The Role of the Aryl Hydrocarbon Receptor in Vascular Factors Related to Preeclampsia in a Smoking Mouse Model.

Smoking cigarettes is known to lower the risk of preeclampsia. The objective of this study is to evaluate the effect of smoking on the expression of soluble FMS-like tyrosine kinase-1 (sFlt-1), vascular endothelial growth factor (VEGF), and endoglin (sEng)-1 and the role of the aryl hydrocarbon receptor (AhR) in pregnant mice. We developed a smoking mouse model using a gas-filling system. One or two cigarettes per day were exposed to each of the five pregnant mice for five days a week throughout pregnancy. AhR agonist and antagonist were injected. Serum levels and expression in the placenta of sFlt-1, VEGF, and sEng-1 were analyzed and compared among the cigarette smoke and no-exposure groups after delivery. Compared to the no-smoke exposure group, the serum level of sFlt-1 was significantly decreased in the two-cigarette-exposed group (p < 0.001). When the AhR antagonist was added to the two-cigarette-exposed group, sFlt-1 levels were significantly increased compared to the two-cigarette group (p = 0.002). The levels of sFlt-1 in the AhR antagonist group did not change regardless of two-cigarette exposure (p = 0.064). With the AhR agonist, sFlt-1 decreased significantly compared to the control (p = 0.001) and AhR antagonist group (p = 0.002). The sFlt-1 level was significantly decreased after the injection of the AhR agonist compared to the control group (p = 0.001). Serum levels of VEGF were significantly decreased in the one-cigarette-exposed group compared to the control group; however, there was no difference between the control and the two-cigarette-exposed groups. The placental expression of sFlt-1, VEGF, and sEng were inconsistent. This study offers insights into the potential role of AhR on antiangiogenic sFlt-1 associated with preeclampsia. It may support the invention of a new treatment strategy for preeclampsia using AhR activation.

Differences in maternal subgingival microbiome between preterm and term births: The MOHEPI study.

AIM: Periodontitis is a potential risk factor for preterm birth (PTB) in women; however, the causal relationship or the exact mechanism remain unknown. This study aimed to compare the oral microbiome features of mothers with full-term birth (FTB) with those who had preterm delivery. METHODS: This study prospectively enrolled 60 women (30 mothers with PTB and 30 mothers with FTB), and subgingival plaque samples were collected and analysed by metagenomic 16S rDNA sequencing. Clinical measurements, including periodontal probing depth, clinical attachment level, modified gingival index (mGI) and plaque index, were performed to determine the periodontal state of the participants. Medical and obstetric data were collected as well. RESULTS: Among the periodontal measurements, mGI score, reflecting the level of gingival inflammation, exhibited a statistically significant association with PTB (adjusted odds ratio 2.705, 95% confidence interval 1.074-6.811, p = .035). When subgroup analysis was conducted based on mean mGI scores (mGI ≥ 2, high inflammation [HI] versus mGI < 2, low inflammation [LI]), microbiome analysis revealed clear distinctions in microbial compositions between PTB and FTB mothers in both the HI and LI groups. Especially in the HI group, alpha diversity exhibited a decreasing trend in PTB mothers compared to FTB mothers. Beta diversity also revealed significant differences between the two groups. In Linear Discriminant Analysis Effect Size analysis, certain anaerobic taxa, including the genera Spirochaetes, Treponema and Porphyromonas, were relatively abundant in the FTB/HI group, whereas the PTB/HI group showed a high abundance of the order Actinomycetales. Network analysis showed that the FTB/HI had relatively stronger connectivity in microbial composition than the PTB/HI group. Dysbiosis ratio of plaque microbiome, in terms of periodontitis, was significantly lower in PTB/HI group compared to FTB/HI group. CONCLUSION: The compositions of maternal subgingival microbiomes differed between PTB and FTB mothers in both the high and low levels of gingival inflammation groups. In the presence of high level of gingival inflammation, dysbiosis in plaque microbiome, in terms of periodontitis, was decreased in PTB mothers compared to FTB mothers.

The Risk of Hypertension and Diabetes Mellitus According to Offspring's Birthweight in Women With Normal Body Mass Index: A Nationwide Population-Based Study.

BACKGROUND: Maladaptation to vascular, metabolic, and physiological changes during pregnancy can lead to fetal growth disorders. Moreover, adverse outcomes during pregnancy can further increase the risk of cardiovascular and metabolic diseases in mothers. Delivering a large-for-gestational-age (LGA) baby may indicate a pre-existing metabolic dysfunction, whereas delivering a small-for-gestational-age (SGA) baby may indicate a pre-existing vascular dysfunction. This study aims to assess the risk of hypertension (HTN) and diabetes mellitus (DM) in women with normal body mass index (BMI) scores who did not experience gestational DM or hypertensive disorders during pregnancy based on the offspring's birthweight. METHODS: This retrospective nationwide study included women with normal BMI scores who delivered a singleton baby after 37 weeks. Women with a history of DM or HTN before pregnancy and those with gestational DM or hypertensive disorders, were excluded from the study. We compared the risk of future maternal outcomes (HTN and DM) according to the offspring's birthweight. Multivariate analyses were performed to estimate the hazard ratio (HR) for the future risk of HTN or DM. RESULTS: A total of 64,037 women were included in the analysis. Of these, women who delivered very LGA babies (birthweight > 97th percentile) were at a higher risk of developing DM than those who delivered appropriate-for-gestational-age (AGA) babies (adjusted HR = 1.358 [1.068-1.727]), and women who delivered very SGA babies (birthweight < 3rd percentile) were at a higher risk of developing HTN than those who delivered AGA babies (adjusted HR = 1.431 [1.181-1.734]), even after adjusting for age, parity, gestational age at delivery, fetal sex, maternal BMI score, and a history of smoking. CONCLUSION: These findings provide a novel support for the use of the offspring's birthweight as a predictor of future maternal diseases such as HTN and DM.

Explainable Model Using Shapley Additive Explanations Approach on Wound Infection after Wide Soft Tissue Sarcoma Resection: "Big Data" Analysis Based on Health Insurance Review and Assessment Service Hub.

Background and Objectives: Soft tissue sarcomas represent a heterogeneous group of malignant mesenchymal tissues. Despite their low prevalence, soft tissue sarcomas present clinical challenges for orthopedic surgeons owing to their aggressive nature, and perioperative wound infections. However, the low prevalence of soft tissue sarcomas has hindered the availability of large-scale studies. This study aimed to analyze wound infections after wide resection in patients with soft tissue sarcomas by employing big data analytics from the Hub of the Health Insurance Review and Assessment Service (HIRA). Materials and Methods: Patients who underwent wide excision of soft tissue sarcomas between 2010 and 2021 were included. Data were collected from the HIRA database of approximately 50 million individuals' information in the Republic of Korea. The data collected included demographic information, diagnoses, prescribed medications, and surgical procedures. Random forest has been used to analyze the major associated determinants. A total of 10,906 observations with complete data were divided into training and validation sets in an 80:20 ratio (8773 vs. 2193 cases). Random forest permutation importance was employed to identify the major predictors of infection and Shapley Additive Explanations (SHAP) values were derived to analyze the directions of associations with predictors. Results: A total of 10,969 patients who underwent wide excision of soft tissue sarcomas were included. Among the study population, 886 (8.08%) patients had post-operative infections requiring surgery. The overall transfusion rate for wide excision was 20.67% (2267 patients). Risk factors among the comorbidities of each patient with wound infection were analyzed and dependence plots of individual features were visualized. The transfusion dependence plot reveals a distinctive pattern, with SHAP values displaying a negative trend for individuals without blood transfusions and a positive trend for those who received blood transfusions, emphasizing the substantial impact of blood transfusions on the likelihood of wound infection. Conclusions: Using the machine learning random forest model and the SHAP values, the perioperative transfusion, male sex, old age, and low SES were important features of wound infection in soft-tissue sarcoma patients.

Prepregnancy Glucose Levels Within Normal Range and Its Impact on Obstetric Complications in Subsequent Pregnancy: A Population Cohort Study.

BACKGROUND: We sought to identify the influence of prepregnancy glucose levels on obstetric complications in subsequent pregnancy. METHODS: Women in Republic of Korea who had given birth between January 1st, 2007 and December 31st, 2010 were enrolled. The database of the Health Insurance Review and Assessment Service and data from a national health screening program for infants and children were used. Subjects were divided into seven groups according to their fasting glucose levels. RESULTS: 59,619 women were included for analysis, and 10.4%, 13.7%, 19.1%, 21.5%, 16.0%, 11.6%, and 7.5% women had glucose levels of < 75, 75-79, 80-84, 85-89, 90-94, 95-100 and > 100 mg/dL. Each 5 mg/dL increase in prepregnancy fasting glucose levels was associated with increased risk of gestational diabetes and macrosomia in subsequent pregnancy. Adjusted risk ratio for gestational diabetes per standard deviation prepregnancy glucose > 100 mg/dL was 2.015 (95% confidence interval, 1.649-2.462) and for macrosomia an adjusted risk ratio 1.389 (95% confidence interval, 1.147-1.682). CONCLUSION: Higher prepregnancy glucose level within normal range was related to gestational diabetes and macrosomia in following pregnancy. Our results may aid in the identification of women at future risk of obstetric complications and may guide to stratify women into normal and intensified care. TWEETABLE ABSTRACT: Higher prepregnancy glucose in normal range is associated with gestational diabetes and macrosomia.

Effect of a Patient Blood Management Program on the Appropriateness of Red Blood Cell Transfusion and Clinical Outcomes in Elderly Patients Undergoing Hip Fracture Surgery.

BACKGROUND: Elderly patients with hip fractures frequently receive perioperative transfusions, which are associated with increased morbidity and mortality. This study aimed to evaluate the impact of a patient blood management (PBM) program on the appropriateness of red blood cell (RBC) transfusion and clinical outcomes in geriatric patients undergoing hip fracture surgery. METHODS: In 2018, the revised PBM program was implemented at the Korea University Anam Hospital, Seoul, Republic of Korea. Elderly patients aged ≥ 65 years who underwent hip fracture surgery from 2017 to 2020 were evaluated. Clinical characteristics and outcomes were analyzed according to the timing of PBM implementation (pre-PBM, early-PBM, and late-PBM). Multiveriate regression analysis was used to evaluate the risk factors of the adverse outcomes, such as in-hospital mortality or 30-day readmission. RESULTS: A total of 884 elderly patients were included in this study. The proportion of patients who received perioperative RBC transfusions decreased significantly (43.5%, 40.1%, and 33.2% for pre-PBM, early-PBM, and late-PBM, respectively; P = 0.013). However, the appropriateness of RBC transfusion significantly increased (54.0%, 60.1%, and 94.7%, respectively; P < 0.001). The duration of in-hospital stay and 30-day readmission rates significantly decreased. Multivariable regression analysis revealed that RBC transfusion (odds ratio, 1.815; 95% confidence interval, 1.137-2.899; P = 0.013) was significantly associated with adverse outcomes. CONCLUSION: Implementing the PBM program increased the appropriateness of RBC transfusion without compromising transfusion quality and clinical outcomes. Therefore, adopting the PBM program may improve the clinical management of elderly patients following hip fracture surgery.

Real-time Classification of Fetal Status Based on Deep Learning and Cardiotocography Data.

This study uses convolutional neural networks (CNNs) and cardiotocography data for the real-time classification of fetal status in the mobile application of a pregnant woman and the computer server of a data expert at the same time (The sensor is connected with the smartphone, which is linked with the web server for the woman and the computer server for the expert). Data came from 5249 (or 4833) cardiotocography traces in Anam Hospital for the mobile application (or the computer server). 150 data cases of 5-minute duration were extracted from each trace with 141,001 final cases for the mobile application and for the computer server alike. The dependent variable was fetal status with two categories (Normal, Abnormal) for the mobile application and three categories (Normal, Middle, Abnormal) for the computer server. The fetal heart rate served as a predictor for the mobile application and the computer server, while uterus contraction for the computer server only. The 1-dimension (or 2-dimension) Resnet CNN was trained for the mobile application (or the computer server) during 800 epochs. The sensitivity, specificity and their harmonic mean of the 1-dimension CNN for the mobile application were 94.9%, 91.2% and 93.0%, respectively. The corresponding statistics of the 2-dimension CNN for the computer server were 98.0%, 99.5% and 98.7%. The average inference time per 1000 images was 6.51 micro-seconds. Deep learning provides an efficient model for the real-time classification of fetal status in the mobile application and the computer server at the same time.

A Randomized, Multicenter, Double-Blind, Parallel, Non-Inferiority Clinical Study to Compare the Efficacy and Safety of Unicenta and Melsmon for Menopausal Symptom Improvement.

This study was conducted to evaluate the efficacy and safety of Unicenta in female subjects with menopausal symptoms by analyzing the changes in the Kupperman index (primary endpoint) and hormonal changes (secondary endpoint). It was a randomized, multi-center, double-blind, parallel, non-inferiority clinical study conducted at two different tertiary medical centers. A Unicenta injection was shown to be non-inferior to Melsmon based on the Kupperman index in both the intent-to-treat and per-protocol populations (p = 0.789 and p = 0.826, respectively). Additionally, there were no statistically significant differences in hormone levels (estradiol, follicular-stimulating hormone) or in the evaluation of facial flushes. There was no statistically significant difference in the incidence rate of adverse events between the two groups (p = 0.505). The study demonstrated that Unicenta is not inferior to Melsmon in terms of the change in the Kupperman index after 12 days of injection. The efficacy and safety of Unicenta were shown, resulting in the improvement of menopausal symptoms.

A Survey on Public Perceptions of Low Fertility: A Social Research Panel Study.

BACKGROUND: It was reported that South Korea showed the greatest decline in the fertility rate among the entire OECD countries over the last 30 years with the total fertility rate (TFR) of 0.84 persons in 2020. Despite the efforts of the Korean government, the TFR has decreased constantly. This study intended to analyze the perception of Koreans toward pregnancy and childbirth regarding the low fertility rate in South Korea for understanding the causes of constantly decreased low fertility. METHODS: This study carried out an online survey based on 1,002 men and women aged 19 to 59 years old for six days from October 21 to October 26 in 2021 in cooperation with Gallup Korea. This study analyzed the perception of people toward low fertility, the severity of low fertility, and level of interest in low fertility to inspect awareness of the severity of low fertility in South Korea through a survey. RESULTS: It was found that 62%, 52%, and 72% of entire participants, women, and men agreed on a question "It is better to get married". As for women's age, a positive response for this question was derived from 34.2% (20s), 43.1% (30s), 53.4% (40s), and 71.4% (50s), respectively (P < 0.001). In a question "the necessity of children", a positive response for this question was derived from 34.7% (20s), 58.3% (30s), 75.9% (40s), and 83.5% (50s) of female respondents, respectively (P < 0.001). Positive responses were shown 39.2%, 60.0%, 79.7%, and 81.5% of female participants in their 20s, 30s, 40s, and 50s agreed on the question "My children make me happy in my life", respectively (P < 0.001). CONCLUSION: This study found that a decrease in the TFR was affected mainly by the negative perception of women in their 20s and 30s toward marriage, childbirth, and the necessity of children. Therefore, further research should be conducted to develop policies that focus on these significant variables to overcome the worsening low fertility problem.

Association of preterm birth with medications: machine learning analysis using national health insurance data.

PURPOSE: To use machine learning and population data for testing the associations of preterm birth with socioeconomic status, gastroesophageal reflux disease (GERD) and medication history including proton pump inhibitors, sleeping pills and antidepressants. METHODS: Population-based retrospective cohort data came from Korea National Health Insurance Service claims data for all women who aged 25-40 years and gave births for the first time as singleton pregnancy during 2015-2017 (405,586 women). The dependent variable was preterm birth during 2015-2017 and 65 independent variables were included (demographic/socioeconomic determinants, disease information, medication history, obstetric information). Random forest variable importance (outcome measure) was used for identifying major determinants of preterm birth and testing its associations with socioeconomic status, GERD and medication history including proton pump inhibitors, sleeping pills and antidepressants. RESULTS: Based on random forest variable importance, major determinants of preterm birth during 2015-2017 were socioeconomic status (645.34), age (556.86), proton pump inhibitors (107.61), GERD for the years 2014, 2012 and 2013 (106.78, 105.87 and 104.96), sleeping pills (97.23), GERD for the years 2010, 2011 and 2009 (95.56, 94.84 and 93.81), and antidepressants (90.13). CONCLUSION: Preterm birth has strong associations with low socioeconomic status, GERD and medication history such as proton pump inhibitors, sleeping pills and antidepressants. For preventing preterm birth, appropriate medication would be needed alongside preventive measures for GERD and the promotion of socioeconomic status for pregnant women.

Ultrasonographic evaluation of ovarian mass for predicting malignancy in pregnant women.

OBJECTIVE: The purpose of this study is to compare ultrasonographic ovarian mass scoring systems in pregnant women. STUDY DESIGN: This multicenter study included women with an ovarian mass during pregnancy who were evaluated using ultrasound and underwent surgery in 11 referral hospitals. The ovarian mass was evaluated and scored using three different scoring systems(International Ovarian Tumor Analysis Assessment of Different NEoplasias in the adnexa[IOTA ADNEX], Sassone, and Lerner). The final diagnosis was made histopathologically. Receiver operating characteristic(ROC) curves were generated for each scoring system. RESULTS: During the study period, 236 pregnant women underwent surgery for an ovarian mass, including 223 women(94.5%) with a benign ovarian mass and 13 women(5.5%) with a malignant ovarian mass. Among 10 ultrasound image findings, six findings were different between benign and ovarian masses(maximal diameter of mass, maximal diameter of solid mass, wall thickness of mass, inner wall structure, thickness of septations, and papillarity). In all three scoring systems, the ovarian mass scores were significantly higher in malignant masses than in benign masses, with the highest area under the ROC curve(AUROC) in the Sassone scoring system(AUROC: 0.831 for Sassone, 0.710 for Lerner vs 0.709 for IOTA ADNEX; p < 0.05, between the Sassone and Lerner/ IOTA ADNEX). A combined model was developed with the six different ultrasound findings, and the AUROC of the combined model was 0.883(p = not significant between the combined model and Sassone). CONCLUSION: In pregnant women, malignant ovarian tumors can be predicted with high accuracy using either the Sassone scoring system or the combined model.

Women with multiple gestations have an increased risk of development of hypertension in the future.

BACKGROUND: Multiple gestations are associated with an increased incidence of preeclampsia. However, there exists no evidence for an association between multiple gestations and development of hypertension(HTN) later in life. This study aimed to determine whether multiple gestations are associated with HTN beyond the peripartum period. METHODS: In this retrospective nationwide population-based study, women who delivered a baby between January 1, 2007, and December 31, 2008, and underwent a national health screening examination within one year prior to their pregnancy were included. Subsequently, we tracked the occurrence of HTN during follow-up until December 31, 2015, using International Classification of Diseases-10th Revision codes. RESULTS: Among 362,821 women who gave birth during the study period, 4,944 (1.36%) women had multiple gestations. The cumulative incidence of HTN was higher in multiple gestations group compared with singleton group (5.95% vs. 3.78%, p < 0.01, respectively). On the Cox proportional hazards models, the risk of HTN was increased in women with multiple gestations (HR 1.35, 95% CI 1.19, 1.54) compared with those with singleton after adjustment for age, primiparity, preeclampsia, atrial fibrillation, body mass index, blood pressure, diabetes mellitus, high total cholesterol, abnormal liver function test, regular exercise, and smoking status. CONCLUSIONS: Multiple gestations are associated with an increased risk of HTN later in life. Therefore, guidelines for the management of high-risk patients after delivery should be established.

Prediction of newborn's body mass index using nationwide multicenter ultrasound data: a machine-learning study.

BACKGROUND: This study introduced machine learning approaches to predict newborn's body mass index (BMI) based on ultrasound measures and maternal/delivery information. METHODS: Data came from 3159 obstetric patients and their newborns enrolled in a multi-center retrospective study. Variable importance, the effect of a variable on model performance, was used for identifying major predictors of newborn's BMI among ultrasound measures and maternal/delivery information. The ultrasound measures included biparietal diameter (BPD), abdominal circumference (AC) and estimated fetal weight (EFW) taken three times during the week 21 - week 35 of gestational age and once in the week 36 or later. RESULTS: Based on variable importance from the random forest, major predictors of newborn's BMI were the first AC and EFW in the week 36 or later, gestational age at delivery, the first AC during the week 21 - the week 35, maternal BMI at delivery, maternal weight at delivery and the first BPD in the week 36 or later. For predicting newborn's BMI, linear regression (2.0744) and the random forest (2.1610) were better than artificial neural networks with one, two and three hidden layers (150.7100, 154.7198 and 152.5843, respectively) in the mean squared error. CONCLUSIONS: This is the first machine-learning study with 64 clinical and sonographic markers for the prediction of newborns' BMI. The week 36 or later is the most effective period for taking the ultrasound measures and AC and EFW are the best predictors of newborn's BMI alongside gestational age at delivery and maternal BMI at delivery.

Effect of patient blood management system and feedback programme on appropriateness of transfusion: An experience of Asia's first Bloodless Medicine Center on a hospital basis.

BACKGROUND: Patient blood management (PBM) programmes minimise red blood cell (RBC) transfusion and improve patient outcomes worldwide. This study evaluated the effect of a multidisciplinary, collaborative PBM programme on the appropriateness of RBC transfusion in medical and surgical departments at a hospital level. METHODS/MATERIALS: In 2018, the revised PBM programme was launched at the Korea University Anam Hospital, a tertiary hospital with 1048 hospital beds and the first Asian institution where a new computer PBM programme was implemented. Monthly RBC usage and adequacy were analysed from January 2018 to December 2019. The trend of adequacy over time was assessed. RESULTS: A total of 2 201 021 patients were hospitalised and visited an outpatient clinic. The number of RBC units transfused per 10 000 patients decreased from 139.8 for 2018 to 137.3 for 2019. The proportion of patients with Hb <7 g/dL receiving RBC transfusion increased significantly: 29.1%, 34.5%, 40.4% and 40.6% for periods 1, 2, 3 and 4, respectively (p < 0.001). The appropriateness of RBC transfusion significantly increased for medical (35.2%, 41.5%, 49.6% and 74.3% for periods 1, 2, 3 and 4, respectively [p < 0.001]) and surgical (37.8%, 33.3%, 45.5% and 71.1% for periods 1, 2, 3 and 4, respectively [p < 0.001]) departments. CONCLUSION: Implementation of a PBM programme through a multidisciplinary clinical community approach increased the appropriateness of RBC transfusion in medical and surgical departments. Therefore, expanding publicity and PBM education to health care providers is important to maintain the appropriateness of blood transfusion.

Association of Gastroesophageal Reflux Disease with Preterm Birth: Machine Learning Analysis.

BACKGROUND: This study used machine learning and population data for testing the associations of preterm birth with gastroesophageal reflux disease (GERD) and periodontitis. METHODS: Retrospective cohort data came from Korea National Health Insurance Service claims data for all women who aged 25-40 years and gave births for the first time as singleton pregnancy during 2015-2017 (405,586 women). The dependent variable was preterm birth during 2015-2017 and the independent variables were GERD (coded as no vs. yes) for each of the years 2002-2014, periodontitis (coded as no vs. yes) for each of the years 2002-2014, age (year) in 2014, socioeconomic status in 2014 measured by an insurance fee, and region (city) (coded as no vs. yes) in 2014. Random forest variable importance was adopted for finding main predictors of preterm birth and testing its associations with GERD and periodontitis. RESULTS: Based on random forest variable importance, main predictors of preterm birth during 2015-2017 were socioeconomic status in 2014, age in 2014, GERD for the years 2012, 2014, 2010, 2013, 2007 and 2009, region (city) in 2014 and GERD for the year 2006. The importance rankings of periodontitis were relatively low. CONCLUSION: Preterm birth has a stronger association with GERD than with periodontitis. For the prevention of preterm birth, preventive measures for GERD would be essential together with the improvement of socioeconomic status for pregnant women. Especially, it would be vital to promote active counseling for general GERD symptoms (neglected by pregnant women).

Role of sex hormones in cervical changes in a cervical excision-related preterm delivery mouse model.

Progesterone and oestrogen play important roles during parturition; however, their roles in the uterine cervix during preterm labour and delivery are unknown. We evaluated the serum progesterone and oestrogen levels and changes in their receptors (PR and ER) in the cervix in a cervical excision-associated preterm delivery mouse model. Adult female C57BL/6 mice were divided into four groups: sham, cervical excision (Ex), lipopolysaccharide (LPS) and Ex + LPS. Mating was permitted at 3 weeks post-Ex. On gestation day 16, mice were administered LPS intrauterine (100 µg/100 µL/mouse) or physiological saline (100 µL) via laparotomy. Uterine cervices and blood were sampled immediately postpartum. As a result, epithelial PR and muscular ERα were down- and upregulated, respectively, in the proximal cervix in Ex + LPS group compared to in the sham group. These results indicate that unique sex hormone effects are exerted on the uterine cervix during cervical excision-associated spontaneous preterm labour and delivery.Impact statementWhat is already known on this subject? Preterm and term parturition require the withdrawal of progesterone and the activation of oestrogen in the uterine body and systemic levels. However, we have little understanding of the role of the sex hormones in the uterine cervix.What do the results of this study add? Increased ERα-to-PR expression ratio in the proximal cervix was associated with preterm labour and delivery. ERα expression in the smooth muscle layer of the proximal cervix was higher and PR expression in the proximal cervix epithelium was lower during preterm labour and delivery.What are the implications of these findings for clinical practice and/or further research? This study revealed the differences between the roles of sex hormones and their receptors in epithelial and muscle layers of proximal and distal cervices in preterm labour and delivery.

Determinants of Spontaneous Preterm Labor and Birth Including Gastroesophageal Reflux Disease and Periodontitis.

BACKGROUND: Periodontitis is reported to be associated with preterm birth (spontaneous preterm labor and birth). Gastroesophageal reflux disease (GERD) is common during pregnancy and is expected to be related to periodontitis. However, little research has been done on the association among preterm birth, GERD and periodontitis. This study uses popular machine learning methods for analyzing preterm birth, GERD and periodontitis. METHODS: Data came from Anam Hospital in Seoul, Korea, with 731 obstetric patients during January 5, 1995 - August 28, 2018. Six machine learning methods were applied and compared for the prediction of preterm birth. Variable importance, the effect of a variable on model performance, was used for identifying major determinants of preterm birth. RESULTS: In terms of accuracy, the random forest (0.8681) was similar with logistic regression (0.8736). Based on variable importance from the random forest, major determinants of preterm birth are delivery and pregestational body mass indexes (BMI) (0.1426 and 0.1215), age (0.1211), parity (0.0868), predelivery systolic and diastolic blood pressure (0.0809 and 0.0763), twin (0.0476), education (0.0332) as well as infant sex (0.0331), prior preterm birth (0.0290), progesterone medication history (0.0279), upper gastrointestinal tract symptom (0.0274), GERD (0.0242), Helicobacter pylori (0.0151), region (0.0139), calcium-channel-blocker medication history (0.0135) and gestational diabetes mellitus (0.0130). Periodontitis ranked 22nd (0.0084). CONCLUSION: GERD is more important than periodontitis for predicting and preventing preterm birth. For preventing preterm birth, preventive measures for hypertension, GERD and diabetes mellitus would be needed alongside the promotion of effective BMI management and appropriate progesterone and calcium-channel-blocker medications.

Effect of Cervical Cerclage on the Risk of Recurrent Preterm Birth after a Twin Spontaneous Preterm Birth.

BACKGROUND: This study aimed to evaluate the effect of cervical cerclage on the recurrence risk for preterm birth in singleton pregnant women after a twin spontaneous preterm birth (sPTB). METHODS: This multicenter retrospective cohort study included women who had a singleton pregnancy from January 2009 to December 2018 at 10 referral hospitals and a twin sPTB before the current pregnancy. We compared the cervical lengths during pregnancy and pregnancy outcomes, according to the placement of prophylactic or emergency cerclage. We evaluated the independent risk factors for sPTB (< 37 weeks of gestation) in a subsequent singleton pregnancy. RESULTS: For the index singleton pregnancy, preterm birth occurred in seven (11.1%) of 63 women. There was no significant difference in the cervical lengths during pregnancy in women with and without cerclage. In a multivariate logistic regression analysis, the placement of emergency cerclage was an independent risk factor for subsequent singleton preterm birth (odds ratio [OR], 93.188; 95% confidence interval [CI], 1.633-5,316.628; P = 0.027); however, the placement of prophylactic cerclage (OR, 19.264; 95% CI, 0.915-405.786; P = 0.057) was not a factor. None of the women who received prophylactic cerclage delivered before 35 weeks' gestation in the index singleton pregnancy. CONCLUSION: Cerclage did not lower the risk of preterm birth in a subsequent singleton pregnancy after a twin sPTB. However, emergency cerclage was an independent risk factor for preterm birth and there was no preterm birth before 35 weeks' gestation in the prophylactic cerclage group. Therefore, close monitoring of the cervical length and prophylactic cerclage might be considered in women who have experienced a twin sPTB at extreme gestation.

Serum sFlt-1, cystatin C and cathepsin B are potential severity markers in preeclampsia: a pilot study.

PURPOSE: Preeclampsia is associated with abnormal invasion of the trophoblast through decidua and subsequently altered remodeling of the maternal spiral arteries and endothelial dysfunction. This phenomenon is explained by the dysregulation of various kinds of vascular factors and proteases. The purpose of this study was to compare the circulating levels of sFlt-1, cathepsin B, and cystatin C in preeclamptic and normotensive pregnancies. STUDY DESIGN: Sixty-two pregnant women were enrolled in this prospective study. Twenty women were preeclamptic and 42 were normotensive. Serum levels of sFlt-1, cathepsin B, and cystatin C were measured using an enzyme-linked immunosorbent assay kit. RESULTS: Circulating levels of sFlt-1, cathepsin B, and cystatin C were significantly higher in preeclamptic than in normotensive pregnant women (p < 0.001; p = 0.017; p = 0.003). Preeclamptic women with severe features demonstrated significantly higher levels of cathepsin B (p = 0.05). Serum sFlt-1 and cystatin C levels were positively correlated with elevated systolic and diastolic blood pressure. The levels of cathepsin B were positively correlated with alanine and aspartate aminotransferase. The amount of 24 h proteinuria was positively, but non-significantly correlated with sFlt-1 and cystatin C. CONCLUSIONS: In addition to sFlt-1 levels, the serum levels of cathepsin B and cystatin C significantly change when preeclampsia develops. These markers are associated with severity markers of elevated blood pressure and liver injury in preeclampsia.

Predicting peripartum blood transfusion: focusing on pre-pregnancy characteristics.

BACKGROUND: Obstetric hemorrhage is one of the most common causes of obstetrical morbidity and mortality, and transfusion is the most important management for hemorrhage. The aim of our study was to investigate the pre-pregnancy and pregnancy risk factors for peripartum transfusion. METHODS: Women who delivered a baby from 2010 to 2014 in Korea and participated in the Korean National Health Screening Program for Infants and Children were included. To analyze pre-pregnant risk factors for peripartum transfusion, an additional analysis was done for women who underwent a National Health Screening Examination within 1 year before pregnancy, including maternal waist circumference, body mass index, blood pressure, laboratory tests and history of smoking. Multivariable logistic regression analysis was used to estimate the risk factors for peripartum transfusion. RESULTS: Of the total 1,980,126 women who met the inclusion criteria, 36,868 (1.86%) were transfused at peripartum. In a multivariable regression model, the pregnancy risk factors for peripartum transfusion included maternal age above 35 years [odds ratio (OR): 1.41; 95% confidence interval (CI): 1.32-1.50], preterm birth (OR: 2.39; 95% CI: 2.15-2.65), and maternal hypertension (OR: 2.49; 95% CI: 2.24-2.77). Pre-pregnancy risk factors including fasting glucose level of more than 126 mg/dL (OR: 1.11; 95% CI: 1.02-1.20), current-smoker status (OR: 1.20; 95% CI: 1.06-1.37), and waist-circumference less than 80 cm (OR: 1.18; 95% CI: 1.06-1.30) were independently associated with peripartum blood transfusion. CONCLUSIONS: Several pre-pregnancy and pregnancy risk factors were associated with peripartum blood transfusion. Some identified factors are modifiable before conception, and our study validated peripartum blood transfusion as a form of triage.