関谷 隆夫

Serum 25-hydroxyvitamin D (25-OHD) concentrations are thought to accurately reflect vitamin D stores, and vitamin D deficiency causes secondary hyperparathyroidism, irreversible bone loss, and increased risk of fracture. Recent studies suggest that decrease of serum 25-OHD level in mothers could increase the risk of preeclampsia, cesarean section, and craniotabes. Furthermore, this deficiency may affect bone mass and the incidence of neuromuscular diseases of their children in the future. In the present study, the serum concentration of 25-OHD in 93 pregnant women after the 30th week of their gestation was determined by direct radioimmunoassay. Mean 25-OHD levels in spring, summer, fall, and winter were 14.3 ± 5.1, 15.7 ± 6.4, 13.7 ± 5.1, and 13.9 ± 4.2 ng/ml, respectively. Severe vitamin D deficiency (25-OHD < 10 ng/ml) was found in 10 of these 93 women. Overall, hypovitaminosis D, which was defined as serum 25-OHD concentration equal to or less than 20 ng/ml, was revealed in 85 mothers (89.5%). Serum 25-OHD levels were not associated with either intact parathyroid hormone or corrected calcium concentrations, but were negatively associated with serum type I collagen N-terminal telopeptide and bone-specific alkaline phosphatase in these subjects. Mothers with threatened premature delivery had significantly lower 25-OHD levels (11.2 ± 3.2 ng/ml) than those in mothers with normal delivery (15.6 ± 5.1 ng/ml). In conclusion, the present data suggest a high prevalence of hypovitaminosis D in perinatal pregnant Japanese women throughout the year, which seems to affect bone metabolism and to be associated with threatened premature delivery.

BACKGROUND: It has been well documented that pre-eclampsia and unexplained fetal growth restriction (FGR) have a common etiological background, but little is known about their linkage at the molecular level. The aim of this study was to further investigate the mechanisms underlying pre-eclampsia and unexplained FGR. METHODS: We analyzed differentially expressed genes in placental tissue from severe pre-eclamptic pregnancies (n = 8) and normotensive pregnancies with or (n = 8) without FGR (n = 8) using a microarray method. RESULTS: A subset of the FGR samples showed a high correlation coefficient overall in the microarray data from the pre-eclampsia samples. Many genes that are known to be up-regulated in pre-eclampsia are also up-regulated in FGR, including the anti-angiogenic factors, FLT1 and ENG, believed to be associated with the onset of maternal symptoms of pre-eclampsia. A total of 62 genes were found to be differentially expressed in both disorders. However, gene set enrichment analysis for these differentially expressed genes further revealed higher expression of TP53-downstream genes in pre-eclampsia compared with FGR. TP53-downstream apoptosis-related genes, such as BCL6 and BAX, were found to be significantly more up-regulated in pre-eclampsia than in FGR, although the caspases are expressed at equivalent levels. CONCLUSIONS: Our current data indicate a common pathophysiology for FGR and pre-eclampsia, leading to an up-regulation of placental anti-angiogenic factors. However, our findings also suggest that it may possibly be the excretion of these factors into the maternal circulation through the TP53-mediated early-stage apoptosis of trophoblasts that leads to the maternal symptoms of pre-eclampsia.

24歳。月経過多と倦怠感を主訴とした。経腟超音波で子宮体部後壁に子宮内膜変形を伴う84×76×84mmの低輝度の腫瘤を認め、子宮筋腫の診断で腹腔鏡下筋腫核出術を施行した。子宮後壁筋層に切開を加えた途端、動脈性の強出血を認め、止血に難渋した。筋腫核出時に子宮内膜の一部が穿破し、術中出血が多いため1層での全層縫合を行い、その後子宮筋層の2層縫合を行った。術後経過は良好であったが、25日目の経腟超音波で筋腫核出部に最大径23mmの嚢胞性病変があり、カラードップラーで拍動性の噴水状血流を認めた。検査直後に突発的な大量性器出血を来たし、嚢胞性病変の破綻と考え緊急開腹術を施行した。嚢胞性病変内背側より直径1mmほどの動脈が数ミリ突出しており、拍動性出血を認め、単離結紮で完全止血可能であった。その後、嚢胞壁の穿孔部を含め筋層の3層縫合を行った。術後経過は良好で、77日目の超音波では子宮後壁の筋層切開部付近に異常血流を認めた。現在まで再発は認めていない。

Indoleamine 2,3-dioxygenase (IDO) is the rate limiting enzyme of the kynurenine pathway that degrades L-tryptophan, but a wider range of functions have now been proposed for this enzyme, including antioxidant activity. Our previous study revealed that reduced IDO expression in the placenta induces defective feto-maternal immuno-tolerance leading to the onset of pre-eclampsia. In our present study, we assessed the effects of low placental IDO activity as an antioxidant. The placental levels of 8-hydroxy-2'-deoxy-guanosine (8-OHdG), a maker for oxidative damage to DNA, were significantly higher in pre-eclamptic than normotensive pregnancies (P<0.05). Immunohistochemical signals of 8-OHdG were detected mainly in syncytiotrophoblasts and vascular endothelial cells, and co-localized with those for IDO. Furthermore, a significant inverse correlation was found between the IDO activity and 8-OhdG levels. These results show that oxidative stress is associated with decreased IDO activity in the pre-eclamptic placenta and suggest an impact of low IDO activity other than immune modulation in promoting the onset of this disorder.

1946年にPotterが両側性腎無形成と特徴的な顔貌を呈する症候群を記載して以来、Potter sequenceの報告は数多くみられるが、長期生存したという報告は調べた限りではみられない。今回著者等は、母体が高度の羊水過少をきたし、児のPotter sequenceが疑われる症例に対して、妊娠継続と肺低形成予防を目的に頻回の人工羊水注入療法を行い出生した2例を経験した。両例とも出生後は腹膜透析を必要としたが、肺低形成は軽度であり、人工羊水注入療法はPotter sequence児の生命予後を改善させる可能性があると考えられた。

妊娠高血圧症候群(pregnancy induced hypertension;PIH)と子宮内胎児発育遅延(fetal growth restriction;FGR)の一病態として胎盤形成障害や機能不全が考えられ、こうした例では胎盤内血流が減少することが指摘されている。近年3D power Doppler法におけるvolume histogram機能の開発も相まって、胎盤内血流の分布ならびに強度の立体的評価が可能となった。今回我々は、PIHとFGRにおける病態解明に関する研究の一環として、妊娠29週〜40週のPIH14例、FGR15例および正常妊娠18例を対象に、vascularization-index(VI)、flow-index(FI)およびvascularization-flow-index(VFI)を用いた胎盤内血流の評価を行った。各項目に関して比較検討した結果、PIH群ではcontrol群と比べVI、FIおよびVFIがともに有意に低下し(P<0.001)、またFGR群に比しFIの有意に低下が認められた(P=0.03)。一方、FGR群ではcontrol群と比べVIおよびVFIはともに低下する傾向を認めたが(P=0.07、P=0.05)、FIは有意差を認めなかった(P=0.17)。以上の結果から、PIH群においてほぼすべての症例で胎盤血流が低下しているのに対し、FGR群では胎盤血流の低下を認めない症例も含まれており、胎盤の血管構築に起因しない病態の多様性が反映されたものと考えられた。しかしながら、超音波3D power Doppler法を用いた胎盤血流評価は、構築障害や血流異常に基づく胎盤機能不全と関連する疾患を評価する一助となる可能性が示唆され、胎児胎盤機能を推測する新たな検査法になり得る。(著者抄録)

妊娠中の子宮頸管の熟化に伴って、経腟超音波検査にて観察できる子宮頸管腺領域像(cervical gland area:以下CGA)は不明瞭化する。今回我々は、妊娠36〜41週の初産単胎妊娠117例を対象として、医学的介入なく経腟分娩に至った正常群(68症例)と医学的介入を要した介入群(49症例)に分類し、さらに分娩予後規定因子として、妊娠36週以降の妊婦健診における内診によるBishop score、経腟超音波検査による頸管長の測定とCGA不明瞭化の検出を行い、各所見と分娩予後との関連を検討した。さらに子宮頸管粘液中のmatrix metalloproteinase-2(MMP-2)、matrix metalloproteinase-9(MMP-9)およびtissue inhibitors of metalloproteinases-1(TIMP-1)を測定して、CGAの不明瞭化と頸管熟化の関連についても検討した。各予後規定因子の検討では、CGA陽性率、Bishop score(38週、39週のみ)が介入群で高く(p<0.05)、頸管長は両群間で差を認めなかった。頸管粘液中のMMP-2、MMP-9およびTIMP-1は、正常群と介入群の間に差を認めなかったが、CGA陰性群では陽性群に比してMMP-2が高かった(p<0.01)。今回の検討より、妊娠末期の経腟超音波検査によるCGAの評価は、分娩予後を予測する因子として有用で、CGAの不明瞭化とMMP-2の関連も示唆された。(著者抄録)

The prenatal diagnosis of fetal bone and small parts is a challenging task to the variable disorders and large number of possible diagnosis. Fetal limb anomalies may be congenital or acquired in utero. The former occur as anomalies either systemically or, in some limbs, due to hereditary or sporadic impairment in the formation or development of bone, cartilage or soft tissue. Acquired anomalies are caused by mechanical factor of an amniotic band or oligohydramnios. Both types present functional and cosmetic abnormalities, and skeletal dysplasia in particular includes lethal diseases, which makes prenatal diagnosis in such cases highly important, both medically and societally. Diagnostic imaging for prenatal diagnosis is accomplished by ultrasound, MRI and CT scan, and chromosomal and genetic diagnosis is also performed as needed. We focus on skeletal dysplasia to review prenatal diagnosis of fetal bone and small part anomalies by noninvasive ultrasound. For the authors as perinatologists, this is the imaging modality of choice.

35歳(2経妊1経産)。患者は妊娠29週1日に意識障害を認め、母体搬送された。所見ではJCSII-10で、CTでは延髄左側くも膜下腔に高吸収域が認められた。そして、3D-CT angioより左前下小脳動脈の解離性動脈瘤破裂によるくも膜下出血(SAH)と診断され、29週3日目に血管内手術による脳動脈瘤塞栓術が行われ、妊娠は継続した。術後、意識レベルは徐々に改善したが、頭痛と左下肢麻痺がみられ、MRIによる検査を行ったところ、T1強調で右前頭葉皮質静脈のflow void消失、拡散強調で右前頭葉大脳皮質部の高信号域が認められ、あわせてMR venographyでは直静脈洞の陰影欠損と上矢状静脈洞の血流低下が確認された。以上より、本症例はSAHに合併した脳静脈洞血栓症と診断され、31週1日目に低分子ヘパリンの投与を開始した。その結果、頭痛や左下肢麻痺の回復、画像所見の改善を認め、以後、38週6日目にオキシトシンによる分娩誘発を行い、経腟分娩にて3105gの男児が出産した(Apgar score9点/10点)。尚、母子はともに産褥20日目に退院となった。