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

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

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.

A case report of torsion of the gravid uterus caused by pelvic adhesion.

Key Clinical Message: In this case, a patient experienced rare uterine torsion during pregnancy, detected by MRI. Diagnosis before Cesarean is helpful to achieve better outcomes, highlighting the importance of attention in high-risk groups. Abstract: Uterine torsion during pregnancy is a rare complication and its risk factors and diagnostic modalities have not yet been clearly defined. Here we present a case of uterine torsion due to unexpected pelvic adhesion. A 34-years-old primigravida patient underwent an emergency cesarean section for aggravated maternal preeclampsia symptoms at 34 + 0 weeks of gestation. Intraoperatively, after the baby was out, it was found that the uterus was rotated about 90 degrees to the right by dense pelvic adhesion in posterior uterine wall. In this patient, a rightward vaginal stretch was represented through a retrospective review of magnetic resonance imaging (MRI) before childbirth. To our knowledge, this is the first reported case of uterine torsion during pregnancy with MRI. Diagnosing uterine torsion in advance or paying attention to incisions during operative delivery will lead to better management in this condition and good perinatal outcomes.

Leukotriene B4 Receptor 2 Mediates the Production of G-CSF That Plays a Critical Role in Steroid-Resistant Neutrophilic Airway Inflammation.

Granulocyte colony-stimulating factor (G-CSF) has been suggested to be closely associated with neutrophilic asthma pathogenesis. However, little is known about the factors regulating the production of G-CSF in neutrophilic asthma. We previously reported that a leukotriene B4 receptor 2, BLT2, played an important role in neutrophilic airway inflammation. Therefore, in the current study, we investigated whether BLT2 plays a role in the production of G-CSF in lipopolysaccharide/ovalbumin (LPS/OVA)-induced steroid-resistant neutrophilic asthma. The data showed that BLT2 critically mediated G-CSF production, contributing to the progression of neutrophilic airway inflammation. We also observed that 12-lipoxygenase (12-LO), which catalyzes the synthesis of the BLT2 ligand 12(S)-HETE, was also necessary for G-CSF production. Together, these results suggest that the 12-LO-BLT2-linked signaling network is critical for the production of G-CSF, contributing to the development of neutrophilic airway inflammation. Our findings can provide a potential new target for the therapy of severe neutrophilic asthma.

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.

Insufficient weight management in pregnant women with gestational diabetes mellitus.

OBJECTIVES: This study investigated whether weight was managed appropriately in pregnant women with gestational diabetes mellitus (GDM) and examined the association between insufficient gestational weight gain (GWG) and adverse pregnancy outcomes. METHODS: The study included 235 pregnant women with GDM from the Korean Pregnancy Outcome Study. GWG from the second to the third trimester (kg/wk) and total GWG (kg) were classified as insufficient, appropriate, or excessive according to the 2009 Institute of Medicine guidelines. Adverse pregnancy outcomes included maternal (hypertensive disorders of pregnancy, preterm birth, cesarean delivery, and delivery complications) and infant (low birth weight, high birth weight, neonatal intensive care unit admission, and congenital anomalies) outcomes. RESULTS: The proportion of pregnant women with GDM who had insufficient GWG from the second to the third trimester was 52.3%, and that of participants with total insufficient GWG was 48.1%. There were no significant associations between insufficient GWG from the second to the third trimester and adverse pregnancy outcomes. Participants with total insufficient GWG had a significantly lower risk of preterm birth (odds ratio [OR], 0.17; 95% confidence interval [CI], 0.05-0.60) and high birth weight (OR, 0.23; 95% CI, 0.07-0.80). CONCLUSION: Our findings suggest the importance of appropriate weight management and the need for GWG guidelines for pregnant women with GDM.

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

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

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.

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.

Contributory Role of BLT2 in the Production of Proinflammatory Cytokines in Cecal Ligation and Puncture-Induced Sepsis.

BLT2 is a low-affinity receptor for leukotriene B4, a potent lipid mediator of inflammation generated from arachidonic acid via the 5-lipoxygenase pathway. The aim of this study was to investigate whether BLT2 plays any role in sepsis, a systemic inflammatory response syndrome caused by infection. A murine model of cecal ligation and puncture (CLP)-induced sepsis was used to evaluate the role of BLT2 in septic inflammation. In the present study, we observed that the levels of ligands for BLT2 (LTB4 [leukotriene B4] and 12(S)-HETE [12(S)-hydroxyeicosatetraenoic acid]) were significantly increased in the peritoneal lavage fluid and serum from mice with CLP-induced sepsis. We also observed that the levels of BLT2 as well as 5-LO and 12-LO, which are synthesizing enzymes for LTB4 and 12(S)-HETE, were significantly increased in lung and liver tissues in the CLP mouse model. Blockade of BLT2 markedly suppressed the production of sepsis-associated cytokines (IL-6 [interleukin-6], TNF-α [tumor necrosis factor alpha], and IL-1ß [interleukin-1ß] as well as IL-17 [interleukin-17]) and alleviated lung inflammation in the CLP group. Taken together, our results suggest that BLT2 cascade contributes to lung inflammation in CLP-induced sepsis by mediating the production of inflammatory cytokines. These findings suggest that BLT2 may be a potential therapeutic target for sepsis patients.

Leukotriene B4 receptor-2 contributes to KRAS-driven lung tumor formation by promoting interleukin-6-mediated inflammation.

Although lung cancer is the leading cause of cancer-related deaths worldwide and KRAS is the most frequently mutated oncogene in lung cancer cases, the mechanism by which KRAS mutation drives lung cancer has not been fully elucidated. Here, we report that the expression levels of leukotriene B4 receptor-2 (BLT2) and its ligand-producing enzymes (5-LOX, 12-LOX) were highly increased by mutant KRAS and that BLT2 or 5-/12-LOX blockade attenuated KRAS-driven lung cell proliferation and production of interleukin-6 (IL-6), a principal proinflammatory mediator of lung cancer development. Next, we explored the roles of BLT2 and 5-/12-LOX in transgenic mice with lung-specific expression of mutant KRAS (KrasG12D) and observed that BLT2 or 5-/12-LOX inhibition decreased IL-6 production and tumor formation. To further determine whether BLT2 is involved in KRAS-driven lung tumor formation, we established a KrasG12D/BLT2-KO double-mutant mouse model. In the double-mutant mice, we observed significantly suppressed IL-6 production and lung tumor formation. Additionally, we observed high BLT2 expression in tissue samples from patients with KrasG12D-expressing lung adenocarcinoma, supporting the contributory role of BLT2 in KRAS-driven human lung cancer. Collectively, our results suggest that BLT2 is a potential contributor to KRAS-driven lung cancer and identify an attractive therapeutic target for KRAS-driven lung cancer.

Leukotriene B4 Receptors Are Necessary for the Stimulation of NLRP3 Inflammasome and IL-1ß Synthesis in Neutrophil-Dominant Asthmatic Airway Inflammation.

The stimulation of the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome and IL-1ß synthesis are associated with chronic respiratory diseases such as neutrophil-dominant severe asthma. Leukotriene B4 (LTB4) is a principal chemoattractant molecule for neutrophil recruitment, and its receptors BLT1 and BLT2 have been suggested to contribute to neutrophil-dominant asthmatic airway inflammation. However, the relationship between BLT1/2 and NLRP3 in neutrophil-dominant asthmatic airway inflammation has not been previously studied. In the present study, we investigated whether BLT1/2 play any roles in stimulating the NLRP3 inflammasome and IL-1ßsynthesis. The blockade of BLT1 or BLT2 clearly suppressed the stimulation of the NLRP3 inflammasome and IL-1ß synthesis in house dust mite (HDM)/lipopolysaccharide (LPS)-induced neutrophilic airway inflammation. The enzymes 5-lipoxygenase and 12-lipoxygenase, which catalyze the synthesis of BLT1/2 ligands [LTB4, 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE), and 12-hydroxyheptadecatreinoic acid (12-HHT)], were also critically associated with the stimulation of NLRP3 and IL-1ß synthesis. Together, our results suggest that the 5-/12-LOX-BLT1/2-linked cascade are necessary for the simulation of the NLRP3 inflammasome and IL-1ß synthesis, thus contributing to HDM/LPS-induced neutrophil-dominant airway inflammation.

Leukotriene B4 receptors contribute to house dust mite-induced eosinophilic airway inflammation via TH2 cytokine production.

Leukotriene B4 (LTB4) is a lipid mediator of inflammation that is generated from arachidonic acid via the 5-lipoxygenase pathway. Previous studies have reported that the receptors of LTB4, BLT1, and BLT2 play mediatory roles in the allergic airway inflammation induced by ovalbumin (OVA). However, considering that house dust mites (HDMs) are the most prevalent allergen and well-known risk factor for asthmatic allergies, we are interested in elucidating the contributory roles of BLT1/2 in HDMinduced allergic airway inflammation. Our aim in this study was to investigate whether BLT1/2 play any roles in HDM-induced allergic airway inflammation. In this study, we observed that the levels of ligands for BLT1/2 [LTB4 and 12(S)-HETE (12(S)- hydroxyeicosatetraenoic acid)] were significantly increased in bronchoalveolar lavage fluid (BALF) after HDM challenge. Blockade of BLT1 or BLT2 as well as of 5-lipoxygenase (5-LO) or 12-lipoxygenase (12-LO) markedly suppressed the production of TH2 cytokines (IL-4, IL-5, and IL-13) and alleviated lung inflammation and mucus secretion in an HDM-induced eosinophilic airway-inflammation mouse model. Together, these results indicate that the 5-/12-LO-BLT1/2 cascade plays a role in HDMinduced airway inflammation by mediating the production of TH2 cytokines. Our findings suggest that BLT1/2 may be a potential therapeutic target for patients with HDM-induced allergic asthma. [BMB Reports 2021; 54(3): 182-187].

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.

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.

Leukotriene B4 receptors play critical roles in house dust mites-induced neutrophilic airway inflammation and IL-17 production.

Increased levels of neutrophils in bronchoalveolar lavage fluid (BALF) were associated with asthma severity. As leukotriene B4 (LTB4) is a principal chemoattractant molecule for neutrophils, its receptors, BLT1 and BLT2, may contribute to neutrophil-dominant airway inflammation. In the present study, we established a mouse model of steroid-resistant, neutrophil-dominant airway inflammation by house dust mite (HDM)/lipopolysaccharide (LPS) sensitization and HDM challenge, and we investigated whether BLT1/BLT2 signaling was associated with the development of neutrophilic airway inflammation. Blockade of BLT1 or BLT2 significantly suppressed airway inflammation and IL-17 production in this mouse model. The 5-LO and 12-LO enzymes, which catalyze the synthesis of BLT1/BLT2 ligands, were also critically associated with neutrophil-dominant airway inflammation and the synthesis of IL-17. Collectively, our results suggest that the 5-/12-LO-BLT1/BLT2-linked cascade significantly contributes to neutrophil-dominant severe airway inflammation via IL-17 synthesis in HDM-induced neutrophilic asthma.

Epigenome-wide DNA methylation profiling of preeclamptic placenta according to severe features.

BACKGROUND: Preeclampsia (PE) is an obstetric disorder with significant morbidities for both the mother and fetus possibly caused by a failure of the placental trophoblast invasion. However, its pathophysiology largely remains unclear. Here, we performed DNA methylation profiling to determine whether differential patterns of DNA methylation correlate with PE and severe features of PE. MATERIALS AND METHODS: We extracted DNA from placental tissues of 13 normal, five PE, and eight PE pregnant women with severe features. Genome-wide DNA methylation analysis was performed using the Illumina HumanMethylation 850K BeadChip. New functional annotations of differentially methylated CpGs (DMCs) in PE were predicted using bioinformatics tools. RESULTS: Significant differences were evident for 398 DMCs, including 243 DMCs in PE and 155 DMCs in PE with severe features, compared with normal placental tissues. Of these, 12 hypermethylated DMCs and three hypomethylated DMCs were observed in both PE groups, thus were independent from severe features. Three hundred seventy-nine DMCs were identified by the presence or absence of severe features. Two hundred genes containing these DMCs were associated with developmental processes and cell morphogenesis. These genes were significantly associated with various PE complications such as disease susceptibility, viral infections, immune system diseases, endocrine disturbance, seizures, hematologic diseases, and thyroid diseases. CONCLUSIONS: This is the first study to investigate the genome-scale DNA methylation profiles of PE placentas according to severe features. The epigenetic variation in the placentas probably resulted in altered developmental processes and immune dysregulation, contributing to PE. This study provides basic information to refine the clinical and pathological mechanisms of the severe features in placenta-mediated PE.

Maternal total cell-free DNA in preeclampsia with and without intrauterine growth restriction.

Elevation of total cell-free DNA (cfDNA) in patients with preeclampsia is well-known; however, whether this change precedes the onset of symptoms remains inconclusive. Here, we conducted a nested case-control study to determine the elevation of cfDNA levels in women who subsequently developed preeclampsia. Methylated HYP2 (m-HYP2) levels were determined in 68 blood samples collected from women with hypertensive disorders of pregnancy, along with 136 control samples, using real-time quantitative PCR. The measured m-HYP2 levels were converted to multiples of the median (MoM) values for correction of maternal characteristics. The m-HYP2 levels and MoM values in patients with preeclampsia were significantly higher than in controls during the third trimester (P < 0.001, both), whereas those for women who subsequently developed preeclampsia did not differ during the second trimester. However, when patients with preeclampsia were divided based on the onset-time of preeclampsia or 10th percentile birth weight, both values were significantly higher in women who subsequently developed early-onset preeclampsia (P < 0.05, both) and preeclampsia with small-for-gestational-age (SGA) neonate (P < 0.01, both) than controls. These results suggested that total cfDNA levels could be used to predict early-onset preeclampsia or preeclampsia with SGA neonate.

Effect of Cervical Cerclage on the Risk of Recurrent Preterm Birth after a Twin Spontaneous Preterm Birth.

BACKGROUND: This study aimed to evaluate the effect of cervical cerclage on the recurrence risk for preterm birth in singleton pregnant women after a twin spontaneous preterm birth (sPTB). METHODS: This multicenter retrospective cohort study included women who had a singleton pregnancy from January 2009 to December 2018 at 10 referral hospitals and a twin sPTB before the current pregnancy. We compared the cervical lengths during pregnancy and pregnancy outcomes, according to the placement of prophylactic or emergency cerclage. We evaluated the independent risk factors for sPTB (< 37 weeks of gestation) in a subsequent singleton pregnancy. RESULTS: For the index singleton pregnancy, preterm birth occurred in seven (11.1%) of 63 women. There was no significant difference in the cervical lengths during pregnancy in women with and without cerclage. In a multivariate logistic regression analysis, the placement of emergency cerclage was an independent risk factor for subsequent singleton preterm birth (odds ratio [OR], 93.188; 95% confidence interval [CI], 1.633-5,316.628; P = 0.027); however, the placement of prophylactic cerclage (OR, 19.264; 95% CI, 0.915-405.786; P = 0.057) was not a factor. None of the women who received prophylactic cerclage delivered before 35 weeks' gestation in the index singleton pregnancy. CONCLUSION: Cerclage did not lower the risk of preterm birth in a subsequent singleton pregnancy after a twin sPTB. However, emergency cerclage was an independent risk factor for preterm birth and there was no preterm birth before 35 weeks' gestation in the prophylactic cerclage group. Therefore, close monitoring of the cervical length and prophylactic cerclage might be considered in women who have experienced a twin sPTB at extreme gestation.

Reliability of strain elastography using in vivo compression in the assessment of the uterine cervix during pregnancy.

Objective To determine the reproducibility of the mean strain value in various cervical areas and new elastographic parameters for measuring cervical stiffness evaluated by strain elastography using in vivo compression generated by internal organ movement. Methods A prospective observational study (140 singleton pregnant women; 15-33 weeks of gestation) was performed at two tertiary centers. Cervical strain was evaluated using E-cervix™ elastography. The mean strain levels of various cervical areas [internal os (IOS), external os (EOS) and endocervical area] and several new parameters [i.e. the ratio of the strain level of IOS and EOS, elasticity contrast index (ECI), and hardness ratio] were assessed twice by two independent examiners. The inter-observer and intra-observer variances were calculated using the intraclass correlation coefficient (ICC) with a 95% confidence interval (CI). Bland-Altman (B-A) analysis was also performed. Results The median gestational age was 24.0 weeks, and the mean cervical length (CL) was 3.8 cm. The intra-observer and inter-observer ICCs of the mean strain levels of the specified cervical area and new elastographic parameters were statistically significant (P < 0.001, all); the intra-observer ICC was 0.639-0.725, and the inter-observer ICC was 0.538-0.718. Conclusion The reproducibility of elastographic parameter measurements using in vivo compression is improvable.