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.

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.

Impact of COVID-19 Mitigation Policy in South Korea on the Reduction of Preterm or Low Birth Weight Birth Rate: A Single Center Experience.

The government of South Korea implemented social distancing measures to control the coronavirus disease 2019 (COVID-19) outbreak. This study aimed to compare the composite preterm (PT) or low birth weight (LBW) birth rates during the COVID-19 pandemic period in South Korea to those during the prior decade, and to find out the associations of childbirth during the pandemic period with PT or LBW births. Over a ten-year period, this retrospective cohort study was performed in a single hospital in the Seoul metropolitan city. The COVID-19 period was defined as running from 22 March 2020, to 31 October 2020, and the pre-COVID-19 period as the sum of parallel periods from 2011 to 2019. Trends in composite birth rates were investigated, and logistic regression analysis was conducted to investigate independent factors associated with composite births. There were 246 and 2765 singleton deliveries during the COVID-19 period and the pre-COVID-19 period, respectively. The composite birth rate decreased from 16.5% to 9.8%. Childbirth during the pandemic was independently associated with a decreased composite birth rate (adjusted odds ratio, 0.563; 95% confidence interval, 0.355-0.844, p = 0.015). These findings suggested that the COVID-19 pandemic might provide an opportunity to find out preventive factors for PT or LBW births.

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

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

Effect of Childbirth Age on Bone Mineral Density in Postmenopausal Women.

BACKGROUND: In postmenopausal women, there is rapid bone loss due to estrogen depletion. In women, reproductive factors such as age at menarche, breastfeeding, and parity are considered risk factors of osteoporosis. Many reports suggest that obesity is associated with a reduced risk of osteoporosis. This nationwide, population-based study aims to identify the association between maternal age and osteoporosis risk in postmenopausal women of different obesity classifications. METHODS: We assessed data from the Korean National Health and Nutrition Examination Survey 2010-2012. The study included 1,328 postmenopausal women, after excluding women with missing data for reproductive history among 4,546 postmenopausal women in the survey. Multivariate regression was used to identify the association between childbirth age and postmenopausal bone mineral density after adjustments for confounding factors. RESULTS: The prevalence of postmenopausal osteoporosis was 35.24% (n = 468). After dividing the subjects into obese and non-obese groups based on body mass index (BMI) and waist circumference, there were significant differences between non-osteoporosis and osteoporosis groups with regard to age at first childbirth, age at last childbirth, and parity in the BMI-based general obesity group. The prevalence of osteoporosis was highest in women older than 35 years old at last childbirth. The prevalence of osteoporosis was also greater in women with parity ≥ 4 compared to those with lower parity levels. CONCLUSION: Postmenopausal women of older age at last childbirth and higher parity were at increased risk of osteoporosis in the BMI-based non-general obesity group.

Regenerative efficacy of mesenchymal stromal cells from human placenta in sensorineural hearing loss.

INTRODUCTION: Hearing loss is a common chronic disorder characterized by decline of auditory function. The global population have suffered from deafness and the transplantation of stem cells is regarded as a therapeutic strategy for this disease. METHODS: We collected placenta from a total of 13 samples of full term pregnant women and isolated MSCs derived from human placenta and transplanted MSCs on deaf animal model. The normal group and the sensorineural hearing loss (SNHL) group and the experimental (transplanted MSCs) group were compared and estimated hearing level using auditory brainstem response (ABR) recordings and the otoacoustic emission (OAE) test. RESULTS: ABR threshold value and DPOAE level showed that MSCs transplantation groups was improved than the SNHL group. And the number of spiral ganglion neurons were increased in all turn of the cochlea. And there was no evidence of acute immunological rejection and inflammation response was not observed. DISCUSSION: This study is to evaluate regenerative efficacy of hearing loss by transplanting mesenchymal stromal cells (MSCs) derived from human placenta (amnion and chorion) in deaf animal model. We identified that MSCs transplantation restored auditory impairment and promoted cell regeneration. We hope to overcome sensorineural hearing loss by transplanting stem cells such as mesenchymal stromal cells (MSCs) from easily accessible adult stem cell source in placenta.

In Vitro Differentiation of Human Wharton's Jelly-Derived Mesenchymal Stem Cells into Auditory Hair Cells and Neurons.

OBJECTIVE: We attempted to induce mesenchymal stem cells (MSCs) from human Wharton's jelly (WJ) to differentiate into neuronal progenitor cells, neurons, and auditory hair cells. MATERIALS AND METHODS: MSCs were isolated from WJ from human umbilical cords and cultured in medium containing epidermal growth factor and basic fibroblast growth factor. Differentiation into hair cells and neurons was induced using a neurobasal medium containing glial cell-derived neurotrophic factor, brain-derived neurotrophic factor, and neurotrophic factor 3. Fluorescence-activated cell sorting (FACS), immunocytochemistry, and reverse transcription polymerase chain reaction were performed to characterize the differentiated auditory hair cells and neurons. RESULTS: MSCs isolated from human WJ were confirmed by FACS. Double immunocytochemistry confirmed the expression of the hair cell markers myosin VIIA and TRPA1 and the functional marker C-terminal binding protein 2. Differentiation into neurons was revealed using neurofilament and ßIII-tubulin markers. Gene expression of neuronal lineage-specific markers confirmed the neuronal differentiation state. CONCLUSION: MSCs from human WJ can be successfully induced to differentiate into auditory hair cells and neurons in vitro.

Effect of Maternal Age at Childbirth on Obesity in Postmenopausal Women: A Nationwide Population-Based Study in Korea.

The object of this study was to assess the obesity in postmenopausal women, according to age at childbirth.We analyzed the association between age at first childbirth, age at last childbirth, parity, and subject obesity status (general obesity; BMI >25 kg/m, nongeneral obesity; BMI ≤25 kg/m, abdominal obesity; waist circumference >85 cm, nonabdominal obesity; waist circumference ≤85 cm), using data from a nationwide population-based survey, the 2010 to 2012 Korean National Health and Nutrition Examination Survey. Data from a total of 4382 postmenopausal women were analyzed using multivariate regression analysis with complex survey design sampling. And, the subjects were subdivided into groups according to obesity or not. Age, smoking, alcohol consumption, exercise, education, income level, number of pregnancies, oral contraceptive uses, breast feeding experience were adjusted as the confounders.The prevalence of general obesity among Korean postmenopausal women was 37.08%. Women with general obesity and abdominal obesity were significantly younger at first childbirth compared with women with nongeneral obesity and no abdominal obesity (23.89 ±â€Š0.1 vs. 23.22 ±â€Š0.1, P <0.001). Age at first childbirth was inversely associated with obesity, while age at last childbirth was not associated with obesity or abdominal obesity. Women with a higher number of pregnancies were also more likely to have obesity and abdominal obesity. Age at first childbirth remained significantly associated with obesity, after adjusting for confounding factors.Obesity in postmenopausal women is associated with first childbirth at a young age, and higher parity. Further research is needed to clarify the association between obesity and reproductive characteristics.

Effect of maternal age at childbirth on insulin resistance: the 2010 Korean National Health and Nutrition Examination Survey.

OBJECTIVE: This study aimed to assess insulin resistance according to maternal age at childbirth. PATIENTS AND METHODS: The data used in this study were obtained from the 2010 Korean National Health and Nutrition Examination Survey. This study included a total of 2233 nondiabetic female subjects ≥30 years of age that were subdivided into groups according to their obesity and abdominal obesity (AOB) statuses. The homoeostasis model assessment of insulin resistance (HOMA-IR) was used to quantify the insulin resistance according to age at first childbirth and last childbirth. RESULTS: Age at first childbirth showed a negative relationship with HOMA-IR in both the nonobese and non-AOB groups, while age at last childbirth showed a positive relationship with HOMA-IR in both the nonobese and non-AOB groups. A multivariate logistic regression analysis revealed that ages at first and last childbirth were significantly associated with the highest HOMA-IR quartile. The odds ratio was 0·9 (95% confidence interval: 0·82-0·98) for age at first childbirth, and 1·07 (95% confidence interval: 1·01-1·14) for age at last childbirth in the nonobese and non-AOB groups. CONCLUSION: In conclusion, this study suggests that insulin resistance is increased in females who experienced their first childbirth at a younger age or their last childbirth at a later age, particularly in nonobese individuals. Because these data suggest that childbearing age could be an independent risk factor for diabetes, a high-quality prospective study assessing the relationship between childbearing age and insulin resistance should be performed.

Usefulness of CA125 in the differential diagnosis of uterine adenomyosis and myoma.

OBJECTIVES: To evaluate the usefulness of CA125 levels in the differential diagnosis of adenomyosis and myoma. This has been addressed by few, if any, previous studies. STUDY DESIGN: Preoperative serum CA125 levels were measured in 2149 women who were diagnosed at total hysterectomy as having adenomyosis, myoma, endometriosis, and/or normal pelvis. Their medical records were retrieved and reviewed. RESULTS: The mean serum CA125 level in the adenomyosis patients was significantly greater than that in the patients diagnosed with myoma (65.21±96.60 U/mL vs.12.86±14.23 U/mL, respectively; P<0.001). In the differential diagnosis of adenomyosis and myoma, the cut-off serum CA125 level with the highest accuracy (78.8%) and highest diagnostic value (61.2%) was 19 U/mL. Using this cut-off value, the negative predictive value was 69.5%, and the positive predictive value was 76.5%. These results are clearly superior to those of the empirical single cut-off value of 35 U/mL. Receiver operating characteristic curve analysis revealed the area under the curve for differentiating adenomyosis from myoma was 0.776, indicating good diagnostic performance. CONCLUSION: In the differential diagnosis of adenomyosis and myoma, cut-off values for CA125, particularly the cut-off value of 19 U/mL, provide improved diagnostic performance. Serum CA125 testing can be performed during the initial screening of women with possible adenomyosis to differentiate this condition from myoma, although the diagnostic accuracy of using CA125 testing alone is limited.

Interaction between human placental microvascular endothelial cells and a model of human trophoblasts: effects on growth cycle and angiogenic profile.

Abstract Intrauterine growth restriction (IUGR) is a leading cause of perinatal complications, and is commonly associated with reduced placental vasculature. Recent studies demonstrated over-expression of IGF-1 in IUGR animal models maintains placental vasculature. However, the cellular environment of the placental chorionic villous is unknown. The close proximity of trophoblasts and microvascular endothelial cells in vivo alludes to autocrine/paracrine regulation following Ad-HuIGF-1 treatment. We investigated the co-culturing of BeWo Choriocarcinoma and Human Placental Microvascular Endothelial Cells (HPMVECs) on the endothelial angiogenic profile and the effect Ad-HuIGF-1 treatment of one cell has on the other. HPMVECs were isolated from human term placentas and cultured in EGM-2 at 37°C with 5% CO2. BeWo cells were maintained in Ham's F12 nutrient mix with 10% FBS and 1% pen/strep. Co-cultured HPMVECS+BeWo cells were incubated in serum-free control media, Ad-HuIGF-1, or Ad-LacZ at MOI 0 and MOI 100:1 for 48 h. Non-treated cells and mono-cultured cells were compared to co-cultured cells. Angiogenic gene expression and proliferative and apoptotic protein expression were analysed by RT-qPCR and immunocytochemistry, respectively. Statistical analyses was performed using student's t-test with P < 0.05 considered significant. Direct Ad-HuIGF-1 treatment increased HPMVEC proliferation (n = 4) and reduced apoptosis (n = 3). Co-culturing HPMVECs+BeWo cells significantly altered RNA expression of the angiogenic profile compared to mono-cultured HPMVECs (n = 8). Direct Ad-HuIGF-1 treatment significantly increased Ang-1 (n = 4) in BeWo cells. Ad-HuIGF-1 treatment of HPMVECs did not alter the RNA expression of angiogenic factors. Trophoblastic factors may play a key role in placental vascular development and IGF-1 may have an important role in HPMVEC growth.