高橋 宏典

OBJECTIVE: To investigate whether conisation increases chorioamnionitis (CAM) and assess whether this risk differs between preterm and term periods. Furthermore, we estimated mediation effects of CAM between conisation and preterm birth (PTB). DESIGN: A nationwide observational study. SETTING: Japan. POPULATION: Singleton pregnant women derived from the perinatal registry database of the Japan Society of Obstetrics and Gynaecology between 2013 and 2019. METHODS: The association between a history of conisation and clinical CAM was examined using a multivariable logistic regression model with multiple imputation. We conducted mediation analysis to estimate effects of CAM on PTB following conisation. MAIN OUTCOME MEASURES: Clinical CAM. RESULTS: Of 1 500 206 singleton pregnant women, 6961 (0.46%) underwent conisation and 1 493 245 (99.5%) did not. Clinical CAM occurred in 150 (2.2%) and 11 484 (0.8%) women with and without conisation, respectively. Conisation was associated with clinical CAM (odds ratio [OR] 3.09; 95% confidence interval (CI) 2.63-3.64; p < 0.001) (risk difference 1.57%; 95% CI 1.20-1.94). The association was detected among 171 440 women with PTB (OR 3.09; 95% CI 2.57-3.71), whereas it was not significant among 1 328 284 with term birth (OR 0.88; 95% CI 0.58-1.34). OR of total effect of conisation on PTB was 2.71, OR of natural indirect effect (effect explained by clinical CAM) was 1.04, and OR of natural direct effect (effect unexplained by clinical CAM) was 2.61. The proportion mediated was 5.9%. CONCLUSIONS: Conisation increased CAM occurrence. Obstetricians should be careful regarding CAM in women with conisation, especially in preterm period. Bacterial infections may be an important cause of PTB after conisation.

Retained products of conception(RPOC)は,流産や分娩後に絨毛,胎盤組織が子宮内に残存する状態を指し,癒着胎盤と関連している。ARTは癒着胎盤のリスク因子の1つだが,ARTによる妊娠において,その分娩後に形成されたRPOCの臨床的特徴は十分に分かっていない。今回,2006年1月～2021年6月の間に,当院において分娩後に形成されたRPOCをARTで妊娠した群(ART妊娠:21症例)とART以外で妊娠した群(非ART妊娠:38症例)とに分け,後方視的に比較検討した。帝王切開既往,分娩週数,胎盤用手剥離,分娩時出血量,輸血は,ART妊娠と非ART妊娠で有意差を認めなかったが,RPOC消失までの期間はART妊娠で有意に長かった(P=0.015)。ART妊娠で形成されるRPOCは非ART妊娠のそれとは自然史が異なる可能性があり,さらなる検討を要する。(著者抄録)

Assisted reproductive technology (ART) requires transvaginal oocyte retrieval (TVOR), and ovarian bleeding after TVOR rarely occurs. We present a case of a 37-year-old woman (0-gravida) who was diagnosed with possible hemorrhagic telangiectasia (HHT) and had a history of three laparotomies for ovarian bleeding and an inclusion cyst adjacent to the right ovary after the third operation. HHT is a hereditary disease characterized by spontaneous hemorrhage of some organs, such as the nose, brain, lungs, gastrointestinal tract, and liver. She desired ART after fertility treatment and then had abdominal pain with ovarian swelling five days after TVOR. Moreover, both the right ovary and inclusion cyst were gradually swollen with hematoma. Finally, abdominal pain and the hemoglobin level deteriorated, necessitating an emergency surgery on the eighth day. We notify reproductive physicians that patients with HHT may readily develop ovarian bleeding with or without inclusion cysts after TVOR, although inclusion cysts may also be associated with late-onset bleeding.

Some specialties require publishing a paper as a prerequisite for becoming a Japanese Medical Specialty Board Specialist. Taking obstetrics and gynecology as an example, we wish to describe some concerns about this. Time limitations oblige residents to publish papers in non-PubMed journals with smaller circulations. Once data have been published, later attempts at secondary publication are difficult. This may bury some important data. Requiring an English presentation and writing an English abstract as a prerequisite for a board specialty may be an option to avoid this. Although we believe that the experience of publishing a paper during residency is important, how to deal with this issue needs further consideration.

INTRODUCTION: Placental abruption is a serious complication, especially when accompanied by intrauterine fetal death. The optimal delivery route for placental abruption with intrauterine fetal death for reducing maternal complications is still unclear. In this study we aimed to compare the maternal outcomes between cesarean delivery and vaginal delivery in women with placental abruption with intrauterine fetal death. MATERIAL AND METHODS: Using the Japan Society of Obstetrics and Gynecology nationwide perinatal registry database, we identified pregnant women with placental abruption with intrauterine fetal death between 2013 and 2019. The following women were excluded: those with multiple pregnancies, placenta previa, placenta accreta spectrum, amniotic fluid embolism, or whose delivery route was missing data. The association between delivery routes (cesarean delivery and vaginal delivery) and the maternal outcome was examined using a linear regression model with inverse probability weighting. The primary outcome was the amount of bleeding during delivery. Missing data were imputed using multiple imputation. RESULTS: The number of women with placental abruption with intrauterine fetal death was 1218/1601932 (0.076%). Of 1134 women analyzed, 608 (53.6%) underwent cesarean delivery. Bleeding during delivery (median [interquartile range]) was 1650.00 (950.00-2450.00) (mL) and 1171.00 (500.00-2196.50) (mL) in cesarean and vaginal delivery, respectively. Bleeding during delivery (mL) was significantly greater in cesarean delivery than in vaginal delivery (regression coefficient, 1086.39; 95% confidence interval, 130.96-2041.81; p = 0.026). Maternal death and uterine rupture occurred in four (0.4%) and five (0.4%) women, respectively. The four maternal deaths were noted in the vaginal delivery group. CONCLUSIONS: Bleeding during delivery was significantly greater in cesarean delivery than that in vaginal delivery in women with placental abruption with intrauterine fetal death. However, severe complications, including maternal death and uterine rupture, occurred in vaginal delivery-related cases. The management of women with placental abruption with intrauterine fetal death should be cautious regardless of the delivery route.

Pregnancy following adenomyomectomy is challenging because uterine rupture or placenta accreta spectrum (PAS) is more likely to occur; however, optimal management has not yet been established. We herein present a case of uterine rupture with placenta percreta in a pregnant woman who underwent adenomyomectomy twice before pregnancy. Magnetic resonance imaging (MRI) was performed in the second trimester and imminent uterine rupture concomitant with PAS was suspected. The patient was immediately admitted to hospital for careful management. Although failed tocolysis forced delivery at 29 weeks of gestation, managed hospitalization allowed cesarean hysterectomy to be performed uneventfully. Extensive PAS was proven pathologically in the removed uterus. Pregnancies following multiple adenomyomectomies are considered to be high-risk. Therefore, a sufficient explanation of the risks associated with future pregnancies is needed, particularly following second adenomyomectomy.

The clinical signs of cervico-isthmic pregnancy during pregnancy remain unknown. We herein report a case of cervico-isthmic pregnancy showing placental insertion into the cervix with cervical shortening, with a final diagnosis of placenta increta at the uterine body and cervix. A 33-year-old multiparous woman with a history of cesarean section was referred to our hospital at 7 weeks of gestation with suspected cesarean scar pregnancy. Cervical shortening with a cervical length of 14 mm was noted at 13 weeks of gestation. The placenta is gradually inserted into the cervix. An ultrasonographic examination and magnetic resonance imaging strongly suggested placenta accreta. We planned elective cesarean hysterectomy at 34 weeks of gestation. The pathological diagnosis was cervico-isthmic pregnancy with placenta increta at the uterine body and cervix. In conclusion, placental insertion into the cervix with cervical shortening in the early pregnancy period may be a clinical sign to suspect cervico-isthmic pregnancy.

BACKGROUND: Intraperitoneal adhesion is a common complication of cesarean section, and adhesion barriers are often used to prevent postoperative adhesion. However, the association between the use of adhesion barriers and infections after cesarean section remains unknown. This study aimed to evaluate the association. METHODS: Using the administrative claims database of a single prefecture in Japan, we identified all patients who underwent cesarean section from June 2014 to February 2019. A multivariable logistic regression model fitted with a generalized estimating equation was used to compare the postoperative outcomes between patients who received intraperitoneal adhesion barriers during cesarean section and those who did not. The primary outcome was intraperitoneal or uterine infections within 3 months after cesarean section, including intraperitoneal abscess, pelvic inflammatory disease, peritonitis, uterine wound infection, endometritis, and adnexitis. RESULTS: A total of 1,392 patients with 1,498 cesarean section cases were reviewed. Adhesion barriers were used in 1,153/1,498 (77.0%) cases. One hundred and fourteen (9.9%) intraperitoneal or uterine infections occurred in the group with and 15 (4.3%) in the group without adhesion barriers. The proportion of intraperitoneal or uterine infections was significantly higher in the group with than in the group without adhesion barriers (9.9% and 4.3%, respectively; adjusted odds ratio = 2.59; 95% confidence interval, 1.40-4.77; P = .002). CONCLUSION: The use of adhesion barriers was associated with an increase in intraperitoneal or uterine infections after cesarean section.

Preeclampsia (PE) is a major cause of maternal and perinatal morbidity and mortality. The only fundamental treatment for PE is the termination of pregnancy. Therefore, not only severe maternal complications but also perinatal complications due to immaturity of the infant associated with early delivery are serious issues. The treatment and prevention of preterm onset preeclampsia (POPE) are challenging. In 2017, the ASPRE trial showed that a low oral dose of aspirin administered to POPE high-risk women in early pregnancy reduced POPE by 62%. A prediction algorithm at 11-13 weeks of gestation identifies POPE with 75% sensitivity when the false positive rate is set at 10%. New biomarkers to increase the accuracy of the prediction model for POPE high-risk women in early pregnancy are needed. In this review, we focused on non-coding RNAs (ncRNAs) as potential biomarkers for the prediction of POPE. Highly expressed ncRNAs in the placenta in early pregnancy may play crucial roles in placentation. Furthermore, placenta-specific ncRNAs have been detected in maternal blood. In this review, we summarized ncRNAs that were highly expressed in the primary human placenta in early pregnancy. We also presented highly expressed ncRNAs in the placenta that were associated with or predictive of the development of PE in an expression analysis of maternal blood during the first trimester of pregnancy. These previous studies showed that the chromosome 19 microRNA (miRNA) -derived miRNAs (e.g., miR-517-5p, miR-518b, and miR-520h), the hypoxia-inducible miRNA (miR-210), and long non-coding RNA H19, were not only highly expressed in the early placenta but were also significantly up-regulated in the blood at early gestation in pregnant women who later developed PE. These maternal circulating ncRNAs in early pregnancy are expected to be possible biomarkers for POPE.

Caudal regression syndrome (CRS) is rare congenital malformation, which is characterized by abnormal development of the lower end of the spine and complicated with neurodevelopmental disorders of vesico-rectal functions and the lower extremities. We report the case of a woman with CRS who became pregnant and gave birth following continent bladder reconstruction (CBR) for intractable urinary incontinence. A 25-year-old primigravida woman with CRS became pregnant naturally and was referred to our department. She had undergone CBR in our institute at 14 years old. Emergency cesarean section (CS) was performed at 30 + 5 weeks of gestation due to severe preeclampsia. This is the first report of a woman with CRS who became pregnant and gave birth following CBR. A multidisciplinary team is needed to manage pregnant women with CRS following CBR. Collaboration with a urologist is especially important for managing pregnancy and performing CS. The CBR is performed for the purpose of improving quality of life by gaining urinary continence and may increase sexual behavior in women with CRS, and so obstetricians may encounter pregnancies more frequently in the future.

INTRODUCTION: To clarify the perinatal outcome of retained products of conception (RPOC) after 22 weeks or more. METHODS: The retrospective cohort study reviewed medical records of patients with RPOC without placenta previa at 186 Japanese perinatal centers. RESULTS: Of the 323 patients with RPOC, pregnancies after assisted reproductive technology (ART) accounted for 43%. Transfusion at delivery was required in 33% of the patients. Logistic regression analyses revealed that transfusion was significantly required in the following situations: ART pregnancy (aOR: 6.0, 95%CI: 2.3-16, P < 0.001), and RPOC length ≥4 cm (aOR: 5.3, 95%CI: 2.1-13, P < 0.001). Transarterial embolization (TAE) and/or hysterectomy for subsequent RPOC-related bleeding was performed in 60 patients with RPOC. Logistic regression analysis revealed that additional interventions were significantly required in the following situations: multiparity (aOR: 6.1, 95%CI: 2.1-17.2, P < 0.001), and hypervascular RPOC (aOR: 12.8, 95%CI: 3.2-51.1, P < 0.001). TAE and/or hysterectomy was also frequently employed in ART pregnancy, although this was not significant (aOR: 2.8, 95%CI: 0.9-8.2, P = 0.063). DISCUSSION: Patients with RPOC were significantly more likely to require transfusion at delivery in the presence of large RPOC and ART. They were also more likely to require hemostatic procedures for subsequent bleeding in the presence of hypervascular RPOC and ART.

Fetoscopic laser surgery occasionally causes amniotic band syndrome, in which the disrupted amniotic membrane constricts fetal body parts, leading to functional or morphological loss. We report a case of fetal distress at 31 weeks of gestation in the larger surviving twin after fetoscopic laser surgery for selective intrauterine growth restriction, necessitating emergent cesarean section. Physical examination of the infant showed constriction rings caused by a disrupted amniotic membrane on the digits, and the distal part of the right index finger was necrotic because of tight strangulation by an amniotic band with the umbilical cord of the deceased smaller twin. Laboratory data showed severe coagulopathy, and the infant was diagnosed with disseminated intravascular coagulation (DIC). Immediate treatment improved his condition. DIC may have been associated with the necrotic finger, which was strangulated by the umbilical cord of the deceased fetus, because neither maternal coagulopathy nor an underlying neonatal disorder was detected.

OBJECTIVE: To clarify whether "low-risk total PP" patients bleed more than partial/marginal PP patients. MATERIALS AND METHODS: The retrospective cohort study was performed involving patients with PP between April 2006 and December 2018. The placental position was determined by ultrasound. From medical charts, the backgrounds as well as obstetric and neonatal outcomes of PP patients were retrieved. RESULTS: This study included 349 patients with PP, which was classified into three types according to the distance between the placenta and internal ostium: total (n = 174), partial (n = 52), and marginal (n = 123) PP. In total PP patients, three factors (prior CS, anterior placenta, and placental lacunae on ultrasound) significantly increased blood loss at CS, the need for hysterectomy, homologous transfusion (≥10 U), and ICU admission. No significant difference was observed in bleeding-related poor outcomes (rate of blood loss ≥2000 mL, amount of homologous transfusion, need for hysterectomy, and ICU admission) between total PP patients without all three factors: "low-risk total PP patients" and partial/marginal PP patients (19.8 vs. 17.1%; p = 0.604, 3.7 vs. 1.1%; p = 0.330, 1.2 vs. 1.1%; p = 1.000, and 1.2 vs. 1.1%; p = 1.000, respectively). CONCLUSION: Prior CS, anterior placenta, and placental lacunae on ultrasound were risk factors for a bleeding-related poor outcome in total PP patients. Total PP patients without these three factors showed the same bleeding-related poor outcome as partial/marginal PP patients.

36歳。妊娠26週頃から目のかすみと視力低下を自覚し、近医眼科を受診したところ視野異常を指摘され、妊娠29週に当院眼科を紹介受診した。視野検査で両耳側半盲と診断された。頭蓋内病変評価のため頭部MRIを施行され、下垂体腫大(長径17.2mm)を認められた。妊娠中に高度の下垂体腫大を認めたことからリンパ球性下垂体炎の可能性が高いと判断され、治療と妊娠管理目的で当科に緊急入院となった。入院後ステロイド療法(PSL 50mg/dayから漸減)を開始し、3日目に目のかすみは消失し、6日目に施行したMRIで下垂体長径は11.5mmに縮小していた。視野障害も改善し、それに伴い視力も回復した。胎児の発育も順調で、PSLを15mg/dayまで漸減し、妊娠33週2日に退院とした。以後外来で経過観察し、症状の再燃は認めなかった。妊娠37週3日に選択的帝王切開で出産し、産後はPSLを10mg/dayに減量したが症状の再燃はなかった。産後1ヵ月時にMRIで下垂体を再評価したところ長径は10.5mmとほぼ正常大まで縮小していた。

OBJECTIVE: X-linked hydrocephalus (XLH), the most common genetic hydrocephalus, is caused by mutation of the L1 cell adhesion molecule (L1CAM). A fetus/neonate with this disorder frequently shows an adducted thumb, which has been employed as a helpful finding in the prenatal diagnosis of XLH. MATERIALS AND METHODS: We describe a male fetus with hydrocephalus without an adducted thumb: the pregnancy was terminated at 21 weeks' gestation on the parents' request. Direct sequencing of the umbilical cord revealed L1CAM mutation, which confirmed the diagnosis of XLH. RESULTS: Our literature review demonstrated that while an adducted thumb was observed in almost all fetuses with this disorder after 24 weeks' gestation, it was noted in only 57% (8/14) of fetuses/neonates at less than 24 weeks: it was absent in 43%. CONCLUSION: Even if an adducted thumb is not observed, XLH should not be ruled out, especially in early gestation.

AIM: The study aimed to examine the usefulness of modified transabdominal cervicoisthmic cerclage (TAC) using monofilament thread for the prevention of preterm delivery in women with an extremely short cervix after deep conization. METHODS: We devised a monofilament thread for picking up the seromuscular layer of the site that is slightly cephalad to the internal ostium to prevent injury of the vessels around the uterine cervix. From 2017 to 2020, we performed this modified operation in eight women (nine pregnancies) at 12-16 weeks of gestation with a history of deep cervical conization. RESULTS: A modified TAC was successfully performed in all patients. There was no measurable bleeding, and all patients were discharged without postoperative complications. Their pregnancy courses after the operation were uneventful. Of nine, one patient had premature uterine contractions and underwent cesarean section at 36 weeks (preterm delivery). In the other eight pregnancies, planned cesarean section was performed after 37 weeks of gestation. The median birth weight of the babies was 2996 g (range 2604-3374 g). All patients were discharged on the sixth postoperative day without complications. CONCLUSION: A modified TAC can be safely performed and may prolong pregnancy without adverse events in patients with an extremely short cervix.

The incidence of chromosomal abnormalities in twin pregnancies is not well-studied. In this retrospective study, we investigated the frequency of chromosomal abnormalities in twin pregnancies and compared the incidence of chromosomal abnormalities in dichorionic diamniotic (DD) and monochorionic diamniotic (MD) twins. We used data from 57 clinical facilities across Japan. Twin pregnancies of more than 12 weeks of gestation managed between January 2016 and December 2018 were included in the study. A total of 2899 and 1908 cases of DD and MD twins, respectively, were reported, and the incidence of chromosomal abnormalities in one or both fetuses was 0.9% (25/2899) and 0.2% (4/1908) in each group (p = 0.004). In this study, the most common chromosomal abnormality was trisomy 21 (51.7% [15/29]), followed by trisomy 18 (13.8% [4/29]) and trisomy 13 (6.9% [2/29]). The incidence of trisomy 21 in MD twins was lower than that in DD twins (0.05% vs. 0.5%, p = 0.007). Trisomy 21 was less common in MD twins, even when compared with the expected incidence in singletons (0.05% vs. 0.3%, RR 0.15 [95% CI 0.04-0.68]). The risk of chromosomal abnormality decreases in twin pregnancies, especially in MD twins.

Disruption of well-controlled reproductive functions leads to pregnancy complications such as hypertensive disorders of pregnancy (HDP). Uncaria tomentosa (Wild), known as cat's claw, is widely used for the treatment of a various types of health problems; AC-11 (AC-11®, hot-water extract of U. tomentosa) is unique phytochemical compound and has potential roles as anti-inflammatory or anti-oxidant processes. We investigated whether AC-11 has a protective effect on pathogenesis of HDP in vivo and production of anti-angiogenic factors (sFlt-1 and sEng, major factors for the onset of HDP) in in vitro. Non-pregnant or pregnant mice were administered AC-11 (4 mg/mL), then, angiotensin II (Ang II) was subcutaneously infused to increase blood pressure. Human placental tissues or human umbilical vein endothelial cells (HUVECs) were incubated with or without AC-11. Treatment with AC-11 significantly reduced blood pressure induced by Ang II infusion. The population of CD8+T cells, the ratio of CD8/CD4, and plasma interleukin-6 levels were increased by Ang II infusion, and were decreased by AC-11 both in pregnant and non-pregnant mice. In pregnant mice, plasma levels of sFlt-1 and sEng were decreased by AC-11. In in vitro cell culture of HUVECs or placental tissue culture, treatment with AC-11 significantly inhibited secretion of sFlt-1 and sEng. We suggest a novel role of AC-11 in regulating blood pressure by controlling the balance of T cell population and inflammatory cytokine production both in non-pregnant and pregnant conditions. In addition, AC-11 inhibits HDP-related factors, including sFlt-1 and sEng, suggesting that AC-11 may useful for relieving HDP.

OBJECTIVES: Various procedures have been introduced to achieve hemostasis for postpartum hemorrhage (PPH) in placenta previa (PP). This study attempted to clarify the effectiveness of the combined use of three hemostatic procedures: Matsubara-Takahashi cervix-holding (MT-holding), intrauterine balloon (IUB), and uterine compression suture (UCS). STUDY DESIGN: This was a historical cohort study on the hemostatic effect of combined procedures for patients with placenta previa (PP) undergoing cesarean section between April 2006 and December 2018. Until 2011 (2006-2011), we used MT-holding alone, whereas since 2012 we have also been using IUB and UCS: MT-holding alone was used in the former period whereas three procedures (MT-holding, IUB, UCS, and their combinations) have been used in the latter period. Perinatal outcomes were compared between 2006-2011 (before group) and 2012-2018 (after group). RESULTS: Of 416 patients with PP, excluding 273 patients with cesarean hysterectomy or no hemostatic procedure, the remaining 143 patients were analyzed. In the after group, intraoperative blood loss, the percentage of patients with postoperative blood loss ≥ 500 ml, and incidence of autologous blood transfusion were significantly lower than in the before group. Multivariate analysis showed that postoperative blood loss ≥ 500 ml decreased in the after group (adjusted OR: 0.3, 95%CI: 0.1-0.8, compared with the before group). CONCLUSION: PPH decreased after introducing the combination of hemostatic procedures in patients with PP. Further studies are needed to determine the best combination and optimal indication for combining hemostatic procedures for PP.

The immune system contributes to the regulation of pregnancy, and the disruption of well-controlled immune functions leads to pregnancy complications. Recently, the nucleotide-binding oligomerization domain, leucine-rich repeat-, and pyrin domain-containing 3 (NLRP3) inflammasome mechanisms [(a protein complex of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and caspase-1)] have been reported to play roles in controlling placental inflammation involved in pregnancy pathologies. The ketone body β-hydroxybutyrate (BHB) can suppress NLRP3 inflammasome activation and improve various inflammatory diseases. Therefore, we hypothesized that BHB could suppress activation of the NLRP3 inflammasome in the placenta, resulting in the improvement of pregnancy complications. In human placental tissue culture, treatment with BHB suppressed the secretion levels of inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and IL-8, but did not affect the mRNA expression levels of NLRP3 inflammasome-associated factors. Treatment with BHB reduced IL-1β secretion and the amount of mature IL-1β protein induced by lipopolysaccharide (LPS) stimulation in the placenta. In human trophoblast cells, BHB reduced ASC and activated-caspase-1 expression, resulting in the inhibition of IL-1β secretion. To investigate the effect of BHB during pregnancy, we used an animal model of LPS (100 μg/kg intraperitoneally [i.p.] on gestational day 14)-induced pregnancy complications. Administration of BHB (100 mg/kg i.p.) clearly suppressed the absorption rate and IL-1β production in the placenta induced by LPS in pregnant mice. Moreover, LPS-induced pregnancy abnormalities were improved in NLRP3-deficient mice. These findings suggest that BHB play a role in reducing placental inflammation and pregnancy complications via inhibition of NLRP3 inflammasome activation.

OBJECTIVE: To validate the use of placenta accreta risk-antepartum (PAR-A) score as a predictive tool of clinical outcomes of placenta accreta spectrum (PAS). METHODS: This is a prospective study, conducted in six PAS specialized centers in six different countries. The study was conducted between October 1, 2020 and March 31, 2021. Women who were provisionally diagnosed with PAS during pregnancy were considered eligible. A machine-learning-based PAR-A score was calculated. Diagnostic performance of the PAR-A score was evaluated using a receiver operating characteristic curve, for perioperative massive blood loss and admission to intensive care unit (ClinicalTrials.gov identifier NCT04525001). RESULTS: Of 97 eligible women, 86 were included. PAS-associated massive blood loss occurred in 10 patients (11.63%). Median PAR-A scores of massive blood loss in the current cohort were 8.9 (interquartile range 6.9-14.1). In predicting massive blood loss, the area under the curve of PAR-A scores was 0.85 (95% confidence interval [CI] 0.74-0.95), which was not significantly different from the original cohort (P = 0.2). PAR-A score prediction of intensive care unit admission was slightly higher compared with the original cohort (0.88, 95% CI 0.81-0.95; P = 0.06). CONCLUSION: PAR-A score is a novel scoring system of PAS outcomes, which showed external validity based on current data.

OBJECTIVE: Cystic hygroma often ameliorates or disappears with pregnancy progression. Fetuses/neonates with amelioration, when without chromosomal or major structural abnormality, generally show a favorable outcome at birth. The present study was aimed to clarify the short/long-term outcomes of fetuses/neonates with the amelioration of cystic hygroma during pregnancy. MATERIAL AND METHODS: This was a retrospective observational study. We focused on fetuses with cystic hygroma managed in our institute between January 2006 and June 2019. The infants were followed by pediatricians (neonatologist, pediatric cardiologist, and pediatric neurologist) and pediatric outcomes were retrieved from the medical records up to 3 years old. RESULTS: One hundred and seven fetuses with cystic hygroma were included. Of the 107, cystic hygromas ameliorated in 31 fetuses (31/107: 29%). Of the 31, there were 26 livebirths. Half (n = 13) of the 26 fetuses had a good outcome, whereas the remaining half (n = 13) had abnormalities. Various abnormalities were detected in their infancies. A nuchal thickness (diameter of hygroma) of ≥5 mm was significantly correlated with abnormalities (P = 0.047). CONCLUSION: Physicians should pay attention to fetuses/neonates with ameliorated cystic hygroma. Of those, special attention should be paid to fetuses/neonates with a nuchal thickness at diagnosis ≥5 mm.

Advanced maternal age is a risk factor for female infertility, and placental dysfunction is considered one of the causes of pregnancy complications. We investigated the effects of advanced maternal aging on pregnancy outcomes and placental senescence. Female pregnant mice were separated into three groups: young (3 months old), middle (8-9 months old), and aged (11-13 months old). Although the body weights of young and middle dams gradually increased during pregnancy, the body weight of aged dams only increased slightly. The placental weight and resorption rate were significantly higher, and live fetal weights were reduced in a maternal age-dependent manner. Although mRNA expression of senescence regulatory factors (p16 and p21) increased in the spleen of aged dams, mRNA expression of p16 did not change and that of p21 was reduced in the placenta of aged dams. Using a cytokine array of proteins extracted from placental tissues, the expression of various types of senescence-associated secretory phenotype (SASP) factors was decreased in aged dams compared with young and middle dams. The aged maternal placenta showed reduced immune cell accumulation compared with the young placenta. Our present results suggest that models using pregnant mice older than 8 months are more suitable for verifying older human pregnancies. These findings suggest that general cellular senescence programs may not be included in the placenta and that placental functions, including SASP production and immune cell accumulation, gradually decrease in a maternal age-dependent manner, resulting in a higher rate of pregnancy complications.

OBJECTIVES: Maternal systemic and placental inflammatory responses participate in the pathogenesis of hypertensive disorders of pregnancy including preeclampsia, a pregnancy-specific syndrome, although the role of inflammation remains unclear. The NLRP3 inflammasome has been implicated in the control of sterile inflammation involved in preeclampsia. In the present study, we hypothesized that S100A9, as major alarmin, are associated with the pathogenesis of preeclampsia and induction of a preeclampsia-like phenotype in pregnant mice. METHODS: Plasma were taken from normal pregnant women and preeclampsia patients. Human placental tissues, trophoblast cell line Sw.71 cells, and human umbilical vein endothelial cells (HUVEC) were treated with S100A9 with or without inhibitors associated with NLRP3 inflammasome. Pregnant mice were administered S100A9. RESULTS: S100A9 was elevated in plasma and released from placentas of preeclampsia patients. S100A9 activated the NLRP3 inflammasome, resulting in IL-1β secretion, by human placental tissues and trophoblasts. In addition, secretion of soluble endoglin, a main contributor to the pathogenesis of preeclampsia, is regulated via S100A9-stimulated NLRP3 inflammasome activation in the human placenta and HUVECs. S100A9 administration significantly elevated maternal blood pressure and neutrophil accumulation within the placentas of pregnant mice, and both were significantly decreased in Nlrp3-knock out pregnant mice. CONCLUSION: The results of this study demonstrated that S100A9 acts as a danger signal to activate the NLRP3 inflammasome in the placenta, associating with hypertension during pregnancy.