scoring method that comprehensively evaluates the videos related to cesarean delivery by including the necessary information for each element of the cesarean delivery and whether scientific evidence was presented. RESULTS: Of the 100 videos analyzed, the most prevalent content (n=28) was videos that contained the actual surgical procedure of a cesarean delivery, and the most common source of cesarean delivery videos was physicians (n=30). Videos directly related to cesarean delivery, such as explanation of the surgery and the actual surgical procedure, were mainly uploaded by medical groups and scored higher than the videos indirectly related to cesarean delivery, which were mainly uploaded by nonmedical groups. In addition, videos directly related to cesarean delivery were more often uploaded earlier in time, with lower like ratios compared to indirect videos. CONCLUSIONS: YouTube is currently not an appropriate source for patients seeking information on cesarean delivery.

The Role of Antimicrobial Peptides in Preterm Birth.

Antimicrobial peptides (AMPs) are short cationic amphipathic peptides with a wide range of antimicrobial properties and play an important role in the maintenance of immune homeostasis by modulating immune responses in the reproductive tract. As intra-amniotic infection and microbial dysbiosis emerge as common causes of preterm births (PTBs), a better understanding of the AMPs involved in the development of PTB is essential. The altered expression of AMPs has been reported in PTB-related clinical presentations, such as preterm labor, intra-amniotic infection/inflammation, premature rupture of membranes, and cervical insufficiency. Moreover, it was previously reported that dysregulation of AMPs may affect the pregnancy prognosis. This review aims to describe the expression of AMPs associated with PTBs and to provide new perspectives on the role of AMPs in PTB.

The Clinical Usefulness of Predictive Models for Preterm Birth with Potential Benefits: A KOrean Preterm collaboratE Network (KOPEN) Registry-Linked Data-Based Cohort Study.

Background: Preterm birth is strongly associated with increasing mortality, incidence of disability, intensity of neonatal care required, and consequent costs. We examined the clinical utility of the potential preterm birth risk factors from admitted pregnant women with symptomatic preterm labor and developed prediction models to obtain information for prolonging pregnancies. Methods: This retrospective study included pregnant women registered with the KOrean Preterm collaboratE Network (KOPEN) who had symptomatic preterm labor, between 16 and 34 gestational weeks, in a tertiary care center from March to November 2016. Demographics, obstetric and medical histories, and basic laboratory test results obtained at admission were evaluated. The preterm birth probability was assessed using a nomogram and decision tree according to birth gestational age: early preterm, before 32 weeks; late preterm, between 32 and 37 weeks; and term, after 37 weeks. Results: Of 879 registered pregnant women, 727 who gave birth at a designated institute were analyzed. The rates of early preterm, late preterm, and term births were 18.16%, 44.02%, and 37.83%, respectively. With the developed nomogram, the concordance index for early and late preterm births was 0.824 (95% CI: 0.785-0.864) and 0.717 (95% CI: 0.675-0.759) respectively. Preterm birth was significantly more likely among women with multiple pregnancy and had water leakage due to premature rupture of membrane. The prediction rate for preterm birth based on decision tree analysis was 86.9% for early preterm and 73.9% for late preterm; the most important nodes are watery leakage for early preterm birth and multiple pregnancy for late preterm birth. Conclusion: This study aims to develop an individual overall probability of preterm birth based on specific risk factors at critical gestational times of preterm birth using a range of clinical variables recorded at the initial hospital admission. Therefore, these models may be useful for clinicians and patients in clinical decision-making and for hospitalization or lifestyle coaching in an outpatient setting.

YouTube as a Source of Information and Education on Hysterectomy.

BACKGROUND: Globally, YouTube is one of the most popular websites, and the content is not restricted to entertainment. The purpose of this study was to assess the quality of information in YouTube videos pertaining to hysterectomy. METHODS: We explored YouTube using the search terms "hysterectomy" and "remove uterus." The videos that appeared were sorted using the filter "sort by view count." Of the initial 100 videos, the top 50 videos for each search term were included for review, as determined by the "relevance" filter based on YouTube's algorithm. After excluding 34 videos for various reasons, 66 were included in the final analysis. Each video rated as "useful" was further analyzed for reliability and completeness of information; a set of pre-determined criteria were modified from a previous study and used to grade the quality of videos. RESULTS: The top 66 videos on hysterectomy had a total of 4,679,118 views. Based on authorship, the videos were categorized as follows: videos uploaded by patients, 37%; academic videos, 35%; videos uploaded by physicians, 13%; commercial videos, 4%; and videos uploaded by non-physicians, 2%. The type of content was also categorized: 50% of the videos recorded personal experiences, 23% recorded surgical techniques, 21% involved explanations of the surgery, and 4% were commercial videos. The majority of the videos made by patients were negatively biased toward hysterectomy surgery (71.72%), while the majority of those made by academics or physicians were surgical educational videos for doctors, not patients. CONCLUSION: YouTube is currently not an appropriate source for patients to gain information on hysterectomy. Physicians should be aware of the limitations and provide up-to-date and peer-reviewed content on the website.

Post-translational modifications of FLOWERING LOCUS C modulate its activity.

Flowering Locus C (FLC) is a key floral repressor that precisely controls flowering time. The role of FLC has been extensively studied at the transcriptional level using molecular biological and epigenetic approaches. However, how FLC functions and how its stability is controlled at the post-translational level are only beginning to be understood. Recent studies show that various post-translational modifications (PTMs) control the stability and activity of FLC. In this review, we focus on three types of PTMs that regulate FLC function: phosphorylation, ubiquitination, and sumoylation. This report should serve as a model to guide post-translational studies of other important floral regulators.

Use of a uniconcave balloon in emergency cerclage.

Pushing bulging fetal membranes back into the uterine cavity effectively without rupture of fetal membranes during emergency cerclage is a concern to obstetricians. We have developed a new uniconcave balloon device for repositioning fetal membranes into the uterus during emergency cerclage. Our technique can be accomplished easily with few complications.

FLC-mediated flowering repression is positively regulated by sumoylation.

Flowering locus C (FLC), a floral repressor, is a critical factor for the transition from the vegetative to the reproductive phase. Here, the mechanisms regulating the activity and stability of the FLC protein were investigated. Bimolecular fluorescence complementation and in vitro pull-down analyses showed that FLC interacts with the E3 small ubiquitin-like modifier (SUMO) ligase AtSIZ1, suggesting that AtSIZ1 is an E3 SUMO ligase for FLC. In vitro sumoylation assays showed that FLC is modified by SUMO in the presence of SUMO-activating enzyme E1 and conjugating enzyme E2, but its sumoylation is inhibited by AtSIZ1. In transgenic plants, inducible AtSIZ1 overexpression led to an increase in the concentration of FLC and delayed the post-translational decay of FLC, indicating that AtSIZ1 stabilizes FLC through direct binding. Also, the flowering time in mutant FLC (K154R, a mutation of the sumoylation site)-overexpressing plants was comparable with that in the wild type, whereas flowering was considerably delayed in FLC-overexpressing plants, supporting the notion that sumoylation is an important mechanism for FLC function. The data indicate that the sumoylation of FLC is critical for its role in the control of flowering time and that AtSIZ1 positively regulates FLC-mediated floral suppression.

Risk factors for cesarean delivery after induction of labor in nulliparous women with an unfavorable cervix at or beyond 41 weeks of gestation.

AIMS: To investigate risk factors for cesarean section (CS) following labor induction in nulliparas with an unfavorable cervix at or beyond 41 weeks of gestation. METHODS: In this retrospective cohort study, a total of 276 nulliparas with an unfavorable cervix (Bishop score ≤6) who underwent labor induction for prolonged pregnancies were included out of a total of 646 patients who delivered ≥41 weeks (2002-2011). RESULTS: 82 (29.7%) patients of the 276 delivered by CS. The patients who underwent CS had less cervical dilatation and a lower Bishop score on admission than those patients who delivered vaginally (0.76 ± 0.47 vs. 0.92 ± 0.58 cm, p = 0.03 and 1.16 ± 1.25 vs. 1.51 ± 1.34, p = 0.04, respectively). Neonatal birth weight and biparietal diameter (BPD) were significantly smaller in the vaginal delivery group (3,414.93 ± 361.37 vs. 3,534.81 ± 383.05 g, p = 0.01 and 9.43 ± 0.35 vs. 9.65 ± 0.42 cm, p < 0.01). After multiple logistic regression analysis, maternal height, BPD, and early rupture of membranes (ROM) were independently related with CS. Early ROM was defined as spontaneous ROM that occurred before the onset of the active phase of labor. CONCLUSION: Maternal height, BPD, and early ROM were risk factors for CS following labor induction in nulliparas at or beyond 41 weeks of gestation.

Danazol as a Treatment for Uterine Arteriovenous Malformation: A Case Report.

Uterine arteriovenous malformation (AVM) is associated with a risk of massive uterine bleeding. Although uterine artery embolization remains the first-line treatment for AVM, there has been a recent exploration of pharmacological options. Danazol is known to reduce blood flow to the uterus; however, our understanding of its therapeutic efficacy for AVM remains limited. Herein, we present the results of danazol use in patients with uterine AVM. We retrospectively reviewed the medical records of patients who received danazol for the treatment of AVM between January 2013 and November 2022. The cohort comprised 10 patients who developed AVM after dilatation and curettage (D&C), abortion, or cesarean section. Danazol was administered twice daily at a total dose of 400 mg/day, and was employed for AVM treatment in hemodynamically stable patients who provided consent and were devoid of massive bleeding. Outpatient follow-ups (ultrasound measurements of AVM size and symptom assessment) were performed every 2 weeks. AVM was successfully treated with danazol in most patients with no adverse event. Eight postabortal patients had complete resolution of AVM after an average of 45 days (range 14-70 days). Of two patients who developed AVM after a cesarean section, one experienced AVM reduction, and the other developed massive bleeding, requiring emergency uterine artery embolization. In light of these outcomes, danazol can be potentially prioritized over uterine artery embolization in the treatment of AVM after abortion in hemodynamically stable patients.

Factors Associated with Spontaneous Preterm Birth after Ultrasound-Indicated Cerclage.

Ultrasound-indicated cerclage (UIC) is recommended to prevent spontaneous preterm birth (sPTB) in women with a short cervix at mid-trimester and a history of PTB. We assessed the factors related to sPTB after UIC and determined the corresponding risks. This retrospective cohort study was conducted at a university hospital. UIC was performed between 15 and 26 weeks of gestation in women with a cervical length of <2.5 cm. Univariate and multivariate analyses were used to examine factors associated with sPTB after UIC. An earlier gestational age and shorter cervical length at UIC were associated with sPTB after UIC. While PTB history was not associated with an increased risk of sPTB, it did increase the risk of repeat cerclage after UIC. Higher levels of preoperative serum inflammatory markers and obesity significantly increased the risk of sPTB after UIC. These findings provide helpful guidance for patient counseling and management in predicting the delivery timing after UIC in women with a short cervix in the mid-trimester.

Expression of antimicrobial peptides in the amniotic fluid of women with cervical insufficiency.

PROBLEM: Cervical insufficiency (CI) is associated with intra-amniotic infection or inflammation. Antimicrobial peptides (AMPs) in amniotic fluid may protect the fetus against microbial invasion, giving their broad-spectrum microbiocidal properties. We evaluated changes in amniotic fluid AMP expression in women with CI and assessed whether these changes are related to their pregnancy outcomes. METHOD OF STUDY: We evaluated amniotic fluid human neutrophil peptide 3 (HNP-3), human ß-defensin-2 (hBD-2), and LL-37 levels in 66 women with CI and 25 normal controls at 16-24 weeks of gestation. The CI group was divided into short cervix and cervical dilation groups, and the cervical dilation group was further divided into preterm and full-term delivery groups according to the pregnancy outcomes, and AMP expression was analyzed in each group. RESULTS: HNP-3 and hBD-2 levels were higher in women with CI than in normal controls and in the cervical dilation as compared to the short cervix group. Among women with cervical dilation, 22 delivered at full-term, and 23 had spontaneous preterm births. The hBD-2 level in amniotic fluid mid-pregnancy was higher in the full-term delivery than in the preterm delivery groups. However, LL-37 levels in amniotic fluid were low in women with CI and normal controls. CONCLUSIONS: Amniotic fluid HNP-3 and hBD-2 levels increased in women with CI compared with normal controls. Moreover, increased amniotic fluid hBD-2 levels mid-pregnancy were associated with favorable pregnancy outcomes in women with CI. AMPs in the amniotic fluid may participate in host defense against ascending infection in women with CI.

Fetal MR imaging of constriction band syndrome involving the skull and brain.

We present here the case of a fetus with constriction band syndrome involving the skull and brain. Whereas prenatal ultrasound did not show direct signs of this condition, fetal magnetic resonance imaging (MRI) revealed it clearly. This may be the first case of constriction band syndrome to be diagnosed using fetal MRI. As a supplementary tool, fetal MRI may lead to an accurate diagnosis when prenatal ultrasound presents equivocal findings with respect to central nervous system development.

Mode of delivery influences the regression of abnormal cervical cytology.

AIMS: The purpose was to investigate the influence of delivery mode on the postpartum regression of abnormal cervical cytology. METHODS: A retrospective review was conducted of 64 pregnant women with abnormal cervical cytology at Yonsei University Health System in Korea between 2001 and 2008. A Papanicolaou smear and pathological data were categorized into three groups by cervical intraepithelial neoplasia classification. Postpartum evaluation was taken 3-6 months after delivery. The regression rates of cervical cytologic findings were compared between the vaginal delivery group and Cesarean section group. p < 0.05 was considered significant. RESULTS: Of the 64 women, 45 (70.3%) were delivered vaginally and 19 (29.7%) by cesarean section. No significant difference was found between the two groups with respect to age, gestational age, parity, smoking, and HPV (human papilloma virus) screening. Postpartum regression was shown in 39 (92.9%) women who delivered vaginally and in 12 (63.2%) women who underwent cesarean section (p = 0.016). In the cesarean section group, 1 patient had progressed from CIN2 to microinvasive cancer and 2 patients from carcinoma in situ to invasive cancer. CONCLUSION: The rate of spontaneous regression of antepartum abnormal cervical cytology was higher after vaginal delivery.

Maternal serum triglycerides as predictive factors for large-for-gestational age newborns in women with gestational diabetes mellitus.

OBJECTIVE: To determine the contribution of maternal lipids in predicting large-for-gestational age (LGA) newborns born to women with gestational diabetes mellitus (GDM). DESIGN: Retrospective study. SETTING: Yonsei University Health System, Korea. POPULATION: A total of 104 women diagnosed with GDM between January 2000 and June 2008. METHODS: Women who were positive on the 50 g oral glucose challenge test (24-28 weeks' gestation) and who were referred patients suspected of GDM underwent a 3 hours, 100 g oral glucose tolerance test for GDM diagnosis. Maternal fasting serum triglycerides and total, high-density lipoprotein (HDL), and low-density lipoprotein cholesterol levels were determined at 24-32 weeks' gestation. Logistic regression analysis was performed to determine maternal parameters independently associated with delivering LGA newborns at term. MAIN OUTCOME MEASURES: Risk contributions for LGA newborns. RESULTS: Maternal fasting serum triglyceride levels were significantly higher in mothers of LGA newborns compared with other mothers; however, no significant correlations were found between newborn birthweight and maternal fasting glucose, total cholesterol, or HDL cholesterol levels. After adjusting for confounding variables including prepregnancy body mass index, weight gain during pregnancy, age, and parity, maternal hypertriglyceridemia at 24-32 weeks' gestation remained an independent parameter for identifying term LGA newborns. CONCLUSIONS: In GDM pregnancies, determining maternal serum triglyceride levels during midpregnancy may help identify women likely to give birth to LGA newborns.

Frontomaxillary facial angle measurements in euploid Korean fetuses at 11 weeks' to 13 weeks 6 days' gestation.

OBJECTIVE: The purpose of this study was to evaluate the distribution of fetal frontomaxillary facial angles in a euploid Korean population at 11 weeks' to 13 weeks 6 days' gestation. METHODS: Three-dimensional volumes of the fetal head were obtained from women with low-risk singleton pregnancies at 11 weeks' to 13 weeks 6 days' gestation who consented to this prospective study. Only fetuses with either a normal karyotype confirmed by amniocentesis or no abnormalities after delivery were considered eligible for analysis and were characterized as euploid for the purposes of this study. Women with multiple pregnancies and those who were lost to follow-up and fetuses with abnormal karyotypes or anomalies diagnosed in utero or postnatally were excluded. The frontomaxillary facial angle was measured twice offline by a single examiner. Cases were categorized by crown-rump length (CRL) in 10-mm intervals for analysis of the frontomaxillary facial angle. RESULTS: Among 375 enrolled cases, 158 were eligible for frontomaxillary facial angle analysis. The overall mean frontomaxillary facial angle ± SD was 88.6° ± 9.7°. The mean frontomaxillary facial angle for fetuses with a CRL of 40 to 49 mm (n = 35) was 93.7°; 50 to 59 mm (n = 53), 92.6°; 60 to 69 mm (n = 36), 85.3°; and 70 to 79 mm (n = 34), 81.0°, showing an inverse relationship between the mean frontomaxillary facial angle and CRL (r = -0.5334; P < .0001). The proportion of cases with frontomaxillary facial angles of 85° or greater was 60.8%, and that of cases with angles of 90° or greater was 37.3%. CONCLUSIONS: Ethnic differences in frontomaxillary facial angle measurements should be considered when incorporating the frontomaxillary facial angle in fetal aneuploidy screening in the Korean population.

Outcomes after transabdominal cerclage in twin pregnancy with previous unsuccessful transvaginal cerclage.

Transabdominal cerclage (TAC) is reported to be effective for preventing preterm birth in women with unsuccessful transvaginal cerclage (TVC) history. However, TAC has rarely been performed in twin pregnancy given the lack of sufficient evidence and the technical difficulty of the operation. Thus, it is unclear whether TAC is an effective procedure for twin pregnancy in women with a history of unsuccessful TVC. The aim of this study is to compare the characteristics and pregnancy outcomes after TAC in twin pregnancy versus singleton pregnancy, to examine whether twin pregnancy is a risk factor for very preterm birth (before 32 weeks) after TAC, and to determine whether TAC is effective in preventing preterm birth in twin pregnancy. This single-center retrospective cohort study included women who underwent TAC because of unsuccessful TVC history between January 2007 and June 2018. Of 165 women who underwent TAC, 19 had twins and 146 had singletons. Our results showed that the neonatal survival rate improved dramatically when TAC was performed (15.4% (prior pregnancy) vs 94.0% (after TAC) in twins, p<0.01; 22.8% (prior pregnancy) vs 91.1% (after TAC) in singletons, p<0.01). Moreover, the risk of very preterm birth was significantly decreased after TAC in both groups (36/39 (92.3%) (prior pregnancy) vs 2/19 (10.5%) (after TAC) in twins, p<0.01; 290/337 (86.1%) (prior pregnancy) vs 17/146 (11.6%) (after TAC) in singletons, p<0.01). More advanced maternal age and history of prior preterm delivery between 26+0 and 36+6 weeks were independently associated with very preterm birth, whereas the presence of a twin pregnancy was not associated with very preterm birth on multivariate logistic regression analysis. These results suggest that TAC is associated with successful prevention of very preterm birth and improved neonatal survival rates in the absence of procedure-related major complications in women with twin pregnancy and previous unsuccessful TVC history.

Classification of cervical neoplasms on colposcopic photography using deep learning.

Colposcopy is widely used to detect cervical cancers, but experienced physicians who are needed for an accurate diagnosis are lacking in developing countries. Artificial intelligence (AI) has been recently used in computer-aided diagnosis showing remarkable promise. In this study, we developed and validated deep learning models to automatically classify cervical neoplasms on colposcopic photographs. Pre-trained convolutional neural networks were fine-tuned for two grading systems: the cervical intraepithelial neoplasia (CIN) system and the lower anogenital squamous terminology (LAST) system. The multi-class classification accuracies of the networks for the CIN system in the test dataset were 48.6 ± 1.3% by Inception-Resnet-v2 and 51.7 ± 5.2% by Resnet-152. The accuracies for the LAST system were 71.8 ± 1.8% and 74.7 ± 1.8%, respectively. The area under the curve (AUC) for discriminating high-risk lesions from low-risk lesions by Resnet-152 was 0.781 ± 0.020 for the CIN system and 0.708 ± 0.024 for the LAST system. The lesions requiring biopsy were also detected efficiently (AUC, 0.947 ± 0.030 by Resnet-152), and presented meaningfully on attention maps. These results may indicate the potential of the application of AI for automated reading of colposcopic photographs.

MicroRNA-548 regulates high mobility group box 1 expression in patients with preterm birth and chorioamnionitis.

High mobility group box 1 (HMGB1) is a prototypic alarmin and plays an important role in the pathogenesis of inflammatory process in spontaneous preterm birth. This study was conducted to compare the levels of HMGB1 in amniotic fluid and amnion membranes in women with chorioamnionitis/intra-amniotic inflammation to the levels in healthy controls. We also aimed to elucidate the involvement of microRNA-548 (miR-548) in regulating HMGB1 expression and its function in human amniotic epithelial cells (hAECs). A bioinformatics analysis predicted the binding of HMGB1 by the miR-548 cluster. A repressed and forced expression assay in hAECs was performed to investigate the causal relationship between the miR-548 cluster and HMGB1. The levels of HMGB1 in amniotic fluid and amnion membranes were significantly higher in patients with intra-amniotic inflammation/chorioamnionitis than in those without inflammation. The miR-548 was significantly under-expressed in amnion membranes from patients with chorioamnionitis than in normal term controls. Repressed expression of miR-548 up-regulated HMGB1 expression in hAECs and increased its release from hAECs. Moreover, forced expression of miR-548 suppressed HMGB1 and inflammatory cytokines in hAECs, which increased when treated with lipopolysaccharide. These results suggest miR-548 can alter the inflammatory responses in hAECs, and might be involved in the pathogenesis of preterm birth by regulating HMGB1.