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Objective Adenomyosis impacts pregnancy outcomes, although there is a lack of consensus regarding the actual effects. It is likely, however, that the severity of adenomyosis or ultrasound findings or timing of diagnosis can have different effects on adverse pregnancy outcomes (APOs). Methods In this study, we aimed to investigate the impact of the timing of adenomyosis diagnosis on pregnancy outcomes. Singleton pregnant women who delivered between 2017 and 2022 were analyzed based on the timing of adenomyosis diagnosis, using a national database. The final cohort was classified into three groups: 1) group 1, without adenomyosis; 2) group 2, those diagnosed with adenomyosis before pregnancy; and 3) group 3, those diagnosed with adenomyosis during pregnancy. Results A total of 1,226,475 cases were ultimately included in this study. Women with a diagnosis of adenomyosis had a significantly higher risk of APOs including hypertensive disorder during pregnancy (HDP), gestational diabetes mellitus (GDM), postpartum hemorrhage, placental abruption, preterm birth, and delivery of a small-for-gestational-age infant even after adjusting for covariates. In particular, concerning HDP, the risk was highest in group 3 (group 2: adjusted odds ratio [aOR], 1.15 vs. group 3: aOR, 1.36). However, the highest GDM risk was in group 2 (GDM; group 2: aOR, 1.24 vs. group 3: aOR, 1.04). Conclusion The increased risk of APO differed depending on the timing of adenomyosis diagnosis. Therefore, efforts for more careful monitoring and prevention of APOs may be necessary when such women become pregnant.

Abstract Recent studies reported the long-term cardiovascular risk of preeclampsia. However, only a few studies have investigated the association between preeclampsia and long-term cardiovascular disease in Asian populations, although there could be racial/ethnic differences in the risk of cardiovascular diseases. Therefore, we aimed to evaluate the long-term effects of preeclampsia on cardiovascular disease in an Asian population. This study included 68,658 parous women in the Health Examinees Study (HEXA) cohort of South Korea and compared the risk of long-term cardiovascular disease, including ischemic heart disease and stroke, according to the history of preeclampsia. We also performed a meta-analysis combining current study data with data from existing literature in the Asian population. Among the study population, 3413 (5.23%) women had a history of preeclampsia, and 767 (1.12%) and 404 (0.59%) women developed ischemic heart disease and stroke for 22 years. Women with a history of preeclampsia were at a higher risk for both ischemic heart disease (adjusted hazard ratio 1.66 [1.19–2.04]) and stroke (adjusted hazard ratio 1.48 [1.02–2.16]) than those without. In the meta-analysis, the pooled hazard ratio of ischemic heart disease and stroke were also increased in women with a history of preeclampsia (ischemic heart disease 1.65 [1.51–1.82]; stroke 1.78 [1.52–2.10]).

Background Perioperative stroke is a severe complication following surgery. To identify patients at risk for perioperative stroke, several prediction models based on the preoperative factors were suggested. Prediction models often focus on preoperative patient characteristics to assess stroke risk. However, most existing models primarily base their predictions on the patient's baseline characteristics before surgery. We aimed to develop a machine‐learning model incorporating both pre‐ and intraoperative variables to predict perioperative stroke. Methods and Results This study included patients who underwent noncardiac surgery at 2 hospitals with the data of 15 752 patients from Seoul National University Hospital used for development and temporal internal validation, and the data of 449 patients from Boramae Medical Center used for external validation. Perioperative stroke was defined as a newly developed ischemic lesion on diffusion‐weighted imaging within 30 days of surgery. We developed a prediction model composed of pre‐ and intraoperative factors (integrated model) and compared it with a model consisting of preoperative features alone (preoperative model). Perioperative stroke developed in 109 (0.69%) patients in the Seoul National University Hospital group and 11 patients (2.45%) in the Boramae Medical Center group. The integrated model demonstrated superior predictive performance with area under the curve values of 0.824 (95% CI, 0.762–0.880) versus 0.584 (95% CI, 0.499–0.667; P

IntroductionAlthough the safety and effectiveness of COVID-19 vaccination during pregnancy have been proven, there is still little data explaining neonatal outcomes of maternal pre-pregnancy vaccination.MethodsHere, we investigated the impact of vaccination and SARS-CoV-2 infection on maternal-neonate immune response in a cohort study involving 141 pregnant individuals, and defined the importance of maternal COVID-19 vaccination timing for its effectiveness.Results and discussionOur data indicate that vertically transferred maternal hybrid immunity provides significantly better antiviral protection for a neonate than either maternal post-infection or post-vaccination immunity alone. Higher neutralization potency among mothers immunized before pregnancy and their newborns highlights the promising role of pre-pregnancy vaccination in neonatal protection. A comparison of neutralizing antibody titers calculated for each dyad suggests that infection and pre-/during-pregnancy vaccination all support transplacental transfer, providing the offspring with strong passive immunity against SARS-CoV-2. Analysis of neutralizing antibody levels in maternal sera collected during pregnancy and later during delivery shows that immunization may exert a positive effect on maternal protection.

This study aimed to assess the current status of gestational diabetes mellitus (GDM) diagnosis and management, and the demand for a digital healthcare system, in order to develop an optimal digital-based management model for GDM. An anonymous online survey was conducted targeting pregnant/postpartum women (Group W), internal medicine physicians (Group P), and obstetricians (group O) from September 6, 2022 to December 31, 2022. The survey assessed the women’s knowledge of GDM and gathered information about healthcare professionals’ (HCPs) current GDM management practices. All groups were asked about their acceptance of and demands for a digital healthcare system for GDM. Statistical comparisons between groups were conducted using the chi-square test or Fisher’s exact test where appropriate. A total of 168 participants were in Group W, 185 in Group P, and 256 in Group O. Participants from all groups recognized the need for a digital healthcare system for GDM (Group W: 95.8%, Group P: 85.9%, Group O: 60%). However, HCPs showed less willingness to integrate these systems into their clinics than pregnant/postpartum women. Essential features identified were recording blood glucose levels and insulin, along with automatic data linkage from self-monitoring devices. Group W showed a higher preference for lab test access, search functionality, and fetal weight assessment than groups P and O (all P

Background & Aims: Adverse pregnancy outcomes (APOs) can worsen cardiometabolic risk factors in women, raising their likelihood of developing cardiometabolic diseases at a young age after their initial pregnancy. Nevertheless, there are limited data on the risk of newly developing metabolic dysfunction-associated steatotic liver disease (MASLD) in women who have had APOs. This study aimed to evaluate the risk of new-onset MASLD after experiencing APOs. Methods: Singleton pregnant women who underwent national health screenings 1 year before pregnancy and 1 year after delivery were included in this study. APOs were defined as the presence of at least one of the followings: hypertensive disorders of pregnancy (HDP), gestational diabetes mellitus (GDM), preterm birth, low birth weight, and placental abruption. The primary outcome was new-onset MASLD based on the presence of APOs. Results: Among 80,037 study participants, 9,320 (11.6%) experienced APOs during pregnancy. Women who experienced APOs had an increased risk of developing new-onset MASLD after delivery even after adjustments for various covariates (adjusted odds ratio [OR] 1.58, 95% CI 1.45–1.72). In particular, women who experienced either HDP or GDM showed a significantly increased risk of developing new-onset MASLD (adjusted OR 2.20, 95% CI 1.81–2.67, for HDP and adjusted OR 1.83, 95% CI 1.65–2.03, for GDM). Moreover, there was a tendency toward an increased risk of new-onset MASLD according to the number of APOs (p

Summary: Expression quantitative trait loci (eQTL) analysis measures the contribution of genetic variation in gene expression on complex traits. Although this methodology has been used to examine gene regulation in numerous human tissues, eQTL research in solid tissues is relatively lacking. We conducted eQTL analysis on placentas collected from an East Asian population in an effort to identify gene regulatory mechanisms in this tissue. Placentas (n = 102) were collected at the time of cesarean delivery. mRNA was extracted, sequenced with NGS, and compared with matched maternal and fetal DNA arrays performed using maternal and neonatal cord blood. Linear regression modeling was performed using tensorQTL. Fine-mapping along with epigenomic annotation was used to select putative functional variants. We identified 2,703 coding genes that contained at least one eQTL with statistical significance (false discovery rate 0.1. Of these, 19% were located in genomic regions with evidence from public placental epigenome suggesting that they may be functionally relevant. For example, variant rs28379289 located in the placenta-specific regulatory region changes the binding affinity of transcription factor leading to higher expression of LGALS3, which is known to affect placental function. This study expands the knowledge base of regulatory elements within the human placenta and identifies 108 previously unreported placenta eQTL signals, which are listed in our publicly available GMI eQTL database. Further studies are needed to identify and characterize genetic regulatory mechanisms that affect placental function in normal pregnancy and placenta-related diseases.

Abstract Background Computational drug repurposing is crucial for identifying candidate therapeutic medications to address the urgent need for developing treatments for newly emerging infectious diseases. The recent COVID-19 pandemic has taught us the importance of rapidly discovering candidate drugs and providing them to medical and pharmaceutical experts for further investigation. Network-based approaches can provide repurposable drugs quickly by leveraging comprehensive relationships among biological components. However, in a case of newly emerging disease, applying a repurposing methods with only pre-existing knowledge networks may prove inadequate due to the insufficiency of information flow caused by the novel nature of the disease. Methods We proposed a network-based complementary linkage method for drug repurposing to solve the lack of incoming new disease-specific information in knowledge networks. We simulate our method under the controlled repurposing scenario that we faced in the early stage of the COVID-19 pandemic. First, the disease-gene-drug multi-layered network was constructed as the backbone network by fusing comprehensive knowledge database. Then, complementary information for COVID-19, containing data on 18 comorbid diseases and 17 relevant proteins, was collected from publications or preprint servers as of May 2020. We estimated connections between the novel COVID-19 node and the backbone network to construct a complemented network. Network-based drug scoring for COVID-19 was performed by applying graph-based semi-supervised learning, and the resulting scores were used to validate prioritized drugs for population-scale electronic health records-based medication analyses. Results The backbone networks consisted of 591 diseases, 26,681 proteins, and 2,173 drug nodes based on pre-pandemic knowledge. After incorporating the 35 entities comprised of complemented information into the backbone network, drug scoring screened top 30 potential repurposable drugs for COVID-19. The prioritized drugs were subsequently analyzed in electronic health records obtained from patients in the Penn Medicine COVID-19 Registry as of October 2021 and 8 of these were found to be statistically associated with a COVID-19 phenotype. Conclusion We found that 8 of the 30 drugs identified by graph-based scoring on complemented networks as potential candidates for COVID-19 repurposing were additionally supported by real-world patient data in follow-up analyses. These results show that our network-based complementary linkage method and drug scoring algorithm are promising strategies for identifying candidate repurposable drugs when new emerging disease outbreaks.

Fetal growth restriction (FGR) is one of the leading causes of perinatal morbidity and mortality. Many studies have reported an association between FGR and fetal Doppler indices focusing on umbilical artery (UA), middle cerebral artery (MCA), and ductus venosus (DV). The uteroplacental-fetal circulation which affects the fetal growth consists of not only UA, MCA, and DV, but also umbilical vein (UV), placenta and uterus itself. Nevertheless, there is a paucity of large-scale cohort studies that have assessed the association between UV, uterine wall, and placental thickness with perinatal outcomes in FGR, in conjunction with all components of the uteroplacental-fetal circulation. Therefore, this multicenter study will evaluate the association among UV absolute flow, placental thickness, and uterine wall thickness and adverse perinatal outcome in FGR fetuses. This multicenter retrospective cohort study will include singleton pregnant women who undergo at least one routine fetal ultrasound scan during routine antepartum care. Pregnant women with fetuses having structural or chromosomal abnormalities will be excluded. The U-AID indices (UtA, UA, MCA, and UV flow, placental and uterine wall thickness, and estimated fetal body weight) will be measured during each trimester of pregnancy. The study population will be divided into two groups: (1) FGR group (pregnant women with FGR fetuses) and (2) control group (those with normal growth fetus). We will assess the association between U-AID indices and adverse perinatal outcomes in the FGR group and the difference in U-AID indices between the two groups.

Objective Hypertensive disease during pregnancy increases the risk of maternal morbidity and mortality and leads to the development of multi-organ dysfunction, including kidney dysfunction. Complicated pregnancies require careful postpartum management to prevent sequelae. It is believed that kidney injury can consistently occur even after delivery; therefore, defining the chronicity and endpoint is essential for establishing diagnostic criteria. However, data on the prevalence of persistent renal complications following hypertensive disease during pregnancy are limited. In this study, we evaluated the risk of developing renal disorders in patients with a history of hypertensive disease during pregnancy. Methods Participants who gave birth between 2009 and 2010 were followed up for 8 years after delivery. The risk of renal disorder development after delivery was determined according to a history of hypertensive disease during pregnancy. Different factors that could affect the course of pregnancy, including age, primiparity, multiple pregnancy, preexisting hypertension, pregestational diabetes, hypertensive disease during pregnancy, gestational diabetes, postpartum hemorrhage, and cesarean section, were adjusted for using the Cox hazard model. Results Women with hypertension during pregnancy had a higher risk of developing renal disorders after delivery (0.23% vs. 1.38%; P

Adnexal masses detected during pregnancy require a prompt and accurate diagnosis to ensure fetal safety and good oncological outcomes. Computed tomography is the most common and useful diagnostic imaging modality for diagnosing adnexal masses; however, it is contraindicated in pregnant women because of the teratogenic effect of radiation on the fetus. Therefore, ultrasonography (US) is commonly used as the main alternative for the differential diagnosis of adnexal masses during pregnancy. Additionally, magnetic resonance imaging (MRI) can assist in the diagnosis when US findings are inconclusive. As each disease has characteristic US and MRI findings, understanding these features is important for the initial diagnosis and subsequent treatment. Thus, we thoroughly reviewed the literature and summarized the key findings of US and MRI to apply these in real-world clinical practice for various adnexal masses detected during pregnancy.

Abstract Background In twin pregnancies complicated by selective fetal growth restriction (sFGR), if the smaller twin is in the state of impending intra-uterine death (IUD), immediate delivery will reduce the risk of IUD of the smaller twin while exposing the larger twin to iatrogenic preterm birth (PTB). Therefore, the management options would either be to maintain pregnancy for the maturation of the larger twin despite the risk of IUD of the smaller twin or immediate delivery to prevent IUD of the smaller twin. However, the optimal gestational age of management transition from maintaining pregnancy to immediate delivery has not been established. The objective of this study was to evaluate the physician’s perspective on the optimal timing of immediate delivery in twin pregnancies complicated by sFGR. Methods An online cross-sectional survey was performed with obstetricians and gynecologists (OBGYN) in South Korea. The questionnaire asked the following: (1) whether participants would maintain or immediately deliver a twin pregnancy complicated by sFGR with signs of impending IUD of the smaller twin; (2) the optimal gestational age of management transition from maintaining pregnancy to immediate delivery in a twin pregnancy with impending IUD of the smaller twin; and (3) the limit of viability and intact survival in general preterm neonates. Results A total of 156 OBGYN answered the questionnaires. In a clinical scenario of dichorionic (DC) twin pregnancy complicated by sFGR with signs of impending IUD of the smaller twin, 57.1% of the participants answered that they would immediately deliver the twin pregnancy. However, 90.4% answered that they would immediately deliver the pregnancy in the same scenario for monochorionic (MC) twin pregnancy. The participants designated 30 weeks for DC twin and 28 weeks for MC twin pregnancies as the optimal gestational age of management transition from maintaining pregnancy to immediate delivery. The participants regarded 24 weeks as the limit of viability and 30 weeks as the limit of intact survival in general preterm neonates. The optimal gestational age of management transition for DC twin pregnancy was correlated with the limit of intact survival in general preterm neonates (p

Abstract Background Cleansing of the vulva and perineum is recommended during preparation for vaginal delivery, and special attention is paid to cleansing before episiotomy because episiotomy is known to increase the risk of perineal wound infection and/or dehiscence. However, the optimal method of perineal cleansing has not been established, including the choice of antiseptic agent. To address this issue, we designed a randomized controlled trial to examine whether skin preparation with chlorhexidine-alcohol is superior to povidone-iodine for the prevention of perineal wound infection after vaginal delivery. Methods In this multicenter randomized controlled trial, term pregnant women who plan to deliver vaginally after episiotomy will be enrolled. The participants will be randomly assigned to use antiseptic agents for perineal cleansing (povidone-iodine or chlorhexidine-alcohol). The primary outcome is superficial or deep perineal wound infection within 30 days after vaginal delivery. The secondary outcomes are the length of hospital stay, physician office visits, or hospital readmission for infection-related complications, endometritis, skin irritations, and allergic reactions. Discussion This study will be the first randomized controlled trial aiming to determine the optimal antiseptic agent for the prevention of perineal wound infections after vaginal delivery. Trial registration ClinicalTrials.gov NCT05122169. First submitted date on 8 November 2021. First posted date on 16 November 2021

Abstract Background Pre-eclampsia (PE) is a pregnancy disorder that is related to an enhanced immune response. Immune cell characteristics such as neutrophil or monocyte to lymphocyte ratios (NLR, MLR) are known to be related to kidney and liver dysfunction in hypertensive patients. Here, we aimed to analyze the correlations between NLR, MLR and platelet to lymphocyte ratio (PLR) and liver, renal and coagulation functional parameters and the impacts of these immune cell profiles to the prognostic significance in PE patients. Methods Pre-delivery hematological and biochemical parameters of 320 first-time pregnant women registered at the Obstetrics Department of Yanbian University Hospital from 2016 to 2019 were analyzed retrospectively. Patients were divided into normal pregnancy (normal, n = 161), mild PE (mPE, n = 28) and severe PE (sPE, n = 131) groups according to diagnostic criteria. Pearson correlation analysis were performed and area under the curve (AUC) were conducted for the diagnostic values of NLR, MLR and PLR. Results were validated with data from the Department of Obstetrics and Gynecology of Seoul National University Hospital (SNUH). Results Kidney functional indexes were adversative in mPE and sPE and liver and coagulation indexes were worse in sPE compared to normal groups. Among immune cells, lymphocytes were increased in mPE and sPE patients, resulted in reduced NLR, MLR and PLR in PE groups, more significant difference were shown in sPE. NLR and PLR were associated with CREA and/or BUN negatively and positive associations were observed with total protein (TP) and albumin (ALB) in sPE. Only NLR showed positive associations with coagulation indexes (PT and APTT) in sPE. AUC analysis for NLR, MLR and PLR were 0.700, 0.656, 0.643, respectively, and NLR

Abstract Background Previous studies showed that gestational diabetes mellitus (GDM) can be a risk factor for subsequent atherosclerotic cardiovascular disease. However, there is a paucity of information regarding diverse cardiovascular outcomes in elderly women after GDM. In the current study, we examined whether women with a history of GDM have an increased risk for long-term overall cardiovascular outcomes. Methods Among the UK participants, we included 219,330 women aged 40 to 69 years who reported at least one live birth. The new incidence of diverse cardiovascular outcomes was compared according to GDM history by multivariable Cox proportional hazard models. In addition, causal mediation analysis was performed to examine the contribution of well-known risk factors to observed risk. Results After enrollment, 13,094 women (6.0%) developed new overall cardiovascular outcomes. Women with GDM history had an increased risk for overall cardiovascular outcomes [adjusted HR (aHR) 1.36 (95% CI 1.18–1.55)], including coronary artery disease [aHR 1.31 (1.08–1.59)], myocardial infarction [aHR 1.65 (1.27–2.15)], ischemic stroke [aHR 1.68 (1.18–2.39)], peripheral artery disease [aHR 1.69 (1.14–2.51)], heart failure [aHR 1.41 (1.06–1.87)], mitral regurgitation [aHR 2.25 (1.51–3.34)], and atrial fibrillation/flutter [aHR 1.47 (1.18–1.84)], after adjustment for age, race, BMI, smoking, early menopause, hysterectomy, prevalent disease, and medication. In mediation analysis, overt diabetes explained 23%, hypertension explained 11%, and dyslipidemia explained 10% of the association between GDM and overall cardiovascular outcome. Conclusions GDM was associated with more diverse cardiovascular outcomes than previously considered, and conventional risk factors such as diabetes, hypertension, and dyslipidemia partially contributed to this relationship.

Abstract Nanoscale defects in two-dimensional (2D) transition metal dichalcogenides (TMDs) alter their intrinsic optical and electronic properties, and such defects require investigation. Atomic-resolution techniques such as transmission electron microscopy detect nanoscale defects accurately but are limited in terms of clarifying precise chemical and optical characteristics. In this study, we investigated nanoscale heterogeneous defects in a single-crystalline hexagonal WS2 monolayer using tip-enhanced Raman spectroscopy (TERS). We observed the Raman properties of heterogeneous defects, which are indicated by the shifted A 1′(Γ) modes appearing on the W- and S-edge domains, respectively, with defect-induced Raman (D) mode. In the edge region, various Raman features occur with nanoscale defects. In addition, the TERS signals from single-crystalline WS2 indicate the existence of two majority defects in each domain, which imply S- and W-dominated vacancies. Quantum mechanical computations were performed for each majority defect and demonstrated the defect-induced variation in the vibrational phonon modes. TERS imaging promises to be a powerful technique for determining assorted nanoscale heterogeneous defects as well as for investigating the properties of other nanomaterials.

Abstract Clinical guidelines recommend several risk factors to identify women in early pregnancy at high risk of developing pregnancy-associated hypertension. However, these variables result in low predictive accuracy. Here, we developed a prediction model for pregnancy-associated hypertension using graph-based semi-supervised learning. This is a secondary analysis of a prospective study of healthy pregnant women. To develop the prediction model, we compared the prediction performances across five machine learning methods (semi-supervised learning with both labeled and unlabeled data, semi-supervised learning with labeled data only, logistic regression, support vector machine, and random forest) using three different variable sets: [a] variables from clinical guidelines, [b] selected important variables from the feature selection, and [c] all routine variables. Additionally, the proposed prediction model was compared with placental growth factor, a predictive biomarker for pregnancy-associated hypertension. The study population consisted of 1404 women, including 1347 women with complete follow-up (labeled data) and 57 women with incomplete follow-up (unlabeled data). Among the 1347 with complete follow-up, 2.4% (33/1347) developed pregnancy-associated HTN. Graph-based semi-supervised learning using top 11 variables achieved the best average prediction performance (mean area under the curve (AUC) of 0.89 in training set and 0.81 in test set), with higher sensitivity (72.7% vs 45.5% in test set) and similar specificity (80.0% vs 80.5% in test set) compared to risk factors from clinical guidelines. In addition, our proposed model with graph-based SSL had a higher performance than that of placental growth factor for total study population (AUC, 0.71 vs. 0.80, p

The application of explainable artificial intelligence in nanomaterial research has emerged in the past few years, which has facilitated the discovery of novel physical findings. However, a fundamental question arises concerning the physical insights presented by deep neural networks; the model interpretation results have not been carefully evaluated. Herein, explainable artificial intelligence and quantum mechanical calculations is bridged to investigate the correlation between light scattering and emission in a WSe2 monolayer. Convolutional neural networks using light scattering and emission data are first trained, while expecting the networks to determine the relationships between them. The trained models are interpreted and the specific phonon contribution during the exciton relaxation process is derived. Finally, the findings are independently evaluated through quantum mechanical calculations, such as the Born–Oppenheimer molecular dynamics simulation and density functional perturbation theory. The study provides reliable fundamental physical insight by evaluating the results of neural networks and suggests a novel methodology that can be applied in materials science.

Objectives The aim of this study was to determine the risk of congenital malformations in offspring born to women with systemic lupus erythematosus (SLE).Methods This nationwide population-based study included Korean women who had a singleton pregnancy. The risk of congenital malformations in women with SLE was compared with those without SLE. Multivariable analyses were performed to estimate the OR of congenital malformations. In a sensitivity analysis, the risk of malformation was compared between the offspring of women with SLE and those of propensity-matched women without SLE.Results Of a total of 3 279 204 pregnant women, 0.1% had SLE and their offspring had a higher frequency of congenital malformations (17.13% vs 11.99%, p

Abstract Background Hypertension has been known to increase the risk of obstetric complications. Recently, the American College of Cardiology endorsed lower thresholds for hypertension as systolic blood pressure of 130-139 mmHg or diastolic blood pressure 80-89 mmHg. However, there is a paucity of information regarding the impact of pre-pregnancy blood pressure on pregnancy outcomes. We aimed to evaluate the effect of pre-pregnancy blood pressure on maternal and neonatal complications. Methods In this nationwide, population based study, pregnant women without history of hypertension and pre-pregnancy blood pressure

Background: In the era of coronavirus disease 2019 (COVID-19) pandemic, there is a paucity of information regarding actual prevalence of COVID-19 in pregnant women compared to non-pregnant women. The purpose of this study was to investigate the prevalence of COVID-19 infection and clinical outcome in pregnant women and non-pregnant women. Methods: This is a nationwide cross-sectional study in South Korea between January 2020 and February 2021 using the claim database. The primary outcome was the prevalence of COVID-19 in pregnant women, and the secondary outcome was the occurrence of severe COVID-19 illness among infected patients. Severity of COVID-19 was classified into four categories according to WHO ordinal scale. Results: The prevalence of COVID-19 infection was lower in pregnant women than non-pregnant women aged 20–44 (0·02% vs. 0.14%, p

Abstract To examine the detection performance of a peptide nucleic acid (PNA) probe-based real-time time polymerase chain reaction (PCR) assay to detect common aneuploidies. Using amniotic fluid samples, PNA probe based real-time PCR (Patio DEP Detection Kit; SeaSun Biomaterials, Korea) assay was performed. PNA probe was designed to hybridize to similar sequences located on different segments of target chromosomes (21, 18, and 13) and a reference chromosome. Amplification of target sequences and melting curve analysis was performed. When analyzing the melting curve, the ratio of the peak height of the target and reference chromosome was calculated and determined as aneuploidy if the ratio of peak height was abnormal. All the results from the PNA probe-based real-time PCR and melting curve analyses were compared to those from conventional karyotyping. Forty-two cases with common aneuploidies (24 of trisomy 21, 12 of trisomy 18, and 6 of trisomy 13) and 131 cases with normal karyotype were analyzed. When comparing the karyotyping results, the sensitivity and specificity of the PNA probe-based real-time PCR assay were both 100%. The level of agreement was almost perfect (k = 1.00). PNA real-time PCR assay is a rapid and easy method for detecting common aneuploidies.

Background/Aims To develop an early prediction model for gestational diabetes mellitus (GDM) using machine learning and to evaluate whether the inclusion of nonalcoholic fatty liver disease (NAFLD)-associated variables increases the performance of model. Methods This prospective cohort study evaluated pregnant women for NAFLD using ultrasound at 10–14 weeks and screened them for GDM at 24–28 weeks of gestation. The clinical variables before 14 weeks were used to develop prediction models for GDM (setting 1, conventional risk factors; setting 2, addition of new risk factors in recent guidelines; setting 3, addition of routine clinical variables; setting 4, addition of NALFD-associated variables, including the presence of NAFLD and laboratory results; and setting 5, top 11 variables identified from a stepwise variable selection method). The predictive models were constructed using machine learning methods, including logistic regression, random forest, support vector machine, and deep neural networks. Results Among 1,443 women, 86 (6.0%) were diagnosed with GDM. The highest performing prediction model among settings 1–4 was setting 4, which included both clinical and NAFLD-associated variables (area under the receiver operating characteristic curve [AUC] 0.563–0.697 in settings 1–3 vs. 0.740–0.781 in setting 4). Setting 5, with top 11 variables (which included NAFLD and hepatic steatosis index), showed similar predictive power to setting 4 (AUC 0.719–0.819 in setting 5, P=not significant between settings 4 and 5). Conclusions We developed an early prediction model for GDM using machine learning. The inclusion of NAFLD-associated variables significantly improved the performance of GDM prediction. (ClinicalTrials.gov Identifier: NCT02276144)

During routine antenatal ultrasound examinations, an ovarian mass can be found incidentally. In clinical practice, the differential diagnosis between benign and malignant ovarian masses is essential for planning further management. Ultrasound imaging has become the most popular diagnostic tool during pregnancy, with the recent development of ultrasonography. In non-pregnant women, several methods have been used to predict malignant ovarian masses before surgery. The International Ovarian Tumor Analysis (IOTA) group reported several scoring systems, such as the IOTA simple rules, IOTA logistic regression models, and IOTA assessment of different NEoplasias in the adneXa. Other researchers have also evaluated the malignancy of ovarian masses before surgery using scoring systems such as the Sassone score, pelvic mass score, DePriest score, Lerner score, and Ovarian-Adnexal Reporting and Data System. These researchers suggested specific features of ovarian masses that can be used for differential diagnosis, including size, proportion of solid tissue, papillary projections, inner wall structure, locules, wall thickness, septa, echogenicity, acoustic shadows, and presence of ascites. Although these factors can also be measured in pregnant women using ultrasound, only a few studies have applied ovarian scoring systems in pregnant women. In this article, we reviewed various scoring systems for predicting malignant tumors of the ovary and determined whether they can be applied to pregnant women.

Abstract We evaluated the relationship between maternal cholesterol levels and its biologically active precursors and metabolites in the first trimester and subsequent risk for small-for-gestational-age birthweight (SGA). This is a secondary analysis of a prospective cohort study which enrolled healthy singleton pregnancies (n = 1337). Maternal fasting blood was taken in the first trimester and followed up till delivery. The lipid parameters were compared between women who delivered SGA neonates (SGA-group, birthweight

Abstract Background To evaluate the self-reported pain scores as a predictor of preterm birth (PTB) in symptomatic twin pregnancy and to develop a nomogram for the prediction model. Methods We conducted a retrospective study of 148 cases of symptomatic twin pregnancies before 34 weeks of gestation visited at Seoul national university hospital from 2013 to 2018. With other clinical factors, self-reported pain score was evaluated by the numerical rating scale (NRS) pain scores for pain intensity. By multivariate analyses and logistic regression, we developed a prediction model for PTB within 7 days. Using the Cox proportional hazards model, the curves were plotted to show the predictability of the PTB according to NRS pain score, while adjusting the other covariates. Results Twenty-three patients (15.5 %) delivered preterm within 7 days. By a logistic regression analysis, higher NRS pain score (OR 1.558, 95 % CI 1.093–2.221, P

Abstract Background The non-invasive prenatal test (NIPT) is based on next generation sequencing (NGS) and is used for screening for fetal trisomy. However, it is time-consuming and technically difficult. Recently, peptide nucleic acid (PNA) probe-based real-time polymerase chain reaction (RT-PCR) was developed. This study aimed to examine the performance of the RT-PCR-based NIPT for screening of common fetal trisomies Methods From stored maternal plasma, RT-PCR was performed using Patio™ NIPT Detection Kit. In melting curve analysis, the height of melting peaks of target chromosome and reference chromosome was calculated as a peak ratio. The adjusted peak ratio of 8 markers with correction factors in each target chromosome was summated and calculated to z-score. The cut-off value for each target chromosome was established for classification (low risk vs. high risk for trisomy) whose performance was obtained in the validation phase. Results 330 plasma samples from pregnant women with normal fetus and 22 trisomy cell-line samples were used to establish the optimal cut-off values for z-score of each target chromosome. In the validation phase, 1023 samples from pregnant women including 22 cases with fetal trisomy and 1001 cases of normal control were used. The RT-PCR-based NIPT showed 95.45% sensitivity [95% confidence interval (CI) 77.16–99.88%], 98.60% specificity (95% CI 97.66–99.23%), and 98.53% accuracy (95% CI 97.59–99.18%) for the identification of trisomy 21, 18, or 13. Of 1023 samples, fifteen cases were mismatched for classification [one case as a false negative (false negative rate: 4.5%) and 14 cases as false positives (false positive rate: 1.4%)]. Conclusion The RT-PCR-based NIPT showed high sensitivity and specificity for the detection of common fetal trisomies and it could be a feasible alternative to NGS-based NIPT.

Background/Aims Because ankylosing spondylitis (AS) mainly affects sacroiliac joints, special attention should be given to normal labour and pregnancy outcomes. Here, we investigate pregnancy outcomes in Korean women with AS. Methods Based on data from the Korean Health Insurance Review and Assessment Service claims database since July 2007, maternal complications were compared between women with AS and 1:10 matched general population by maternal age and year of delivery. Additionally, the 27 deliveries from 21 patients with AS who were seen at a tertiary hospital were retrospectively evaluated using 1:4 matched control group by maternal and gestational age. Results In the population-based cohort, there were 1,293 deliveries in 996 patients with AS. Higher maternal age and more comorbidities were reported than in the general population. However, compared to age and delivery-year matched population, only the rate of Caesarean section (CS) was higher in women with AS (odds ratio, 1.52; 95% confidence interval, 1.36 to 1.70). Incidence of other maternal complications was comparable between women with AS and control subjects. In the hospital-based cohort, the CS rate was higher in women with AS (44.4% vs. 20.4%, p = 0.002). Causes of CS was not different in both groups, including previous uterine surgery. There were no significant differences in foetal outcomes, including growth restriction, foetal malformations and Apgar score. Conclusions CS deliveries were performed more often in women with AS. However, other maternal complications and offspring complications were similar between women with AS and healthy control subjects.

Background: Antenatal magnesium sulfate is widely used as a tocolytic, for maternal seizures, and for seizure prophylaxis in preeclampsia. Recent studies have suggested that antenatal magnesium sulfate use is associated with favorable neurodevelopmental outcomes in preterm infants. However, there are concerns regarding the effects of antenatal magnesium sulfate on neonates, especially regarding gastrointestinal morbidities. This study aims to explore the effects of antenatal magnesium sulfate on intestinal morbidities requiring surgery in preterm infants. Methods: This was a retrospective cohort study of 181 preterm infants who were born at less than 28 weeks of gestational age. Subjects were categorized as infants exposed to antenatal magnesium sulfate and those not exposed to antenatal magnesium sulfate. Results: Antenatal magnesium sulfate was associated with a decreased risk of surgical conditions of the intestine (OR 0.393, 95% CI 0.170–0.905). The multivariate analysis showed that the duration of antenatal magnesium sulfate use was associated with surgical conditions of the intestine (adjusted OR 0.766, 95% CI 0.589–0.997). In the

Abstract Background The introduction of generics after the loss of patent exclusivity plays a major role in budget savings by significantly decreasing drug prices. The aims of this study were to estimate the budget savings from off-patent cancer drugs in 2020–2024 and to inform decision makers on how these savings could be used to improve the affordability of innovative cancer treatments in South Korea. Methods A model was developed to calculate budget savings from off-patent cancer drug use in Korea over 5 years (2020–2024). Cancer drugs with one or more valid patents that expire between 2020 and 2024 in Korea were selected. Key input parameters in the model included market share of generics, market growth, and prices of originators and generics. To reflect market dynamics after patent expiration, the trends of the off-patent market were estimated using historical sales volume data of IQVIA from 2012 to 2018. The study assumed that the prices of off-patent drugs decreased according to the price regulations set by the Korean government and that the off-patent market sales volume did not grow. Sensitivity analyses were performed to investigate the uncertainty in model input parameters. Results A total of 24 cancer drugs which met selection criteria were identified. In the base case analysis, patent expiration of cancer drugs between 2020 and 2024 could lead to a spending reduction of ₩234,429 million ($203 million), which was 20% of the cancer drug expenditure in the 5-year period. The savings ranged from ₩157,633 million ($136 million) to ₩434,523 million ($376 million) depending on the scenarios in sensitivity analyses. Conclusions The findings indicate that patent loss of cancer drugs could lead to a 20% reduction in spending on cancer drugs over the next 5 years in South Korea. The savings could be used to improve the affordability of innovative, advanced cancer drugs for 94,000 cancer patients by reallocating the budget savings from patent expiration.

Background The definition of the high-risk group for gestational diabetes mellitus (GDM) defined by the American College of Obstetricians and Gynecologists was changed from the criteria composed of five historic/demographic factors (old criteria) to the criteria consisting of 11 factors (new criteria) in 2017. To compare the predictive performances between these two sets of criteria. Methods This is a secondary analysis of a large prospective cohort study of non-diabetic Korean women with singleton pregnancies designed to examine the risk of GDM in women with nonalcoholic fatty liver disease. Maternal fasting blood was taken at 10 to 14 weeks of gestation and measured for glucose and lipid parameters. GDM was diagnosed by the two-step approach. Results Among 820 women, 42 (5.1%) were diagnosed with GDM. Using the old criteria, 29.8% (n=244) of women would have been identified as high risk versus 16.0% (n=131) using the new criteria. Of the 42 women who developed GDM, 45.2% (n=19) would have been mislabeled as not high risk by the old criteria versus 50.0% (n=21) using the new criteria (1-sensitivity, 45.2% vs. 50.0%, P>0.05). Among the 778 patients who did not develop GDM, 28.4% (n=221) would have been identified as high risk using the old criteria versus 14.1% (n=110) using the new criteria (1-specificity, 28.4% vs. 14.1%, P

Objective Here, we investigated whether cytokines in the cervicovaginal fluid (CVF) can be predictive markers of preterm birth (PTB). Methods A multi-center prospective cohort study was conducted on 59 singleton pregnant women hospitalized for preterm labor (PTL) and/or preterm premature rupture of membranes (pPROM) between 22 weeks and 36 weeks 6 days of gestation from 2014 to 2015. The levels of 13 inflammatory cytokines (macrophage inflammatory protein [MIP]-1α, MIP-1β, tumor necrosis factor [TNF]-α, interleukin [IL]-1β, IL-6, IL-8, IL-17α, granulocyte colony stimulating factor [G-CSF], IL-7, IL-4, IL-5, IL-10, and IL-13) were measured using a multiplex bead-based immunoassay and that of fetal fibronectin (fFN) was measured using enzyme-linked immunosorbent assay (ELISA). Statistical analyses were performed using Student’s t-test, Mann-Whitney U test, Pearson’s correlation, and receiver operating characteristic (ROC) curve analysis in SPSS version 20.0. Results Among the 13 cytokines assessed, the levels of 3 cytokines (MIP-1α, IL-6, and IL-7) were negatively correlated with gestational age at delivery (P=0.028, P=0.002, and P=0.018, respectively). Sensitivities of MIP-1α, IL-6, and IL-17α were 70%, 80%, and 75%, respectively, and their specificities were 57%, 65%, and 69%, respectively. The sensitivity and specificity of fFN were 33% and 95%, respectively. Conclusion In symptomatic women diagnosed with PTL and/or pPROM, cytokines from cervicovaginal fluid, especially IL-6 and IL-17α, could be better predictive markers of PTB than fFN.

Abstract Background Antenatal corticosteroids have been proven to prevent adverse outcomes including respiratory morbidities in preterm neonates before 34 weeks of gestation. Recently, it has been suggested that antenatal corticosteroids may also be effective in singleton late preterm pregnancies, and guidelines recommend the use of corticosteroids in singleton pregnant women who are at risk for late preterm birth. On the contrary, there is a paucity of information regarding the effectiveness of corticosteroids in twin neonates with late preterm birth. This study aims to determine the effectiveness of antenatal corticosteroids in late preterm twin neonates. Methods In this multicentre randomized controlled trial, women who are at risk for late preterm birth will be enrolled at 34 0/7 to 36 5/7 weeks of gestation. The participants will be randomly assigned to receive antenatal corticosteroids (betamethasone 12 mg, 3 mL intramuscularly [IM]) or placebo (normal saline 3 mL IM). The perinatal outcomes will be compared between the two groups of cases. The primary outcome is severe respiratory complications (the use of continuous positive airway pressure or high-flow nasal cannula for at least 12 h, supplemental oxygen administration with a fraction of oxygen 0.3 or more for at least 24 h, mechanical ventilation, or extracorporeal membranes oxygenation) or perinatal death within the first 72 h of delivery. The secondary outcomes are neonatal mortality and/or other neonatal morbidities. Discussion This study will be the first randomized controlled trial that evaluates the effectiveness of antenatal corticosteroids in late preterm twin neonates. Trial registration NCT03547791(ClinicalTrials.gov), first submitted date: March 29, 2018, first posted date: June 6, 2018 (retrospectively registered).

OBJECTIVE:To evaluate not only the risk of total preterm birth (PTB) but also spontaneous preterm birth (sPTB) and indicated preterm birth (iPTB) in vanishing twin (VT). STUDY DESIGN:This is a secondary analysis of a multicenter prospective cohort study. In 12 different healthcare institutions, women with singleton pregnancies were enrolled in early pregnancy and followed up till delivery. RESULTS:A total of 4,746 women were included in the final analysis, and. the frequency of VT was 1.1% (54/4746). VT group had a higher risk for total PTB (PTB

We aimed to explore the proteomic profiles of mid-trimester amniotic fluid in pregnant women with systemic lupus erythematosus (SLE) according to the occurrence of adverse pregnancy outcome (APO). The study population included 35 pregnant women with SLE who underwent clinically indicated amniocentesis at 15-24 weeks of gestation. Patients were divided into two groups according to pregnancy outcomes: SLE patients without APO (Group 1) and SLE patients with APO (Group 2). Stored samples of amniotic fluid were analyzed using mass spectrometry (MS)-based proteomics with two-step approach, consisting of discovery and verification phase. In the discovery phase, 44 proteins were differentially expressed between Group 1 and Group 2. In the verification phase, differentially expressed proteins (DEPs) were verified in independent samples using DIA method. Four proteins including filamin A (FLNA), sushi, von Willebrand factor type A, EGF and pentraxin domain containing 1 (SVEP1), lecithin-cholesterol acyltransferase (LCAT), and transglutaminase 2 (TGM2) were differentially expressed both in discovery and verification phase. To select the best combination of proteins for discriminating two groups, three-fold cross validation (CV) with repetition of one hundred times was performed. The multi-marker model with three biomarkers (SVEP1, LCAT, TGM2) had a high discriminatory power to distinguish between the two groups (the area under the receiver operating characteristic, AUROC = 0.946, p

IntroductionRitodrine is one of the most commonly used tocolytics in preterm labor, acting as a ß2-adrenergic agonist that reduces intracellular calcium levels and prevents myometrial activation. Ritodrine infusion can result in serious maternal complications, and pulmonary edema is a particular concern among these. The cause of pulmonary edema following ritodrine treatment is multifactorial; however, the contributing genetic factors remain poorly understood. This study investigates the genetic variants associated with ritodrine-induced pulmonary edema.MethodsIn this case-control study, 16 patients who developed pulmonary edema during ritodrine infusion [case], and 16 pregnant women who were treated with ritodrine and did not develop pulmonary edema [control] were included. The control pregnant women were selected after matching for plurality and gestational age at the time of tocolytic use. Maternal blood was collected during admission for tocolytic treatment, and whole exome sequencing was performed with the stored blood samples.ResultsGene-wise variant burden (GVB) analysis resulted in a total of 71 candidate genes by comparing the cumulative effects of multiple coding variants for 19729 protein-coding genes between the patients with pulmonary edema and the matched controls. Subsequent data analysis selected only the statistically significant and deleterious variants compatible with ritodrine-induced pulmonary edema. Two final candidate variants in CPT2 and ADRA1A were confirmed by Sanger sequencing.ConclusionsWe identified new potential variants in genes that play a role in cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) regulation, which supports their putative involvement in the predisposition to ritodrine-induced pulmonary edema in pregnant women.

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.

Abstract Background Among the non-invasive screening methods for the identification of fetal aneuploidy, NIPT (non-invasive prenatal testing) shows the highest sensitivity and specificity in high-risk pregnancies. Due to the low false positive rate of NIPT, it is assumed that the implementation of NIPT as a primary screening method may reduce the number of invasive fetal tests and result in a similar or lowered cost in the overall detection of Down syndrome. However, most previous studies are based on theoretical economic analysis. This study aims to determine the cost effectiveness of various prenatal test strategies, including NIPT, in real clinical settings in both low risk and high risk pregnancies. Methods/design In this prospective observational study, women (

It has been demonstrated that risk-appropriate perinatal and obstetric care can improve perinatal morbidity and mortality. Recently, various studies focus on the importance of evaluation for maternal conditions and allocation of high risk pregnant women to highly qualified facilities. Therefore, it is necessary to develop the conceptualized framework for levels of obstetric care and establish the guidelines for the situations that should be cared in each level of facility. In this review article, we reviewed several classifications of obstetric care in eastern and western countries, and conditions in which transfer should be recommended depending on the risk and capacity of centers.

ObjectiveIn terms of efficacy, several previous studies have shown that the success rate in inhibiting preterm labor was not different between magnesium sulfate and ritodrine. However, there is a paucity of information regarding the efficacy of both medications after consideration of intra-amniotic infection, which is one of the most important prognostic factors in patients of threatened preterm birth. The objective of this study was to compare the efficacy and safety of magnesium sulfate with that of ritodrine in preterm labor.MethodsIn this retrospective cohort study, we included patients who were admitted and treated with either ritodrine or magnesium sulfate with the diagnosis of preterm labor at 24–33.6 weeks of gestational age between January 2005 to April 2015. Patients were divided into 2 groups according to the first-used tocolytics (ritodrine group and magnesium sulfate group). We compared the efficacy and prevalence of side effect in each group. The efficacy of both tocolytics was evaluated in terms of preterm delivery within 48 hours, 7 days, or 37 weeks of gestation and need for 2nd line therapy.ResultsA total number of 201 patients were enrolled including 177 cases in ritodrine group and 24 cases in magnesium sulfate group. The efficacy of both tocolytics (preterm delivery within 48 hours, 7 days, or 37 weeks of gestation and need for 2nd line therapy) was not different between the 2 groups of cases. In multivariate analysis, gestational age at treatment, twin gestation, intra-amniotic infection and maternal C-reactive protein (CRP) was associated with treatment failure (preterm delivery within 48 hours), but the type of tocolytics was not significantly associated with treatment failure. The type of side effect was different in the 2 groups, but the frequency of total adverse effect, need for discontinuation of therapy because of maternal adverse effect, and severe adverse effect were not different between the two groups of cases.ConclusionThe efficacy and safety of magnesium sulfate was similar to ritodrine, and can be a substitute tocolytics. Additionally, failure of tocolytic therapy was determined by gestational age at treatment, twin gestation, intra-amniotic infection, and maternal CRP, not by the type of tocolytics.

Abstract Background Low socioeconomic status can increase the risk of adverse pregnancy outcomes, but it remains unclear whether this negative association is attributed to inadequate prenatal care. Korea has been adopting a universal healthcare system. All Korean citizens must be enrolled National Health Insurance (NHI) or be recipient of Medical Aid (MA). In addition, Korean government launched a financial support system for antenatal care for all pregnant women in 2008. Therefore, in theory, there is no financial barrier to receive prenatal cares regardless of someone’s social class. However, it is still unclear whether adverse pregnancy outcomes observed in low-income women are attributable to low SES or to economic barriers specific to the utilization of medical services. The purpose of this study was to investigate whether socioeconomic status affects pregnancy outcomes after the introduction of this support system, which allows all pregnant women to receive adequate prenatal care regardless of socioeconomic status. Methods Using the National Health Insurance database in Korea, we selected women who gave birth between January 1, 2010 and December 31, 2010. As a proxy indicator reflecting socioeconomic status, we classified subjects as MA recipient (“low” SES) or a NHI beneficiary (“middle/high” SES). Results In the MA group, 29.4% women received inadequate prenatal care, compared to 11.4% in the NHI group. Mothers in the MA group were more likely to have an abortion (30.1%), rather than deliver a baby, than those in the NHI group (20.7%, P

Two dimensional monolayer transition metal ditellurides and their alloys are interesting but their growth has been difficult. Herein, Yun et al. demonstrate the use of sodium salts to convert transition metal disulfide to ditelluride and alloys in tellurium vapor at low temperature.

Objectives Access to a delivery unit is a major factor in determining maternal morbidity and mortality. However, there is little information about the optimal access time to a delivery unit. This study aimed to establish the optimal hospital access time (OHAT) for pregnant women in South Korea.Design Nationwide cross-sectional study.Setting We used the National Health Insurance System database of South Korea.Participants We analysed the data of 371 341 women who had experienced pregnancy in 2013.Primary and secondary outcome measures Access time to hospital was defined as the time required to travel from the patient’s home to the delivery unit. The incidence of obstetric complications was plotted against the access time to hospital. Change-point analysis was performed to identify the OHAT by determining a point wherein the incidence of obstetric complications changed significantly. As a final step, the risk of obstetric complications was compared by type among pregnant women who lived within the OHAT against those who lived outside the OHAT.Results The OHAT associated with each adverse pregnancy outcomes were as follows: inadequate prenatal care, 41–50 min; preeclampsia, 51–60 min; placental abruption, 51–60 min; preterm delivery, 31–40 min; postpartum transfusion, 31–40 min; uterine artery embolisation, 31–40 min; admission to intensive care unit, 31–40 min; and caesarean hysterectomy, 31–40 min. Pregnant women who lived outside the OHAT had significantly higher risk for obstetric complications than those who lived within the OHAT.Conclusions Our results showed that the OHAT for each obstetric complication ranged between 31 and 60 min. The Korean government should take the OHAT under consideration when establishing interventions for pregnant women who live outside OHAT to reduce maternal morbidity and mortality.

[This corrects the article DOI: 10.1371/journal.pone.0221400.].

ObjectiveNonalcoholic fatty liver disease (NAFLD) is a well-recognized hepatic manifestation of metabolic disease in adults and has been associated with the development of gestational diabetes (GDM). Hepatic insulin resistance can result in increased release of glucose (from gluconeogenesis) and free fatty acids (due to enhanced lipolysis), which can lead in turn to fetal overgrowth. However, the relationship between maternal metabolic factors (such as circulating levels of triglycerides, free fatty acids [FFA], or adipokines) and excessive fetal birthweight in NAFLD has not been carefully examined. In this study, we evaluated the relationship between NAFLD and the subsequent risk of large-for-gestational-age (LGA) birthweight.MethodSingleton nondiabetic pregnant women were evaluated for the presence of fatty liver at 10-14 weeks of gestation by abdominal ultrasound. The degree of fatty liver was classified as Grade 0-3 steatosis. At the time of liver ultrasound, maternal blood was taken after fasting and measured for adiponectin and FFA. LGA was defined as birthweight >90th percentile for gestational age.ResultsA total of 623 women were included in the analysis. The frequency of LGA was 10.9% (68/623), and the frequency of NAFLD was 18.9%. The risk of LGA increased significantly in patients with Grade 2-3 steatosis in the first trimester. The relationship between Grade 2-3 steatosis and LGA remained significant after adjustment for maternal age, pre-pregnancy BMI, GDM, and maternal serum triglyceride levels. The concentration of maternal blood adiponectin at 10-14 weeks was significantly lower in cases with LGA than non-LGA, but the maternal blood FFA concentrations were not different between the groups.ConclusionThe presence of Grade 2-3 steatosis on ultrasound in early pregnancy was associated with the increased risk of delivering an LGA infant, even after adjustment for multiple confounding factors including GDM. Adiponectin may be the linking biomarker between NAFLD and LGA.

Various intriguing quantum transport measurements for carbon nanotubes (CNTs) based on their unique electronic band structures have been performed adopting a field-effect transistor (FET), where the contact resistance represents the interaction between the one-dimensional and three-dimensional systems. Recently, van der Waals (vdW) gap tunneling spectroscopy for single-walled CNTs with indium–metal contacts was performed adopting an FET device, providing the direct assignment of the subband location in terms of the current–voltage characteristic. Here, we extend the vdW gap tunneling spectroscopy to multi-walled CNTs, which provides transport spectroscopy in a tunneling regime of ~1 eV, directly reflecting the electronic density of states. This new quantum transport regime may allow the development of novel quantum devices by selective electron (or hole) injection to specific subbands.

OBJECTIVE:We aimed to assess the correlations among multiple cytokine concentrations in the maternal plasma, cervicovaginal fluid (CVF), and amniotic fluid (AF) compartments in women with preterm premature rupture of membranes (pPROM), and to develop a prediction model based on non-invasive measures, having better sensitivity and specificity for the identification of microbial invasion of amniotic cavity (MIAC). METHOD:This retrospective study included 75 consecutive women with pPROM (20+0-34+0 weeks), who underwent amniocentesis. Both maternal plasma and CVF samples were collected at the time of amniocentesis. Stored AF, plasma and CVF samples were assayed for cytokine levels [interleukin (IL)-6, IL-8, monocyte chemotactic protein-1, macrophage inflammatory protein (MIP)-1α, MIP-1β] using a multiplex immunoassay kit. RESULTS:Levels of inflammatory proteins measured in the CVF were significantly correlated with AF proteins levels, whereas none of the proteins in plasma correlated significantly with any in the AF or CVF. Proteins levels measured in the AF and CVF were significantly higher in women with MIAC compared to those without, whereas only high levels of IL-6 in plasma were significantly associated with MIAC. By using stepwise regression analysis, a non-invasive model (using clinical factors and CVF cytokine levels) for the prediction of MIAC was developed; the area under curve of this non-invasive model was similar to that of the invasive model (using clinical factors and AF cytokines). CONCLUSIONS:The levels of inflammatory proteins in the CVF correlated with those in the AF, whereas those in the plasma showed no correlation. A non-invasive model using clinical factors and CVF cytokine levels predicted the risk of MIAC in women with pPROM.

OBJECTIVE:Cervical length measurement has been uggested as a useful tool for predicting intra-amniotic infection/inflammation in preterm labor, but little information is available in the setting of preterm premature rupture of membranes (pPROM). We aimed to determine whether a short cervical length is independently associated with an increased risk of intra-amniotic infection or inflammation and impending preterm delivery in women with pPROM. METHODS:This was a retrospective cohort study involving 171 consecutive singleton pregnant women with pPROM (21+0-33+6 weeks' gestation), who underwent amniocentesis. Amniotic fluid (AF) was cultured, and assayed for interleukin (IL)-6 and IL-8. Cervical length was measured at the time of amniocentesis by transvaginal ultrasonography with an aseptic technique. Short cervical length was defined as a cervical length of ≤15 mm. Intra-amniotic infection was defined as a positive AF culture for microorganisms and intra-amniotic inflammation was defined as elevated AF concentrations of IL-6 or IL-8 (IL-6 ≥1.5 ng/mL and/or IL-8 ≥1.3 ng/mL). RESULTS:Fifty (29.2%) women had a sonographic cervical length of ≤15mm. On univariate analysis, short cervical length was associated with an increased risk for intra-amniotic infection and/or inflammation; no other parameters studied showed a significant association. Multivariable analyses indicated that short cervical length was significantly associated with a higher risk of impending preterm delivery (within 2 days of measurement, within 7 days of measurement, and before 34 weeks), and remained significant after adjustment for potential confounders. CONCLUSION:In women with pPROM, short cervical length is associated with an increased risk for intra-amniotic infection/inflammation and associated with impending preterm delivery, independent of the presence of intra-amniotic infection/inflammation.

OBJECTIVE:Non-alcoholic fatty liver disease (NAFLD) has become a common and important chronic liver disease worldwide. Previous studies have indicated that NAFLD has an adverse effect on the quality of life, but information is lacking about the impact of NAFLD on female sexual dysfunction. The aim of this study was to determine the association between NAFLD and female sexual dysfunction in premenopausal women. METHODS:This retrospective study consisted of premenopausal women who were sexually active and visited the outpatient clinic for a routine health check-up between January 2010 and December 2011. Based on the examination of the liver ultrasound scan, the study population was divided into 2 groups: cases with NAFLD and normal controls (cases without NAFLD). The female sexual function was compared between the two groups of cases. For the assessment of sexual function, a female sexual function index (FSFI) questionnaire was used. RESULTS:Four hundred seventy women were included, and the prevalence of NAFLD and female sexual dysfunction were 67/470 (14.3%) and 238/470 (50.6%), respectively. Cases with NAFLD had a lower total FSFI score and higher rate of female sexual dysfunction than the normal control [median score of total FSFI (interquartile range): 24.7 (21.9-27.8) in NAFLD vs. 26.7 (23.7-29.8) in normal control, p