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.

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.

The Correlation between Sex Hormone-Binding Globulin and Clinical Characteristics According to Anti-Müllerian Hormone in Women with Regular Menstrual Cycles: A Prospective Study.

BACKGROUND: Polycystic ovarian syndrome (PCOS) can be diagnosed when the anti-Müllerian hormone (AMH) levels are high, but in clinic, women who do not meet the diagnosis of PCOS but have elevated AMH levels are often seen. This study aimed to compare the differences in menstrual cycle patterns and hormone levels in women with regular menstrual cycles, but not PCOS, by dividing them into high and low AMH groups. MATERIAL AND METHODS: This multicenter prospective study included 68 healthy women. Participants with regular menstrual cycles were divided into two groups according to their AMH levels. The main outcome measures were menstrual cycle pattern, body mass index, and hormone levels (thyroid stimulating hormone, prolactin, testosterone, sex hormone-binding globulin, and free androgen index), which were compared between the groups according to AMH levels. The ovulation was assessed by performing pelvic ultrasound, and by assessing the hormone levels of the luteinizing hormone and progesterone. RESULTS: The criteria for determining normal and high AMH levels were based on previous literatures. The participants were divided into normal (39 people) and high (29 people) AMH group. No differences were found in age or BMI between the two groups, and no other differences were observed in TSH, prolactin, testosterone, or free androgen index. However, the high AMH group had significantly higher SHBG levels than the normal group (normal group: 65.46 ± 25.78 nmol/L; high group: 87.08 ± 45.05 nmol/L) (p = 0.025). CONCLUSIONS: This study is the first to analyze the association between SHBG and AMH levels in women with regular menstrual cycles. Elevated AMH levels are associated with increased levels of SHBG levels.

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.

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.

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 Emergency Cesarean Section Using Machine Learning Methods: Development and External Validation of a Nationwide Multicenter Dataset in Republic of Korea.

This study was a multicenter retrospective cohort study of term nulliparous women who underwent labor, and was conducted to develop an automated machine learning model for prediction of emergent cesarean section (CS) before onset of labor. Nine machine learning methods of logistic regression, random forest, Support Vector Machine (SVM), gradient boosting, extreme gradient boosting (XGBoost), light gradient boosting machine (LGBM), k-nearest neighbors (KNN), Voting, and Stacking were applied and compared for prediction of emergent CS during active labor. External validation was performed using a nationwide multicenter dataset for Korean fetal growth. A total of 6549 term nulliparous women was included in the analysis, and the emergent CS rate was 16.1%. The C-statistics values for KNN, Voting, XGBoost, Stacking, gradient boosting, random forest, LGBM, logistic regression, and SVM were 0.6, 0.69, 0.64, 0.59, 0.66, 0.68, 0.68, 0.7, and 0.69, respectively. The logistic regression model showed the best predictive performance with an accuracy of 0.78. The machine learning model identified nine significant variables of maternal age, height, weight at pre-pregnancy, pregnancy-associated hypertension, gestational age, and fetal sonographic findings. The C-statistic value for the logistic regression machine learning model in the external validation set (1391 term nulliparous women) was 0.69, with an overall accuracy of 0.68, a specificity of 0.83, and a sensitivity of 0.41. Machine learning algorithms with clinical and sonographic parameters at near term could be useful tools to predict individual risk of emergent CS during active labor in nulliparous women.

Effects of polycyclic aromatic hydrocarbons on the proliferation and differentiation of placental cells.

BACKGROUND: The purpose of this study was to investigate the effects of polycyclic aromatic hydrocarbons (PAHs) other than bisphenol A (BPA) and BPA substitutes on placental cells. METHODS: HTR-8/SVneo cells were treated with anthracene, benzo[k]fluoranthene, benzo[a]pyrene, and 4,4-(9-fluorenylidene)diphenol, which is used as a substitute for BPA-free products. After confirming the dose response for each reagent using the prepared cells, the cells were incubated for 24, 48, and 72 h. Cell viability was confirmed using the XTT assay. Each experiment was performed with the minimum number of samples (n = 3) required for statistical analysis. The results were analyzed using t-tests; p < 0.05 was considered statistically significant. RESULTS: After treatment with anthracene, benzo[k]fluoranthene, benzo[a]pyrene, and 4,4-(9-fluorenylidene)diphenol, the absorbance measured using the XTT assay decreased significantly with increasing concentration. The absorbance decreased significantly over time following treatment with each endocrine disruptor at the concentration confirmed by the dose-response analysis. CONCLUSIONS: This study showed that anthracene, benzo[k]fluoranthene, benzo[a]pyrene, and 4,4-(9-fluorenylidene)diphenol-a BPA substitute-affect cell viability and necrosis in the placental cell line. The study indicates the serious effects of PAHs that negatively affect pregnancy but were previously unknown. Further, this study would serve as a reference for the identification of harmful PAHs during pregnancy prognosis in women who are more susceptible to PAH exposure.

Clinical significance of soft markers in second trimester ultrasonography for pregnant Korean women: a multicenter study and literature review.

OBJECTIVE: To evaluate the clinical significance of soft markers for aneuploidy screening in Korean women. METHODS: We retrospectively reviewed the medical records of 5,428 singleton pregnant women who underwent sonography during the second trimester at seven institutions in South Korea. We evaluated the prevalence of the following soft markers: intracardiac echogenic focus, choroid plexus cysts, pyelectasis, echogenic bowel, and mild ventriculomegaly. We developed best-fitted regression equations for the fetal femur and humerus length using our data and defined a short femur and humerus as both long bones below the fifth centile. The results of genetic testing and postnatal outcomes were investigated in patients who had been diagnosed with aforementioned soft markers. RESULTS: The median maternal age of our study population was 33 years, and the median gestational age at the time of ultrasonographic examination was 21 weeks. We detected soft markers in 10.0% (n=540) of fetuses: 9.3% (n=504) were isolated cases and 0.7% (n=36) of cases had two or more markers. We identified only two aneuploides (trisomy 18, 46,XX,t[8;10][q22.1;p13]), of which one was clinically significant. We presented the neonatal outcomes of the fetuses with the respective soft markers. Preterm delivery, low birth weight, and small-for-gestational-age (SGA) were significantly more common in women with a shortened fetal femur (P<0.001, all). However, the presence of a shortened fetal humerus was not associated with those outcomes excluding SGA. CONCLUSION: Soft markers in second-trimester ultrasonography have limited use in screening for fetal aneuploidy in Korean women. However, these markers can be used as a screening tool for adverse outcomes other than chromosomal abnormality.

Elevated methylation of the vault RNA2-1 promoter in maternal blood is associated with preterm birth.

BACKGROUND: Preterm birth, defined as parturition before 37 completed weeks of gestation, is associated with an increased risk of neonatal complications and death, as well as poor health and disease later in life. Epigenetics could contribute to the mechanism underlying preterm birth. RESULTS: Genome-wide DNA methylation analysis of whole blood cells from 10 women (5 term and 5 preterm deliveries) was performed using an Illumina Infinium HumanMethylation450 BeadChips array. We identified 1,581 differentially methylated CpG sites in promoter regions between term and preterm birth. Although the differences were not significant after correcting for multiple tests, seven CpGs on the genomically imprinted vault RNA2-1 (VTRNA2-1; also known as non-coding RNA, nc886 or miR-886) showed the largest differences (range: 26-39 %). Pyrosequencing verification was performed with blood samples from pregnant women recruited additionally (39 term and 43 preterm deliveries). In total, 28 (34.1 %) samples showed hypomethylation of the VTRNA2-1 promoter (< 13 % methylation), while 54 (65.9 %) samples showed elevated methylation levels between 30 and 60 %. Elevated methylation of VTRNA2-1 promoter was associated with an increased risk of preterm birth after adjusting for maternal age, season of delivery, parity and white blood cell count. The mRNA expression of VTRNA2-1 was 0.51-fold lower in women with preterm deliveries (n = 20) compared with women with term deliveries (n = 20). CONCLUSIONS: VTRNA2-1 is a noncoding transcript to environmentally responsive epialleles. Our results suggest that elevated methylation of the VTRNA2-1 promoter may result in increased risk of PTB caused by the pro-inflammatory cytokines. Further studies are needed to confirm the association of VTRNA2-1 methylation with preterm birth in a large population, and to elucidate the underlying mechanism.

The degree of cervical length shortening as a predictor of successful or failed labor induction.

OBJECTIVE: To evaluate whether the degree of cervical length change was associated with successful cervical dilatation during labor induction. MATERIALS AND METHODS: We conducted a secondary analysis of a prospective observational study of term singleton pregnant women who underwent labor inductions. Cases of Cesarean section due to fetal distress or maternal request during the first stage of labor were excluded. The enrolled women were categorized into two groups according to achievement of full cervical dilatation. The cervical length near induction and cervical length shortening over the last four weeks of pregnancy were compared between the two groups. A receiver operating characteristics (ROC) analysis was performed to evaluate the screening performance for failed cervical dilatation during labor induction. RESULTS: A total of 165 women were enrolled for the final analysis; of these, 145 (87.9%) women reached the second stage of labor and 20 (12.1%) women failed to achieve full cervical dilatation. Women who failed to achieve full cervical dilatation had a significantly longer cervical length near induction and less cervical length change over previous four weeks compared with women who achieved full cervical dilatation (P = 0.018 and 0.005, respectively). Multivariate analysis showed that cervical length >29 mm (odds ratios [OR], 4.15; 95% confidence interval [CI], 1.290-13.374, P = 0.017) and cervical length shortening â‰¦ 6 mm (OR, 5.87; 95% CI, 1.552-22.271, P = 0.009) were significantly associated with failed cervical dilatation after adjusting for birthweight and previous history of vaginal delivery. Cervical length shortening alone provided a better prediction of failed cervical dilatation than the combination of cervical length and shortening (sensitivity, 76.9%; specificity, 63.8%). CONCLUSION: The probability of failed cervical dilatation during labor induction was significantly increased in cases when the cervical length was greater than 29 mm near induction or when the cervical length shortening was less than 6 mm over the last four weeks.

Cervicovaginal fluid cytokines as predictive markers of preterm birth in symptomatic women.

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

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.

Vaginal microbiome profiles of pregnant women in Korea using a 16S metagenomics approach.

PROBLEM: The stability and dominance of Lactobacillus spp. in vaginal fluid are important for reproductive health. However, the characterization of the vaginal microbiota of women with preterm labor (PTL) or preterm premature rupture of membranes (P-PROM), and its association with preterm birth (PTB) are poorly understood. METHOD OF STUDY: We collected vaginal fluid from women at risk of PTB (n = 58) in five university hospitals in Korea. We performed a hierarchical clustering analysis and classification according to the Lactobacillus spp. and Lactobacillus abundance using Illumina MiSeq sequencing of 16S rRNA gene amplicons. RESULTS: Women at risk for PTB caused by P-PROM had greater bacterial richness and diversity at the time of admission than those with PTL (P < 0.05). However, they were not significantly different between term and preterm samples. In the classification by Lactobacillus spp., the community commonly dominated by Bacteroides and Lactobacillus crispatus was found for the first time in pregnant women in Korea, and all women with this community delivered preterm. Intriguingly, women with an abundance of Weissella in a Bacteroides-dominant community delivered at term. Moreover, in the classification by Lactobacillus proportion, the abundances of Weissella and Rickettsiales were associated with term deliveries, but the abundances of Bacteroides and Escherichia-Shigella were associated with PTBs (P < 0.05). CONCLUSION: This result suggests that Lactobacillus abundance-based classification of vaginal fluid may reveal the microbiome associated with PTB. Further studies are needed to investigate the mechanism underlying the link between the microbiome and PTB.

Opioid analgesics are the leading cause of adverse drug reactions in the obstetric population in South Korea.

Medication use during pregnancy is gradually increasing; however, the safety of this practice remains largely unknown.We investigated medications with the most adverse drug reactions (ADRs) among pregnant women and the clinical features of those medications.Reports of ADRs among pregnant women were extracted from the Korea Adverse Events Reporting System (January 2012-December 2015). We analyzed the data of drugs frequently reported to cause ADRs and their clinical features among 3 age groups.A total of 5642 ADRs among 3428 patients were analyzed. The number of ADR reports increased annually. The most common drug categories causing ADRs were analgesics, followed by gynecologic, uterotocolytic, anti-infective, antidiabetic, analgesic, and antihypertensive drugs. Analgesics comprised 6 opioids (morphine, fentanyl, hydromorphone, oxycodone, tramadol, pethidine) and an anti-pyretics (nefopam and ketorolac). As an individual drug, ritodrine (24.4%) was the most frequently reported, followed by morphine, 5-HT3 serotonin antagonist, nefopam, fentanyl, magnesium sulfate, insulin lispro, cefazedone, sodium chloride, hydromorphone, oxycodone, cefotetan, nifedipine, human insulin, tramadol, ketorolac, pethidine, methylergometrine, metoclopramide, and misoprostol (in that order). ADRs most frequently occurred in women aged 25 to 34 years, and the trend of ADR with the 20 most commonly reported medications significantly differed among the age groups (P = .011). In addition, the kind of common causative drugs was different among the age groups.Knowledge of medications and clinical conditions resulting in the highest ADR rates among pregnant women is necessary for medical practitioners to administer proper care.

Addition of Cervical Elastography May Increase Preterm Delivery Prediction Performance in Pregnant Women with Short Cervix: a Prospective Study.

BACKGROUND: We investigated whether there is a difference in elastographic parameters between pregnancies with and without spontaneous preterm delivery (sPTD) in women with a short cervix (≤ 25 mm), and examined the ability of elastographic parameters to predict sPTD in those women. METHODS: E-CervixTM (WS80A; Samsung Medison, Seoul, Korea) elastography was used to examine the cervical strain. Elastographic parameters were compared between pregnancies with and without sPTD. Diagnostic performance of elastographic parameters to predict sPTD ≤ 37 weeks, both alone and in combination with other parameters, was compared with that of cervical length (CL) using area under receiver operating characteristic curve (AUC) analysis. RESULTS: A total of 130 women were included. Median gestational age (GA) at examination was 24.4 weeks (interquartile range, 21.4-28.9), and the prevalence of sPTD was 20.0% (26/130). Both the elastographic parameters and CL did not show statistical difference between those with and without sPTD. However, when only patients with CL ≥ 1.5 cm (n = 110) were included in the analysis, there was a significant difference between two groups in elasticity contrast index (ECI) within 0.5/1.0/1.5 cm from the cervical canal (P < 0.05) which is one of elastographic parameters generated by E-Cervix. When AUC analysis was performed in women with CL ≥ 1.5 cm, the combination of parameters (CL + pre-pregnancy body mass index + GA at exam + ECI within 0.5/1.0/1.5 cm) showed a significantly higher AUC than CL alone (P < 0.05). CONCLUSION: An addition of cervical elastography may improve the ability to predict sPTD in women with a short CL between 1.5 and 2.5 cm.

Late-preterm infants, early-term infants, and timing of elective deliveries; current status in a Korean medical center.

OBJECTIVE: The aim of this study was to examine the current perinatal outcomes among infants born late-preterm and early-term compared to those born full-term and evaluate the optimal gestational age for delivery. METHODS: We performed a retrospective cohort study for births occurred at Seoul St. Mary's Hospital over the past 7 years. Statistical comparison was performed using χ2 test and multivariable logistic regression models. RESULTS: A total of 7580 women met the study criteria. Compared to 39 weeks, delivery at late-preterm and early-term had higher risk of composite morbidity, including respiratory morbidities, intracranial hemorrhage (ICH), and admission to neonatal intensive care unit (NICU) (34 weeks adjusted odds ratio [aOR]: 132.54; 95% confidence interval (CI): 74.00-240.10; 37 weeks aOR: 2.14; 95%CI: 1.65-2.77). The risks of sepsis and necrotizing enterocolitis in deliveries before 36 weeks and the risk of feeding difficulty in deliveries before 37 weeks were significantly higher than those of 39 weeks. Neonatal morbidity at deliveries was not significantly different between 38 and 39 weeks. CONCLUSIONS: Neonatal morbidities at late-preterm births are significant and surveillance for them seems increasing. Obstetricians should recognize the risk of respiratory morbidity, ICH, and NICU admission for deliveries before 38 weeks' gestation.

Optimal time of delivery to reduce the risk of infant mortality in small and normally grown fetuses: A national cohort study in Korea.

PURPOSE: To examine the competing risks of stillbirth versus infant death and to evaluate the optimal time of delivery in the population of small for gestational age (SGA) and non-SGA late preterm and term fetuses. METHODS: This was a retrospective national cohort study of all singleton births between 34 0/7 and 42 6/7 weeks of gestation using the Korean vital statistics (n = 2,106,159). We compared the risk of infant mortality with a composite of fetal-infant mortality risk that would occur after expectant management for one additional week and evaluated the optimal time of delivery, in SGA and non-SGA pregnancies. RESULTS: In the total population, the risk of expectant management became significantly higher than the risk of delivery, at 39 weeks and beyond, similar with non-SGA group. In the SGA group, the risk of stillbirth was significantly greater at all GAs than for non-SGA pregnancies, and the risk of infant death was significantly increased until 38 weeks (25.8 per 10,000 live births, 95% CI 20.11-32.47), and the risk of stillbirth was significantly increased at 41 weeks (11.65 per 10,000 ongoing pregnancies, 95% CI 6.95-18.09), compared to 39 weeks (12 per 10,000 live births, 95% CI 8.98-15.64 and 5.12 per 10,000 ongoing pregnancies, 95% CI 3.84-6.66, respectively). CONCLUSION: In Korean women, delivery between 39 and 41 weeks minimizes fetal/infant mortality, in non-SGA pregnancies. In uncomplicated SGA pregnancies, delivery between 39 and 40 weeks can be considered to decrease risk of infant death and stillbirths.

Challenging management of chorioamnionitis with placental listeriosis: lessons from 2 cases.

Listeriosis is a rare foodborne infection caused by Listeria monocytogenes. It is 12-20 times more prevalent in pregnant women compared to the general population, with a 20-40% mortality rate in neonates. Early treatment with appropriate antimicrobial agents is critical for pregnancy outcomes; however, the infection is difficult to control because the nonspecific clinical manifestations and rarity of the disease often preclude early diagnosis. We encountered 2 cases of pregnancy-associated listeriosis that occurred at 29 and 37 weeks of gestation. Both neonates were delivered by emergent cesarean section due to fetal condition, and one of the preterm infants died immediately after birth. Pregnancy-associated listeriosis should be considered in the management of unexplained fever or inflammatory conditions in pregnant women.

Comparative study of substrate free and amniotic membrane scaffolds for cultivation of limbal epithelial sheet.

Transplantation of cultivated limbal epithelial transplantation has been proven to restore the corneal surface in limbal stem cell deficiency (LSCD). Here we comparatively investigated the optimized conditions and the efficiency of limbal epithelial sheet growth in three media conditions as well as with substrate free (transwell), human amniotic membrane (HAM) sutured onto transwell inserts (HAMTW), and HAM slide scaffold (HAMS). Outcomes evaluated were outgrowth sheet size from limbal explants, expression of stem/progenitor cell markers p63α, ABCG2 and CK15, and colony formation efficiency (CFE). Additionally, limbal epithelial sheets on HAMS were transplanted into corneas of LSCD rabbit models. Limbal epithelial sheets with 5% human AB serum showed the greatest increase in ABCG2 efflux activity (JC1low), p63α expression, and CFE compared in both conditions without HAM and with HAM, respectively. The outgrowth sheet size, cell yield, and Ki67 expression were increased in limbal epithelial sheets on HAMS compared to transwell and HAMTW. ABCG2 efflux activity, p63α and CK15 expressions, and CFE were also increased in limbal epithelial sheets on HAMS as well. In corneas of transplanted rabbit LSCD models, p63α expressions were noted in the basal layers and CK12 expressions were observed in superficial layers. Cultivation of limbal epithelial sheet on HAMS with xeno-free medium enhances the growth and stemness of limbal epithelial sheets.