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Intrapartum transperineal ultrasound is considered useful in judging fetal head descent; however, the inability to detect ischial spines on ultrasound images has been a drawback to its legitimacy. The current study aimed to determine the anatomical location of ischial spines, which can be directly applied to intrapartum transperineal ultrasound images. Based on magnetic resonance imaging (MRI) of 67 pregnant women at 33+2 [31+6-34+0] weeks gestation (median [interquartile range: IQR]), we calculated the angle between the pubic symphysis and the midpoint of ischial spines (midline symphysis-ischial spine angle; mSIA), which is theoretically equivalent to the angle of progression at fetal head station 0 on ITU, by determining spatial coordinates of pelvic landmarks and utilizing spatial vector analysis. Furthermore, we measured symphysis-ischial spine distance (SID), defined as the distance between the vertical plane passing the lower edge of the pubic symphysis and the plane that passes the ischial spines. As a result, mSIA was 109.6° [105.1–114.0] and SID 26.4 mm [19.8–30.7] (median, [IQR]). There was no correlation between mSIA or SID and maternal characteristics, including physique. We established a novel method to measure the components of the pelvic anatomy by analyzing the three-dimensional coordinates of MRI data and identified the anatomical location of ischial spines which can be applied to ultrasound images. Our results provide valuable evidence to enhance the reliability of intrapartum transperineal ultrasound in assessing fetal head descent by considering the location of ischial spines.

Background Adenomyosis is known to be associated with unfavorable perinatal outcomes, but the patient population among women with adenomyosis who is at high risk for adverse perinatal outcomes remains unclear. Recent case reports show that some women with adenomyosis experience pain at the adenomyosis lesion during pregnancy and have detrimental perinatal outcomes. However, the prevalence of pain onset in women with adenomyosis has not been studied, nor has its influence on perinatal outcomes. This study aimed to clarify the clinical characteristics of pain developing in adenomyosis lesions during pregnancy and the perinatal outcomes associated with this phenomenon. Methods This was a single-center retrospective analysis of a cohort of women with adenomyosis who delivered between 2011 and 2021. The incidence of pain onset at adenomyosis lesions among women with adenomyosis during pregnancy was analyzed retrospectively from medical records. Pain during pregnancy was defined as persistent pain at the adenomyosis site with administration of analgesics for pain relief, and its association with perinatal outcomes was analyzed. Results Among 91 singleton pregnancies with adenomyosis, 12 pregnancies (13.2%) presented with pain at the adenomyosis site during pregnancy. In total, 5 of the 12 pregnancies (41.7%) developed preeclampsia, which resulted in preterm delivery, and only 3 of the 12 pregnancies (25.0%) achieved term delivery. The incidence of preeclampsia and preterm delivery was higher in those who experienced pain than in those who did not (41.7% vs. 13.9%; p p p

Introduction Disturbance in placental epigenetic regulation contributes to the pathogenesis of preeclampsia (PE). Although aberrant placental DNA methylation status in PE has been thoroughly studied, the role of histone modifications, including histone methylation, in PE remains unclear. Moreover, no study has ever reported the association between PE and placental histone methylation status by focusing on histone methyltransferases. The present study aimed to investigate the possible involvement of placental epigenetic regulation by histone methylation via histone methyltransferases in the pathophysiology of PE. Methods Placental mRNA expression of histone methyltransferases was examined using quantitative RT-PCR. Protein expression of histone methyltransferases and histone methylation status in placentas and trophoblast cell lines were assessed by immunoblotting and immunohistochemistry. Results Expression profile of histone methyltransferases in the placentas using quantitative RT-PCR revealed that the mRNA expression levels of histone 3 lysine 4 (H3K4) methyltransferases, SETD1A and SMYD3, were significantly increased in placentas from PE patients. Immunoblotting and immunohistochemistry revealed that not only protein expression levels of SETD1A and SMYD3, but also H3K4 methylation status was increased in the trophoblasts from PE placentas. In vitro studies using HTR-8/SV-neo and BeWo cells showed that hypoxia induced the expression levels of SETD1A and SMYD3, and subsequently enhanced H3K4 methylation. Furthermore, the overexpression of SETD1A and SMYD3 in HTR-8/SV-neo cells enhanced H3K4 methylation in response to hypoxia. Discussion Our study results suggest that placental epigenetic alteration by enhanced histone H3K4 methylation through upregulated SETD1A and SMYD3 might play a role in the pathophysiological process of PE associated with hypoxia.

Since fetal presentation is an essential factor for planning mode of delivery, the estimation of fetal presentation at delivery is important in prenatal management. This study aimed to clarify the transition of fetal presentation during pregnancy and to propose practical strategy to predict final fetal presentation.During the period of 2 years, fetal presentations were analyzed using ultrasonography during the prenatal visits at and after 22 weeks of gestation in a single facility. The relationship between the transition of fetal presentation and final presentation at delivery was analyzed. Further, a prediction model was developed to predict the final fetal presentation at birth.Among 1737 singleton pregnancies with full-term delivery, non-cephalic delivery occurred in 76 pregnancies (4.4%). Non-cephalic presentation in later half of the gestational period was associated with low incidence of spontaneous cephalic version. Furthermore, we found that in 46% of women with a final non-cephalic delivery, the non-cephalic presentation continued during whole of the observational period without spontaneous cephalic version. Based on the analyzed data of this cohort, we show that in a group of women with non-cephalic presentation at 35/36 weeks, the best predictability for spontaneous cephalic version depended on whether the cephalic presentation was observed at least once at and after 30 weeks of gestation.Our findings suggest that information on the changes in fetal presentation during gestation contributes to the prediction of the fetal presentation at delivery and planning mode of delivery.

Objective To clarify the clinical characteristics of pain developing in adenomyosis lesions during pregnancy and the perinatal outcomes associated with this phenomenon. Study Design Retrospective cohort study. Setting A tertiary hospital in Japan. Patients and methods Ninety one singleton pregnancies with adenomyosis who delivered between 2011 and 2021 were retrospectively analyzed. Pain during pregnancy was defined as persistent pain at the adenomyosis site with analgesics administration, and its association with perinatal outcomes was analyzed. Main outcome measures Pain at the adenomyosis lesion and its onset and duration, maximum C-reactive protein level during pain, and perinatal outcomes such as preterm delivery, preeclampsia, and blood loss. Results Among 91 singleton pregnancies with adenomyosis, 12 pregnancies (13.2%) presented with pain at the adenomyosis site. In total, 5 of the 12 pregnancies (41.7%) developed preeclampsia, which resulted in preterm delivery. The incidence of preeclampsia and preterm delivery was higher in those who experienced pain than in those without (41.7% vs. 13.9%; p

Objective We experienced a case of 22q11.2 deletion syndrome (22qDS), with severe polyhydramnios, and dysphagia, which prompted us to review prognosis in neonates with 22qDS, with a focus on dysphagia. Case report A patient was referred to our hospital at 35 gestational weeks because of polyhydramnios. After amniotic fluid reduction, labor was induced at 38 weeks. The neonate had serious dysphagia, and 22qDS was diagnosed postnatally by fluorescent in situ hybridization analysis. This prompted a retrospective analysis of 9 cases with 22qDS experienced in our facility. Three out of these nine cases showed polyhydramnios, and had severe dysphagia postnatally. In total, 4 cases had dysphagia, while mortality was observed in 2 of these 4 cases. Additionally, 5 cases without dysphagia had normal development and no major complications. Conclusion Polyhydramnios associated with postnatal dysphagia might be a risk factor related to short-term prognostic outcomes in newborns with 22qDS.

Aim This study aimed at evaluating the additional anti-tumor effects of exogenous rVEGFR1 (sFlt1) on conventional chemotherapy in ovarian cancer cell lines. Methods We utilized cells from two ovarian cancer cell lines, SKOV3 and HeyA8, and treated them with a combination of rVEGFR1 (sFlt1) and carboplatin as well as rVEGFR1 (sFlt1) alone. First, we evaluated cell survival after treatment by using cell counting and MTS assays. Next, we performed Ki67 staining for evaluating the inhibitory effects of the treatment on cell proliferation, and a lactate dehydrogenase (LDH) assay for evaluating cytotoxicity. Finally, to determine whether MAP kinase signaling is involved in this process, we performed western blot analysis of extracellular signal-regulated kinase (ERK), phospho-ERK, c-jun n-terminal kinase (JNK) and phospho-JNK. Results The cytotoxic and growth-restriction effects were more pronounced in the group co-administered with rVEGFR1 (sFlt1) and carboplatin than in cells treated with either rVEGFR1 (sFlt1) or carboplatin alone. Quantitative analysis of Ki67-positive cells also showed a decreased proportion of Ki67-positive cells in SKOV3 cells treated with a combination of exogeneous rVEGFR1 (sFlt1) and carboplatin compared to that in cells treated with either rVEGFR1 (sFlt1) or carboplatin alone. In the LDH assay, we also found significantly enhanced cell toxicity from the combination therapy. Finally, western blotting analysis showed that the MAPK signaling pathway was not affected by sFlt1 treatment. Conclusion This study confirmed the additive effects of rVEGFR1 (sFlt1) combined with conventional chemotherapy for ovarian cancer growth in in vitro assays, thus suggesting the combination of rVEGFR1 (sFlt1) and carboplatin as a potential novel therapeutic option for ovarian cancer.

HELLP syndrome is sometimes followed by massive bleeding, leading to DIC. In cases of intra‐abdominal compartment syndrome due to massive intra‐abdominal bleeding after cesarean section, if preeclampsia and partial HELLP syndrome persist, hematoma removal helps in the recovery from preeclampsia and partial HELLP syndrome.

Recent evidence indicates that elevated placental adenosine signaling contributes to preeclampsia (PE). However, the molecular basis for the chronically enhanced placental adenosine signaling in PE remains unclear. Here, we report that hypoxia-inducible factor-1α (HIF-1α) is crucial for the enhancement of placental adenosine signaling. Utilizing a pharmacologic approach to reduce placental adenosine levels, we found that enhanced adenosine underlies increased placental HIF-1α in an angiotensin receptor type 1 receptor agonistic autoantibody (AT1 -AA)-induced mouse model of PE. Knockdown of placental HIF-1α in vivo suppressed the accumulation of adenosine and increased ecto-5'-nucleotidase (CD73) and adenosine A2B receptor (ADORA2B) in the placentas of PE mouse models induced by AT1 -AA or LIGHT, a TNF superfamily cytokine (TNFSF14). Human in vitro studies using placental villous explants demonstrated that increased HIF-1α resulting from ADORA2B activation facilitates the induction of CD73, ADORA2B, and FLT-1 expression. Overall, we demonstrated that (a) elevated placental HIF-1α by AT1 -AA or LIGHT upregulates CD73 and ADORA2B expression and (b) enhanced adenosine signaling through upregulated ADORA2B induces placental HIF-1α expression, which creates a positive feedback loop that promotes FLT-1 expression leading to disease development. Our results suggest that adenosine-based therapy targeting the malicious cycle of placental adenosine signaling may elicit therapeutic effects on PE.

Loeys-Dietz syndrome (LDS) is a connective tissue disorder with a high incidence of aortic dissection (AD). After treating two previously reported cases of postpartum AD in women with LDS following prophylactic aortic root replacement (ARR), we succeeded in managing a 30-year-old primigravida with no AD during her peripartum period. On the basis of the patient's stated desire to conceive during preconception counseling, a multidisciplinary team was assembled. She conceived naturally after receiving prophylactic ARR and beta-blocker treatment. Multidisciplinary patient care included precise blood pressure management, continuation of beta-blocker treatment, cardiovascular assessment with echocardiogram, regional anesthesia during labor, prevention of lactation, and resumption of angiotensin II receptor blocker therapy immediately after delivery. On the basis of our assessment of three cases, including this case, and a literature review, we propose a peripartum management strategy for patients with LDS following prophylactic ARR.

No previous study has evaluated the transitions of intrapartum transperineal ultrasound parameters during labor progression in cephalic malposition.We aimed to quantitate the characteristic trends of fetal head position and descent in cephalic malposition by analyzing the transitions of intrapartum transperineal ultrasound parameters and explore an indicator associated with the degree of cephalic malposition.We retrospectively analyzed pregnant women who delivered at term from January 2018 to December 2020 at the University of Tokyo Hospital. The fetal occipital position was classified as occiput anterior and nonocciput anterior according to the fetal occipital angle of 0° to 75° and 75° to 180°, respectively. Fetal occipital angle was defined by the midline angle and position of the ocular orbit. The differences in the trends of head direction, head-symphysis distance, and progression distance relative to the angle of progression between occiput anterior and nonocciput anterior cases were evaluated. In addition, the parameters that showed differences were analyzed to evaluate their relationship to the degree of cephalic malposition.A total of 502 images (occiput anterior, 319; nonocciput anterior, 183) met the inclusion criteria. The distribution of head direction values relative to the angle of progression was smaller in the nonocciput anterior group than in the occiput anterior group, whereas the head-symphysis distance and progression distance values relative to the angle of progression showed no difference in their distribution between the occiput anterior and nonocciput anterior groups. The ratio of head direction to the angle of progression was significantly smaller in the nonocciput anterior group than in the occiput anterior group (median [interquartile range], 0.03 [-0.02 to 0.10] vs 0.21 [0.12-0.28]; P.0001). Furthermore, this ratio was negatively correlated with fetal occipital angle (Spearman correlation coefficient, -0.66).Our results indicated that the head direction to angle of progression ratio reflects the deviation in the fetal head direction toward the maternal dorsal side, and decreases in proportion to the degree of cephalic malposition. This concept of deviation in the head direction as an indicator for evaluating cephalic malposition with intrapartum transperineal ultrasound may contribute to improving labor management in the case of cephalic malposition.

We aimed to assess the impact of fetal growth restriction (FGR) as a diagnostic criterion for preeclampsia (PE) on the severity of maternal preeclamptic features by comparing it with other diagnostic criteria for PE, maternal organ dysfunction.We performed a retrospective cohort study of singleton pregnancies. Based on the status at diagnosis, PE cases preceded by FGR without maternal organ dysfunction (Group F; n = 28) and those preceded by maternal organ dysfunction without FGR (Group M; n = 87) were analyzed.Group F had an earlier PE diagnosis (32.5 ± 4.9 vs. 36.7 ± 3.5 weeks, p 0.01) and delivery (33.7 ± 4.5 vs. 37.5 ± 3.1 weeks, p 0.01) than Group M. No significant differences in maternal morbidities were observed between the groups, including severe hypertension (75.0 vs. 60.0%), need for intravenous antihypertensives (42.9 vs. 48.3%) or magnesium sulfate (60.7 vs. 54.5%), or a composite of major maternal complications (17.9 vs. 21.8%). When limited to early-onset PE diagnosed before 34 weeks of gestation (17 and 17 cases in Group F and M, respectively), the frequencies of maternal morbidities (severe hypertension: 70.6 vs. 52.9%, intravenous antihypertensives: 35.3 vs. 35.3%, magnesium sulfate: 58.8 vs. 47.1%, major complications: 29.4 vs. 23.5%) and the duration from diagnosis until delivery (11.2 ± 14.7 vs. 16.5 ± 21.7 days) were comparable between two groups.Our results suggest that the presence of FGR on PE diagnosis is associated with the development of severe maternal symptoms as much as that of maternal organ dysfunction at diagnosis, and it may be reasonable to include FGR in PE diagnostic criteria.

Preeclampsia (PE) is a hypertensive obstetric disorder with poor prognosis for both the mother and offspring. Infants born to mothers with PE are known to be at increased risk of developing higher brain dysfunction, such as autism. However, how maternal PE can affect the environment in the fetal brain has not been fully elucidated. Here, we examined the impact of PE on the fetal brain in a mouse model of PE induced by angiotensin II (Ang II), focusing on changes in the inflammatory condition. We confirmed that pregnant mice which were continuously administered Ang II exhibited PE phenotypes, including high blood pressure, proteinuria, and fetal growth restriction. Quantitative RT-PCR analysis demonstrated that the brain of fetuses on embryonic day 17.5 (E17.5) in the Ang II-administered pregnant mice showed increased expression of cytokines, interleukin (IL)- 6, IL-17a, tumor necrosis factor-α, interferon-γ, IL-12, IL-4, and IL-10. Immunohistochemical analysis over a wide area, from the tip of the frontal lobe to the posterior cerebral end, on E17.5 revealed that the microglia in the fetal brain of the Ang II-administered group displayed higher solidity and circularity than those of the control group, indicating that the microglia had transformed to an amoeboid morphology and were activated. Our findings suggest that maternal PE may cause altered inflammatory conditions in the fetal brain, which might be associated with the pathological mechanism connecting maternal PE and brain dysfunction in the offspring.

Objectives: To investigate the spontaneous outcomes of vascularized retained products of conception (RPOC) detected by ultrasonography after second-trimester abortion, and to identify the predictiv...

The disruption of adaptive immune response has adverse effects on the establishment and maintenance of pregnancy. The adaptive immune system is regulated by several types of immune cells. However, there is limited information about cell hierarchy in the adaptive immune response to the establishment and maintenance of pregnancy in women. The assessment of the outcome of pregnancy in primary immunodeficiency diseases could help in understanding the cell hierarchy in the adaptive immune system during pregnancy. Common variable immunodeficiency (CVID) is a heterogeneous adaptive immune system disorder characterized by primary hypogammaglobulinemia. A few studies have previously reported the assessment of the T and B cell subpopulations in CVID patients. However, an assessment of the subpopulations of T and B cells and the outcome of pregnancy in women with CVID has not been reported till date. Most CVID patients show a general decrease in the expression of CD27 in B cells. The assessment of pregnancy and the subpopulations of T and B cells in CVID women with severe reduction in the naive T and switched B cells could help understand whether these cells are essential for the establishment and maintenance of pregnancy in women.

Placental dysfunction triggers fetal growth restriction in congenital human cytomegalovirus (HCMV) infection. Studies suggest that HCMV infection interferes with the differentiation of human trophoblasts. However, the underlying mechanisms have not been clarified. This study investigated the impact of HCMV infection on gene transcriptomes in cytotrophoblasts (CTBs) associated with placental dysfunction.CTBs were isolated from human term placentas, and spontaneous syncytialization was observed in vitro. The transcriptome profiles were compared between CTB groups with and without HCMV infection by cap analysis gene expression sequencing. The effect of HCMV infection on trophoblast differentiation was evaluated by examining cell fusion status using immunocytochemical staining for desmoplakin and assessing the production of cell differentiation markers, including hCG, PlGF, and soluble Flt-1, using ELISA.The expression of the genes categorized in the signaling pathways related to the cell cycle was significantly enhanced in CTBs with HCMV infection compared with uninfected CTBs. HCMV infection hindered the alteration of the gene expression profile associated with syncytialization. This suppressive effect under HCMV infection was concurrent with the reduction in hCG and PlGF secretion. Immunostaining for desmoplakin revealed that HCMV infection reduced the cell fusion of cultured CTBs. These findings imply that HCMV infection has a negative impact on syncytialization, which is indispensable for the maintenance of villous function.HCMV infection interferes with gene expression profiles and functional differentiation of trophoblasts. Suppression of syncytialization may be a survival strategy for HCMV to expand infection and could be associated with placental dysfunction.

Pulmonary hypoplasia is a rare entity in a fetus with imperforate anus. The fetus was diagnosed with high-type imperforate anus with rectourethral fistula based on the dilated fetal bowel and the presence of bowel calcification at 19 weeks of gestation. As gestation advanced, fetal ultrasonography demonstrated development of pulmonary hypoplasia, progressive bowel dilation, and persistent oligohydramnios from 28 weeks of gestation despite a fluid-filled bladder without hydroureter or hydronephrosis. To prevent further worsening of pulmonary hypoplasia caused by thoracic compression due to bowel dilation and oligohydramnios, a male neonate was delivered by cesarean section at 32 weeks of gestation. The neonate showed respiratory failure requiring full respiratory support. Although a catheter did not pass through the urethra into the bladder at birth, cystourethrography revealed the patency of fistula and stenosed lower urinary tract. Prenatal and postnatal findings strongly suggested that the meconium in the colon might have passed into the urethra in the penis, resulting in the physical blockage of urine outflow to the amniotic space which leads urine flow from the bladder to the colon through the fistula, which resulted in subsequent oligohydramnios and bowel dilation. To the best of our knowledge, this is the first case report of a fetus with imperforate anus developing pulmonary hypoplasia possibly due to urethral obstruction.

This chapter deals with the contribution of regulatory T cells (Tregs) in maintaining the immunological balance during pregnancy. We discuss the discovery of Treg cells and their role in a healthy pregnancy, in rodents and humans. We describe the relationship between obstetrical complications such as preeclampsia and Tregs function. We emphasize the relationship between pregnancy and autoimmune diseases and discuss the critical role that Tregs play in the progress of the autoimmune disease during pregnancy.

Two prospective multicenter studies demonstrated that a soluble fms-like tyrosine kinase 1 (sFlt-1)/placental growth factor (PlGF) ratio cutoff of ≤38 can rule out preeclampsia within 1 week with a negative predictive value (NPV) of 99.3% (PROGNOSIS) and 98.6% (PROGNOSIS Asia). We report a subanalysis of the Japanese cohort from the PROGNOSIS Asia study. Pregnant women with suspected preeclampsia between gestational weeks 18 + 0 days and 36 + 6 days were enrolled at eight Japanese sites. Primary objectives: Assess the performance of the Elecsys® sFlt-1/PlGF ratio cutoff ≤38 to rule out preeclampsia within 1 week and of the cutoff >38 to rule in preeclampsia within 4 weeks. Key secondary objectives: Prediction of maternal and fetal adverse outcomes (MAOs/FAOs) and their relationship with duration of pregnancy. Of 192 women enrolled, 180 (93.8%)/175 (91.1%) were evaluable for primary/combined endpoint analyses. Overall preeclampsia prevalence was 13.3%. A sFlt-1/PlGF ratio of ≤38 provided an NPV of 100% (95% confidence interval [CI], 97.5–100) for ruling out preeclampsia within 1 week, and a ratio of >38 provided a positive predictive value of 32.4% (95% CI, 18.0–49.8) for ruling in preeclampsia within 4 weeks. The area under the curve for the prediction of preeclampsia/maternal/fetal adverse outcomes within 1 week was 94.2% (95% CI, 89.3–97.8). After adjusting for gestational age and final preeclampsia status, Cox regression indicated a 2.8-fold greater risk of imminent delivery for women with a sFlt-1/PlGF ratio >38 versus ≤38. This subanalysis of Japanese women with suspicion of preeclampsia showed high predictive value for a Elecsys sFlt-1/PlGF ratio cutoff of 38 for short-term prediction of preeclampsia.

Previous studies have reported that congenital heart diseases (CHDs) develop in patients with genetic and environmental predisposition. Compared to CHDs, the significance of hereditary factors in the pathogenesis of congenital venous system anomalies remains unclear. Additionally, reports describing the pathogenic relationship between venous system anomalies and increased nuchal translucency (NT) are few. We report sibling recurrence of congenital venous system anomalies. In the prenatal periods of both siblings, increased NT without aneuploidy was confirmed. In the first sibling, the absence of ductus venosus (ADV) and umbilical vein-coronary sinus anastomosis was detected using prenatal ultrasonography. In the second sibling, abnormality of the pulmonary vein was suspected prenatally, leading to a final diagnosis of infracardiac total anomalous pulmonary venous return (TAPVR). This is the first report of extracardiac venous anomaly-associated recurrence of increased NT among siblings. We conclude that a hereditary factor may be responsible for the development of ADV and TAPVR.