Chromosomal Microarray Analysis in Fetuses With Ultrasonographic Soft Markers: A Meta-Analysis of the Current Evidence.

BACKGROUND: Ultrasonographic soft markers are normal variants, rather than fetal abnormalities, and guidelines recommend a detailed survey of fetal anatomy to determine the necessity of antenatal karyotyping. Anecdotal reports have described cases with ultrasonographic soft markers in which chromosomal microarray analysis (CMA) revealed pathogenic copy number variants (CNVs) despite normal results on conventional karyotyping, but CMA for ultrasonographic soft markers remains a matter of debate. In this systematic review, we evaluated the clinical significance of CMA for pregnancies with isolated ultrasonographic soft markers and a normal fetal karyotype. METHODS: An electronic search was conducted by an experienced librarian through the MEDLINE, Embase, and Cochrane CENTRAL databases. We reviewed 3,338 articles (3,325 identified by database searching and 13 by a hand search) about isolated ultrasonographic soft markers, and seven ultrasonographic markers (choroid plexus cysts, echogenic bowel, echogenic intracardiac focus, hypoplastic nasal bone, short femur [SF], single umbilical artery, and urinary tract dilatation) were included for this study. RESULTS: Seven eligible articles were included in the final review. Pathogenic or likely pathogenic CNVs were found in fetuses with isolated ultrasonographic soft markers and a normal karyotype. The overall prevalence of pathogenic or likely pathogenic CNVs was 2.0% (41 of 2,048). The diagnostic yield of CMA was highest in fetuses with isolated SF (9 of 225, 3.9%). CONCLUSION: CMA could aid in risk assessment and pregnancy counseling in pregnancies where the fetus has isolated ultrasonographic soft markers along with a normal karyotype.

Identification of Preeclamptic Placenta in Whole Slide Images Using Artificial Intelligence Placenta Analysis.

BACKGROUND: Preeclampsia (PE) is a hypertensive pregnancy disorder linked to placental dysfunction, often involving pathological lesions like acute atherosis, decidual vasculopathy, accelerated villous maturation, and fibrinoid deposition. However, there is no gold standard for the pathological diagnosis of PE and this limits the ability of clinicians to distinguish between PE and non-PE pregnancies. Recent advances in computational pathology have provided the opportunity to automate pathological analysis for diagnosis, classification, prediction, and prediction of disease progression. In this study, we assessed whether computational pathology could be used to identify PE placentas. METHODS: A total of 168 placental whole-slide images (WSIs) of patients from Seoul National University Hospital (comprising 84 PE cases and 84 normal controls) were used for model development and internal validation. For external validation of the model, 76 placental slides (including 38 PE cases and 38 normal controls) were obtained from the Boramae Medical Center (BMC). To establish standard criteria for diagnosing PE and distinguishing it from controls using placental WSIs, patch characteristics and quantification of terminal and intermediate villi were employed. In unsupervised learning, K-means clustering was conducted as a feature obtained through an Auto Encoder to extract the ratio of each cluster for each WSI. For supervised learning, quantitative assessments of the villi were obtained using a U-Net-based segmentation algorithm. The prediction model was developed using an ensemble method and was compared with a clinical feature model developed by using placental size features. RESULTS: Using ensemble modeling, we developed a model to identify PE placentas. The model showed good performance (area under the precision-recall curve [AUPRC], 0.771; 95% confidence interval [CI], 0.752-0.790), with 77.3% of sensitivity and 71.1% of specificity, whereas the clinical feature model showed an AUPRC 0.713 (95% CI, 0.694-0.732) with 55.6% sensitivity and 86.8% specificity. External validation of the predictive model employing the BMC-derived set of placental slides also showed good discrimination (AUPRC, 0.725; 95% CI, 0.720-0.730). CONCLUSION: The proposed computational pathology model demonstrated a strong ability to identify preeclamptic placentas. Computational pathology has the potential to improve the identification of PE placentas.

Long-term adverse neurodevelopmental outcomes of discordant twins delivered at term: A nationwide population-based study.

OBJECTIVE: To evaluate long-term adverse neurodevelopmental outcomes of discordant twins delivered at term. DESIGN: Retrospective cohort study. SETTING: Nationwide (Republic of Korea). POPULATION: All twin children delivered at term between 2007 and 2010. METHODS: The study population was divided into two groups according to inter-twin birthweight discordancy: the 'concordant twin group', twin pairs with inter-twin birthweight discordancy less than 20%; and the 'discordant twin group', twin pairs with inter-twin birthweight discordancy of 20% or more. The risk of long-term adverse neurodevelopmental outcomes was compared between the concordant twin group and the discordant twin group. Long-term adverse neurodevelopmental outcomes between smaller and larger twin children within twin pairs were further analysed. The composite adverse neurodevelopmental outcome was defined as the presence of at least one of the following: motor developmental delay, cognitive developmental delay, autism spectrum disorders/attention deficit hyperactivity disorders, tics/stereotypical behaviour or epileptic/febrile seizure. MAIN OUTCOME MEASURES: Long-term adverse neurodevelopmental outcome. RESULTS: Of 22 468 twin children (11 234 pairs) included, 3412 (15.19%) twin children were discordant. The risk of composite adverse neurodevelopmental outcome was higher in the discordant twin group than in the concordant twin group (adjusted hazard ratio [HR] 1.13, 95% CI 1.03-1.24). The long-term adverse neurodevelopmental outcomes were not significantly different between smaller and larger twin children in discordant twin pairs (adjusted HR 1.01, 95% CI 0.81-1.28). CONCLUSION: In twin pairs delivered at term, an inter-twin birthweight discordancy of 20% or greater was associated with long-term adverse neurodevelopmental outcomes; and long-term adverse neurodevelopmental outcomes were not significantly different in smaller or larger twin children in discordant twin pairs.

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.

Ultrasonographic monitoring of fetal eye growth parameters throughout gestation in the common marmoset (Callithrix jacchus).

The common marmoset (Callithrix jacchus) is considered an ideal species for developing genetically modified nonhuman primates (NHP) models of human disease, particularly eye disease. They have been proposed as a suitable bridge between rodents and other NHP models due to their similar ophthalmological features to humans. Prenatal ultrasonography is an accurate and reliable diagnostic tool for monitoring fetal development and congenital malformation. We monitored fetal eye growth and development using noninvasive ultrasonography in 40 heads of clinically normal fetuses during pregnancy to establish the criteria for studying congenital eye anomalies in marmosets. The coronal, sagittal, and transverse planes were useful to identify the facial structures for any associated abnormalities. For orbital measurements, biorbital distance (BOD), ocular diameter (OD), interorbital distance (IOD), and total axial length (TAL) were measured in the transverse plane and carefully identified for intraorbital structures. As a result, high correlations were observed between delivery-based gestational age (GA) and biparietal diameter (BPD), BOD, OD, and TAL. The correlation assessments based on BOD provide more reliable results for monitoring eye growth and development in normal marmosets than any other parameters since BOD has the highest correlation coefficient according to both delivery-based GA and BPD among ocular measurements. In conclusion, orbital measurements by prenatal ultrasonography provide reliable indicators of marmoset eye growth, and it could offer early diagnostic criteria to facilitate the development of eye disease models and novel therapies such as genome editing technologies in marmosets.

The Effect of Vanishing Twin on First- and Second-Trimester Maternal Serum Markers and Nuchal Translucency: A Multicenter Prospective Cohort Study.

BACKGROUND: The purpose of this study was to evaluate the effect of vanishing twin (VT) on maternal serum marker concentrations and nuchal translucency (NT). METHODS: This is a secondary analysis of a multicenter prospective cohort study in 12 institutions. Serum concentrations of pregnancy-associated plasma protein-A in the first trimester and alpha-fetoprotein (AFP), total human chorionic gonadotrophin, unconjugated estriol, and inhibin A in the second trimester were measured, and NT was measured between 10 and 14 weeks of gestation. RESULTS: Among 6,793 pregnant women, 5,381 women were measured for serum markers in the first or second trimester, including 65 cases in the VT group and 5,316 cases in the normal singleton group. The cases in the VT group had a higher median multiple of the median value of AFP and inhibin A than the normal singleton group. The values of other serum markers and NT were not different between the two groups. After the permutation test with adjustment, AFP and inhibin A remained significant differences. The frequency of abnormally increased AFP was also higher in the VT group than in the normal singleton group. CONCLUSION: VT can be considered as an adjustment factor for risk assessment in the second-trimester serum screening test.

Metabolic Dysfunction-Associated Fatty Liver Disease and Subsequent Development of Adverse Pregnancy Outcomes.

BACKGROUND & AIMS: Recently, metabolic dysfunction-associated fatty liver disease (MAFLD), rather than nonalcoholic fatty liver disease (NAFLD), was proposed to better describe liver disease associated with metabolic dysfunction (MD). In this study, we attempted to investigate the impact of MAFLD on pregnancy complications. METHODS: The current study is a secondary analysis of a multicenter prospective cohort designed to examine the risk of NAFLD during pregnancy. In the first trimester, enrolled pregnant women were evaluated for hepatic steatosis by liver ultrasonography, and blood samples were collected for biochemical measurements. The study population was divided into 3 groups: no NAFLD, hepatic steatosis but without metabolic dysfunction (non-MD NAFLD), and MAFLD. The primary outcome was the subsequent development of adverse pregnancy outcomes, including gestational diabetes mellitus, pregnancy-associated hypertension, preterm birth, and fetal growth abnormalities. RESULTS: The study population consisted of 1744 pregnant women, including 1523 with no NAFLD, 43 with non-MD NAFLD, and 178 with MAFLD. The risk of subsequent development of adverse pregnancy outcomes was higher in MAFLD than in non-MD NAFLD (adjusted odds ratio, 4.03; 95% CI, 1.68-9.67), whereas the risk was not significantly different between no NAFLD and non-MD NAFLD. Among women with no NAFLD, the presence of MD increased the risk of adverse pregnancy outcomes. However, women with MAFLD were at higher risk for adverse pregnancy outcomes than women with no NAFLD without MD or those with no NAFLD with MD. CONCLUSIONS: In pregnant women, MAFLD may be associated with an increased risk of subsequent adverse pregnancy outcomes.

Self-healing nanocomposites via N-doped GO promoted "click chemistry".

N-doped graphene stabilized Cu(I)-catalyzed self-healing nanocomposites are developed. This study found the use of N-doped graphene as both a nanostructured material for enhancing mechanical and conductive properties and a catalyst promoter (a scaffold for catalytic copper(I) particles), helpful to trigger self-healing via "click chemistry". Due to an increase in electron density on nitrogen atom doping, including the coordination of N-doped rGO with Cu+ ions, nitrogen-doped graphene-supported copper particles demonstrate a higher reaction yield at room temperature without adding any external ligand/base. In this study, only one component (an azide moiety containing a healing agent) was encapsulated, whereas another component (an alkyne moiety containing a healing agent) was as such (without encapsulation) homogeneously dispersed in a matrix. Triggered capsule rupture then induces the contact of the healing agents with the N-doped graphene-based catalyst and the alkyne molecules dispersed in the matrix, inducing a "click"-reaction, allowing onsite damage to be repaired as determined by mechanical measurements entirely. Tensile measurements were also performed using molecular dynamics (MD) simulations to support the findings. Given the enormous importance of autonomic repair of materials damage, this concept here reports a trustworthy and reliable chemical system with a high level of robustness.

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.

Self-reported pain scores as a predictor of preterm birth in symptomatic twin pregnancy: a retrospective study.

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 < 0.05), shorter cervical length (OR 3.164, 95 % CI 1.262-7.936, P < 0.05) and positive fibronectin results (OR 8.799, 95 % CI 1.101-70.330, P < 0.05) affect PTB within 7 days. Using the variables, the area under the receiver operating characteristic curve (AUROC) of the prediction model was 0.917. In addition, we developed a nomogram for the prediction of PTB within 7 days. CONCLUSIONS: Self-reported pain scores combined with cervical length and fetal fibronectin are useful in predicting impending PTB in symptomatic twin pregnancy.

The risk of pregnancy-associated hypertension in women with nonalcoholic fatty liver disease.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is an independent predictor of cardiovascular disease (CVD) in non-pregnant adults. Although the biological mechanisms underlying this association are not completely understood, metabolic factors, inflammation, and endothelial dysfunction are likely all involved. The association between NAFLD and pregnancy-associated hypertension (HTN) has not been systematically examined. The aim of this study is to assess the risk of pregnancy-associated HTN in pregnant women with NAFLD. METHODS: This is secondary analysis of a prospective study of healthy pregnant women. Liver ultrasonography was performed at 10-14 weeks of gestation and maternal blood was taken for the measurement of selenoprotein P (SeP), a hepatokine independently associated with both NAFLD and CVD. Pregnancy-associated HTN was defined as the development of gestational HTN, preeclampsia, or eclampsia. RESULTS: Among 877 pregnant women, the risk of developing pregnancy-associated HTN was significantly increased in women with NAFLD compared to those without NAFLD. Grade 2-3 steatosis was a significant predictor of pregnancy-associated HTN, even after adjustment for metabolic risk factors. Circulating levels of SeP were significantly higher in women with versus those without NAFLD (P = .001) and was significantly higher also in women who subsequently developed pregnancy-associated HTN compared with those who did not (P < .005). CONCLUSIONS: Sonographic evidence of NAFLD at 10-14 weeks is an independent predictor of pregnancy-associated HTN. Circulating levels of SeP at that same gestational age are significantly increased in pregnant women with NAFLD who subsequently develop pregnancy-associated HTN.

Short- and long-term outcomes of preterm spontaneous twin anemia-polycythemia sequence.

Background In 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. Methods The 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. Results During 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. Conclusion The 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.

Non-alcoholic fatty liver disease in the first trimester and subsequent development of gestational diabetes mellitus.

AIMS/HYPOTHESIS: Although there is substantial evidence that non-alcoholic fatty liver disease (NAFLD) is associated with impaired glucose homeostasis, the clinical significance of NAFLD in pregnant women has not been well determined. This study investigates the relationship between NAFLD in the first trimester and the subsequent development of gestational diabetes mellitus (GDM). METHODS: A multicentre, prospective cohort study was conducted in which singleton pregnant Korean women were assessed for NAFLD at 10-14 weeks using liver ultrasound, fatty liver index (FLI) and hepatic steatosis index (HSI). Maternal plasma adiponectin and selenoprotein P concentrations were measured. Participants were screened for GDM using the two-step approach at 24-28 weeks. RESULTS: Six hundred and eight women were included in the final analysis. The prevalence of NAFLD was 18.4% (112/608) and 5.9% (36/608) developed GDM. Participants who developed GDM had a higher prevalence of radiological steatosis (55.6% vs 16.1%; p < 0.001) and higher FLI (40.0 vs 10.7; p < 0.001) and HSI (35.5 vs 29.0; p < 0.001). The risk of developing GDM was significantly increased in participants with NAFLD and was positively correlated with the severity of steatosis. This relationship between NAFLD and GDM remained significant after adjustment for metabolic risk factors, including measures of insulin resistance. Maternal plasma adiponectin and selenoprotein P levels were also correlated with both NAFLD severity and the risk of developing GDM. CONCLUSIONS/INTERPRETATION: NAFLD in early pregnancy is an independent risk factor for GDM. Adiponectin may be a useful biomarker for predicting GDM in pregnant women.

Effects of antenatal corticosteroids in twin neonates with late preterm birth (ACTWIN [Antenatal Corticosteroids in TWIN late preterm neonates] trial): study protocol for a randomized controlled trial.

BACKGROUND: 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. METHODS: 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. DISCUSSION: This study will be the first randomized controlled trial that evaluates the effectiveness of antenatal corticosteroids in late preterm twin neonates. TRIAL REGISTRATION: NCT03547791 (ClinicalTrials.gov), first submitted date: March 29, 2018, first posted date: June 6, 2018 (retrospectively registered).

Fetal Survival Immediate after Fetoscopic Laser Ablation in Twin to Twin Transfusion Syndrome.

BACKGROUND: The purpose of this study was to determine prognostic factors that can affect the fetal survival immediate after fetoscopic laser ablation. METHODS: The study population consisted of consecutive twin pregnant women who underwent fetoscopic laser ablation with the diagnosis of twin to twin transfusion syndrome (TTTS) from 2011 to 2018 in Seoul National University Hospital. Fetal survival immediate after procedure was defined as survival to 48 hours after procedure and neonatal survival was defined as survival to 28 days of life. Clinical characteristics and ultrasound findings were compared according to the fetal survival immediate after procedure. RESULTS: A total of 57 pregnant women with TTTS were included, and the overall fetal survival immediate after procedure was 71.1% (81/114) after fetoscopic laser ablation. Fetuses who survived immediate after procedure had higher gestational age at procedure and lower frequency of abnormal Doppler studies than those did not survive. However, the frequency of hydrops was not different between cases with fetal survival and those with fetal death. The earlier gestational age at procedure and the presence of abnormal Doppler studies were significant risk factors for fetal death even after adjustment. CONCLUSION: Based on this data, the fetal survival immediate after procedure (fetoscopic laser treatment) in TTTS can be affected by the gestational age at procedure and the presence of abnormal Doppler studies.

Antenatal Prediction of Neonatal Survival in Sacrococcygeal Teratoma.

OBJECTIVES: In sacrococcygeal teratoma, the presence of high-output cardiac failure resulting from arteriovenous shunting through the large tumor has been associated with an adverse outcome. The objective of this study was to determine whether the tumor size and cardiac biomarkers in cord blood can predict neonatal survival in sacrococcygeal teratoma. METHODS: The study population consisted of 25 neonates with sacrococcygeal teratoma. Tumor size was calculated by the ellipsoid formula using dimensions measured by antenatal ultrasound ([length × width × depth in cm] × 0.52= volume in cm3 ). To adjust the gestational age, the tumor volume index (tumor volume/biparietal diameter) was adopted in the analysis. Cardiac biomarkers for heart failure (N-terminal pro-B-type natriuretic peptide [NT-pro-BNP] and cardiac troponin T [cTnT]) were measured in cord blood taken at the time of delivery. RESULTS: The rate of neonatal death was 24% (6 of 25). The cases that resulted in neonatal death had a higher tumor volume index and higher concentrations of NT-pro-BNP and cTnT than those with survival. A tumor volume index of greater than 60 cm3 /cm, elevated NT-pro-BNP (>2000 pg/mL), and elevated cTnT (>0.08 ng/mL) had sensitivity of 100% for prediction of neonatal death. CONCLUSIONS: The tumor volume index and cord blood biomarkers for heart failure can be promising prognostic markers for neonatal survival in sacrococcygeal teratoma.

The risk of neonatal respiratory morbidity according to the etiology of late preterm delivery.

OBJECTIVE: The risk of neonatal respiratory morbidity between indicated deliveries vs. spontaneous deliveries has not been consistent in previous studies, in spite of the traditional belief that chronic intrauterine stress might have protective effect on fetal lung maturation. We hypothesized that the heterogeneous etiology of indicated preterm delivery may obscure the relationship between the etiologies of preterm birth and neonatal respiratory morbidity. To address this issue, we divided the indicated preterm birth (PTB) into medically-indicated (without fetal compromise) PTB and maternal/fetal-indicated PTB, and compared the neonatal respiratory morbidity according to the etiology of late PTB. STUDY DESIGN: Neonatal respiratory morbidities were examined in neonates who were delivered between 34+0 and 36+6 weeks of gestation according to the etiology of PTB: 1) medically-indicated PTB (but without fetal compromise), 2) maternal/fetal-indicated PTB, or 3) spontaneous PTB such as preterm labor or preterm premature rupture of membranes. RESULTS: A total of 710 late preterm neonates were included in the study population, including 31 cases of medically-indicated PTB, 202 cases of maternal/fetal-indicated PTB, and 477 cases of spontaneous PTB. The rate of composite respiratory morbidity in cases of medically-indicated PTB is higher than both maternal/fetal-indicated PTB and spontaneous PTB (19% in medically-indicated PTB, 6% in maternal/fetal-indicated PTB, and 7% in spontaneous PTB). This difference between medically-indicated PTB and maternal/fetal-indicated PTB remained significant after adjustment for confounding variables. CONCLUSION: The medically-indicated PTB is associated with highest risk of neonatal respiratory morbidity in late PTB.

Expression changes of proteins associated with the development of preeclampsia in maternal plasma: A case-control study.

Defective deep placentation, involving abnormal transformation of the spiral arteries in the junctional zone of the myometrium, is known to cause significant obstetric complications, such as preeclampsia (PE), fetal growth restriction, and placental infarction leading to fetal death. Serological biomarkers to predict and diagnose PE would help antenatal care and reduce obstetric complications. To discover candidate PE biomarkers, we first performed global proteomic profiling of three pairs of plasma samples obtained from pregnant women in the early second trimester, who subsequently developed PE, and controls to identify candidate proteins that were abundant in the patients. We further evaluated the changes in the expression of PE-representing proteins in stored plasma samples of a cohort that subsequently developed PE and their matched controls by MRM-MS analysis. We identified that both complement C1s subcomponent (C1S) and protein AMBP were elevated in the plasma samples of the PE cohort before the manifestation of clinical disease. We propose that these proteins may be involved in the remodeling process of the spiral arteries even before PE manifestation. These proteins can serve as potential plasma biomarkers to predict the pregnant women having an increased risk of developing PE.

Preterm labor and preterm premature rupture of membranes have a different pattern in the involved compartments of acute histologoic chorioamnionitis and/or funisitis: Patho-physiologic implication related to different clinical manifestations.

It is unknown whether histo-topographic findings about the involved compartments (i.e., choriodecidua, amnion, chorionic-plate) of acute-histologic chorioamnionitis (acute-HCA) and/or funisitis according to the presence or absence of intra-amniotic inflammation (IAI) and/or fetal inflammatory response syndrome (FIRS) are different between preterm labor and intact membranes (PTL) and preterm premature rupture of membranes (preterm-PROM). The involved compartments of acute-HCA and/or funisitis were examined in 161 singleton preterm-births (<34 weeks) due to PTL (n = 88) and preterm-PROM (n = 73). The study-population was divided into IAI(-)/FIRS(-), IAI(+)/FIRS(-), and IAI(+)/FIRS(+) groups according to the presence or absence of IAI (amniotic-fluid MMP-8 ≥ 23 ng/ml) and/or FIRS (umbilical-cord plasma CRP ≥ 200 ng/ml). Histological inflammation was not detected in any-compartment except choriodecidua in IAI(-)/FIRS(-) group with PTL while inflammation appeared in all-compartment0s (choriodeciduitis-46.2 %; amnionitis-23.1 %; funisitis-30.8 %; chorionic-plate inflammation-7.7 %) in IAI(-)/FIRS(-) group with preterm-PROM. IAI(+)/FIRS(-) group had a significantly higher frequency of inflammation in each-compartment than IAI(-)/FIRS(-) group in PTL (each-for P < 0.01), but not preterm-PROM (each-for P > 0.1). However, IAI(+)/FIRS(+) group had a significantly higher rate of inflammation in each compartment than IAI(+)/FIRS(-) group in both PTL and preterm-PROM (each-for P < 0.05). We first demonstrated that PTL and preterm-PROM had a different pattern in the involved compartments of acute-HCA and/or funisitis in the IAI(-)/FIRS(--) group and in the change of involved compartments from IAI(-)/FIRS(-) to IAI(+)/FIRS(-).

Prenatal prediction of neonatal death in single ventricle congenital heart disease.

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.