Ultrasonographic assessment of abnormal fetal growth related to uteroplacental-fetal biometrics and Doppler (U-AID) indices: Protocol for multicenter retrospective cohort study trial.

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

Sialylated IVIg promotes clinical improvements in a rabbit dry eye model by regulating inflammatory cytokines.

Dry eye disease (DED) is caused by a loss of homeostasis of the tear film, which results in visual disturbance, ocular surface inflammation and damage, and neurosensory abnormalities. Although it is prevalent in 5-50% of the global population, there are limited clinical options for its treatment. This study explored the potential use of human intravenous immunoglobulin (IVIg) and its enriched fractions of sialylation, sialylated IVIg (sIVIg), as a treatment for DED. Fifteen female New Zealand white rabbits were topically instilled with 0.2% benzalkonium chloride (BAC) twice daily for five consecutive days to induce experimental dry eye. Saline, 0.4% IVIg, or 0.04% sIVIg eye drops were instilled twice daily for 20 consecutive days. Clinical evaluations, such as non-invasive tear break-up time (NIBUT) and corneal fluorescein staining (CFS), were conducted. mRNA levels of mucin 4, mucin 16, TNF-α, IL-1ß, MMP9, IL-10, TGF-ß, and CD209 in rabbit conjunctival tissues were examined using reverse transcription polymerase chain reaction (RT-PCR) or quantitative RT-PCR (qRT-PCR). The relationships between CD209 family members in rabbits and various mammalian species were analyzed using a phylogenetic tree. IVIg or sIVIg treatment resulted in clinical improvements in the rabbit DED model. The inflammatory cytokines, TNF-α and IL-1ß, were increased and mucin 4 and mucin 16, cell surface-associated mucins, were decreased in BAC-induced dry eye. Following IVIg or sIVIg treatment, inflammatory cytokines decreased, whereas the anti-inflammatory cytokine, IL-10, increased substantially. Moreover, a 10-fold lower sIVIg treatment dose resulted in prolonged IL-10 production, representing a significantly improved DED compared to IVIg. Furthermore, the expression of rabbit CD209 mRNA in the rabbit conjunctiva and its close relationship with primate homologs suggest that it may interact with IVIg or sIVIg to promote IL-10 expression, as previously described in humans. At a lower dosage, sIVIg showed a more efficient improvement in DED, making it a promising new candidate medication for DED.

Management of the smaller twin with impending compromise in twin pregnancies complicated by selective fetal growth restriction: a questionnaire-based study of clinical practice patterns.

BACKGROUND: In twin pregnancies complicated by selective fetal growth restriction (sFGR), if the smaller twin is in the state of impending intra-uterine death (IUD), immediate delivery will reduce the risk of IUD of the smaller twin while exposing the larger twin to iatrogenic preterm birth (PTB). Therefore, the management options would either be to maintain pregnancy for the maturation of the larger twin despite the risk of IUD of the smaller twin or immediate delivery to prevent IUD of the smaller twin. However, the optimal gestational age of management transition from maintaining pregnancy to immediate delivery has not been established. The objective of this study was to evaluate the physician's perspective on the optimal timing of immediate delivery in twin pregnancies complicated by sFGR. METHODS: An online cross-sectional survey was performed with obstetricians and gynecologists (OBGYN) in South Korea. The questionnaire asked the following: (1) whether participants would maintain or immediately deliver a twin pregnancy complicated by sFGR with signs of impending IUD of the smaller twin; (2) the optimal gestational age of management transition from maintaining pregnancy to immediate delivery in a twin pregnancy with impending IUD of the smaller twin; and (3) the limit of viability and intact survival in general preterm neonates. RESULTS: A total of 156 OBGYN answered the questionnaires. In a clinical scenario of dichorionic (DC) twin pregnancy complicated by sFGR with signs of impending IUD of the smaller twin, 57.1% of the participants answered that they would immediately deliver the twin pregnancy. However, 90.4% answered that they would immediately deliver the pregnancy in the same scenario for monochorionic (MC) twin pregnancy. The participants designated 30 weeks for DC twin and 28 weeks for MC twin pregnancies as the optimal gestational age of management transition from maintaining pregnancy to immediate delivery. The participants regarded 24 weeks as the limit of viability and 30 weeks as the limit of intact survival in general preterm neonates. The optimal gestational age of management transition for DC twin pregnancy was correlated with the limit of intact survival in general preterm neonates (p < 0.001), but not with the limit of viability. However, the optimal gestational age of management transition for MC twin pregnancy was associated with both the limit of intact survival (p = 0.012) and viability with marginal significance (p = 0.062). CONCLUSIONS: Participants preferred to immediately deliver twin pregnancies complicated by sFGR with impending IUD of the smaller twin at the limit of intact survival (30 weeks) for DC twin pregnancies and at the midway between the limit of intact survival and viability (28 weeks) for MC twin pregnancies. More research is needed to establish guidelines regarding the optimal delivery timing for twin pregnancies complicated by sFGR.

Risk of adverse obstetric outcomes in patients with a history of endometrial cancer: A nationwide population-based cohort study.

OBJECTIVE: To evaluate adverse obstetric outcomes in women with a history of endometrial cancer (EC). DESIGN: Population-based cohort study. SETTING: The Korean National Health Insurance (KNHI) claims database. POPULATION: Women who gave birth between 2009 and 2016, with a history of EC prior to pregnancy. METHODS: The KNHI database was used to compare obstetric outcomes of women with and without a history of EC, using the ICD-10 codes. Multivariable logistic regression models were used to determine the associations between a history of EC and adverse obstetric outcomes. MAIN OUTCOMES MEASURES: Adverse obstetric outcomes. RESULTS: Overall, 248 and 3 335 359 women with and without a history of EC, respectively, gave birth. When adjusted for age, primiparity and comorbidities, an increased risk of multiple gestations (odds ratio [OR] 4.925, 95% confidence interval [CI] 3.394-7.147), caesarean delivery (OR 2.005, 95% CI 1.535-2.62) and preterm birth (OR 1.941, 95% CI 1.107-3.404) was observed among women with a history of EC. We were unable to demonstrate significant differences in the risk of pre-eclampsia, gestational diabetes, vacuum delivery, placenta praevia, placenta accreta spectrum, placental abruption and postpartum haemorrhage between the groups. In the sensitivity analyses excluding multiple gestations, an increased risk of preterm birth was not observed among women with a history of EC (OR 1.276, 95% CI 0.565-2.881). CONCLUSIONS: There is no convincing evidence of an increased risk of adverse obstetric outcomes among women with a history of EC. Our findings would be useful in counselling of patients with EC who are undergoing fertility-sparing treatment.

Risk of retinopathy in women with pregnancy-induced hypertension: a nationwide population-based cohort study of 9-year follow-up after delivery.

BACKGROUND: The retina is potentially associated with several physiological, hormonal, and metabolic changes during pregnancy. The few available epidemiologic studies of ocular changes in pregnancy have mainly concerned retinopathies. Pregnancy-induced hypertension, which leads to ocular manifestations including blurred vision, photopsia, scotoma, and diplopia, might induce reactive changes in the retinal vessels. Although several studies have suggested the existence of pregnancy-induced hypertension-related retinal ocular disease, there are few large cohort studies on this topic. OBJECTIVE: This study aimed to investigate the risk of major retinal diseases including central serous chorioretinopathy, diabetic retinopathy, retinal vein occlusion, retinal artery occlusion, and hypertensive retinopathy in the long-term postpartum stage according to the presence of previous pregnancy-induced hypertension in a large cohort based on the Korean National Health Insurance Database. STUDY DESIGN: On the basis of Korean health data, 909,520 patients who delivered from 2012 to 2013 were analyzed. Among them, patients who had previous ocular diseases or hypertension and multiple births were excluded. Finally, 858,057 mothers were assessed for central serous chorioretinopathy (ICD-10: H35.70), diabetic retinopathy (ICD-10: H36.0, E10.31, E10.32, E11.31, E11.32, E12.31, E13.31, E13.32, E14.31, E14.32), retinal vein occlusion (ICD-10: H34.8), retinal artery occlusion (ICD-10: H34.2), and hypertensive retinopathy (ICD-10: H35.02) for 9 years after delivery. Enrolled patients were divided into 2 groups: 10,808 patients with and 847,249 without pregnancy-induced hypertension. The primary outcomes were the incidence of central serous chorioretinopathy, diabetic retinopathy, retinal vein occlusion, retinal artery occlusion, and hypertensive retinopathy 9 years after delivery. Clinical variables were age, parity, cesarean delivery, gestational diabetes mellitus, and postpartum hemorrhage. In addition, pregestational diabetes mellitus, kidney diseases, cerebrovascular diseases, and cardiovascular diseases were adjusted. RESULTS: Postpartum retinal disease during the 9 years after delivery and total retinal diseases showed higher rates in patients with pregnancy-induced hypertension. In detail, the rates of central serous chorioretinopathy (0.3% vs 0.1%), diabetic retinopathy (1.79% vs 0.5%), retinal vein occlusion (0.19% vs 0.1%), and hypertensive retinopathy (0.62% vs 0.05%) were higher than those found in patients without pregnancy-induced hypertension. After adjusting for confounding factors, pregnancy-induced hypertension was associated with development of postpartum retinopathy, with a >2-fold increase (hazard ratio, 2.845; 95% confidence interval, 2.54-3.188). Furthermore, pregnancy-induced hypertension affected the development of central serous chorioretinopathy (hazard ratio, 3.681; 95% confidence interval, 2.667-5.082), diabetic retinopathy (hazard ratio, 2.326; 95% confidence interval, 2.013-2.688), retinal vein occlusion (hazard ratio, 2.241; 95% confidence interval, 1.491-3.368), and hypertensive retinopathy (hazard ratio, 11.392; 95% confidence interval, 8.771-14.796) after delivery. CONCLUSION: A history of pregnancy-induced hypertension increases the risk of central serous chorioretinopathy, diabetic retinopathy, retinal vein occlusion, and hypertensive retinopathy according to 9-year long-term ophthalmologic follow-up.

Sialylated IVIg binding to DC-SIGN+ Hofbauer cells induces immune tolerance through the caveolin-1/NF-kB pathway and IL-10 secretion.

Although the use of IVIg has increased in various immune-driven diseases and even in pregnancy, the exact action mechanisms of IVIg are not fully understood. Dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN) is a known receptor for α-2,6-sialylated IgG (sIVIg), which is responsible for the anti-inflammatory effect of IVIg. DC-SIGN is expressed on Hofbauer cells (HBCs) of the fetal villi of the placenta which act as an innate immune modulator at the maternal-fetal interface. Preeclampsia is a major complication in pregnancy and is related to IL-10, a cytokine with an important role in immune tolerance. DC-SIGN interaction with sIVIg in HBCs promoted IL-10 secretion through the activation of the caveolin-1/NF-κB pathway, especially in plasma lipid rafts. Consistent results were obtained for HBCs from patients with preeclampsia. Collectively, the stimulation of DC-SIGN+ HBCs with sIVIg enhanced immune tolerance in the feto-maternal environment, suggesting the therapeutic application of sIVIg to prevent preeclampsia.

Distribution of Presepsin, Krebs von den Lungen 6, and Surfactant Protein A in Umbilical Cord Blood.

Presepsin is an early indicator of infection, and Krebs von den Lungen 6 (KL-6) and Surfactant Protein A (SP-A) are related to the pathogenesis of pulmonary infection and fibrosis. This study aimed to establish reference intervals (RIs) of presepsin, KL-6, and SP-A levels and to evaluate the possible influence of neonatal and maternal factors on presepsin, KL-6, and SP-A levels in umbilical cord blood (UCB). Among a total of 613 UCB samples, the outliers were removed. The RIs for presepsin, KL-6, and SP-A levels were defined using non-parametric percentile methods according to the Clinical and Laboratory Standards Institute guidelines (EP28-A3C). These levels were analyzed according to neonatal and maternal factors: neonatal sex, gestational age (GA), birth weight (BW), Apgar score, delivery mode, the presence of premature rupture of membranes (PROM), gestational diabetes mellitus (GDM), and pre-eclampsia. Presepsin, KL-6, and SP-A levels showed non-parametric distributions and left-skewed histograms. The RIs of presepsin, KL-6, and SP-A levels were 64.9-428.3 pg/mL, 43.0-172.0 U/mL, and 2.1-36.1 ng/mL, respectively. Presepsin, KL-6, and SP-A levels did not show significant differences according to sex, GA, BW, Apgar score, delivery mode, PROM, GDM, and pre-eclampsia. The median level and 97.5th centile RI of KL-6 showed a slight increase with increased GA. We established RIs for presepsin, KL-6, and SP-A levels in large-scaled UCB samples. Further investigation would be needed to determine the clinical significance.

Midtrimester cervical elastography in pregnant women with a history of loop electrosurgical excision procedure (LEEP).

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.

Associations of GNAS and RGS Gene Polymorphisms with the Risk of Ritodrine-Induced Adverse Events in Korean Women with Preterm Labor: A Cohort Study.

Ritodrine, a ß2-adrenergic receptor agonist, is among most commonly prescribed tocolytic agents. This study aimed to evaluate the associations of single nucleotide polymorphisms in GNAS, RGS2, and RGS5 with the risk of ritodrine-induced adverse events (AEs) and develop a risk scoring system to identify high-risk patients. This is the prospective cohort study conducted at the Ewha Woman's University Mokdong Hospital between January 2010 and October 2016. Pregnant women were included if they were treated with ritodrine for preterm labor with regular uterine contractions (at least 3 every 10 min) and cervical dilation. A total of 6, 3, and 5 single nucleotide polymorphisms (SNPs) of GNAS, RGS2, and RGS5 genes were genotyped and compared in patients with and without ritodrine-induced AEs. A total of 163 patients were included in this study. After adjusting confounders, GNAS rs3730168 (per-allele odds ratio (OR): 2.1; 95% confidence interval (95% CI): 1.0-4.3) and RGS2 rs1152746 (per-allele OR: 2.6, 95% CI: 1.1-6.5) were significantly associated with ritodrine-induced AEs. According to the constructed risk scoring models, patients with 0, 1, 2, 3, 4, and 5 points showed 0%, 13%, 19%, 31%, 46%, and 100% risks of AEs. This study suggested that GNAS and RGS2 polymorphisms could affect the risk of AEs in patients treated with ritodrine.

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.

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.

Enhancement of proliferation of human umbilical cord blood-derived CD34+ hematopoietic stem cells by a combination of hyper-interleukin-6 and small molecules.

Umbilical cord blood (UCB) is an alternative source of allogeneic hematopoietic stem cells (HSCs) for transplantation to treat various hematological disorders. The major limitation to the use of UCB-derived HSCs (UCB-HSCs) in transplantation, however, is the low numbers of HSCs in a unit of cord blood. To overcome this limitation, various cytokines or small molecules have been used to expand UCB-HSCs ex vivo. In this study, we investigated a synergistic effect of the combination of HIL-6, SR1, and UM171 on UCB-HSC culture and found that this combination resulted in the highest number of CD34+ cells. These results suggest that the combination of SR1, UM171 and HIL-6 exerts a synergistic effect in the proliferation of HSCs from UCB and thus, SR1, UM171 and HIL-6 is the most suitable combination for obtaining HSCs from UCB for clinical transplantation.

Ultrasonographic ovarian mass scoring system for predicting malignancy in pregnant women with ovarian mass.

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

Risk factors associated with idiopathic sudden sensorineural hearing loss in pregnant South Korean women: a nationwide population-based study.

OBJECTIVE: Sudden sensorineural hearing loss (SSNHL) is rare in pregnancy and can be attributed to pregnancy-induced changes in hormone levels that increase thrombogenic risk and alter cochlear microcirculation with consequent development of sudden deafness. The study aimed to analyze the risk factors associated with SSNHL in pregnant South Korean. METHODS: A retrospective study of the incidence and risk factors associated with SSNHL before pregnancy enrolled 401,470 Korean women who delivered between January 2010 and December 2014. All participants underwent a pre-pregnancy national health screening examination through the National Health Insurance Corporation. We investigated the risk factors in 459 pregnant women with sudden sensorineural hearing loss and in 401,011 pregnant women without SSNHL through the pre-pregnancy national health screening examination and adverse perinatal outcome. RESULTS: No statistically significant intergroup differences were observed in the maternal age, parity, method of delivery, gestational age at delivery, body mass index, blood pressure, as well as fasting blood glucose and cholesterol levels. After adjusting for maternal age, the pre-pregnancy body mass index was associated with an increased risk of sensorineural hearing loss in pregnancy (adjusted odds ratio 1.52, 95% confidence interval 1.04-2.22). The sensorineural hearing loss did not increase the risk for gestational hypertension, preterm birth (<37 weeks' gestation), small- and large-for-gestational-age infants, postpartum hemorrhage, placenta previa, and placental abruption. CONCLUSION: SSNHL can occur throughout pregnancy and is associated with maternal pre-pregnancy obesity. Notably, it does not increase risks during delivery or cause adverse perinatal outcomes.

Association between ADCY9 Gene Polymorphisms and Ritodrine Treatment Outcomes in Patients with Preterm Labor.

The purpose of this study was to investigate the genetic effects of ADCY9 on ritodrine responses in patients with preterm labor. Five single nucleotide polymorphisms (SNPs) of the ADYC9 gene in 163 patients in preterm labor were genotyped: rs879619, rs2601796, rs2531988, rs2531995, and rs2230739. Additionally, rs598961 of the PDE4B gene and rs1042719 of the ADRB2 gene were included for analysis. Patients with CC genotype of ADCY9 rs879619 had a 2.0-fold (95% confidence interval [CI]: 1.3, 3.2) higher hazard of time to delivery than T allele carriers. Patients with combined genotypes of CC in ADCY9 rs879619, AA in PDE4B rs598961, and GC, CC in ADRB2 rs1042719 showed a greater hazard of time to delivery than patients with other combinations (adjusted hazard ratio [AHR] 3.2; 95% CI: 1.7, 6.3), whereas patients carrying the C allele of ADCY9 rs2531995, G allele of PDE4B rs598961, and GG genotype of ADRB2 rs1042719 had a lower hazard of time to delivery than patients carrying other genotypes (AHR 0.4; 95% CI: 0.2, 0.7). Regarding ritodrine-induced adverse drug events (ADEs), height less than 160 cm and CC genotype of ADCY9 rs2531995 showed a greater risk of ADEs. The results of our study suggest that ADCY9 polymorphisms could affect the efficacy and safety of ß2-adrenergic agonists.

Does the Summer Season Affect the Amniotic Fluid Volume during Pregnancy?

Amniotic fluid is crucial for the well-being of the fetus. Recent studies suggest that dehydration in a pregnant woman leads to oligohydramnios. We assessed the variation in the amniotic fluid index (AFI) during the summer and non-summer seasons and evaluated neonatal outcomes. We retrospectively reviewed electrical medical records of pregnant women who visited the Konkuk University Medical Center for antenatal care, between July 2005 and July 2019. A total of 19,724 cases from 6438 singleton pregnant women were included after excluding unsuitable cases. All AFI values were classified as 2nd and 3rd trimester values. Additionally, borderline oligohydramnios (AFI, 5-8) and normal AFI (AFI, 8-24) were assessed according to the seasons. The average AFI between the summer and non-summer season was statistically different only in the 3rd trimester; but the results were not clinically significant. In the 3rd trimester, the summer season influenced the increased incidence of borderline oligohydramnios. The borderline oligohydramnios group showed an increased small-for-gestational-age (SGA) rate and NICU admission rate. In the summer season, the incidence of borderline oligohydramnios was seen to increase. This result would be significant for both physicians and pregnant women.

Ultrasonographic evaluation of ovarian mass for predicting malignancy in pregnant women.

OBJECTIVE: The purpose of this study is to compare ultrasonographic ovarian mass scoring systems in pregnant women. STUDY DESIGN: This multicenter study included women with an ovarian mass during pregnancy who were evaluated using ultrasound and underwent surgery in 11 referral hospitals. The ovarian mass was evaluated and scored using three different scoring systems(International Ovarian Tumor Analysis Assessment of Different NEoplasias in the adnexa[IOTA ADNEX], Sassone, and Lerner). The final diagnosis was made histopathologically. Receiver operating characteristic(ROC) curves were generated for each scoring system. RESULTS: During the study period, 236 pregnant women underwent surgery for an ovarian mass, including 223 women(94.5%) with a benign ovarian mass and 13 women(5.5%) with a malignant ovarian mass. Among 10 ultrasound image findings, six findings were different between benign and ovarian masses(maximal diameter of mass, maximal diameter of solid mass, wall thickness of mass, inner wall structure, thickness of septations, and papillarity). In all three scoring systems, the ovarian mass scores were significantly higher in malignant masses than in benign masses, with the highest area under the ROC curve(AUROC) in the Sassone scoring system(AUROC: 0.831 for Sassone, 0.710 for Lerner vs 0.709 for IOTA ADNEX; p < 0.05, between the Sassone and Lerner/ IOTA ADNEX). A combined model was developed with the six different ultrasound findings, and the AUROC of the combined model was 0.883(p = not significant between the combined model and Sassone). CONCLUSION: In pregnant women, malignant ovarian tumors can be predicted with high accuracy using either the Sassone scoring system or the combined model.

Risk of Early Childhood Obesity in Offspring of Women with Preeclampsia: A Population-Based Study.

Preeclampsia (PE) is a major disease of pregnancy, with various short- or long-term complications for both the mother and offspring. We focused on the body mass index (BMI) of offspring and compared the incidence of obesity during early childhood between PE- and non-PE-affected pregnancies. Women with singleton births (n = 1,697,432) were identified from the Korea National Health Insurance database. The outcomes of offspring at 30-80 months of age were analyzed. The effects of PE on BMI and the incidence of obesity in the offspring were compared. The incidence of low birth weight (LBW) offspring was higher in the PE group (n = 29,710) than that in the non-PE group (n = 1,533,916) (24.70% vs. 3.33%, p < 0.01). However, BMI was significantly higher in the PE-affected offspring than that in non-PE-affected offspring. After adjusting for various factors, the risk of obesity was higher in the PE-affected offspring (odds ratio = 1.34, 95% confidence interval = 1.30-1.38). The BMI and incidence of obesity were higher during early childhood in the PE-affected offspring, even though the proportion of LBW was higher. These results may support the basic hypotheses for the occurrence of various cardiovascular and metabolic complications in PE-affected offspring. In addition, early-age incidence of obesity could influence PE management and child consultation in clinical applications.

Predictors of Newborn's Weight for Height: A Machine Learning Study Using Nationwide Multicenter Ultrasound Data.

There has been no machine learning study with a rich collection of clinical, sonographic markers to compare the performance measures for a variety of newborns' weight-for-height indicators. This study compared the performance measures for a variety of newborns' weight-for-height indicators based on machine learning, ultrasonographic data and maternal/delivery information. The source of data for this study was a multi-center retrospective study with 2949 mother-newborn pairs. The mean-squared-error-over-variance measures of five machine learning approaches were compared for newborn's weight, newborn's weight/height, newborn's weight/height2 and newborn's weight/hieght3. Random forest variable importance, the influence of a variable over average node impurity, was used to identify major predictors of these newborns' weight-for-height indicators among ultrasonographic data and maternal/delivery information. Regarding ultrasonographic fetal biometry, newborn's weight, newborn's weight/height and newborn's weight/height2 were better indicators with smaller mean-squared-error-over-variance measures than newborn's weight/height3. Based on random forest variable importance, the top six predictors of newborn's weight were the same as those of newborn's weight/height and those of newborn's weight/height2: gestational age at delivery time, the first estimated fetal weight and abdominal circumference in week 36 or later, maternal weight and body mass index at delivery time, and the first biparietal diameter in week 36 or later. These six predictors also ranked within the top seven for large-for-gestational-age and the top eight for small-for-gestational-age. In conclusion, newborn's weight, newborn's weight/height and newborn's weight/height2 are more suitable for ultrasonographic fetal biometry with smaller mean-squared-error-over-variance measures than newborn's weight/height3. Machine learning with ultrasonographic data would be an effective noninvasive approach for predicting newborn's weight, weight/height and weight/height2.

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.