Search

Adnexal masses detected during pregnancy require a prompt and accurate diagnosis to ensure fetal safety and good oncological outcomes. Computed tomography is the most common and useful diagnostic imaging modality for diagnosing adnexal masses; however, it is contraindicated in pregnant women because of the teratogenic effect of radiation on the fetus. Therefore, ultrasonography (US) is commonly used as the main alternative for the differential diagnosis of adnexal masses during pregnancy. Additionally, magnetic resonance imaging (MRI) can assist in the diagnosis when US findings are inconclusive. As each disease has characteristic US and MRI findings, understanding these features is important for the initial diagnosis and subsequent treatment. Thus, we thoroughly reviewed the literature and summarized the key findings of US and MRI to apply these in real-world clinical practice for various adnexal masses detected during pregnancy.

Objective Hypertensive disease during pregnancy increases the risk of maternal morbidity and mortality and leads to the development of multi-organ dysfunction, including kidney dysfunction. Complicated pregnancies require careful postpartum management to prevent sequelae. It is believed that kidney injury can consistently occur even after delivery; therefore, defining the chronicity and endpoint is essential for establishing diagnostic criteria. However, data on the prevalence of persistent renal complications following hypertensive disease during pregnancy are limited. In this study, we evaluated the risk of developing renal disorders in patients with a history of hypertensive disease during pregnancy.Methods Participants who gave birth between 2009 and 2010 were followed up for 8 years after delivery. The risk of renal disorder development after delivery was determined according to a history of hypertensive disease during pregnancy. Different factors that could affect the course of pregnancy, including age, primiparity, multiple pregnancy, preexisting hypertension, pregestational diabetes, hypertensive disease during pregnancy, gestational diabetes, postpartum hemorrhage, and cesarean section, were adjusted for using the Cox hazard model.Results Women with hypertension during pregnancy had a higher risk of developing renal disorders after delivery (0.23% vs. 1.38%; P

To assess the risk gradient of chromosomal abnormalities and fetal or neonatal death across a socioeconomic spectrum of pregnant women.We used the data from the Korean Prenatal Diagnosis Study (KPDS), which included singleton pregnancies who were candidates for fetal aneuploidy screening enrolled from the Seoul Capital Area from December 2016 to April 2018. We analyzed chromosomal abnormalities which were diagnosed pre- or postnatally, and fetal or neonatal death. The highest level of education among the women and the average monthly household income were used as proxies for socioeconomic status.Among the 6,715 women, the majority of were 30-39 years old and university graduates, with a reported household income higher than the national median. Chromosomal abnormalities occurred in 45 women (6.7 per 1,000). Fetal or neonatal death occurred in 70 (11.3 per 1,000), excluding pregnancies affected by chromosomal abnormality diagnosis. The adjusted odds ratio for chromosomal abnormalities was higher when household income was 4,484 USD per month. For fetal or neonatal death, the risk estimates for lower education and lower household income were generally positive but remained imprecise.We observed some evidence of an inverse association between the risk of fetal chromosomal abnormality and level of household income in a prospective cohort of pregnant women. Interventions to reduce socioeconomic disparities in perinatal health should focus on those with a low household income.

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 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.

The objective of this study was to identify predictable maternal serum signatures of cortisol metabolism during the first trimester of women who are expected to deliver small-for-gestational-age (SGA) neonates. This prospective cohort study included 112 pregnant women (with and without SGA, n = 56 each). Maternal serum samples were collected at 10-14 gestational weeks to quantify the levels of cortisol and its precursors and metabolites by liquid chromatography-mass spectrometry. Increased maternal serum levels of tetrahydrocortisol (11.82 ± 8.16 ng/mL vs. 7.51 ± 2.90 ng/mL, P 0.005) and decreased 21-deoxycortisol (2.98 ± 1.36 ng/mL vs. 4.33 ± 2.06 ng/mL, P 0.0001) were observed in pregnant women carrying SGA fetus. In conjunction with individual steroid levels, metabolic ratios corresponding to the activity of related enzymes were calculated. In addition to increased tetrahydrocortisol/cortisol ratio (P 0.006), the SGA group showed a significant increase in the two metabolic ratios including cortisol/11-deoxycortisol (P 0.03) and cortisol/21-deoxycortisol (P 0.0003). The receiver operating characteristic (ROC) curve generated in combination with three variables of 21-deoxycortisol concentration and two metabolic ratios of cortisol/21-deoxycortisol and tetrahydrocortisol/cortisol resulted in an area under the ROC curve = 0.824 (95% confidence interval, 0.713-0.918). A significant decrease in maternal serum levels of 21-deoxycortisol and an increase in two metabolic ratios of cortisol/21-deoxycortisol and tetrahydrocortisol/cortisol, indicating cortisol biosynthetic rate, represent potential biomarkers for the prediction of SGA in the first trimester.

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.

Background Pre-eclampsia (PE) is a pregnancy disorder that is related to an enhanced immune response. Immune cell characteristics such as neutrophil or monocyte to lymphocyte ratios (NLR, MLR) are known to be related to kidney and liver dysfunction in hypertensive patients. Here, we aimed to analyze the correlations between NLR, MLR and platelet to lymphocyte ratio (PLR) and liver, renal and coagulation functional parameters and the impacts of these immune cell profiles to the prognostic significance in PE patients. Methods Pre-delivery hematological and biochemical parameters of 320 first-time pregnant women registered at the Obstetrics Department of Yanbian University Hospital from 2016 to 2019 were analyzed retrospectively. Patients were divided into normal pregnancy (normal, n = 161), mild PE (mPE, n = 28) and severe PE (sPE, n = 131) groups according to diagnostic criteria. Pearson correlation analysis were performed and area under the curve (AUC) were conducted for the diagnostic values of NLR, MLR and PLR. Results were validated with data from the Department of Obstetrics and Gynecology of Seoul National University Hospital (SNUH). Results Kidney functional indexes were adversative in mPE and sPE and liver and coagulation indexes were worse in sPE compared to normal groups. Among immune cells, lymphocytes were increased in mPE and sPE patients, resulted in reduced NLR, MLR and PLR in PE groups, more significant difference were shown in sPE. NLR and PLR were associated with CREA and/or BUN negatively and positive associations were observed with total protein (TP) and albumin (ALB) in sPE. Only NLR showed positive associations with coagulation indexes (PT and APTT) in sPE. AUC analysis for NLR, MLR and PLR were 0.700, 0.656, 0.643, respectively, and NLR p Conclusion NLR could be used as an independent predictor of liver and coagulation dysfunction in PE patients. Our results may provide non-invasive and efficient way of the risk assessment among PE patients.

INTRODUCTION Reproductive endocrinologists recommend selective multifetal pregnancy reduction (MFPR) to save at least one or two babies, because triplet pregnancy is known to increase the risk of miscarriage and preterm delivery. However, recently improved obstetric and neonatal care may affect pregnancy outcomes differently in triplet pregnancies, which could alter practice. We compared the maternal, perinatal, and long-term outcomes of triplet pregnancies managed expectantly with those of pregnancies reduced to twins. MATERIAL AND METHODS In this retrospective cohort study, we reviewed the clinical records of 552 trichorionic triplet pregnancies for obstetric, perinatal, and neurodevelopmental outcomes, which consisted of the expectant management (EM) group (n = 225) and MFPR group (n = 327), in Seoul National University Hospital and CHA Bundang Medical Center from January 2006 to December 2018. Neuromotor development was evaluated using the Korean-Ages and Stages Questionnaire, Bayley-III tests, and/or Gross Motor Function Measure. The two groups were compared for the following outcomes: (1) nonviable pregnancy loss before 23 weeks, (2) preterm birth before 32 weeks of gestation, (3) fetal and neonatal survival and (4) long-term neurodevelopmental outcomes. RESULTS There were no differences in maternal age, body mass index, nulliparity or previous preterm birth between the two groups. The risk of nonviable pregnancy loss was lower in the EM group than that in the MFPR group (2 [0.9%] vs 21 [6.4%], p = 0.001). The risk of preterm delivery before 34 weeks of gestation was lower in the MFPR group (adjusted odds ratios [aOR] = 0.47, 95% confidence interval [CI] 0.30-0.73, p = 0.001). The survival rate of neonates until discharge (644 [95.4%] vs 572 [87.5], p < 0.001) and the rate of pregnancies with at least one survivor (220 [97.8%] vs 301 [92.0], p = 0.002) were higher in the EM group than those in the MFPR group. In the MFPR group, the risk of developmental delay (aOR = 2.89, 95% CI 1.38-6.02, p = 0.005) was higher. CONCLUSIONS In trichorionic triplet pregnancies, the possibility of EM to improve survival and reduce the risk of developmental delay has been shown.

The purpose of this study is to compare ultrasonographic ovarian mass scoring systems in pregnant women.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.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).In pregnant women, malignant ovarian tumors can be predicted with high accuracy using either the Sassone scoring system or the combined model.

Preterm prelabor rupture of membranes (PPROM) is the main cause of preterm delivery, resulting in increased perinatal morbidity and mortality. Several techniques have been studied for the healing of ruptured membranes, with some success. Before new techniques using tissue/organ engineering are applied in clinical practice, these techniques must be validated in clinical trials. To address this issue, the objective of this study was to summarize the current literature on interventions to seal or heal the amniotic membranes after PPROM. An electronic search was conducted using the keywords "fetal membranes," "premature rupture," "amnion," "tissue engineering," "fibrin tissue adhesive," "regenerative medicine," "tissue adhesive," "wound healing," and "fetoscopy" through the MEDLINE, Embase, and Cochrane CENTRAL databases, with the limitation of English-language studies. Through a review of the identified studies, it was found that spontaneous healing of the fetal membrane has not been successful. Several efforts have been made to seal membranes before or after rupture using different methods, including amniopatches, collagen, tissue patches, fibrin sealant, mussel-mimetic sealant, engineered cell matrix, and immunological supplements. However, most studies have been conducted in ex vivo or in vivo settings, so the safety and applicability of these techniques to spontaneous rupture of membranes in clinical settings have not been sufficiently tested. Overall, the current evidence is limited regarding the safety and effectiveness of interventions against PPROM.

To identify potential proteins in the amniotic fluid (AF) that may be associated with histologic chorioamnionitis (HCA) in patients with preterm premature rupture of membranes (PPROM) using antibody-based microarray analysis.This was a retrospective cohort study involving 100 singleton pregnant women with PPROM at 24-34 weeks who underwent amniocentesis and delivered within 120 h of amniocentesis. First, the AF proteomes of 15 patients with PPROM and HCA were compared with those of 15 gestational age-matched patients without HCA using a protein microarray. Next, 12 candidate proteins associated with HCA were further validated in 100 consecutive patients with PPROM by ELISA.Of 507 proteins assessed in the microarray analysis, 46 showed significant intergroup differences. Further quantification confirmed that the levels of EN-RAGE, IL-6, MMP-9, TNFR2, SPARC, TSP2, and uPA were higher in the AF of PPROM patients with HCA than in those without. Multivariate analyses also showed that elevated AF EN-RAGE, IL-6, MMP-9, and TNFR2 levels were independently associated with HCA when adjusted for baseline variables. The frequency of the highest quartile of the aforementioned proteins significantly increased as the total grade of HCA increased; the risk of HCA significantly increased with increasing AF levels of each protein (P for trend.001).Using protein-antibody microarray technology, we discovered several potential AF proteins (EN-RAGE, IL-6, MMP-9, and TNFR2) independently associated with HCA in patients with PPROM. Furthermore, we demonstrated a direct correlation between the gradation of the intra-amniotic inflammatory response and HCA severity.

Background Hypertension has been known to increase the risk of obstetric complications. Recently, the American College of Cardiology endorsed lower thresholds for hypertension as systolic blood pressure of 130-139 mmHg or diastolic blood pressure 80-89 mmHg. However, there is a paucity of information regarding the impact of pre-pregnancy blood pressure on pregnancy outcomes. We aimed to evaluate the effect of pre-pregnancy blood pressure on maternal and neonatal complications. Methods In this nationwide, population based study, pregnant women without history of hypertension and pre-pregnancy blood pressure Results A total of 375,305 pregnant women were included. After adjusting for covariates, the risk of composite morbidity was greater in those with stage I hypertension in comparison with the normotensive group (systolic blood pressure, odds ratio = 1.68, 95% CI: 1.59 – 1.78; diastolic blood pressure, odds ratio = 1.56, 95% CI: 1.42 – 1.72). There was a linear association between pre-pregnancy blood pressure and the primary outcome, with risk maximizing at newly defined stage I hypertension and with risk decreasing at lower blood pressure ranges. Conclusions ‘The lower, the better’ phenomenon was still valid for both maternal and neonatal outcomes. Our results suggest that the recent changes in diagnostic thresholds for hypertension may also apply to pregnant women. Therefore, women with stage I hypertension prior to pregnancy should be carefully observed for adverse outcomes.

This study was aimed to develop models using multiple cytokine/chemokine levels in cervicovaginal fluid (CVF) and plasma and widely used noninvasive parameters that have better accuracy for predicting intra-amniotic infection and/or inflammation (IAI) and imminent spontaneous preterm delivery (SPTD, ≤48 hours) in women with preterm labor (PTL).This was a retrospective cohort study of 95 singleton pregnant women with PTL (23-34 weeks) who underwent amniocentesis. Both CVF and plasma samples were obtained at the time of amniocentesis, and serum C-reactive protein (CRP) levels were measured. The amniotic fluid (AF), CVF, and plasma samples were assayed for interleukin (IL)-6, IL-8, IL-10, monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-1β (MIP-1β) levels using a multiplex immunoassay kit.The levels of most cytokines/chemokines measured in the AF and CVF were significantly higher in the women with than in those without IAI and imminent SPTD, whereas only high-plasma IL-10 level showed a significant association with imminent SPTD. In predicting IAI, proteins in AF had significantly higher areas under the curves (AUCs) than those in CVF and plasma. However, for predicting imminent SPTD, no significant differences in the AUCs of the outcome-associated proteins were observed among the measurements in AF, CVF, and maternal plasma. By using stepwise regression analyses, noninvasive models (using protein levels in CVF and baseline clinical parameters) were developed for the prediction of IAI and imminent SPTD. The AUC of these noninvasive models were similar to those of the invasive models (using AF protein levels and baseline clinical parameters).Noninvasive models based on CVF cytokine/chemokine levels and widely used noninvasive parameters (especially CRP) act as good indicators for predicting the risk of IAI and imminent SPTD in women with PTL. Evaluation of cytokine/chemokine levels in plasma samples did not add valuable information regarding the two outcome measures in the PTL setting.· Markers in either CVF or plasma alone did not have sufficient accuracy for predicting IAI and SPTD.. · Noninvasive models using CVF cytokine and CRP act as effective tools for predicting two outcomes.. · Evaluation of cytokine level in plasma did not add valuable information regarding two outcomes..

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-1β, tumor necrosis factor [TNF]-α, interleukin [IL]-1β, 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.

We aimed to identify cervicovaginal fluid (CVF) biomarkers that can detect microbial invasion of the amniotic cavity (MIAC) in women with preterm labor (PTL) with an antibody microarray and to develop the best combined model for detection of MIAC using these biomarkers in combination with conventional clinical variables. This retrospective cohort study included 168 singleton pregnant women with PTL (23–34 weeks) who underwent amniocentesis. AF was cultured, and CVF samples were obtained at the time of amniocentesis. An antibody microarray was used to analyze the CVF proteome (n = 40). The validation of four candidate biomarkers of interest was performed by enzyme-linked immunosorbent assay (ELISA) in the final cohort (n = 168). For comparison with candidate markers, CVF IL-6 concentration was also measured. Twenty-seven molecules studied exhibited intergroup differences. Validation by ELISA confirmed significantly higher levels of CVF DKK3, M-CSF, and TIMP-1, but not of IGFBP-2, independent of gestational age, in CVF of women with MIAC. The area under the curve (AUC) of DKK3, M-CSF, and TIMP-1 from CVF was not significantly different from the AUC of IL-6 from CVF for detecting MIAC in women with PTL. By using a stepwise regression analysis, a combined detection model was developed, which included the CVF M-CSF, TIMP-1, and gestational age at sampling (AUC = 0.823). An antibody microarray identified useful biomarkers (DKK3, M-CSF, and TIMP-1) in CVF for detection of MIAC, and a combined model including these biomarkers and gestational age can accurately detect MIAC in women with PTL.

Monoamniotic twins have a high risk of mortality and perinatal morbidity due to cord entanglement and vascular anastomosis. Despite efforts to reduce the mortality rate through intensive fetal surveillance and timed delivery, poor long-term neurodevelopmental outcomes remain an unsolved problem. This study aimed to identify novel biomarkers predicting abnormal neurodevelopmental outcomes in monoamniotic twins with cord blood samples taken at the time of delivery. Abnormal neurodevelopmental outcomes were defined as (1) a severe brain lesion on neonatal brain ultrasound, (2) developmental delay, (3) cerebral palsy, and/or (4) blindness or deafness. Cord blood was analyzed with mass spectrometry-based proteomics according to the neurodevelopmental outcomes. Statistical analysis was performed to determine the differentially expressed proteins between neonates with normal and abnormal neurodevelopmental outcomes. Several candidate proteins were further validated with enzyme-linked immunosorbent assays. A total of 20 neonates (10 pairs) of monoamniotic twins were included in the proteomic analysis, of which 25% had abnormal neurodevelopmental outcomes. Eighteen proteins were differentially expressed in neonates with abnormal neurodevelopmental outcomes. The upregulated proteins in the neonates with adverse neurodevelopmental outcome were immunoglobulin (Ig)-gamma-4 chain C region, apolipoprotein E, and alpha-fetoprotein. In contrast, Ig-lambda chain V region 4A, Ig-heavy variable 3, Ig-kappa chain C region, Ig-mu chain C region, C1q, ceruloplasmin, and Ig-lambda chain V-I region were decreased. In the validation experiment, the cord blood concentration of ceruloplasmin was significantly lower in neonates with adverse neurodevelopmental outcomes than in those without. Therefore, ceruloplasmin could be a useful predictive biomarker of adverse neurodevelopmental outcomes in monoamniotic twins.

Background To evaluate the self-reported pain scores as a predictor of preterm birth (PTB) in symptomatic twin pregnancy and to develop a nomogram for the prediction model. Methods We conducted a retrospective study of 148 cases of symptomatic twin pregnancies before 34 weeks of gestation visited at Seoul national university hospital from 2013 to 2018. With other clinical factors, self-reported pain score was evaluated by the numerical rating scale (NRS) pain scores for pain intensity. By multivariate analyses and logistic regression, we developed a prediction model for PTB within 7 days. Using the Cox proportional hazards model, the curves were plotted to show the predictability of the PTB according to NRS pain score, while adjusting the other covariates. Results Twenty-three patients (15.5 %) delivered preterm within 7 days. By a logistic regression analysis, higher NRS pain score (OR 1.558, 95 % CI 1.093–2.221, P P P Conclusions Self-reported pain scores combined with cervical length and fetal fibronectin are useful in predicting impending PTB in symptomatic twin pregnancy.

Antenatal corticosteroids have been proven to prevent adverse outcomes including respiratory morbidities in preterm neonates before 34 weeks of gestation. Recently, it has been suggested that antenatal corticosteroids may also be effective in singleton late preterm pregnancies, and guidelines recommend the use of corticosteroids in singleton pregnant women who are at risk for late preterm birth. On the contrary, there is a paucity of information regarding the effectiveness of corticosteroids in twin neonates with late preterm birth. This study aims to determine the effectiveness of antenatal corticosteroids in late preterm twin neonates. In this multicentre randomized controlled trial, women who are at risk for late preterm birth will be enrolled at 34 0/7 to 36 5/7 weeks of gestation. The participants will be randomly assigned to receive antenatal corticosteroids (betamethasone 12 mg, 3 mL intramuscularly [IM]) or placebo (normal saline 3 mL IM). The perinatal outcomes will be compared between the two groups of cases. The primary outcome is severe respiratory complications (the use of continuous positive airway pressure or high-flow nasal cannula for at least 12 h, supplemental oxygen administration with a fraction of oxygen 0.3 or more for at least 24 h, mechanical ventilation, or extracorporeal membranes oxygenation) or perinatal death within the first 72 h of delivery. The secondary outcomes are neonatal mortality and/or other neonatal morbidities. This study will be the first randomized controlled trial that evaluates the effectiveness of antenatal corticosteroids in late preterm twin neonates. NCT03547791 (ClinicalTrials.gov), first submitted date: March 29, 2018, first posted date: June 6, 2018 (retrospectively registered).

OBJECTIVE To examine the concordance rate of non-chromosomal congenital malformations in twin pairs based on zygosity. DESIGN Retrospective cohort study. SETTING A tertiary hospital in Korea. POPULATION Twin pairs born at Seoul National University Hospital between 2001 and 2019. METHODS Congenital malformations were diagnosed by postnatal workups of neonates or autopsy in cases of stillborn infants. Zygosity was confirmed by sex, chorionicity and DNA analysis. MAIN OUTCOME MEASURES Concordance rate of congenital malformations in twin pairs based on zygosity. RESULTS In total, 3386 twin pairs were included. The risk of a congenital malformation in the index twin increased significantly if the co-twin had the congenital malformation, and the concordance rate was higher in monozygotic (MZ) than in dizygotic (DZ) twins (37.04 versus 16.77, P

Objective To compare the efficacy of two types of progestogen therapy for preventing preterm birth (PTB) and to review the relevant literature. Design A multicentre, randomised, open-label, equivalence trial and a meta-analysis. Setting Tertiary referral hospitals in South Korea. Population Pregnant women with a history of spontaneous PTB or short cervical length ( Methods Eligible women were screened and randomised at 16-22 weeks of gestation to receive either 200 mg of vaginal micronised progesterone daily (vaginal group) or an intramuscular injection of 250 mg 17α-hydroxyprogesterone caproate weekly (IM group). Stratified randomisation was carried out according to participating centres and indications for progestogen therapy. This trial was registered at ClinicalTrials.gov (NCT02304237). Main outcome measure Preterm birth (PTB) before 37 weeks of gestation. Results A total of 266 women were randomly assigned and a total of 247 women (119 and 128 women in the vaginal and IM groups, respectively) were available for the intention-to-treat analysis. Risks of PTB before 37 weeks of gestation did not significantly differ between the two groups (22.7 versus 25.8%, P = 0.571). The difference in PTB risk between the two groups was 3.1% (95% CI -7.6 to 13.8%), which was within the equivalence margin of 15%. The meta-analysis results showed no significant differences in the risk of PTB between the vaginal and IM progestogen treatments. Conclusion Compared with vaginal progesterone, treatment with intramuscular progestin might increase the risk of PTB before 37 weeks of gestation by as much as 13.8%, or reduce the risk by as much as 7.6%, in women with a history of spontaneous PTB or with short cervical length. Tweetable abstract Vaginal and intramuscular progestogen showed equivalent efficacy for preventing preterm birth before 37 weeks of gestation.

OBJECTIVE:To evaluate not only the risk of total preterm birth (PTB) but also spontaneous preterm birth (sPTB) and indicated preterm birth (iPTB) in vanishing twin (VT). STUDY DESIGN:This is a secondary analysis of a multicenter prospective cohort study. In 12 different healthcare institutions, women with singleton pregnancies were enrolled in early pregnancy and followed up till delivery. RESULTS:A total of 4,746 women were included in the final analysis, and. the frequency of VT was 1.1% (54/4746). VT group had a higher risk for total PTB (PTB

We aimed to explore the proteomic profiles of mid-trimester amniotic fluid in pregnant women with systemic lupus erythematosus (SLE) according to the occurrence of adverse pregnancy outcome (APO). The study population included 35 pregnant women with SLE who underwent clinically indicated amniocentesis at 15-24 weeks of gestation. Patients were divided into two groups according to pregnancy outcomes: SLE patients without APO (Group 1) and SLE patients with APO (Group 2). Stored samples of amniotic fluid were analyzed using mass spectrometry (MS)-based proteomics with two-step approach, consisting of discovery and verification phase. In the discovery phase, 44 proteins were differentially expressed between Group 1 and Group 2. In the verification phase, differentially expressed proteins (DEPs) were verified in independent samples using DIA method. Four proteins including filamin A (FLNA), sushi, von Willebrand factor type A, EGF and pentraxin domain containing 1 (SVEP1), lecithin-cholesterol acyltransferase (LCAT), and transglutaminase 2 (TGM2) were differentially expressed both in discovery and verification phase. To select the best combination of proteins for discriminating two groups, three-fold cross validation (CV) with repetition of one hundred times was performed. The multi-marker model with three biomarkers (SVEP1, LCAT, TGM2) had a high discriminatory power to distinguish between the two groups (the area under the receiver operating characteristic, AUROC = 0.946, p

Objective: It is well known that a short cervix at mid-pregnancy is a risk factor for spontaneous preterm birth in both singleton and twin gestations. Recent evidence also suggests that a long cervix at mid-pregnancy is a predictor of the risk of cesarean section (C/S) in singleton gestation. The purpose of this study was to determine whether a long cervix at mid-pregnancy was associated with an increased risk of C/S in women with twin pregnancies. Methods: We enrolled 746 women pregnant with twins whose cervical length was measured by trans-vaginal ultrasonography at a mean of 22 weeks of gestation and who delivered in our institution. Cases with a short cervix [cervical length (CL) Results: The rate of C/S increased according to the quartile of CL (47% in the 1st quartile, 51% in the 2nd quartile, 56% in the 3rd quartile and 62% in the 4th quartile, P2 for trend). CL was an independent risk factor for C/S even after adjustment for confounding variables. When confining analysis to women who delivered after a trial of labor (n=418), to nulliparous women (n=633) or to those who delivered at late preterm or full term (n=666), the rate of C/S also increased according to the quartile of CL, and the relationship between CL and the risk of C/S remained significant after adjustment in each group. Conclusion: In women pregnant with twins, long CL at mid-pregnancy was a risk factor for C/S.

BackgroundIn monochorionic twin pregnancy, placental anastomosis and inter-twin blood transfusion can result in specific complications, such as twin-twin transfusion syndrome (TTTS) and twin anemia-polycythemia sequence (TAPS). It is well established that adverse outcomes are increased in TTTS, but reports on the neonatal and long-term outcomes of TAPS are lacking. The objective of this study was to evaluate the neonatal and neurodevelopmental outcomes in spontaneous TAPS.MethodsThe study population consisted of monochorionic twin pregnancies with preterm birth (24–37 weeks of gestation) between November 2003 and December 2016 and in which cord blood was taken at the time of delivery. According to the result of hemoglobin in cord blood, the study population was divided into two groups: a spontaneous TAPS group and a control group. Neonatal and neurodevelopmental outcomes were compared between the two groups.ResultsDuring the study period, 11 cases were diagnosed as spontaneous TAPS (6.4%). The TAPS group had lower gestational age at delivery and had a higher risk for cesarean delivery. However, neonates with TAPS were not at an increased risk for neonatal mortality and significant neonatal morbidity. In addition, the frequency of severe cerebral lesion during the neonatal period and the risk of cerebral palsy at 2 years of age were not different between the two groups.ConclusionThe spontaneous TAPS diagnosed by postnatal diagnostic criteria was not associated with the increased risk of adverse neonatal and neurodevelopmental outcomes. Further studies are needed to evaluate the morbidity of antenatally diagnosed TAPS.

We aimed to identify cervicovaginal fluid (CVF) protein biomarkers of microbial invasion of the amniotic cavity (MIAC) in women with preterm premature rupture of membranes (PPROM), using an antibody microarray. This retrospective cohort study included 99 consecutive women with singleton pregnancies and PPROM (23–33 weeks) who underwent amniocentesis and who gave CVF samples. CVF proteomes from the MIAC (n = 20) versus non-MIAC groups (n = 20) were comparatively profiled by an antibody microarray using a nested case-control study design. The seven candidate biomarkers of interest were validated in the total cohort (n = 99) by enzyme-linked immunosorbent assays (ELISA). For comparison with candidate markers, amniotic fluid (AF) white blood cell (WBC) count was also measured. The primary outcome measure was MIAC (defined as positive AF culture). Thirty of the proteins studied exhibited significant intergroup differences. Measurements of the total cohort with ELISA confirmed a significant increase in the levels of CVF IL-8, lipocalin-2, MIP-1α, MMP-9, and TIMP-1 in women with MIAC, independent of gestational age at sampling. A combined, non-invasive model was developed by using a stepwise regression procedure, which included CVF IL-8 and CVF MMP-9 (area under the curve [AUC] = 0.763), and this AUC was comparable with the AUC of AF WBC. Using protein–antibody microarray technology, we found several novel, independent, non-invasive biomarkers to identify MIAC in women with PPROM: IL-8, lipocalin-2, MIP-1α, MMP-9, and TIMP-1. Furthermore, the combined non-invasive model (IL-8 and MMP-9) was a useful independent predictor for MIAC with good discriminatory power, similar to AF WBC count.

Red cell distribution width (RDW) is a prognostic marker for adverse outcomes in cardiovascular disease. This association has been attributed to the impaired erythropoiesis and abnormal red blood cell survival originating from chronic hypoxic status or poor nutrition. Considering the pathophysiologic association between fetal growth restriction (FGR) and chronic intrauterine hypoxia, which in turn can result in impaired erythropoiesis, RDW could be a biomarker in FGR. To address this issue, we evaluated the RDW in FGR.The study population consisted of singleton preterm neonates (24-34 weeks of gestation) and RDW in cord blood was measured at delivery, and was compared between small-for-gestational age (SGA) neonates (birthweight10 percentile) and non-SGA neonates (birthweight10 percentile). Among them, RDW was also examined according to the adverse neonatal outcomes.Five hundred eighty-four neonates were included, of these, 117 SGA neonates and 467 non-SGA neonates. RDW in the SGA neonates was significantly higher than that in the non-SGA neonates (18.4 versus 16.4,The RDW was higher in the SGA neonates and was associated with adverse outcomes. RDW can be a prognostic marker in predicting outcomes among preterm neonates.

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

OBJECTIVE To investigate whether the uterine artery pulsatility index (UtA PI) of hypertensive pregnancies is higher than that of normal pregnancies in the puerperium, as well as in the antepartum period. METHODS The UtA PI was measured in hypertensive (group 1) and normal pregnancies (group 2) during antepartum, immediate postpartum or late postpartum periods. Using the transvaginal approach, the bilateral uterine artery indices were measured. RESULTS One hundred twenty-two women were enrolled: group 1, hypertensive disease in pregnancy (11 cases in antepartum, 13 cases in immediate postpartum and 10 cases in late postpartum period); group 2, normal pregnancies (32 cases in antepartum, 29 cases in immediate postpartum and 27 cases in late postpartum). In antepartum and immediate postpartum periods, the mean UtA PI and the proportion of cases with an early diastolic notch were higher in group 1 than in group 2 (antepartum mean UtA PI, 1.14 in group 1 vs. 0.68 in group 2, P

Aim The purpose of this study is to determine whether proinflammatory cytokines and matrix metalloproteinases (MMPs) in amniotic fluid (AF), alone or in combination with clinical risk factors, can predict spontaneous preterm delivery (SPTD) at < 34 weeks in women with cervical insufficiency. Methods This retrospective cohort study included 57 consecutive singleton pregnant women (17–28 gestational weeks) with cervical insufficiency who underwent amniocentesis. AF was assayed for five cytokines (interleukin [IL]-6, IL-8, monocyte chemotactic protein-1, macrophage inflammatory protein [MIP]-1α, and MIP-1β) and five MMPs (MMP-1, MMP-2, MMP-3, MMP-8, and MMP-9) using multiplex immunoassay kits. The primary outcome measure was SPTD at < 34 weeks. Results The AF concentrations of MMP-1, MMP-3, MMP-8, MMP-9, IL-6, IL-8, MIP-1α and MIP-1β were significantly higher in women with SPTD at < 34 weeks. Women who had SPTD at < 34 weeks were younger, had significantly more advanced cervical dilatation at presentation and a higher rate of positive AF cultures. Using stepwise regression analysis, a combined prediction model was developed that included maternal age, cervical dilatation at presentation, AF MMP-1 and AF MMP-8 (area under the curve [AUC] 0.951). The AUC for this model was significantly greater than for any single protein alone in AF or for each of the clinical risk factors alone. Conclusion A model combining proteins in AF and clinical factors can improve the accuracy of risk prediction for preterm birth and this combination is more accurate than each of the biomarkers alone in women with cervical insufficiency.

OBJECTIVE The objective of this study was to determine whether prenatal ultrasound findings and cord blood N-terminal pro-B-type natriuretic peptide (NT pro-BNP) and cardiac troponin T (cTnT) can predict neonatal mortality in single ventricle congenital heart disease. METHODS The association between neonatal mortality and prenatal ultrasound findings/cord blood biomarkers was evaluated in neonates delivered with a diagnosis of single ventricle congenital heart disease. The presence of prenatal ultrasound findings suggesting systemic outflow obstruction (ascending aorta < 2.5 percentile) or ventricular dysfunction (the presence of cardiomegaly or hydrops) was evaluated, and the total number of abnormal findings was converted to a numeric score called the 'single ventricle score'. In addition, NT pro-BNP and cTnT were measured in cord blood taken at the time of delivery. RESULTS A total of 48 cases of single ventricle congenital heart disease were included. The rate of neonatal mortality was 31% (15/48). The presence of either abnormal ultrasound findings (single ventricle score ≥ 2) or elevated concentrations of NT pro-BNP or cTnT was associated with increased risk of neonatal death. CONCLUSION The presence of either abnormal prenatal ultrasound findings or increased cord blood NT pro-BNP and cTnT concentrations was associated with the risk of neonatal death in single ventricle congenital heart disease.

Aim We analyzed the N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT) in non-immune hydrops cases, to determine whether congestive heart failure or inadequate cardiac output may be mechanisms underlying abnormal fluid collection in hydrops. Methods The study population consisted of singleton neonates with non-immune hydrops and healthy control neonates, matched for both gestational age at delivery and mode of delivery. The subjects were divided into three groups: group 1, hydrops of cardiac origin (n=6); group 2, hydrops of non-cardiac origin (n=17); and group 3, control (n=23). The NT-proBNP and cTnT were measured in the cord blood collected at the time of delivery. Results The median cord blood concentrations of NT-proBNP and cTnT were not different between the hydrops (groups 1 and 2) or control cases. However, the NT-proBNP level was elevated in group 1 compared with groups 2 and 3. The concentrations of cTnT did not differ among the three groups. Conclusions The concentration of NT-proBNP was only elevated in cases of hydrops of cardiac origin. Congestive heart failure might not be the underlying mechanism of fluid collection in cases of non-immune hydrops of non-cardiac origin, and NT-proBNP may be a promising tool to differentiate the origin of hydrops.

Introduction Ritodrine is one of the most commonly used tocolytics in preterm labor, acting as a ß2-adrenergic agonist that reduces intracellular calcium levels and prevents myometrial activation. Ritodrine infusion can result in serious maternal complications, and pulmonary edema is a particular concern among these. The cause of pulmonary edema following ritodrine treatment is multifactorial; however, the contributing genetic factors remain poorly understood. This study investigates the genetic variants associated with ritodrine-induced pulmonary edema. Methods In this case-control study, 16 patients who developed pulmonary edema during ritodrine infusion [case], and 16 pregnant women who were treated with ritodrine and did not develop pulmonary edema [control] were included. The control pregnant women were selected after matching for plurality and gestational age at the time of tocolytic use. Maternal blood was collected during admission for tocolytic treatment, and whole exome sequencing was performed with the stored blood samples. Results Gene-wise variant burden (GVB) analysis resulted in a total of 71 candidate genes by comparing the cumulative effects of multiple coding variants for 19729 protein-coding genes between the patients with pulmonary edema and the matched controls. Subsequent data analysis selected only the statistically significant and deleterious variants compatible with ritodrine-induced pulmonary edema. Two final candidate variants in CPT2 and ADRA1A were confirmed by Sanger sequencing. Conclusions We identified new potential variants in genes that play a role in cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) regulation, which supports their putative involvement in the predisposition to ritodrine-induced pulmonary edema in pregnant women.

Objective: Prior studies have suggested that nonpresenting twins are more likely to develop respiratory distress syndrome (RDS) than presenting twins. While the underlying mechanism is not ...