野田 佳照

帝王切開術には様々なバリエーションがあり、各施設や執刀医によって異なった術式で行われているが、腹壁と子宮を切開して胎児と胎盤を娩出し、子宮と腹壁を縫合閉鎖するという基本的操作には変わりがない。しかし、近年では母体年齢の上昇に伴う合併症妊婦の増加をはじめ、超早産例や前置癒着胎盤などのハイリスク分娩への対応も含めて、正しい評価と安全確実な手技の実施が求められている。標準術式として、我が国では腹壁切開はPfannenstiel法が一般的であるが、近年欧米ではJoel-Cohen法が広く行われており、創の鈍的操作と胎盤自然剥離の待機がトレンドである。子宮切開の標準術式は子宮下部横切開法であり、膀胱剥離の有無、創の用指的展開の方向がポイントである。子宮縫合には諸説あり、まだ確立された術式はないが、上下の厚みの差を意識し筋層断面を正しく合わせ、術後に筋層の菲薄化を起こさぬよう心がけることが大切である。母児に対しより良い予後を提供するためには、エビデンスに基づいた標準術式を十分に習得することはもとより、状況に応じて適切な術式を選択する必要がある。(著者抄録)

＜文献概要＞●子宮切開法の種類とバリエーションを理解する.●標準術式としての子宮下部横切開法の意義と,切開の3つのポイントを理解する.●胎児損傷を回避するための方策を理解する.

Objectives: Alterations in the vaginal bacterial flora reflect the status of various obstetric conditions and are associated with mechanisms that underlie certain pregnancy-associated complications. These changes are also a predictive biomarker for clinical outcomes of these adverse events. Methods: We examined the vaginal microbiome in samples from pregnant Japanese women with preterm labor. Results: The microbiota composition in preterm delivery (PD) samples differed from those of control or threatened preterm delivery (TPD) samples in principal component analysis. An increase in Firmicutes and a decrease in Actinobacteria were significantly associated with PD only (both P<0.01). In the Firmicutes phylum, Lactobacillus tended to be abundant, and the abundance of L. iners and L. crispatus was especially high, whereas the L. gasseri population was low in PD samples. Longitudinal analysis showed that the abundance of L. iners decreased after commencing tocolytic treatment in TPD samples compared with before treatment, but it remained high in PD samples. Conclusions: The vaginal microbiome may be a useful prognostic indicator of preterm labor and a monitoring tool for tocolytic treatment to prevent preterm birth.

OBJECTIVE: The proprotein convertase furin is known to be involved in the processing of pro-B-type natriuretic peptide (proBNP) and prorenin receptor (PRR), suggesting that it has a potential function in blood pressure regulation. We investigated the role of furin in the etiology of pre-eclampsia and its related disorder, unexplained fetal growth restriction (FGR) without hypertension. METHODS: We evaluated serum and placental furin levels in pre-eclampsia, FGR and uncomplicated pregnancy. Additionally, we investigated the correlation between the serum furin levels and products of furin enzymatic activity or clinical parameters. RESULTS: We demonstrated that the maternal circulation in cases of pre-eclampsia and FGR had lower levels of soluble furin than uncomplicated pregnancies. Both NT-proBNP and soluble PRR were elevated in pre-eclampsia, whereas only soluble PRR was at higher levels in unexplained FGR. Linear regression analysis revealed a negative correlation between the serum furin level and that of NT-proBNP or soluble PRR. While we observed that the serum furin or soluble PRR level correlated with blood pressure, a stronger correlation was observed with birth and placental weights. Further to this, the FURIN mRNA levels were significantly reduced in placental pre-eclamptic placentas as well as in FGR cases. CONCLUSION: These data suggest the possibility that reduced levels of furin may be the result of a negative feedback from the activation of the renin-angiotensin pathway that leads to feto-placental dysfunction with or without maternal hypertension. This may represent an etiologic pathway of pre-eclampsia and unexplained FGR.

[目的]Retained products of conception(RPOC)とは、妊娠終了後に妊娠に関連する組織が子宮内に残存した状態で、産褥晩期出血の一因となるが、本邦では診断基準や管理方法が確立されていないのが現状である。そこで、本疾患の病態解明と管理指針の確立をめざして、当施設で経験したRPOCとその対応の現状について臨床的検討を行った。[方法]院内倫理審査委員会の承認の下、2012年から2019年の8年間に当院で経験したRPOCの臨床所見と治療について、診療録を用いて後方視的に検討を行った。[成績]対象期間中のRPOCは20例で、平均年齢は34歳(27-40)、先行妊娠の転帰は、流産(人工妊娠中絶含む)が7例、分娩が13例(正期産12例、早産1例)で、分娩様式は、経腟分娩10例、帝王切開分娩3例であった。治療法は、子宮収縮剤投与による保存的治療が4例で、これら全てが自然退縮し、外科的治療を行ったのは16例(子宮内容除去術5例、子宮鏡下経頸管的切除術10例、腹式単純子宮全摘出術1例)であった。超音波ドプラ検査で豊富な腫瘤内血流を認めたのは20例中18例で、このうち15例に外科的治療を行なった。大量出血により緊急対応を必要とした4例中3例に子宮動脈塞栓術(UAE)を実施したが、これら4例の腫瘤最大径は、それ以外の16例に比して有意に大きかった(62.5mm vs 27.2mm)(p<0.05)。[結論]RPOCの病態は多彩であり、保存的治療も選択肢となり得るが、腫瘤の大きさと経腟超音波ドプラ検査による腫瘤内血流所見が外科的治療を考慮するポイントとなる。(著者抄録)

BACKGROUND: Soluble fms-like tyrosine kinase 1 (sFlt-1) is believed to be a prominent component in the pathogenesis of pre-eclampsia, although the precise etiology has remained elusive. In this study, the etiological role of FLT1 variant was further validated in pre-eclampsia by examining this association in a Japanese sample population. METHODS: The genotypes of three variants (rs4769613, rs12050029 and rs149427560) were examined in the upstream region of the FLT1 gene in placentas from pre-eclamptic (n=47) or normotensive control (n=49) pregnancy samples. Additionally, FLT1 mRNA levels in placenta were determined by qRT-PCR. ELISA was further used to detect circulating sFlt-1 levels in maternal sera. The intergroup comparisons were made using the Mann-Whitney U test or one way analysis of variance and P values of less than 0.05 were considered statistically significant. RESULTS: First, the rs4769613 (C>T) and rs12050029 (G>A) genotypes were examined in placentas but no significant differences were found in the genotype or allele-type frequencies. Next, nearby short tandem repeat, rs149427560, was examined which manifested four size variants. In the genotypewise analysis, the frequency of the 474/476 heterozygote was significantly lower in pre-eclampsia (p<0.05). As expected, the FLT1 mRNA levels were significantly elevated in the pre-eclamptic placentas and sFlt-1 was higher in pre-eclamptic maternal sera. However, the genotype of these variants did not affect the FLT1 mRNA or serum sFlt-1 levels. CONCLUSION: Our findings did not support the hypothesis that genetic variations around the FLT1 gene affect the subtle expression changes underlying the etiologic pathway of pre-eclampsia. The hypothesis deserves further investigation through a larger sample size.

＜回答のポイント＞1)ガイドラインに則った医療が実践され、病診・病病連携体制が整備された現在では、里帰り出産自体のリスクは低く、妊婦の社会的背景を念頭に積極的に対応する。2)里帰り出産の帰省時期は妊娠34週前後が一般的であり、その決定にあたっては、母体と胎児のリスク因子の評価を行うとともに妊婦の希望する産科医療施設の情報を収集し、帰省までの妊娠管理と診療情報提供を確実に行う。3)特にハイリスク妊娠・分娩においては、母体および胎児の状態によって対応可能な産科医療施設を選定し、当該施設と綿密な連携のもとで里帰りの時期と方法を決定するとともに家族のバックアップ体制の構築を促す。(著者抄録)

＜回答のポイント＞1)国内線と国際線では、妊婦の搭乗規定が異なる。2)国内線ではほとんどの航空会社の規約は共通しており、自由に搭乗できるのは分娩予定日の29日前までで、28日以内では医師の診断書、7日以内では医師の同伴が必要となる。3)国際線では航空会社によって基準が大きく異なる。自由に乗れるのは妊娠32週あるいは36週前までのことが多く、多胎妊娠では制限を設けている場合もある。稀に目的国が妊婦の入国を制限している場合もある。4)飛行機に搭乗すること自体の胎児への影響についてはエビデンスはないが、一般的な状況では問題はないと考えられている。5)飛行機に搭乗する際には、エコノミークラス症候群の発症を避けるために適度な運動と水分摂取が必要である。6)渡航先の特殊な感染症の情報を取得し、同時に自身の予防接種歴やウイルス感染症を把握しておく。(著者抄録)

BACKGROUND: Nectins are cell adhesion molecules that play a pivotal role in adherens junctions and tight junctions. Our previous study using whole-genome oligonucleotide microarrays revealed that nectin-4 was upregulated in pre-eclamptic placentas. We investigated the role of nectin-4 in the etiology of pre-eclampsia. METHODS: We investigated the expression of nectin-4 using real-time RT-PCR, western blot and immunostaining. Additionally, we performed matrigel invasion assay and cytotoxicity assay using cells overexpressing the nectin-4. RESULTS: NECTIN4 transcripts were elevated in pre-eclamptic placentas relative to uncomplicated pregnancies. Nectin-4 protein levels in pre-eclamptic placentas were higher on a semi-quantitative western blot. Nectin-4 was localized at the apical cell membrane in syncytiotrophoblast cells and not at the adherens junctions. Nectin-4 was also detected in cytotrophoblasts and a subset of cells in the decidua. Nectin-4 overexpressing trophoblast cells migrated normally in the matrix. However, Natural killer (NK) cells showed a strong cytotoxic effect against nectin-4 overexpressing trophoblast cells. No causative genetic variation was evident in the NECTIN4 gene from a pre-eclamptic placenta. CONCLUSIONS: There are as yet unknown factors that induce nectin-4 overexpression in trophoblast cells that may contribute to abnormal placentation via an aberrant immune response and the onset of a pre-eclamptic pregnancy.