The timing of adenomyosis diagnosis and its impact on pregnancy outcomes: a national population-based study.

OBJECTIVE: Adenomyosis impacts pregnancy outcomes, although there is a lack of consensus regarding the actual effects. It is likely, however, that the severity of adenomyosis or ultrasound findings or timing of diagnosis can have different effects on adverse pregnancy outcomes (APOs). METHODS: In this study, we aimed to investigate the impact of the timing of adenomyosis diagnosis on pregnancy outcomes. Singleton pregnant women who delivered between 2017 and 2022 were analyzed based on the timing of adenomyosis diagnosis, using a national database. The final cohort was classified into three groups: 1) group 1, without adenomyosis; 2) group 2, those diagnosed with adenomyosis before pregnancy; and 3) group 3, those diagnosed with adenomyosis during pregnancy. RESULTS: A total of 1,226,475 cases were ultimately included in this study. Women with a diagnosis of adenomyosis had a significantly higher risk of APOs including hypertensive disorder during pregnancy (HDP), gestational diabetes mellitus (GDM), postpartum hemorrhage, placental abruption, preterm birth, and delivery of a small-for-gestational-age infant even after adjusting for covariates. In particular, concerning HDP, the risk was highest in group 3 (group 2: adjusted odds ratio [aOR], 1.15 vs. group 3: aOR, 1.36). However, the highest GDM risk was in group 2 (GDM; group 2: aOR, 1.24 vs. group 3: aOR, 1.04). CONCLUSION: The increased risk of APO differed depending on the timing of adenomyosis diagnosis. Therefore, efforts for more careful monitoring and prevention of APOs may be necessary when such women become pregnant.

Risk Factors of Postpartum Depression Among Korean Women: An Analysis Based on the Korean Pregnancy Outcome Study (KPOS).

BACKGROUND: Postpartum depression (PPD) can negatively affect infant well-being and child development. Although the frequency and risk factors of PPD symptoms might vary depending on the country and culture, there is limited research on these risk factors among Korean women. This study aimed to elucidate the potential risk factors of PPD throughout pregnancy to help improve PPD screening and prevention in Korean women. METHODS: The pregnant women at 12 gestational weeks (GW) were enrolled from two obstetric specialized hospitals from March 2013 to November 2017. A questionnaire survey was administered at 12 GW, 24 GW, 36 GW, and 4 weeks postpartum. Depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale, and PPD was defined as a score of ≥ 10. RESULTS: PPD was prevalent in 16.3% (410/2,512) of the participants. Depressive feeling at 12 GW and postpartum factors of stress, relationship with children, depressive feeling, fear, sadness, and neonatal intensive care unit admission of baby were significantly associated with a higher risk of PPD. Meanwhile, high postpartum quality of life and marital satisfaction at postpartum period were significantly associated with a lower risk of PPD. We developed a model for predicting PPD using factors as mentioned above and it had an area under the curve of 0.871. CONCLUSION: Depressive feeling at 12 GW and postpartum stress, fear, sadness, relationship with children, low quality of life, and low marital satisfaction increased the risk of PPD. A risk model that comprises significant factors can effectively predict PPD and can be helpful for its prevention and appropriate treatment.

Fetal growth changes and prediction of selective fetal growth restriction following fetoscopic laser coagulation in twin-to-twin transfusion syndrome.

OBJECTIVE: To investigate fetal growth changes and predictive factors for selective fetal growth restriction (sFGR) in patients with twin-to-twin transfusion syndrome (TTTS) after fetoscopic laser coagulation (FLC). METHODS: This retrospective study included twin-pregnant women with fetal TTTS who underwent FLC at our institution between 2011 and 2020. Twin pairs who survived at least 28 days after FLC and at least 28 days after birth were included. A paired t-test was used to compare the mean discordance between the estimated fetal weights at the FLC and the birth weights. The predictive factors for sFGR after FLC were evaluated using univariate and multivariate logistic regression analyses. RESULTS: A total of 119 eligible pairs of patients who underwent FLC were analyzed. The weight percentile at birth significantly decreased after FLC in the recipients (53.7±30.4 percentile vs. 43.7±28.0 percentile; P<0.001), but increased in the donors (11.5±17.1 percentile vs. 20.7±22.8 percentile; P<0.001). Additionally, the mean weight discordance of twin pairs significantly decreased after FLC (23.9%±12.7% vs. 17.3%±15.7%; P<0.001). After FLC, Quintero stage ≥3, pre-FLC sFGR, abnormal cord insertion, and post-FLC abnormal umbilical artery Doppler (UAD) were all significantly higher in the sFGR group than the non-sFGR group. The prediction model using these variables indicated that the area under the receiver operating characteristic curve was 0.898. CONCLUSION: The recipient weight percentile decreased, whereas donor growth increased, resulting in reduced weight discordance after FLC. The Quintero stage, pre-FLC sFGR, and post-FLC abnormal UAD were useful predictors of sFGR after FLC in TTTS.

The Skin Antiseptic agents at Vaginal dElivery (SAVE) trial: study protocol for a randomized controlled trial.

BACKGROUND: Cleansing of the vulva and perineum is recommended during preparation for vaginal delivery, and special attention is paid to cleansing before episiotomy because episiotomy is known to increase the risk of perineal wound infection and/or dehiscence. However, the optimal method of perineal cleansing has not been established, including the choice of antiseptic agent. To address this issue, we designed a randomized controlled trial to examine whether skin preparation with chlorhexidine-alcohol is superior to povidone-iodine for the prevention of perineal wound infection after vaginal delivery. METHODS: In this multicenter randomized controlled trial, term pregnant women who plan to deliver vaginally after episiotomy will be enrolled. The participants will be randomly assigned to use antiseptic agents for perineal cleansing (povidone-iodine or chlorhexidine-alcohol). The primary outcome is superficial or deep perineal wound infection within 30 days after vaginal delivery. The secondary outcomes are the length of hospital stay, physician office visits, or hospital readmission for infection-related complications, endometritis, skin irritations, and allergic reactions. DISCUSSION: This study will be the first randomized controlled trial aiming to determine the optimal antiseptic agent for the prevention of perineal wound infections after vaginal delivery. TRIAL REGISTRATION: ClinicalTrials.gov NCT05122169. First submitted date on 8 November 2021. First posted date on 16 November 2021.

Maternal Anemia during the First Trimester and Its Association with Psychological Health.

Anemia during pregnancy is known to be associated with an increased risk of antenatal and/or postnatal depression, as well as adverse pregnancy outcomes. However, there are few studies evaluating psychological health throughout the antepartum and postpartum periods in women with anemia in early pregnancy. This study analyzed data collected by the Korean Pregnancy Outcome Study, a multicenter prospective cohort study conducted in South Korea, to determine the impact of anemia during the first trimester on birth outcomes and maternal mental health during pregnancy and postpartum. Hemoglobin levels were measured during the first trimester, and psychological health was evaluated at 12, 24, and 36 gestational weeks and 4−6 weeks postpartum. Anxiety and depression were defined using the Hospital Anxiety and Depression Scale and the Edinburgh Postnatal Depression Scale, respectively. Among 4067 Korean participants, 119 (2.9%) were diagnosed with anemia during the first trimester. Incidences of anxiety and depression did not differ over the pregnancy period between those with and without anemia during the first trimester. However, postpartum anxiety and depression were significantly more common in participants with anemia than in those without (p < 0.05, both). Hence, obstetricians should pay attention to postpartum mental health in women with anemia during the first trimester.

Prenatal Diagnosis of Congenital Heart Diseases and Associations with Serum Biomarkers of Aneuploidy: A Multicenter Prospective Cohort Study.

PURPOSE: We assessed prenatal detection rates of congenital heart disease (CHD) and associations between maternal serum biomarkers and non-chromosomal CHD in singleton pregnancies. MATERIALS AND METHODS: This study was conducted as a secondary analysis of data obtained during a multicenter prospective cohort study that investigated the cost-effectiveness of prenatal testing for fetal aneuploidy. We analyzed the prenatal detection rate and accuracy for CHD screening via ultrasound during the second trimester, as well as associations between serum biomarkers and CHDs, in singleton newborns without chromosomal abnormalities. RESULTS: Among 6715 women, 142 (2.1%) newborns were born with CHDs, of which 67 (1.0%) newborns had major CHDs. The prenatal detection rate for all CHDs and major CHDs were 34.5% and 58.2%, respectively. After excluding isolated ventricular septal defects, the detection rate for critical CHDs was 85.9%. Women with low pregnancy-associated plasma protein A (PAPP-A) (<0.4 multiples of the median, MOM) face increased risks of non-chromosomal CHDs [adjusted odds ratio (aOR) 2.76; 95% confidence interval (CI) 1.36-5.13] and major CHDs (aOR 7.30; 95% CI 3.18-15.59), compared to those without CHDs. A higher inhibin A level (≥2.5 MOM; aOR 4.84; 95% CI 1.42-12.46) was associated with non-chromosomal major CHDs. CONCLUSION: Ultrasonography performed during the second trimester by obstetricians detected over 85% of critical CHDs. Low maternal serum PAPP-A or high inhibin-A was associated with non-chromosomal CHDs. These results may contribute to an improvement in prenatal diagnosis of CHDs.

Extremely Rare Case of Fetal Anemia Due to Mitochondrial Disease Managed with Intrauterine Transfusion.

This report describes a rare case of fetal anemia, confirmed as a mitochondrial disease after birth, treated with intrauterine transfusion (IUT). Although mitochondrial diseases have been described in newborns, research on their prenatal features is lacking. A patient was referred to our institution at 32 gestational weeks owing to fetal hydrops. Fetal anemia was confirmed by cordocentesis. After IUT had been performed three times, the anemia and associated fetal hydrops showed improvement. However, after birth, the neonate had recurrent pancytopenia and lactic acidosis. He was eventually diagnosed with Pearson syndrome and died 2 months after birth. This is the first case report of fetal anemia associated with mitochondrial disease managed with IUT.

Impact of pre-pregnancy body mass index and gestational weight gain on the risk of maternal and infant pregnancy complications in Korean women.

BACKGROUND/OBJECTIVE: Healthy weight maintenance before and during pregnancy has a significant effect on pregnancy outcomes; however, there are no specific guidelines for gestational weight gain in pregnant Korean women. Therefore, we investigated the impact of pre-pregnancy body mass index (BMI) and gestational weight gain on the risk of maternal and infant pregnancy complications in pregnant Korean women. METHODS: Study participants comprised 3454 singleton pregnant women from the Korean Pregnancy Outcome Study who had baseline examination and pregnancy outcome data. Maternal pre-pregnancy BMI and gestational weight gain were categorized according to the Asia-pacific regional guidelines and the Institute of Medicine recommendations, respectively. The primary outcome was any adverse outcomes, defined as the presence of one or more of the following: hypertensive disorders of pregnancy, gestational diabetes mellitus, peripartum depressive symptom, cesarean delivery, delivery complications, preterm birth, small or large weight infant, neonatal intensive care unit admission, or a congenital anomaly. Multiple logistic regression models were applied to examine the independent and combined impact of pre-pregnancy BMI and gestational weight gain on the risk of maternal and infant outcomes. RESULTS: Obesity before pregnancy significantly increased the risk of perinatal adverse outcomes by more than 2.5 times [odds ratio (OR): 2.512, 95% confidence interval (CI): 1.817-3.473]. Compared to that in women with appropriate gestational weight gain, women with excessive weight gain had a 36.4% incremental increase in the risk of any adverse outcomes [OR: 1.364, 95% CI: 1.115-1.670]. Moreover, women who were overweight or obese before pregnancy and had excessive gestational weight gain had a three-fold increase in the risk of adverse outcomes [OR: 3.460, 95% CI: 2.210-5.417]. CONCLUSION: This study highlights the need for appropriate weight recommendations before and during pregnancy to prevent perinatal complications in Korean women of childbearing age.

Prediction of Adverse Pregnancy Outcomes Using Crown-Rump Length at 11 to 13 + 6 Weeks of Gestation.

OBJECTIVES: To assess the risk of a fetus with a smaller or larger than expected crown-rump length (CRL) for adverse pregnancy outcomes. METHODS: The data of 960 healthy singleton pregnancies conceived via in vitro fertilization were retrospectively collected. Fetal CRL was measured between 11 and 13 + 6 weeks of gestation, and small and large fetal CRLs were defined as fetuses below the 10th and above the 90th centiles, respectively. Multiple logistic regression analysis was performed to assess the risk for adverse pregnancy outcomes. RESULTS: The mean birth weights of fetuses with small, normal, and large CRLs were 3002 g, 3205 g, and 3378 g, respectively. A small fetal CRL was associated with an increased risk of smaller-than-gestational-age neonates (adjusted odds ratio [aOR], 2.79; 95% confidence interval [CI], 1.53-5.08; P < .001) and preterm delivery before 34 gestational weeks (aOR, 6.48; 95% CI, 1.36-30.79; P = .019). A large fetal CRL was associated with an increased risk of large-for-gestational-age (LGA) neonates, and the risk persisted even after adjustment for well-known risk factors of macrosomia, such as pre-pregnancy body mass index, gestational diabetes, and excessive gestational weight gain (aOR, 3.67; 95% CI, 2.04-6.59; P < .001). However, a large fetal CRL was associated with a decreased risk of gestational diabetes (aOR, 0.10; 95% CI, 0.01-0.76; P = .026). CONCLUSIONS: Fetal CRL measured at 11 to 13 + 6 weeks gestation is worth using as a predictor of LGA as well as small for gestational age or preterm delivery.

Clinical Significance of Velamentous Cord Insertion Prenatally Diagnosed in Twin Pregnancy.

BACKGROUND: The purpose of this study was to evaluate the prevalence of velamentous cord insertion (VCI) and the actual association between pathologically confirmed VCI and perinatal outcomes in twins based on the chorionicity. METHODS: All twin pregnancies that received prenatal care at a specialty clinic for multiple pregnancies, from less than 12 weeks of gestation until delivery in a single institution between 2015 and 2018 were included in this retrospective cohort study. RESULTS: A total of 941 twins were included in the study. The prevalence of VCI in dichorionic (DC) twins and monochorionic diamniotic (MCDA) twins was 5.8% and 7.8%, respectively (p = 0.251). In all study population, the prevalence of vasa previa and placenta accreta spectrum was higher in VCI group than that of non-VCI group (p = 0.008 and 0.022). In MCDA twins with VCI, birth weight, 1 and 5-min Apgar score were lower than DC twins with VCI (p = 0.010, 0.002 and 0.000). There was no significant association between VCI and selective fetal growth restriction (p = 0.486), twin-to-twin transfusion syndrome (p = 0.400), and birth-weight discordance (>20% and >25%) (p = 0.378 and 0.161) in MCDA twins. CONCLUSION: There was no difference in the incidence of VCI in twins based on the chorionicity. Moreover, VCI was not a risk factor for adverse perinatal outcomes excepting vasa previa and placenta accreta spectrum, which had a high incidence in twins with VCI.

Clinical Utility of Increased Nuchal Translucency at 11-13 Weeks of Gestation in Twin Pregnancies Based on the Chorionicity.

To assess clinical implications of increased nuchal translucency (INT) in twin pregnancies based on the chorionicity. This was a retrospective review of the twin pregnancies who underwent first trimester ultrasound with nuchal translucency (NT) measurement at 11-13 weeks of gestation from January 2006 to December 2014. Data were collected using the OB database and the chart review. Pregnancy outcomes, including gestational weeks at the delivery, abnormal fetal karyotypes, fetal structural anomalies, and twin-specific complications, were analyzed. A total of 1622 twin pregnancies with INT ≥ 95th percentile in one or both fetuses were identified. In all twin pregnancies with INT, abnormal fetal karyotypes were identified in 17 (8.6%) patients (odds ratio = 13.28, CI = 5.990-29.447, p = 0.000) and twin-specific complications were identified in 23 (11.6%) patients (odds ratio = 2.398, CI = 1.463-3.928, p = 0.001) compared to those with normal NT. Among the INT group, when the groups were subdivided into monochorionic (MC) and dichorionic (DC) pregnancies, 14.8% and 29.6% of the MC pregnancies had structural anomalies in one or both fetuses (odds ratio = 5.774, 95% CI = 1.445-23.071, p = 0.01) and twin-specific complications (odds ratio = 4.379, 95% CI = 1.641-11.684, p = 0.03), respectively, compared to DC pregnancies with 2.9% for structural anomalies and 8.8% for twin-specific complications. The prevalence of abnormal fetal karyotypes was not statistically different in patients with INT when compared between MC and DC pregnancies (p = 0.329). INT was associated with a higher rate of twin-specific complications and fetal structural anomalies in MC twin pregnancies rather than abnormal fetal karyotype. Therefore, NT measurement in MC twin pregnancies can be a useful tool for predicting adverse pregnancy outcomes. Appropriate counseling and surveillance based on the chorionicity are imperative in the prenatal care of twin pregnancies.

The impacts of insufficient sleep and its change during pregnancy on postpartum depression: A prospective cohort study of Korean women.

OBJECTIVE: To determine the association between insufficient sleep in the prenatal period and postpartum depression (PPD), and whether changes in sleep patterns during pregnancy increase the risk of PPD. METHODS: A prospective cohort study was conducted between March 2013 and November 2017. Participants completed a sleep questionnaire pre-pregnancy and at 12, 24 and 36 gestational weeks (GW). Depressive symptoms were assessed by the Edinburgh Postnatal Depression Scale (EPDS) at 4 weeks postpartum, and the cut-off score for PPD was 10 or more. RESULTS: Of 2512 participants, 410 (16.3%) were identified as having PPD. Only insufficient sleep at 36 GW was significantly associated with PPD after adjusting for confounding factors (odds ratio 1.79, 95% confidence interval 1.40-2.27, P < 0.001). Both Group 1 (change from sufficient to insufficient) and Group 3 (sustained insufficient) demonstrated a significant risk of PPD at all starting time-points in the multivariate analysis, but no significant association was evident between Group 2 (change from insufficient to sufficient) and PPD. CONCLUSION: Insufficient sleep at 36 GW was associated with a significant risk of developing PPD. Additionally, regardless of whether women had sufficient sleep, a shift towards worsening sleep at 36 GW was highly associated with PPD.

Perinatal outcome of fetuses with congenital high airway obstruction syndrome: a single-center experience.

OBJECTIVE: To report our experience with management of fetuses with congenital high airway obstruction syndrome (CHAOS). METHODS: We retrospectively reviewed the cases of fetuses who were prenatally diagnosed and postnatally confirmed with CHAOS between 2010 and 2019 at Asan Medical Center, Seoul, Korea. RESULTS: Of 13 fetuses prenatally diagnosed with CHAOS, 7 were lost to follow-up and 6 were postnatally confirmed as having CHAOS. All fetuses, except one were delivered via cesarean section with an ex utero intrapartum treatment (EXIT) procedure. Two patients had coexisting congenital heart diseases requiring several cardiac surgeries following birth. Both of these patients demonstrated developmental delay; however, the remaining 4 had a normal development except for expressive language. Two infants died of respiratory complications, and the remaining 4 were alive at the end of the follow-up period. All 4 live patients underwent tracheostomy with planned reconstruction surgery. Three children are now able to phonate, and 1 can maintain a conservation. CONCLUSION: The proper management of CHAOS using the EXIT procedure results in high survival and low hypoxemia-induced complication rates. Therefore, an accurate prenatal diagnosis is necessary for an appropriate perinatal management.

The Korean Pregnancy Outcome Study (KPOS): Study Design and Participants.

BACKGROUND: The Korean Pregnancy Outcome Study (KPOS) was established to investigate the determinants of adverse pregnancy outcomes among Korean women. METHODS: We recruited 4,537 pregnant women between 2013 and 2017 from two tertiary centers located in Seoul, Korea, and a total of 4,195 Korean women met inclusion criteria in the baseline analysis. A range of data on socio-demographics, past medical histories, reproductive information, health-related behaviors, psychological health and clinical information were obtained using interviewer-based questionnaires and clinical assessment at 12, 24, and 36 gestational weeks (GW), delivery and 6-8 weeks postpartum. Blood samplings were performed at 12, 24 and 36 GW, and placental tissues were obtained after delivery. The main outcome of this study was pregnancy-related complications including gestational diabetes mellitus (GDM), gestational hypertension, and screening positive for peripartum depression. Depression was assessed using the Korean version of the Edinburgh Postnatal Depression Scale, and a score of ≥10 indicated a positive screen for depression. RESULTS: Among 4,195 eligible pregnant women with a median age of 33.0 years, 3,565 (85.0%) pregnancy outcomes were available in this study, including 30 miscarriages, 16 stillbirths, and 3,519 deliveries. Mean gestational age was 38.8 GW, and mean birth weight was 3,236 gram. The prevalence of pregnancy complications of GDM, hypertensive disorders, and screening positive of depression during pregnancy and postpartum was 7.0%, 1.4%, 27.8%, and 16.6%, respectively. CONCLUSIONS: We designed KPOS to identify the determinants of pregnancy-related outcomes, and it may provide effective strategies for the prevention of pregnancy complications in Korean pregnant women.

Height of elevated fetal buttock for prediction of successful external cephalic version.

OBJECTIVE: To increase the rate of successful external cephalic version (ECV) and to minimize the complications, it is important to identify the predictors of success. Therefore, the purpose of this study was to investigate whether the height of the elevated fetal buttock (HOB) is a valuable predictor of successful ECV or not. METHODS: This prospective study was conducted from August 2016 to June 2018. A total of 139 pregnant women with breech presentation were enrolled in the study. HOB from the maternal pubic symphysis was measured on ultrasonography. The predictability and cut-off value of HOB for successful ECV were evaluated. RESULTS: Among the 139 patients, 114 (82%) had successful ECV. The adjusted odds ratio for multiparity, amniotic fluid index (AFI) >14 cm, and HOB >7.8 cm were 10.80 (95% confidence interval [CI], 1.57-74.94), 5.26 (95% CI, 1.06-26.19), and 10.50 (95% CI, 1.03-107.12), respectively. Areas under the curve (AUCs) for AFI, HOB, and parity were 0.66 (95% CI, 0.54-0.78), 0.74 (95% CI, 0.64-0.85), and 0.69 (95% CI, 0.62-0.76), respectively. HOB had the largest AUC, but there were no significant differences among the AUCs of other factors. The cut-off value of HOB was 6 cm. CONCLUSION: This study showed that the AUC of HOB was greater than that of parity and AFI, although it was not statistically significant. As HOB is a noninvasive and comprehensive marker to predict successful ECV, consideration of HOB would be helpful before conducting ECV. Further studies are needed.

Treatment of gestational diabetes diagnosed by the IADPSG criteria decreases excessive fetal growth.

OBJECTIVE: We evaluated the effect on treatment using the new International Association of Diabetes and Pregnancy Study Group (IADPSG) criteria for gestational diabetes mellitus (GDM) diagnosis. METHODS: Singleton pregnant women whose plasma glucose levels were ≥140 mg/dL on the 50 g glucose challenge test (GCT) underwent 75 g oral glucose tolerance for GDM diagnosis. During the first half of the study period, GDM was diagnosed using 2 abnormal values by Carpenter-Coustan (C-C) criteria. In the second half of the study period, 1 or more abnormal values by IADPSG criteria were used for GDM diagnosis. Pregnant women were classified into 5 groups: normal 50 g GCT, positive 50 g GCT but non-GDM, GDM by IADPSG criteria and non-treated, GDM by IADPSG criteria and treated, GDM by C-C criteria and treated. The odds ratios (ORs) for large for gestational age (LGA) and macrosomia were analyzed. RESULTS: Of the 2,678 patients, the frequency of GDM diagnosed by C-C and IADPSG criteria was 2.6% and 7.5%. ORs (95% confidence intervals [CIs]) for LGA and macrosomia in the group with GDM by IADPSG criteria and non-treated were 2.81 (95% CI, 1.47-5.38) and 2.84 (95% CI, 1.08-7.47). The risk of LGA and macrosomia did not increase in the group with GDM by IADPSG criteria and treated. CONCLUSION: The risk of LGA and macrosomia for mild GDM diagnosed solely by IADPSG criteria depends on whether they are treated or not. Treatment of GDM based on IADPSG criteria reduces the risk of excessive fetal growth. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0000776.

Epigenome-wide base-resolution profiling of DNA methylation in chorionic villi of fetuses with Down syndrome by methyl-capture sequencing.

BACKGROUND: Epigenetic mechanisms provide an interface between environmental factors and the genome and are influential in various diseases. These mechanisms, including DNA methylation, influence the regulation of development, differentiation, and establishment of cellular identity. Here, we performed high-throughput methylome profiling to determine whether differential patterns of DNA methylation correlate with Down syndrome (DS). MATERIALS AND METHODS: We extracted DNA from the chorionic villi cells of five normal and five DS fetuses at the early developmental stage (12-13 weeks of gestation). Methyl-capture sequencing (MC-Seq) was used to investigate the methylation levels of CpG sites distributed across the whole genome to identify differentially methylated CpG sites (DMCs) and regions (DMRs) in DS. New functional annotations of DMR genes using bioinformatics tools were predicted. RESULTS: DNA hypermethylation was observed in DS fetal chorionic villi cells. Significant differences were evident for 4,439 DMCs, including hypermethylation (n = 4,261) and hypomethylation (n = 178). Among them, 140 hypermethylated DMRs and only 1 hypomethylated DMR were located on 121 genes and 1 gene, respectively. One hundred twenty-two genes, including 141 DMRs, were associated with heart morphogenesis and development of the ear, thyroid gland, and nervous systems. The genes were significantly associated with DS and various diseases, including hepatopulmonary syndrome, conductive hearing loss, holoprosencephaly, heart diseases, glaucoma, and musculoskeletal abnormalities. CONCLUSIONS: This is the first study to compare the whole-epigenome DNA methylation pattern of the chorionic villi cells from normal and DS fetuses at the early developmental-stage using MC-seq. Overall, our results indicate that the chorionic villi cells of DS fetuses are hypermethylated in all autosomes and suggested that altered DNA methylation may be a recurrent and functionally relevant downstream response to DS in human cells. This study provides basic information for future research focused on the pathophysiology of the DS and its potential effects, as well as the role DNA methylation plays in the early developmental stage of DS fetuses.

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).

Effective Fetal Epigenetic Biomarkers for Noninvasive Fetal Trisomy 21 Detections.

INTRODUCTION: Recently, we identified three novel fetal-specific epigenetic DNA regions (FSERs) on chromosome 21 for detection of noninvasive fetal trisomy 21 (T21). In this study, the diagnostic accuracies of the three FSERs were assessed on a larger panel of the first-trimester pregnant women. MATERIAL AND METHODS: This study was conducted with maternal plasma collected from 167 pregnant women carrying 155 chromosomally normal and 12 T21 fetuses (10-13 gestational weeks). Accuracies of FSERs for noninvasive prenatal test of fetal T21 were estimated by the area under the receiver operator characteristic curve (AUC). RESULTS: The levels of all FSERs increased in pregnant women with T21 fetuses when compared with controls (p < 0.001 for all). The levels of the three FSERs did not differ according to maternal age, body mass index, and fetal sex at maternal blood sampling (p > 0.05 for all). In noninvasive fetal T21 detection, the AUC of FSER1, FSER2, and FSER3 were 0.859 (95% CI: 0.746-0.972), 0.919 (95% CI: 0.856-0.982), and 0.868 (95% CI: 0.746-0.990), respectively. DISCUSSION: The findings of this study suggest that all FSERs may be useful for noninvasive fetal T21 detection, regardless of maternal age, body mass index, and fetal sex.

Cesarean scar pregnancy; Diagnosis and management between 2003 and 2015 in a single center.

OBJECTIVES: We aimed to evaluate diagnosis and management of an ectopic pregnancy developing in a previous cesarean scar. MATERIALS AND METHODS: Between March 2003 and October 2015, total 64 cases of cesarean scar pregnancy (CSP) were retrospectively reviewed. The cliniscal characteristics, diagnosis, various methods of treatment and clinical outcomes were analyzed. RESULTS: The mean gestational age at diagnosis was 6.5 ± 1.1 weeks and the number of previous cesarean section was 1.6 ± 0.6. The main ultrasonographic findings included anterior implantation of gestational sac within the previous CS scar and thinning of anterior myometrium (average: 3.0 ± 2.0 mm). Excluding 6 cases that were lost to follow up after diagnosis, 58 patients underwent first line treatment. The treatment was successful with first line therapy alone in 32 patients (55.2%). Emergency hysterectomy was necessary in 4 cases during following up of first line treatment. In 22 patients who underwent second line treatment, all of them were successfully treated with no additional treatment. CONCLUSIONS: MTX treatment alone as first line treatment showed low success rate (41.3%). Wedge resection (100%) and hysteroscopy (66.7%) were relatively safe and they were the most successful treatment modalities in this study. Dilatation and curettage as first and second line treatment had about 20% and 16.7% risk of emergency hysterectomy due to severe hemorrhage respectively. Therefore, surgical modalities with direct visualization excluding dilatation and curettage seem to be more safe and successful than medical treatment using MTX alone. Early precise diagnosis and management of CSP will be very important to minimize the extent of treatment and thus improve clinical outcomes of the patients.