Risk factors for pregnancy-associated heart failure with preserved ejection fraction and adverse pregnancy outcomes: a cross-sectional study.

BACKGROUND: Although pregnancy-associated heart failure with preserved ejection fraction (HFpEF) is increasing and contributing to maternal morbidity, little is known about its impact on pregnancy. We examined the risk factors for and adverse pregnancy outcomes of HFpEF in pregnant women. METHODS: We conducted a cross-sectional analysis of pregnancy-related hospitalizations from 2009 to 2020 using the perinatal database of seven multicenters. Cases of HFpEF were identified using the International Classification of Diseases and echocardiography findings. The patients were categorized into the HFpEF and control groups. Risk factors were evaluated using multivariate logistic regression analysis to generate odds ratios (OR) and 95% confidence intervals (CI). Furthermore, adjusted associations between HFpEF and adverse pregnancy outcomes were determined. Risk scores for the stratification of women at a high risk of HFpEF were calculated using a statistical scoring model. RESULTS: Of the 34,392 women identified, 258 (0.76%) were included in the HFpEF group. In multivariate analysis, HFpEF was significantly associated with old maternal age (OR, 1.04; 95% CI 1.02-1.07), multiple pregnancy (OR, 2.22; 95% CI 1.53-3.23), rheumatic disease (OR, 2.56; 95% CI 1.54-4.26), pregnancy induce hypertension (OR 6.02; 95% CI 3.61-10.05), preeclampsia (OR 24.66; 95% CI 18.61-32.66), eclampsia or superimposed preeclampsia (OR 32.74; 95% CI 21.60-49.64) and transfusion in previous pregnancy (OR 3.89; 95% CI 1.89-8.01). A scoring model to predict HFpEF with those factors achieved an area under the curve of 0.78 at cutoff value of 3. Women with HFpEF also had increased odds ratios of intensive care unit admission during the perinatal period (odds ratio, 5.98; 95% confidence interval, 4.36-8.21) and of postpartum hemorrhage (odds ratio, 5.98; 95% confidence interval, 2.02-3.64). CONCLUSIONS: Pregnancy-associated HFpEF is associated with adverse pregnancy outcomes. A scoring model may contribute to screening HFpEF using echocardiography and preparing adverse pregnancy outcomes.

Prior pregnancy complications and maternal cardiovascular disease in young Korean women within 10 years after pregnancy.

BACKGROUND: This study aimed to compare obstetric outcomes in Korean women with and without future cardiovascular disease (CVD) within 10 years after pregnancy, and assessed whether pregnancy complications are independent risk factors, and whether the combination of pregnancy complications has an additive function for risk factors for CVD. METHODS: This was a nationwide population-based study combining the database of the Korea National Health Insurance claims and National Health Screening Programs to assess preeclampsia, low birth weight (LBW), and preterm delivery as risk factors for CVD. Cox proportional hazards models was used to evaluate the risk of total CVD, ischemic heart disease (IHD), and stroke after the pregnancy complications, with adjustment for potential confounding variables. RESULTS: Women with CVD were likely to have a higher prevalence of pregnancy complications than women without CVD. The risk of total CVD was associated with preeclampsia (adjusted hazard ratio (HR), 1.60 [95% confidence interval (CI) 1.50-1.72]), LBW (1.20 [1.12-1.28]), and preterm delivery (1.32 [1.22-1.42]), after adjustment for confounders, including cardiovascular risk factors before pregnancy. The risk estimates of pregnancy complications for IHD were higher than those for stroke. In this study, the risk of total CVD was higher in the combined presence of preeclampsia and preterm delivery (2.23 [1.57-3.17] or all three complications (2.06 [1.76-2.40]), relative to no complications. The highest HR was noted in the risk of all pregnancy complications for IHD (2.39 [1.98-2.89]). CONCLUSION: Preeclampsia, preterm delivery, and LBW were independently associated with CVD in young Korean women. In addition, the combination of pregnancy complications had less-than-additive effects on CVD incidence.

Secondhand smoke exposure, diabetes, and high BMI are risk factors for uterine cervical cancer: a cross-sectional study from the Korea national health and nutrition examination survey (2010-2018).

BACKGROUND: Human papilloma virus infection and tobacco smoking are the major risk factors for cervical cancer. There are limited studies searching other risk factors for cervical cancer and the results are not consistent. This study investigated the relations between cervical cancer and possible risk factors, including secondhand cigarette smoke exposure, diabetes, body mass index (BMI), and work schedule. METHODS: In this cross-sectional study, 29,557 women completed a cervical cancer questionnaire and were selected using 2010-2018 data from the Korea National Health and Nutrition Examination Survey. Details in secondhand smoke exposure, diabetes, BMI, and work schedule were assessed with participants' health interviews and health-related surveys. RESULTS: Two hundred sixty-two women (0.89%) in the sample were diagnosed with cervical cancer. Domestic secondhand smoke exposure, diabetes, and high BMI significantly increased cervical cancer risk. Respective odds ratios and 95% confidence intervals were: 1.547 (1.042-2.297), 2.156 (1.535-3.027), and 1.036 (1.006-1.067). Weekly work hours, and work schedule were not significantly related to cervical cancer incidence. CONCLUSION: Among Korean women, passive exposure to cigarette smoke at home, diabetes, and high BMI increase risk for cervical cancer.

Rational Design of Ultrathin Gas Barrier Layer via Reconstruction of Hexagonal Boron Nitride Nanoflakes to Enhance the Chemical Stability of Proton Exchange Membrane Fuel Cells.

Hexagonal boron nitride (hBN) has great potential as a promising gas barrier layer in proton exchange membrane fuel cells (PEMFCs) as it shows high proton conductivity as well as excellent gas-blocking capability. However, structural defects and mechanical damage during the transfer of the hBN layer and membrane swelling have limited the application of hBN sheets to PEMFCs. Here, an ultrathin gas barrier layer is successfully fabricated on a proton exchange membrane via reconstruction of mechanically exfoliated hBN nanoflakes using a direct spin-coating process. The hBN-coated layer effectively suppresses the gas crossover and inhibits the formation of reactive oxygen radicals in the electrodes without reducing the proton conductivity of the membrane. It is also demonstrated that the structural advantages of hBN-coated gas barrier layers promise high performance of a unit cell even after a open-circuit voltage (OCV) hold test for 100 h. Furthermore, through in-depth postmortem analyses, a time-dependent degradation mechanism of membrane electrode assembly under the OCV condition is rationally proposed.

Higher parity and risk of metabolic syndrome in Korean postmenopausal women: Korea National Health and Nutrition Examination Survey 2010-2012.

AIM: We sought to examine whether parity is associated with higher incidence of metabolic syndrome in postmenopausal women. METHODS: We conducted a cross-sectional study on 4098 Korean postmenopausal women by using nationally representative data from the Korea National Health and Nutrition Examination Survey 2010-2012. Multivariate logistic regression was performed to evaluate the relationship between parity and metabolic syndrome, with adjustment for potential confounding variables. RESULTS: The rate of metabolic syndrome was significantly higher with increasing number of parity, with dose-response relationship in univariate analysis (P <0.001). In addition, higher parity (≥3 live births) was associated with more prevalence of all components of metabolic syndrome compared with two live births (parity 2 vs 3 vs ≥4: 5.5 vs 12.1 and 14.4%, respectively; P < 0.001). However, after adjusting for demographic, socioeconomic, lifestyle and reproductive factors, we found that only higher parity was significantly associated with metabolic syndrome compared with two live births, and failed to show a dose-dependent relationship (parity 2 vs 3 vs ≥4: odds ratio 1 vs 1.404 vs 1.379, respectively; P = 0.043). We also proved that among the components of metabolic syndrome, only waist circumference had a significant positive relationship with parity in a multivariable adjusted model (parity 2 vs 3 vs ≥4: odds ratio 1 vs 1.559 vs 1.656, respectively; P < 0.001). CONCLUSION: Higher parity was independently associated with a higher risk of metabolic syndrome in postmenopausal women.

Contribution of Magnetic Resonance Imaging to Ultrasound for the Evaluation of Fetal Central Nervous System Anomalies.

OBJECTIVE: To evaluate whether magnetic resonance imaging (MRI) contributes to ultrasound for the evaluation of fetal central nervous system (CNS) anomalies. The secondary objective was to investigate whether MRI adds more information regarding the evaluation of specific pathologies or conditions. STUDY DESIGN: We retrospectively compared fetal MRI findings with ultrasound findings in CNS anomalies with respect to certain pathologic groups. Additionally, we evaluated diagnostic accuracy by comparing fetal MRI and ultrasound findings with postnatal findings. RESULTS: A total of 34 patients had 40 provisional diagnoses by fetal ultrasound, and of those patients 14 had a provisional diagnosis of ventriculomegaly and 14 had a provisional diagnosis of cerebellar or posterior fossa anomalies. MRI added to or changed the diagnosis in 52.5% of the patients with CNS abnormalities. The contribution rate in ventriculomegaly was 71.4%, and MRI changed the diagnosis in all indefinite diagnoses by ultrasound. Additionally, of the 15 patients with postnatal findings, there were no cases in which only the ultrasound findings were correct, but the MRI findings were incorrect. CONCLUSION: MRI contributes to ultrasound in the diagnosis of CNS anomalies. Cases of indefinite diagnosis and ventriculomegaly by ultrasound had greater benefit from MRI.

Does botulinum toxin injection site determine outcome in post-stroke plantarflexion spasticity? Comparison study of two injection sites in the gastrocnemius muscle: a randomized double-blind controlled trial.

OBJECTIVE: To determine if botulinum toxin type A injection at the proximal 2/10 and 3/10 of calf length, where the intramuscular nerve endings of the gastrocnemius muscle are densely distributed, is more efficacious in controlling plantarflexion spasticity than injection at distant sites within the same muscle. DESIGN: A double-blind randomized controlled trial. SETTTING: Two rehabilitation centres. SUBJECTS: Forty stroke patients were randomly allocated to two groups. Group A received injection at the proximal 2/10 and 3/10 of calf length, group B at and below the midbelly of the muscle. Both groups received 200 IU of botulinum toxin A and were followed up to eight weeks. MAIN MEASURES: Primary variables were the surface electromyography values recorded during plantarflexion; secondary variables were the Modified Ashworth Scale, Modified Tardieu Scale, clonus scale, 10-metre walking test, ABILOCO and Functional Ambulation Categories. RESULTS: At baseline, the median Modified Ashworth Scale was 2.0 (range,1+ -3.0), and there were no significant differences between the two groups in all the parameters, including spasticity. Compared to baseline, no significant differences between the two groups were detected in all the surface electromyography and clinical parameters at week 8 (P > 0.05). Both groups showed significant improvement of spasticity with a median Modified Ashworth Scale of 1+ (range, 0.0-2.0) at eight weeks. CONCLUSIONS: Botulinum toxin A injection was associated with a significant improvement from baseline to week 8 in both treatment groups, however, no significant difference between the 2 groups was observed, based on the electrophysiological and clinical parameters employed in this study.

Congenital Anomalies in Multiple Pregnancy: A Literature Review.

Importance: Multiple pregnancy is relatively common in many countries and is associated with various pregnancy complications, including preterm birth, low birth weight, and congenital anomalies. In particular, a poorer prognosis has been reported when congenital anomalies overlap with other pregnancy complications in multiple pregnancy compared with singleton pregnancy. Objective: This study reviews the characteristics of congenital anomalies that occur in multiple gestations as compared with singleton pregnancies. Evidence Acquisition: An extensive manual search of major electronic databases was conducted in June 2023. This literature review provides a comprehensive coverage of the congenital anomalies in multiple pregnancy. Results: Most studies have shown that multiple gestations are associated with an increased risk of congenital anomalies compared with singleton pregnancies. In addition, higher rates of congenital anomalies and concordance have been observed in monozygotic versus dizygotic twins. The effect of assisted reproductive therapies on the risk of congenital anomalies appears to be smaller in multiple gestations than in singleton pregnancies. Conclusions: Multiple pregnancy is significantly associated with an increased risk of congenital anomalies. Relevance: This review provides obstetrical providers with the requisite knowledge to offer appropriate antenatal care and prenatal anomaly screening to patients with multiple pregnancies.

Deficiency of circadian clock gene Bmal1 exacerbates noncanonical inflammasome-mediated pyroptosis and lethality via Rev-erbα-C/EBPß-SAA1 axis.

Circadian arrhythmia has been linked to increased susceptibility to multiple inflammatory diseases, such as sepsis. However, it remains unclear how disruption of the circadian clock modulates molecular aspects of innate immune responses, including inflammasome signaling. Here, we examined the potential role of the circadian clock in inflammasome-mediated responses through myeloid-specific deletion of BMAL1, a master circadian clock regulator. Intriguingly, Bmal1 deficiency significantly enhanced pyroptosis of macrophages and lethality of mice under noncanonical inflammasome-activating conditions but did not alter canonical inflammasome responses. Transcriptome analysis of enriched peritoneal myeloid cells revealed that Bmal1 deficiency led to a marked reduction in Rev-erbα expression at steady state and a significant increase in serum amyloid A1 (SAA1) expression upon poly(I:C) stimulation. Notably, we found that the circadian regulator Rev-erbα is critical for poly(I:C)- or interferon (IFN)-ß-induced SAA1 production, resulting in the circadian oscillation pattern of SAA1 expression in myeloid cells. Furthermore, exogenously applied SAA1 markedly increased noncanonical inflammasome-mediated pyroptosis of macrophages and lethality of mice. Intriguingly, our results revealed that type 1 IFN receptor signaling is needed for poly(I:C)- or IFN-ß-induced SAA1 production. Downstream of the type 1 IFN receptor, Rev-erbα inhibited the IFN-ß-induced association of C/EBPß with the promoter region of Saa1, leading to the reduced transcription of Saa1 in macrophages. Bmal1-deficient macrophages exhibited enhanced binding of C/EBPß to Saa1. Consistently, the blockade of Rev-erbα by SR8278 significantly increased poly(I:C)-stimulated SAA1 transcription and noncanonical inflammasome-mediated lethality in mice. Collectively, our data demonstrate a potent suppressive effect of the circadian clock BMAL1 on the noncanonical inflammasome response via the Rev-erbα-C/EBPß-SAA1 axis.

Glucose tolerance test with a single abnormal value as a predictor of type 2 diabetes mellitus: a multicenter retrospective study.

Clinical implication of a single abnormal value (SAV) in the 100 g oral glucose tolerance test during pregnancy has not been established. We aimed to evaluate the risk of postpartum type 2 diabetes mellitus (T2DM) and investigate adverse pregnancy outcomes in women with SAV, using a retrospective database, from seven medical centers of Korea. Based on the Carpenter-Coustan criteria using two-step approach, pregnancy and postpartum outcomes were compared, among normoglycemic, SAV, and gestational diabetes mellitus (GDM) groups. Among 9353 women, 342 (3.66%) and 418(4.47%) women were included in SAV and GDM groups, respectively. SAV and GDM groups showed significantly higher rates of postpartum T2DM than normoglycemic group (7.60%, 14.83%, and 1.82%, respectively, p < 0.001). And SAV group showed significantly higher rates of pregnancy associated hypertension, preterm birth, and neonatal hypoglycemia and sepsis, compared to normoglycemic group (neonatal sepsis, p = 0.008; the others, p < 0.001). In multivariate analysis, postpartum T2DM was associated with SAV, GDM (with/without insulin), nulliparity, pre-pregnancy BMI, chronic hypertension, hyperlipidemia, and DM family history. A scoring model to predict postpartum T2DM within 5 years, achieved an area under the curve of 0.74. This study demonstrated that not only GDM, but also SAV is a significant risk factor for postpartum T2DM.

The associations between maternal and fetal exposure to endocrine-disrupting chemicals and asymmetric fetal growth restriction: a prospective cohort study.

Recent evidence has revealed associations between endocrine-disrupting chemicals (EDCs) and placental insufficiency due to altered placental growth, syncytialization, and trophoblast invasion. However, no epidemiologic study has reported associations between exposure to EDCs and asymmetric fetal growth restriction (FGR) caused by placenta insufficiency. The aim of this study was to evaluate the association between EDC exposure and asymmetric FGR. This was a prospective cohort study including women admitted for delivery to the Maternal Fetal Center at Seoul St. Mary's Hospital between October 2021 and October 2022. Maternal urine and cord blood samples were collected, and the levels of bisphenol-A (BPA), monoethyl phthalates, and perfluorooctanoic acid in each specimen were analyzed. We investigated linear and non-linear associations between the levels of EDCs and fetal growth parameters, including the head circumference (HC)/abdominal circumference (AC) ratio as an asymmetric parameter. The levels of EDCs were compared between fetuses with and without asymmetric FGR. Of the EDCs, only the fetal levels of BPA showed a linear association with the HC/AC ratio after adjusting for confounding variables (ß = 0.003, p < 0.05). When comparing the normal growth and asymmetric FGR groups, the asymmetric FGR group showed significantly higher maternal and fetal BPA levels compared to the normal growth group (maternal urine BPA, 3.99 µg/g creatinine vs. 1.71 µg/g creatinine [p < 0.05]; cord blood BPA, 1.96 µg/L vs. -0.86 µg/L [p < 0.05]). In conclusion, fetal exposure levels of BPA show linear associations with asymmetric fetal growth patterns. High maternal and fetal exposure to BPA might be associated with asymmetric FGR.

The Effects of Spatial Complexity on Narrative Experience in Space-Adaptive AR Storytelling.

A critical yet unresolved challenge in designing space-adaptive narratives for Augmented Reality (AR) is to provide consistently immersive user experiences anywhere, regardless of physical features specific to a space. For this, we present a comprehensive analysis on a series of user studies investigating how the size, density, and layout of real indoor spaces affect users playing Fragments, a space-adaptive AR detective game. Based on the studies, we assert that moderate levels of traversability and visual complexity afforded in counteracting combinations of size and complexity are beneficial for narrative experience. To confirm our argument, we combined the experimental data of the studies (n=112) to compare how five different spatial complexity conditions impact narrative experience when applied to contrasting room sizes. Results show that whereas factors of narrative experience are rated significantly higher in relatively simple settings for a small space, they are less affected by complexity in a large space. Ultimately, we establish guidelines on the design and placement of space-adaptive augmentations in location-independent AR narratives to compensate for the lack or excess of affordances in various real spaces and enhance user experiences therein.

Quantitative analysis of choroidal morphology in preeclampsia during pregnancy according to retinal change.

We sought to investigate changes in choroidal hemodynamics in preeclampsia according to presence of retinal change by quantitatively assessing choroidal vessels using optical coherence tomography (OCT). This retrospective study included 106 eyes (of 53 patients) with preeclampsia, including 70 eyes without retinal change in patients with preeclampsia (Group A), 22 eyes with retinal change in patients with preeclampsia (Group B), and 14 eyes of normal pregnant women (controls). Subfoveal choroidal thickness (SFCT) was measured on OCT B-scan images, and choroidal vessel densities (CVDs) were calculated using binarized OCT B-scan and en face images. Their values were then correlated with clinical parameters associated with preeclampsia. SFCT was greater in Group B compared to Group A or controls (354.32 ± 65.13 vs. 288 ± 55.68 or 277.21 ± 50.08, both P < 0.001). CVD on B-scan images was greater in Group B compared to Group A or controls (76.4 ± 4.9 vs. 73.7 ± 5.3 or 71.5 ± 5.1; both P ≤ 0.046). CVD on en face images was also greater in Group B compared to Group A or controls (64.7 ± 0.8 vs. 63.6 ± 1.5 or 63.3 ± 1.3; both P ≤ 0.001). SFCT and CVD positively correlated with each other (P ≤ 0.009) and were greater in patients with blurred vision and vaginal bleeding (P ≤ 0.020 for blurred vision and P ≤ 0.024 for vaginal bleeding). SFCT and CVDs were higher in preeclampsia patients with retinal change compared to those without retinal change or controls. Both SFCT and CVD showed association with blurred vision and vaginal bleeding.

Effects of Avatar Transparency on Social Presence in Task-Centric Mixed Reality Remote Collaboration.

Despite the importance of avatar representation on user experience for Mixed Reality (MR) remote collaboration involving various device environments and large amounts of task-related information, studies on how controlling visual parameters for avatars can benefit users in such situations have been scarce. Thus, we conducted a user study comparing the effects of three avatars with different transparency levels (Nontransparent, Semi-transparent, and Near-transparent) on social presence for users in Augmented Reality (AR) and Virtual Reality (VR) during task-centric MR remote collaboration. Results show that avatars with a strong visual presence are not required in situations where accomplishing the collaborative task is prioritized over social interaction. However, AR users preferred more vivid avatars than VR users. Based on our findings, we suggest guidelines on how different levels of avatar transparency should be applied based on the context of the task and device type for MR remote collaboration.

Association of maternal thyroid disease with obesity in child.

OBJECTIVES: During pregnancy, many women develop thyroid disorders, which can result in fetal and neonatal development defects. We investigated whether maternal thyroid dysfunction would affect their children's growth and obesity. STUDY DESIGN: We conducted a nationwide population-based cohort study using a combination of data from several Korean nationwide registries to investigate the association between maternal thyroid dysfunction, offspring growth, and obesity. Childhood growth was repeatedly measured at three periods of age from 42 to 80 months, using body mass index (BMI). RESULTS: A total of 1,123,499 women were enrolled in this study; 78,902 (7.0 %) had pre-pregnancy thyroid disease. Significant association was found between maternal hyperthyroidism and obesity in all children aged 42-66 months (42-54 months, adjusted odds ratio (aOR) 0.93, 95 % confidence interval (CI) 0.89-0.98; 54-66 months, aOR 0.93, 95 % CI 0.87-0.99), but not at later ages. In the analysis by sex, maternal hyperthyroidism was associated with childhood obesity in boys, whereas it was not associated with those in girls of any age. No association was observed between maternal hypothyroidism and child BMI or obesity. CONCLUSIONS: The association between maternal thyroid function and obesity in offspring is attenuated from early to late childhood, suggesting that many other factors may be involved in developing childhood obesity.

Prediction of Pregnancy-Associated Hypertension Using a Scoring System: A Multicenter Cohort Study.

This study aimed to develop an early pregnancy risk scoring model for pregnancy-associated hypertension (PAH) based on maternal pre-pregnancy characteristics, such as mean arterial pressure (MAP), pregnancy-associated plasma protein-A (PAPP-A) or neither. The perinatal databases of seven hospitals from January 2009 to December 2020 were randomly divided into a training set and a test set at a ratio of 70:30. The data of a total pregnant restricted population (women not taking aspirin during pregnancy) were analyzed separately. Three models (model 1, pre-pregnancy factors only; model 2, adding MAP; model 3, adding MAP and PAPP-A) and the American College of Obstetricians and Gynecologists (ACOG) risk factors model were compared. A total of 2840 (8.11%) and 1550 (3.3%) women subsequently developed PAH and preterm PAH, respectively. Performances of models 2 and 3 with areas under the curve (AUC) over 0.82 in both total population and restricted population were superior to those of model 1 (with AUCs of 0.75 and 0.748, respectively) and the ACOG risk model (with AUCs of 0.66 and 0.66) for predicting PAH and preterm PAH. The final scoring system with model 2 for predicting PAH and preterm PAH showed moderate to good performance (AUCs of 0.78 and 0.79, respectively) in the test set. "A risk scoring model for PAH and preterm PAH with pre-pregnancy factors and MAP showed moderate to high performances. Further prospective studies for validating this scoring model with biomarkers and uterine artery Doppler or without them might be required".

Prediction of gestational diabetes mellitus in Asian women using machine learning algorithms.

This study developed a machine learning algorithm to predict gestational diabetes mellitus (GDM) using retrospective data from 34,387 pregnancies in multi-centers of South Korea. Variables were collected at baseline, E0 (until 10 weeks' gestation), E1 (11-13 weeks' gestation) and M1 (14-24 weeks' gestation). The data set was randomly divided into training and test sets (7:3 ratio) to compare the performances of light gradient boosting machine (LGBM) and extreme gradient boosting (XGBoost) algorithms, with a full set of variables (original). A prediction model with the whole cohort achieved area under the receiver operating characteristics curve (AUC) and area under the precision-recall curve (AUPR) values of 0.711 and 0.246 at baseline, 0.720 and 0.256 at E0, 0.721 and 0.262 at E1, and 0.804 and 0.442 at M1, respectively. Then comparison of three models with different variable sets were performed: [a] variables from clinical guidelines; [b] selected variables from Shapley additive explanations (SHAP) values; and [c] Boruta algorithms. Based on model [c] with the least variables and similar or better performance than the other models, simple questionnaires were developed. The combined use of maternal factors and laboratory data could effectively predict individual risk of GDM using a machine learning model.

Adverse Pregnancy Outcomes and Maternal Chronic Diseases in the Future: A Cross-Sectional Study Using KoGES-HEXA Data.

Adverse pregnancy outcomes (APOs) are associated with an increased risk of chronic diseases, including cardiovascular disease (CVD) and metabolic syndrome (MS), in the future. We designed a large-scale cohort study to evaluate the influence of APOs (preeclampsia, gestational diabetes mellitus (GDM), stillbirth, macrosomia, and low birth weight) on the incidence of chronic diseases, body measurements, and serum biochemistry in the future and investigate whether combinations of APOs had additive effects on chronic diseases. We used health examinee data from the Korean Genome and Epidemiology Study (KoGES-HEXA) and extracted data of parous women (n = 30,174; mean age, 53.02 years) for the analysis. Women with APOs were more frequently diagnosed with chronic diseases and had a family history of chronic diseases compared with women without APOs. Composite APOs were associated with an increased risk of hypertension, diabetes mellitus, hyperlipidemia, angina pectoris, stroke, and MS (adjusted odds ratio: 1.093, 1.379, 1.269, 1.351, 1.414, and 1.104, respectively) after adjustment for family history and social behaviors. Preeclampsia and GDM were associated with an increased risk of some chronic diseases; however, the combination of preeclampsia and GDM did not have an additive effect on the risk. APOs moderately influenced the future development of maternal CVD and metabolic derangements, independent of family history and social behaviors.

Maternal Gestational Diabetes Influences DNA Methylation in the Serotonin System in the Human Placenta.

The offspring of mothers with gestational diabetes mellitus (GDM) are at a higher risk for metabolic dysregulation and neurodevelopmental impairment. Evidence suggests that serotonin, which is present in both the placenta and the brain, programs the development and growth of the fetal brain. In the current study, we tested the hypothesis that GDM affects the methylation of the serotonin transporter gene (SLC6A4) and serotonin receptor gene (HTR2A) in the placenta. Ninety pregnant women were included in this study. Thirty mothers were diagnosed with GDM, and sixty mothers served as controls in a 1:2 ratio. Ten CpG sites within the promoter regions of SLC6A4 and HTR2A were analyzed using pyrosequencing. The relative expression of genes involved in DNA methylation was evaluated using real-time PCR. The average DNA methylation of placental SLC6A4 was higher in the GDM group than in the control group (2.29 vs. 1.16%, p < 0.001). However, the average DNA methylation level of HTR2A did not differ between the two groups. SLC6A4 methylation showed a positive correlation with maternal plasma glucose level and neonatal birth weight percentile and a negative correlation with the neonatal head circumference percentile. This finding suggests that epigenetic modification of the placental serotonin system may affect placental adaptation to a harmful maternal environment, thereby influencing the long-term outcome in the offspring.

Prognostic Significance of Clinical Factors Including BRCA Mutation in Epithelial Ovarian, Peritoneal, Fallopian Tube Cancer.

BACKGROUND/AIM: We analyzed the survival outcomes of patients with epithelial ovarian, peritoneal, or fallopian tube cancer with BRCA1/2 mutations and the clinical factors associated with the prognosis of these cancers. PATIENTS AND METHODS: We included patients who had been diagnosed with and treated for epithelial ovarian, peritoneal, or fallopian tube cancer and had undergone germline BRCA testing in six hospitals between January 2012 and December 2019. RESULTS: Of the 378 identified patients, 76 (20.1%) carried a BRCA1/2 mutation. Progression-free survival (PFS) and overall survival (OS) did not differ between patients with and without BRCA1/2 mutation. Multivariate analysis for 18 months after the primary treatment showed higher PFS in the BRCA1/2 mutation group (p=0.024). Subgroup analysis in patients with high-grade serous carcinoma showed that BRCA1/2 mutation was an independent favorable prognostic factor for PFS (p=0.035). Subgroup analysis of patients with stage III or IV disease demonstrated an independent gain in PFS in patients with BRCA1/2 mutation (p=0.015). Neoadjuvant chemotherapy as a primary treatment was related to poor PFS (p<0.001) and reduced OS (p=0.005). CONCLUSION: Having a germline BRCA1/2 mutation improved short-term PFS in patients with epithelial ovarian, peritoneal, or fallopian tube cancer. Elevated initial CA125 level and primary neoadjuvant chemotherapy were related to poor prognosis.