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Simultaneous myofibril and mitochondrial development is crucial for the cardiac differentiation of pluripotent stem cells (PSCs). Specifically, mitochondrial energy metabolism (MEM) development in cardiomyocytes is essential for the beating function. Although previous studies have reported that MEM is correlated with cardiac differentiation, the process and timing of MEM regulation for cardiac differentiation remain poorly understood. Here, we performed transcriptome analysis of cells at specific stages of cardiac differentiation from mouse embryonic stem cells (mESCs) and human induced PSCs (hiPSCs). We selected MEM genes strongly upregulated at cardiac lineage commitment and in a time-dependent manner during cardiac maturation and identified the protein-protein interaction networks. Notably, MEM proteins were found to interact closely with cardiac maturation-related proteins rather than with cardiac lineage commitment-related proteins. Furthermore, MEM proteins were found to primarily interact with cardiac muscle contractile proteins rather than with cardiac transcription factors. We identified several candidate MEM regulatory genes involved in cardiac lineage commitment (

Objective: To evaluate the association between uterine leiomyoma (UL) and development of type 2 diabetes mellitus in young women using a nationwide database. Design: Nationwide population-based cohort study Setting: South Korea. Population or Sample: Women aged between 20 and 40 years at baseline who underwent at least one health checkup between 2009 and 2012 and followed until December 31, 2018 Methods: We excluded those who were previously diagnosed with type 2 diabetes mellitus (n = 28,136), those diagnosed with type 2 diabetes mellitus within the first year of entry (n = 1,607), those who had hysterectomy during the study period (n = 18,485), and those with missing data (n = 166,012). Cox proportional hazards models were used to analyze the risk of developing type 2 diabetes according to the presence of UL. Main outcome Measures: Incidence of the development of type 2 diabetes mellitus according to the presence of UL Results: 2,755,790 women were selected and he mean age of the enrolled population was 29.70 y, and mean body mass index was 21.31 kg/m . Among 2,541,550 participants, 18,375 (0.72%) women had UL. Over a median 7.45 years of follow-up, 23,829 women (0.94%) were diagnosed with type 2 diabetes. The incidence of type 2 diabetes in women with UL (1.805/1,000 person-years) was higher than in those without UL (1.289/1000 person-years). In the multivariable-adjusted model, the hazard ratio for type 2 diabetes in women with UL was 1.216 (95% confidence interval [CI] 1.071-1.382), as compared to those without UL. Compared to women without UL, women with UL who did not undergo myomectomy had a risk 1.328 times (95% CI 1.143-1.542) higher for developing type 2 diabetes. Interestingly, women with UL who underwent myomectomy had no increased risk for developing type 2 diabetes. Conclusions: This study found that young women with UL are more likely to develop type 2 diabetes than those without UL. In addition, myomectomy seemed to attenuate the risk for developing type 2 diabetes in young women with UL.

Background and Purpose: Stem cell–based therapy is a promising approach to repair brain damage after stroke. This study was conducted to investigate changes in neuroimaging measures using stem cell–based therapy in patients with ischemic stroke. Methods: In this prospective, open-label, randomized controlled trial with blinded outcome evaluation, patients with severe middle cerebral artery territory infarct were assigned to the autologous mesenchymal stem cell (MSC) treatment or control group. Of 54 patients who completed the intervention, 31 for the MSC and 13 for the control groups were included in this neuroimaging analysis. Motor function was assessed before the intervention and 90 days after randomization using the Fugl-Meyer assessment scale. Neuroimaging measures included fractional anisotropy values of the corticospinal tract and posterior limb of the internal capsule from diffusion tensor magnetic resonance imaging and strength of connectivity, efficiency, and density of the motor network from resting-state functional magnetic resonance imaging. Results: For motor function, the improvement ratio of the Fugl-Meyer assessment score was significantly higher in the MSC group compared with the control group. In neuroimaging, corticospinal tract and posterior limb of the internal capsule fractional anisotropy did not decrease in the MSC group but significantly decreased at 90 days after randomization in the control group. Interhemispheric connectivity and ipsilesional connectivity significantly increased in the MSC group. Change in interhemispheric connectivity showed a significant group difference. Conclusions: Stem cell–based therapy can protect corticospinal tract against degeneration and enhance positive changes in network reorganization to facilitate motor recovery after stroke. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01716481.

Background: The objective of this study was to compare maternal and neonatal outcomes in women with non-complicated singleton pregnancies according to timing of planned elective cesarean section (CS). Methods: This was a retrospective cohort study of 2,365 women with singleton pregnancies who were planned for elective CS at term pregnancy in a single institution between 2010 and 2021. Pregnant women with preterm delivery, multiple gestation, vaginal delivery, complicated pregnancy, or non-scheduled emergency CS were excluded. Subjects were categorized into three groups according to planneddate of CS: 37 (37+0‒37+6) weeks (n = 147), 38 (38+0‒38+6) weeks (n = 1,486), and 39 (39+0‒39+6) weeks (n = 732) of gestation. Primary outcomes of this study were emergency CS rate and maternal and neonatal composite morbidity. Results: The rate of emergency CS significantly increased with an increase in planned week of CS. After controlling for confounding factors, the rate of emergency CS significantly higher in the 38-week group (adjusted odds ratio (aOR): 4.70, 95% confidence interval (CI): 1.71‒12.95) and the 39-week group (aOR: 8.78, 95% CI: 3.16‒24.37) than in the 37-week group. The rate of maternal composite morbidity (aOR: 3.22, 95% CI: 1.65‒6.32) was significantly higher in the 37-week group, but not in the 38-week group, than in the 39-week group. Rates of neonatal ventilator use and respiratory distress syndrome significantly decreased, whereas neonatal meconium staining significantly increased with an increase in planned week of CS. The rate of neonatal composite morbidity (aOR: 2.69, 95% CI: 1.22‒5.96) was significantly higher in the 37-week group, but not in the 38-week group, than in the 39-week group. Conclusion: In non-complicated singleton pregnancy, planning elective CS at 37 weeks of gestation was associated with a higher risk of adverse pregnancy outcome. However, planning elective CS at 38 weeks of gestation showed no worse pregnancy outcome than that at 39 weeks of gestation.

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

Cardiomyocyte differentiation occurs through complex and finely regulated processes including cardiac lineage commitment and maturation from pluripotent stem cells (PSCs). To gain some insight into the genome-wide characteristics of cardiac lineage commitment, we performed transcriptome analysis on both mouse embryonic stem cells (mESCs) and human induced PSCs (hiPSCs) at specific stages of cardiomyocyte differentiation. Specifically, the gene expression profiles and the protein-protein interaction networks of the mESC-derived plateletderived growth factor receptor-alpha (PDGFRα)+ cardiac lineagecommitted cells (CLCs) and hiPSC-derived kinase insert domain receptor (KDR)+ and PDGFRα+ cardiac progenitor cells (CPCs) at cardiac lineage commitment were compared with those of mesodermal cells and differentiated cardiomyocytes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that the genes significantly upregulated at cardiac lineage commitment were associated with responses to organic substances and external stimuli, extracellular and myocardial contractile components, receptor binding, gated channel activity, PI3K‑AKT signaling, and cardiac hypertrophy and dilation pathways. Protein-protein interaction network analysis revealed that the expression levels of genes that regulate cardiac maturation, heart contraction, and calcium handling showed a consistent increase during cardiac differentiation; however, the expression levels of genes that regulate cell differentiation and multicellular organism development decreased at the cardiac maturation stage following lineage commitment. Additionally, we identified for the first time the protein-protein interaction network connecting cardiac development, the immune system, and metabolism during cardiac lineage commitment in both mESC-derived PDGFRα+ CLCs and hiPSC-derived KDR+PDGFRα+ CPCs. These findings shed light on the regulation of cardiac lineage commitment and the pathogenesis of cardiometabolic diseases. [BMB Reports 2021; 54(9): 464-469].

The purpose of this study was to check whether the impact of abnormal vaginal colonization on perinatal outcomes would be different in patients with preterm labor (PTL) and premature membrane ruptu...

Hydroxychloroquine, a drug used for malaria and autoimmune diseases reportedly has beneficial effects against preeclampsia in pregnant women with lupus. However, its mechanism against preeclampsia remains unclear. We investigated the effect of hydroxychloroquine on an Nω-nitro-l-arginine methyl ester-induced preeclampsia rat model.Pregnant Sprague-Dawley rats were divided into four groups based on treatment (administered on gestational days 7-18): control, Nω-nitro-l-arginine methyl ester, hydroxychloroquine, and Nω-nitro-l-arginine methyl ester plus hydroxychloroquine. All animals were sacrificed on gestational day 19. We assayed tube formation and determined reactive oxygen species levels using human umbilical vein endothelial cells.Results showed that hydroxychloroquine significantly lowered mean systolic blood pressure (P 0.05) in Nω-nitro-l-arginine methyl ester-treated rats. Hydroxychloroquine did not affect their fetal and placental weights. Hydroxychloroquine mitigated Nω-nitro-l-arginine methyl ester-associated changes in proteinuria (P 0.05). It normalized plasma soluble fms-like kinase-1 (P 0.05) and endothelin-1 (P 0.01) levels. In the tube formation assay, hydroxychloroquine increased the total meshes area (P 0.05) and mitigated Nω-nitro-l-arginine methyl ester-induced reactive oxygen species formation (P 0.05) in human umbilical vein endothelial cells.We conclude that hydroxychloroquine alleviated hypertension, proteinuria, and normalized soluble fms-like kinase-1 and endothelin-1 levels in our preeclampsia model and that these changes may involve the restoration of endothelial dysfunction; thus, hydroxychloroquine could potentially be used for preventing preeclampsia, even in the absence of lupus.

Abnormal vaginal colonisation can lead to adverse pregnancy outcomes such as preterm birth through intra-amniotic inflammation. Despite the concern, little is known about its risk factors and impact in pregnant women at high-risk for spontaneous preterm birth. Thus, we conducted this single-centre retrospective cohort study including 1381 consecutive women who were admitted to the high-risk pregnancy unit. The results of vaginal culture at admission were categorised according to the colonising organism: bacteria (Gram-negative or -positive) and genital mycoplasmas. Maternal baseline socioeconomic, and clinical characteristics, as well as pregnancy, delivery, and neonatal outcomes were compared according to the category. Maternal risk factors for Gram-negative colonisation included advanced maternal age, increased pre-pregnancy BMI, a greater number of past spontaneous abortions, earlier gestational age at admission, and IVF. Gram-positive colonisation was likewise associated with earlier gestational age at admission. Genital mycoplasmal colonisation was associated with a greater number of past induced abortions, a lower level of education completed, and a lower rate of multifetal pregnancy and IVF. The neonates from mothers with Gram-negative colonisation had a greater risk of NICU admission, proven early onset neonatal sepsis, and mortality. However, not Gram-positive bacteria or genital mycoplasma was directly associated with adverse pregnancy outcomes.

Objective: To investigate the severity of histologic chorioamnionitis /funisitis according to the indication for preterm delivery and their corresponding neonatal outcomes. Method: This study included 411 singleton women who delivered between 21+0 and 31+6 week of gestation due to preterm labor (PTL, n = 165), preterm premature rupture of membranes (PPROM, n = 202), or incompetent internal os of the cervix (IIOC, n = 44). The primary outcome measure was the rate of severe histological chorioamnionitis/funisitis. Secondary outcome measure was neonatal outcomes including neonatal and infant death, and neonatal composite morbidity. Results: The PPROM group demonstrated a higher rate of severe histological chorioamnionitis/funisitis compared to the PTL group (severe histological chorioamnionitis; PPROM, 66.3% vs. PTL, 49.1%, p = 0.001, severe funisitis; PPROM, 44.1% vs. PTL, 23.6%, p < 0.001) and this remained significant after multivariable analysis (severe histologic chorioamnionitis, OR 2.367, 95% CI 1.517–3.693; severe funisitis, OR 2.668, 95% CI 1.684–4.226). For neonatal outcomes only, a higher rate of patent ductus arteriosus was observed in the IIOC group compared to the PTL and PPROM groups (IIOC, 77.3% vs. PTL, 54.0% vs. PPROM, 54.0%, p = 0.043) and this remained significant after multivariable analysis. Conclusion: Indication of spontaneous preterm delivery might affect the placental inflammatory pathology and neonatal morbidity.

We aimed to compare cervical elastographic parameters based on a previous loop electrosurgical excision procedure (LEEP) and to determine whether they can predict preterm delivery in pregnant women with a history of LEEP. This multicenter prospective case–control study included 71 singleton pregnant women at 14–24 weeks of gestation with a history of LEEP and 1:2 gestational age-matched controls. We performed cervical elastography using E-cervix and compared maternal characteristics, delivery outcomes, cervical length (CL), and elastographic parameters between the two groups. The median mid-trimester CL was significantly shorter in the LEEP group. Most elastographic parameters, including internal os (IOS), external os (EOS), elasticity contrast index (ECI), and hardness ratio (HR), were significantly different in the two groups. In the LEEP group, the sPTD group compared to the term delivery (TD) group showed a higher rate of previous sPTD (50% vs. 1.7%, p 0.001), higher IOS and ECI (IOS: 0.28 [0.12–0.37] vs. 0.19 [0.10–0.37], p = 0.029; ECI: 3.89 [1.79–4.86] vs. 2.73 [1.48–5.43], p = 0.019), and lower HR (59.97 [43.88–92.43] vs. 79.06 [36.87–95.40], p = 0.028), but there was no significant difference in CL (2.92 [2.16–3.76] vs. 3.13 [1.50–3.16], p = 0.247). In conclusion, we demonstrated that a history of LEEP was associated with a change in cervical strain measured in mid-trimester as well as with CL shortening. We also showed that cervical elastography can be useful in predicting sPTD in pregnant women with previous LEEP.

Objective This study aimed 1) to investigate the clinical characteristics of amniotic fluid embolism (AFE) cases clinically diagnosed by maternal fetal medicine (MFM) specialists in Korea, 2) to check the disagreement with 4 recently proposed criteria by the Society for Maternal-Fetal Medicine (SMFM) for research purpose, and 3) to compare maternal outcomes between cases satisfying all 4 criteria and cases with at least 1 missing criterion. Methods This study included 12 patients clinically diagnosed with AFE from 7 referral hospitals in Korea. We collected information, including maternal age, symptoms of AFE, the amount of transfusion, and maternal mortality. Results The median maternal age was 33 years (range, 28–40 years). Regarding symptoms, cardiovascular arrest, hypotension, respiratory compromise, clinical coagulopathy, and neurologic signs were observed in 41.7%, 83.3%, 83.3%, 100%, and 66.7% of the cases, respectively. Among the 12 cases, 5 women died and 2 suffered severe neurologic disability, showing an intact survival rate of 41.7%. Disagreement with all 4 criteria proposed by the SMFM was found in 66.7% of the cases, due to the lack of criteria for disseminated intravascular coagulation or strict onset time (

Purpose We investigated the validity of quad serum markers for the prediction of adverse pregnancy outcome (APO) in women with antiphospholipid antibody syndrome (APS). Methods We included 75 women with APS delivered at our institution. APO was defined as stillbirth, small for gestational age (SGA), severe preeclampsia, or preterm delivery. First, we compared clinical characteristics between patients with or without composite APO. Second, we compared the rate of APO according to abnormal level of quad serum markers. Lastly, receiver operating characteristic (ROC) curve analysis was performed. Results APS mothers with APO showed higher median α-fetoprotein (AFP) and inhibin A compared with those without APO. They were also associated with higher rates of positive risk of Down syndrome and neural tube defect. Elevated AFP, human chorionic gonadotropin (hCG), and inhibin A level was associated with higher rates of stillbirth, SGA, preterm delivery, and composite APO. ROC curve for prediction of stillbirth revealed an area under the curve of 0.835 for AFP, 0.781 for hCG, and 0.932 for inhibin A. For composite APO, the area under the ROC curve was 0.692 for AFP and 0.810 for inhibin A. Conclusion Elevated AFP, hCG, and inhibin A in women with APS demonstrated a high predictive value for APO, especially stillbirth.

A rapid method for obtaining group B streptococcus (GBS) screening results has been required in the obstetric field. We aimed to determine the diagnostic performance of the Loop-Mediated Isothermal Amplification (LAMP) assay is acceptable compared to the existing polymerase chain reaction (PCR) assay. The study involved 527 pregnant women aged 19 to 44 years. Rectovaginal swabs were collected between 35 and 37 weeks of gestation or prior to impending preterm births or term labor without GBS screening. We presented the diagnostic performance of the LAMP assay with a 95% confidence interval (CI) compared to the PCR and microbiological culture. In total, 115 (21.8%), 115 (21.8%) and 23 (4.4%) patients showed positive results using the LAMP, PCR assay and microbiological culture method, respectively. The LAMP assay showed 100% sensitivity (95% CI, 96.8–100.0), 100% specificity (95% CI, 99.1–100.0) and 100% diagnostic accuracy (95% CI, 99.3–100.0) with the reference being the PCR assay. Meanwhile, the LAMP assay showed 87.0% sensitivity (95% CI, 71.0–100.0), 81.2% specificity (95% CI, 77.6–84.7), and 81.4% diagnostic accuracy (95% CI, 78.0–84.8) with the microbiological culture as a reference. This study presented the LAMP assay as an acceptable method for GBS screening with a similar performance to the existing PCR method.

To investigate the epidemiological changes in extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) vaginal colonisation in pregnant women deemed at high risk, and to identify independent risk factors. Further, the differences in perinatal outcomes according to maternal ESBL-E vaginal colonisation were analysed.Cross-sectional study.Republic of Korea.A cohort of 1460 women admitted to our high-risk pregnancy unit between 14The trend of changes in the association of ESBL-E vaginal colonisation from January 2010 to December 2020 was analysed. The main outcomes were analysed over the study period and ESBL-E vaginal colonisation.Rate of ESBL-E vaginal colonisation, risk factors for ESBL-E vaginal colonisation and perinatal outcomes.The ESBL-E vaginal colonisation rate has tended to increase over the past 11 years, which was attributed to a significantly higher proportion of ESBL-producing Escherichia coli. Cerclage (RR 3.7, 95% CI 2.19-6.40) and prior antibiotic treatment (RR 4.0, 95% CI 2.44-6.54) were found as independent risk factors for ESBL-E vaginal colonisation. Earlier gestational age at delivery and higher proven early-onset neonatal sepsis (EONS) rate were observed in the ESBL-E-positive group.The ESBL-E vaginal colonisation rate in pregnant patients at high risk has increased over the past decade, and the independent risk factors for colonisation are cerclage and prior antibiotic treatment. Additionally, maternal ESBL-E vaginal colonisation is associated with higher rates of proven EONS.

Objective To analyze the changes in the clinical characteristics and perinatal outcomes of twin pregnancies delivered at a tertiary referral center in Korea during a 24-year period. Methods This was a retrospective cohort study of twin pregnancies delivered at 24–40 weeks of gestation, from 1995 to 2018. The subjects were divided into 4 groups according to the year of delivery: 1995–2000, 2001–2006, 2007–2012, and 2013–2018. The trends in the changes in the twin birth rate, maternal age, assisted reproductive technology (ART) pregnancy rate, chorionicity, obstetric complications, delivery outcomes, and neonatal outcomes over the periods were analyzed. Results A total of 2,133 twin pregnancies were included in the study. The twin birth rate increased from 16.7/1,000 in 1995–2000 to 42.2/1,000 in 2001–2006, 49.5/1,000 in 2007–2012, and 61.8/1,000 in 2013–2018. The maternal age and ART pregnancy and dichorionic twin rates increased, while the monochorionic twin rate decreased over the periods. The incidence of fetal congenital anomalies, cervical incompetence, gestational diabetes mellitus, preeclampsia, and placental abruption increased over the periods. The preterm birth (PTB) rate significantly decreased owing to the decreasing elective late-PTB rate; however, the early-PTB rate significantly increased. Conclusion This study found that twin pregnancies increased steadily over the last 24 years and that the increase was related to increased maternal age and ART pregnancy rate. The incidence of obstetric complications increased over the periods; however, the neonatal intensive care unit admission rate decreased, along with decreases in the elective late-PTB rate.

During placentation, cytotrophoblasts differentiate and fuse to form multinucleated cells (syncytiotrophoblasts) in a process that involves autophagy. Appropriate syncytial differentiation is essential for establishing a healthy pregnancy. In this study, we evaluated the effect of two chloroquine compounds, hydroxychloroquine (HCQ) and chloroquine (CQ), on syncytial differentiation and autophagy in cultured primary human trophoblasts (PHTs). PHT cells were isolated from the human term placenta. Bafilomycin, a well-known autophagy inhibitor, was used as a positive control. Biochemical and morphological differentiation was assessed in syncytiotrophoblasts, and autophagy-related proteins and genes were evaluated. Affymetrix Human Gene 2.0 ST Array profiling was used to identify genes affected by HCQ during syncytial differentiation. Chloroquine compounds lowered the production of beta-human chorionic gonadotropin (β-hCG) and the fusion index in PHTs. Syncytial differentiation in PHT was associated with the increased expression of ATG4C mRNA (autophagy-related gene), and this expression was affected by CQ but not by HCQ. Microarray analysis revealed that HCQ or CQ affected several genes (MMP15, GPC3, CXCL10, TET-1, and S100A7) during syncytial differentiation, which were different from that of the syncytial differentiation suppression (Ham's/Waymouth media) or autophagy inhibition (bafilomycin treatment). Using Kyoto Encyclopedia of Genes and Genomes analysis we identified that HCQ might affect JAK2 signaling in the syncytial differentiation of PHT. In conclusion, chloroquine compounds could mitigate biochemical and morphological syncytial trophoblast differentiation in cultured PHT cells through the JAK signaling pathway rather than the inhibition of autophagic activity.

Background To compare obstetric and neonatal outcomes in twin pregnancies with or without gestational diabetes mellitus (GDM) before and after changes in GDM diagnostic criteria. Methods This was a retrospective cohort study of 1,764 twin pregnancies including 130 women with GDM (GDM group) and 1,634 women without GDM (non-GDM group). Patients with pregestational diabetes, unknown GDM status, and fetal death at Results The incidence of GDM in twin pregnancies increased from 4.0% in period 1 to 9.3% in period 2. Composite obstetric complications rate was significantly higher in the GDM group than that in the non-GDM group during period 1 (72.0% vs. 45.5%, P = 0.009). However, it became comparable during period 2 (60.0% vs. 57.4%, P = 0.601). Interaction between GDM and period indicated a significant differential effect of GDM by period on the rate of composite obstetric complications. The rate of composite neonatal complications was similar between the two groups during both periods. The interaction between GDM and period was not significant. Conclusion After changes of GDM diagnostic criteria, the incidence of GDM increased more than twice, and the rate of composite obstetric complications decreased, but the rate of composite neonatal complications did not change significantly.

Background Existing data on the use of nonsteroidal anti-inflammatory drugs (NSAIDs) during late pregnancy is well established, providing assurance. However, the use of NSAIDs during early pregnancy remains inconclusive owing to conflicting findings on adverse neonatal outcomes as well as the limited data on adverse maternal outcomes. Therefore, we sought to investigate whether early prenatal exposure to NSAIDs was associated with neonatal and maternal adverse outcomes. Methods and findings We conducted a nationwide, population-based cohort study using Korea’s National Health Insurance Service (NHIS) database with a mother–offspring cohort constructed and validated by the NHIS to include all live births in women aged 18 to 44 years between 2010 and 2018. We defined exposure to NSAIDs as at least two records of NSAID prescriptions during early pregnancy (first 90 days of pregnancy for congenital malformations and first 19 weeks for nonmalformation outcomes) and compared against three distinct referent groups of (1) unexposed, no NSAID prescription during the 3 months before pregnancy start to end of early pregnancy; (2) acetaminophen-exposed, at least two acetaminophen prescriptions during early pregnancy (i.e., active comparator); and (3) past users, at least two NSAID prescriptions before the start of pregnancy but no relevant prescriptions during pregnancy. Outcomes of interest were adverse birth outcomes of major congenital malformations and low birth weight and adverse maternal outcomes of antepartum hemorrhage and oligohydramnios. We estimated relative risks (RRs) with 95% CIs using generalized linear models within a propensity score (PS) fine stratification weighted cohort that accounted for various potential confounders of maternal sociodemographic characteristics, comorbidities, co-medication use, and general markers of burden of illness. Of 1.8 million pregnancies in the PS weighted analyses, exposure to NSAIDs during early pregnancy was associated with slightly increased risks for neonatal outcomes of major congenital malformations (PS-adjusted RR, 1.14 [CI, 1.10 to 1.18]) and low birth weight (1.29 [1.25 to 1.33]), and for maternal outcome of oligohydramnios (1.09 [1.01 to 1.19]) but not antepartum hemorrhage (1.05 [0.99 to 1.12]). The risks of overall congenital malformations, low birth weight, and oligohydramnios remained significantly elevated despite comparing NSAIDs against acetaminophen or past users. Risks of adverse neonatal and maternal outcomes were higher with cyclooxygenase-2 selective inhibitors or use of NSAIDs for more than 10 days, whereas generally similar effects were observed across the three most frequently used individual NSAIDs. Point estimates were largely consistent across all sensitivity analyses, including the sibling-matched analysis. Main limitations of this study are residual confounding by indication and from unmeasured factors. Conclusions This large-scale, nationwide cohort study found that exposure to NSAIDs during early pregnancy was associated with slightly higher risks of neonatal and maternal adverse outcomes. Clinicians should therefore carefully weigh the benefits of prescribing NSAIDs in early pregnancy against its modest, but possible, risk of neonatal and maternal outcomes, where if possible, consider prescribing nonselective NSAIDs for

Introduction: Simultaneous increase of myofibrils and mitochondria is a key process of cardiomyocyte differentiation from pluripotent stem cells (PSCs). Specifically, development of mitochondrial oxidative energy metabolism in cardiomyocytes is essential to providing the beating function. Although previous studies reported that mitochondrial oxidative metabolism have some correlation with the differentiation of cardiomyocytes, the mechanism by which mitochondrial oxidative metabolism is regulated and the link between cardiomyogenesis and mitochondrial function are still poorly understood. Methods: We performed transcriptome analysis on cells at specific stages of cardiomyocyte differentiation from mouse embryonic stem cells (mESCs) and human induced PSCs (hiPSCs). We selected highly upregulated mitochondrial metabolic genes at cardiac lineage commitment and time-dependent manner during cardiomyocyte differentiation and identified the protein-protein interaction network connecting between mitochondrial metabolic and cardiac developmental genes. Results: We found several mitochondrial metabolic regulatory genes at cardiac lineage commitment (Cck, Bdnf, Fabp4, Cebpa, Cdkn2a in mESC-derived cells and CCK, NOS3 in hiPSC-derived cells) and time-dependent manner during cardiomyocyte differentiation (Eno3, Pgam2, Cox6a2, Fabp3 in mESC-derived cells and PGAM2, SLC25A4 in hiPSC-derived cells). Notably, mitochondrial metabolic proteins are highly interacted with cardiac developmental proteins time-dependent manner during cardiomyocyte differentiation rather than cardiac lineage commitment. Furthermore, mitochondrial metabolic proteins are mainly interacted with cardiac muscle contractile proteins rather than cardiac transcription factors in cardiomyocyte. Conclusions: Mitochondrial metabolism is critical at cardiac maturation rather than cardiac lineage commitment.

Objective To investigate the epidemiological changes in extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) vaginal colonization in high-risk pregnant women and identify independent risk factors. Further, the differences in perinatal outcomes according to maternal ESBL-E vaginal colonization were analyzed. Design Retrospective cohort study. Setting Republic of Korea Population 1,460 women admitted to our high-risk pregnancy unit between 14+0 and 35+6 gestational weeks. Methods The study period was divided into periods 1 (January 2010 to July 2015) and 2 (August 2015 to December 2020). The main outcomes were analyzed according to each period and ESBL-E vaginal colonization. Main Outcome Measures ESBL-E vaginal colonization rate, risk factors for ESBL-E vaginal colonization, and perinatal outcomes. Results The ESBL-E vaginal colonization rate was higher in period 2, which was attributed to a significantly higher proportion of ESBL-producing Escherichia coli. Cerclage (odds ratio [OR]: 3.248; 95% confidence interval [CI]: 1.744–6.049) and prior antibiotic treatment (OR: 3.044; 95% CI: 1.713–5.410) were found as independent risk factors for ESBL-E vaginal colonization. Earlier gestational age at delivery, and higher proven early-onset neonatal sepsis (EONS) rate were observed in the ESBL-E-positive group. Conclusions The ESBL-E vaginal colonization rate in high-risk pregnant patients has increased over the past decade, and the independent risk factors for colonization are cerclage and prior antibiotic treatment. Additionally, maternal ESBL-E vaginal colonization is associated with higher proven EONS rates. Funding This study received no funding. Keywords Extended-spectrum β-lactamase, Enterobacteriaceae, vaginal colonization, antibiotics use, cerclage, neonatal sepsis

The purpose of this study was to check whether the impact of abnormal vaginal colonization on perinatal outcomes would be different in patients with preterm labor (PTL) and premature membrane rupture (PPROM). We also sought to determine the concordance rate of microorganisms isolated from the maternal vagina and neonatal blood in cases of early-onset neonatal sepsis (EONS) in PTL and PPROM.This retrospective study included 996 singleton pregnancies who were admitted to the high risk care unit of our institution due to PTL (The rate of abnormal vaginal colonization in PTL and PPROM was 17.0 and 21.4%, respectively. Both in PTL and PPROM, the gestational age at admission was lower in the abnormal vaginal colonization group (PTL, 27.2 ± 3.5Our data showed that maternal vaginal colonization in PPROM, but not in PTL, is an independent risk factor for EONS.

Simultaneous increase of myofibrils and mitochondria is a key process of cardiomyocyte differentiation from pluripotent stem cells (PSCs). Specifically, development of mitochondrial oxidative energy metabolism in cardiomyocytes is essential to providing the beating function. Although previous studies reported that mitochondrial oxidative metabolism have some correlation with the differentiation of cardiomyocytes, the mechanism by which mitochondrial oxidative metabolism is regulated and the link between cardiomyogenesis and mitochondrial function are still poorly understood. In the present study, we performed transcriptome analysis on cells at specific stages of cardiomyocyte differentiation from mouse embryonic stem cells (mESCs) and human induced PSCs (hiPSCs). We selected highly upregulated mitochondrial metabolic genes at cardiac lineage commitment and time-dependent manner during cardiomyocyte differentiation and identified the protein-protein interaction network connecting between mitochondrial metabolic and cardiac developmental genes. We found several mitochondrial metabolic regulatory genes at cardiac lineage commitment (Cck, Bdnf, Fabp4, Cebpa, Cdkn2a in mESC-derived cells and CCK, NOS3 in hiPSC-derived cells) and time-dependent manner during cardiomyocyte differentiation (Eno3, Pgam2, Cox6a2, Fabp3 in mESC-derived cells and PGAM2, SLC25A4 in hiPSC-derived cells). Notably, mitochondrial metabolic proteins are highly interacted with cardiac developmental proteins time-dependent manner during cardiomyocyte differentiation rather than cardiac lineage commitment. Furthermore, mitochondrial metabolic proteins are mainly interacted with cardiac muscle contractile proteins rather than cardiac transcription factors in cardiomyocyte. Therefore, mitochondrial metabolism is critical at cardiac maturation rather than cardiac lineage commitment.

Background People are generally considered overweight and obese if their body mass index (BMI) is above 25 kg/m2 and 30.0 kg/m2, respectively. The World Health Organization proposed stricter criteria for Asians (≥ 23 kg/m2: overweight, ≥ 25 kg/m2: obese). We aimed to verify whether this criteria could predict adverse pregnancy outcomes in Korean women. Methods We included 7,547 Korean women from 12 institutions enrolled between June 2016 and October 2018. Women with no pre-pregnancy BMI data, not Korean, or lost to follow-up were excluded, leaving 6,331. The subjects were categorized into underweight, normal, overweight, class I obesity, and class II/III obesity based on a pre-pregnancy BMI of < 18.5, 18.5–22.9, 23.0–24.9, 25.0–29.9, and ≥ 30.0 kg/m2, respectively. Results Overall, 13.4%, 63.0%, 11.8%, 9.1%, and 2.6% of women were underweight, normal, and overweight and had class I obesity and class II/III obesity, respectively. In the multivariable analysis adjusted for maternal age, a higher BMI significantly increased the risk of preeclampsia, gestational diabetes, preterm delivery caused by maternal-fetal indications, cesarean section, large for gestational age, and neonatal intensive care unit admission. Conclusion Adverse pregnancy outcomes started to increase in those with a pre-pregnancy BMI ≥ 23.0 kg/m2 after adjusting for maternal age. The modified obesity criteria could help predict adverse pregnancy outcomes in Koreans., Graphical Abstract

Purpose The prevalence of gestational diabetes mellitus (GDM) is increasing, and multifaceted interventions are effective in the management of GDM. This study aimed to develop and evaluate a model for the management of GDM with the use of mobile health care. Methods This was a prospective, randomized controlled pilot study. A total of 21 patients who were diagnosed with GDM during 24–28 weeks of gestation were randomly divided into a conventional management (CM) group (n = 10) and a mobile management (MM) group (n = 11). The CM group received conventional GDM management and could freely use the mobile health care application. The MM group received mobile health care services, including tailored mobile coaching. After delivery, obstetric outcomes were collected, and 75-g oral glucose tolerance test was performed at 5–12 weeks postpartum. Findings Baseline characteristics, including glycosylated hemoglobin (HbA1c), were not significantly different between the 2 groups. No statistically significant differences were found in rates between the 2 groups for (1) neonate large for gestational age and (2) cesarean section at the time of delivery. No significant difference was found in HbA1c between the 2 groups after delivery. However, postpartum homeostatic model assessment insulin resistance, body mass index, weight, and percentage of body fat were significantly lower in the MM group. Implications The MM group had no significant difference in glycemic index compared with the CM group. However, the MM group had effective weight control and improved insulin resistance after delivery. This study indicated that mobile health care services could be an efficient GDM management tool. ClinicalTrials.gov identifier: NCT03838380 .

Purpose of review: The criteria for the diagnosis of intra-amniotic infection (IAI) were derived from a study of women at term in labor but is currently used as the main diagnostic tool for clinica...

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Objectives: Cerclage operation is one of the most common obstetric controversies. The aim of this study was to compare the perinatal outcomes and placental inflammation of cerclage performed adherent and non-adherent to international guidelines. Material and methods: This study included all consecutive women with singleton deliveries who underwent cerclage. According to the current American College of Obstetricians and Gynecologists (ACOG) guideline, we designated our study population into two groups: the adherent-to-guideline and non-adherent groups. Each group was categorized into two groups according to cervical length (CL) at the time of cerclage (

Postpartum pubic symphysis diastasis (PPSD) refers to the separation of pubic symphysis after delivery. It is typically diagnosed based on clinical symptoms and radiologic findings. This study tried to assess clinical characteristics and risk factors of PPSD. This was a nested case–control study matched for year of delivery and gestational age at delivery using a retrospective cohort of women who delivered vaginally at a single institution. The incidence of PPSD was 0.156% (33/21,131). The incidence rate increased from 0.08% (7/9328) in 2000–2004 to 0.13% (9/7138) in 2005–2009 and to 0.36% (17/4665) in 2010–2016, simultaneously with an increase of maternal age (30.7 ± 3.5 years in 2000–2004 to 31.8 ± 3.8 years in 2005–2009 and 32.8 ± 3.8 years in 2010–2016). Nulliparity was associated with a higher incidence of PPSD (81.8% in cases vs. 57.6% in controls, p = 0.01). Other factors including pre-pregnancy body mass index, weight gain during pregnancy, gestational diabetes, induction of labor, duration of labor, epidural anesthesia, vacuum-assisted delivery, episiotomy, neonatal sex and birth weight failed to show difference between the two groups. In short, the incidence of PPSD increased with time along with an increase of maternal age. Nulliparity was the only significant risk factor for PPSD.

Objective We investigated prenatal sonographic characteristics of esophageal atresia (EA) with advancing gestation. We focused on the degree of polyhydramnios and the stomach shape. Methods This study included 27 EA cases (EA group) and 81 idiopathic polyhydramnios cases (non-EA group). The non-EA group consisted of cases without any fetal structural anomaly, musculoskeletal disorder, chromosomal abnormality, or maternal diabetes. Both groups included only singleton pregnancies. Amniotic fluid index (AFI) and width/length (W/L) ratio as well as the product of width and length (W×L) of stomach were serially assessed during gestation and compared between the 2 groups. To predict EA using W/L ratio and W×L, receiver operating characteristic curve analysis was performed. Results Polyhydramnios was evident in 77.8% of EA cases. We observed 25.9% and 22.2% EA cases with an absent stomach and a small visible stomach, respectively. After 28 weeks, the EA group manifested significantly higher AFI than the non-EA group. After 32 weeks, W/L ratio in the EA group tended to be lower than that in the non-EA group (32–36 weeks: 1.36 vs. 1.72, P=0.092; >36 weeks: 1.43 vs. 1.63, P=0.024). To predict EA, the calculated area under the curve for W/L ratio was 0.651 after 32 weeks. The diagnosis of EA using a cut-off value of W/L ratio

The aim of this study was to compare the spillage rate and surgical outcomes between the leak-proof technique and the conventional technique in laparoscopy for large ovarian cysts (more than 15 cm in diameter) presumed to be benign tumours and free from adhesion. Thirty-five consecutive patients who underwent laparoscopy with the leak-proof technique between 2017 and 2019 (the practice change cohort) were compared retrospectively with 35 case-matched consecutive patients who underwent the conventional purse-string method between 2014 and 2016 (the historical cohort). In the practice change cohort, through the wound retractor in the umbilicus, large ovarian cysts were first covered with a sterilised vinyl membrane applied with a skin adhesive, then punctured, and the contents directly aspirated. The primary outcome was tumour spillage. The two cohorts had similar baseline characteristics. The spillage rate in the practice change cohort was significantly lower than in the historical cohort (0% vs 28.6%

Stroke induces complex and dynamic, local and systemic changes including inflammatory reactions, immune responses, and repair and recovery processes. Mesenchymal stem cells (MSCs) have been shown to enhance neurological recovery after stroke. We hypothesized that serum factors play a critical role in the activation of bone marrow (BM) MSCs after stroke such as by increasing proliferation, paracrine effects, and rejuvenation. Human MSCs (hMSCs) were grown in fetal bovine serum (FBS), normal healthy control serum (NS), or stroke patient serum (SS). MSCs cultured in growth medium with 10% SS or NS exhibited higher proliferation indices than those cultured with FBS ( P < 0.01). FBS-, NS-, and SS-hMSCs showed differences in the expression of trophic factors; vascular endothelial growth factor, glial cell–derived neurotrophic factor, and fibroblast growth factor were densely expressed in samples cultured with SS ( P < 0.01). In addition, SS-MSCs revealed different cell cycle– or aging-associated messenger RNA expression in a later passage, and β-galactosidase staining showed the senescence of MSCs observed during culture expansion was lower in MSCs cultured with SS than those cultured with NS or FBS ( P < 0.01). Several proteins related to the activity of receptors, growth factors, and cytokines were more prevalent in the serum of stroke patients than in that of normal subjects. Neurogenesis and angiogenesis were markedly increased in rats that had received SS-MSCs ( P < 0.05), and these rats showed significant behavioral improvements ( P < 0.01). Our results indicate that stroke induces a process of recovery via the activation of MSCs. Culture methods for MSCs using SS obtained during the acute phase of a stroke could constitute a novel MSC activation method that is feasible and efficient for the neurorestoration of stroke.

Objective: The purpose of this study is to investigate the factors associated with successful amniopatch treatment in patients with iatrogenic preterm premature rupture of membranes (iPPROM) or spontaneous PPROM (sPPROM) before 23 weeks' gestation. Materials and methods: This cohort study included 28 women who received amniopatch treatment due to iPPROM or sPPROM at 15-23 weeks' gestation. Patients' clinical characteristics before performing the amniopatch, factors associated with the procedure, pregnancy and neonatal outcomes were compared between the iPPROM and sPPROM groups, and also between the successful and failed groups. Results: The amniopatch was successful in 6 of 28 patients (21.4%) with a success rate of 36.4% (4/11) and 11.8% (2/17) in the iPPROM group and sPPROM group (P = 0.174), respectively. The success group had a longer PPROM-to-delivery interval, fewer cases of clinical chorioamnionitis, larger birth weight, and lower neonatal intensive care unit admission rate than the failed group. The success rate of amniopatch procedure was proportional to maximal vertical pocket prior to procedure, which showed statistically significant association (adjusted odds ratio: 3.62, 95% confidence interval: 1.16-11.31, P = 0.027). Conclusion: The amniopatch treatment success rate was higher in the iPPROM group than the sPPROM group, but was not statistically significant. The neonatal outcome was more favorable when the amniopatch was successful. However, the only predictive factor associated with successful amniopatch was a larger amniotic fluid volume before the procedure. (C) 2017 Taiwan Association of Obstetrics & Gynecology. Publishing services by Elsevier B.V.

BACKGROUND This retrospective study aimed to compare the surgical outcomes and morbidity of the vascular control technique in robotic myomectomy with the conventional technique. METHODS Thirty-two consecutive patients who underwent robotic myomectomy using laparoscopic vascular clamps in 2017 to 2019 (the practice change cohort) were retrospectively comparted with 32 case-matched consecutive patients who underwent the conventional robotic myomectomy (the historical cohort). The primary outcome was the operative blood loss and hemoglobin change. RESULTS The two cohorts had similar baseline characteristics. The mean operative blood loss and hemoglobin changes were lower in the practice change cohort than in the historical cohort (P < .001 and P = .005, respectively). Other postoperative outcomes were similar between two cohorts. CONCLUSION The vascular control technique in robotic myomectomy appears to be effective and safe in the management of selective patients with symptomatic myomas.

Objective To investigate the prevalence of extracardiac anomalies (ECA) in prenatally diagnosed congenital heart diseases (CHD), and to provide more information for counseling of women with prenatally diagnosed fetal CHD. Methods This was a retrospective cohort study of 791 cases of fetal CHD diagnosed by prenatal ultrasound from January 2005 to April 2018. Associated ECAs included extracardiac structural malformation (ECM), chromosomal anomaly, and 22q11.2 microdeletion. CHD was classified into 10 groups according to a modified anatomic and clinical classification of congenital heart defects. Results The overall prevalence of ECA in our CHD cohort was 28.6% (226/791): ECM, 25.3%; chromosomal anomaly, 11.7%; and 22q11.2 microdeletion, 5.5%. For those with ECM, ventricular septal defect (VSD) had the highest prevalence (34.5%), followed by anomalies of atrioventricular junctions and valves (28.8%) and heterotaxy (26.9%). For those with chromosomal anomaly, anomalies of atrioventricular junctions and valves had the highest prevalence (37.5%), followed by anomalies of atria and interatrial communications (25.0%) and VSD (22.9%). 22q11.2 microdeletion was detected only in those with anomalies of extrapericardial arterial trunks (14.3%) or ventricular outflow tracts (6.4%). Conclusion ECM, chromosomal anomaly, and 22q11.2 microdeletion have different prevalence according to the type of CHD.

In animal models of stroke, behavioral assessments could be complemented by a variety of neuroimaging studies to correlate them with recovery and better understand mechanisms of improvement after stem cell therapy. We evaluated morphological and connectivity changes after treatment with human mesenchymal stem cells (hMSCs) in a rat stroke model, through quantitative measurement of T2-weighted images and diffusion tensor imaging (DTI). Transient middle cerebral artery occlusion rats randomly received PBS (PBS-only), FBS cultured hMSCs (FBS-hMSCs), or stroke patients’ serum cultured hMSCs (SS-hMSCs). Functional improvement was assessed using a modified neurological severity score (mNSS). Quantitative analyses of T2-weighted ischemic lesion and ventricular volume changes were performed. Brain microstructure/connectivity changes were evaluated in the ischemic recovery area by DTI-derived microstructural indices such as relative fractional anisotropy (rFA), relative axial diffusivity (rAD), and relative radial diffusivity (rRD), and relative fiber density (rFD) analyses. According to mNSS results, the SS-hMSCs group showed the most prominent functional improvement. Infarct lesion volume of the SS-hMSCs group was significantly decreased at 2 weeks when compared to the PBS-only groups, but there were no differences between the FBS-hMSCs and SS-hMSCs groups. Brain atrophy was significantly decreased in the SS-hMSCs group compared to the other groups. In DTI, rFA and rFD values were significantly higher and rRD value was significant lower in the SS-hMSCs group and these microstructure/connectivity changes were correlated with T2-weighted morphological changes. T2-weighted volume alterations (ischemic lesion and brain atrophy), and DTI microstructural indices and rFD changes, were well matched with the results of behavioral assessment. These quantitative MRI measurements could be potential outcome predictors of functional recovery after treatment with stem cells for stroke.

Down syndrome is the most common trisomy abnormality, and generally occurs in about 1 in 700 surviving children. According to a Korean study, the prevalence of Down syndrome was about 5.03 out of 10,000 surviving children born from 2007 to 2016 and about 200-277 newborns with Down syndrome were born every year. In the past, the average survival age of Down syndrome was low, but recently it has been extended to 60 years and the quality of life is improving. Recently, there have been many improvements in the education of children with Down syndrome, and various studies have been conducted at the preclinical and clinical stages about cognitive impairment, which was thought to be impossible to treat previously. In Korea, obstetricians mainly play the role of providing medical information in the process of screening and confirming Down syndrome. Therefore, medical staff need to be familiar with the latest knowledge on medical conditions, treatment and prognosis, and quality of life of Down syndrome. Through this review, we provide information on prenatal diagnosis and counseling for Down syndrome and medical problems that may occur in Down syndrome. We also review the latest research on improving cognitive function of Down syndrome. In addition, we summarize literature in Korean about Down syndrome from a social point of view and introduce websites and social media related to Down syndrome, as well as an economic support system in Korea. By providing comprehensive and contemporary information, we ultimately hope to help families with Down syndrome.

Alzheimer's disease (AD) is characterized by progressive loss of memory in addition to cortical atrophy. Cortical atrophy in AD brains begins in the parietal and temporal lobes, which are near the subventricular zone (SVZ). The aim of this study was to activate the neurogenesis in the SVZ of AD brains by human mesenchymal stem cells (hMSCs). Neural stem cells (NSCs) were isolated from SVZ of 4-month-old 5XFAD mice. Co-culture of hMSCs with SVZ-derived NSCs from 5XFAD mice induced neuronal development and neurite outgrowth. To examine the inducing factor of neurogenesis, human cytokine array was performed with co-cultured media, and revealed elevated release of activin A from hMSCs. Also, we confirmed that the mRNA levels of activin A and activin receptor in the SVZ of 5XFAD mice were significantly lower than normal mice. Treatment of human recombinant activin A in SVZ-derived NSCs from 5XFAD mice induced neuronal development and neurite outgrowth. These data suggest that use of hMSCs and activin A to recover neurogenesis in future studies of cortical regeneration to treat AD.