Fetal movement counting is associated with the reduction of delayed maternal reaction after perceiving decreased fetal movements: a prospective study.

Maternal perception of decreased fetal movement is associated with adverse perinatal outcomes. Although there have been several studies on interventions related to the fetal movements count, most focused on adverse perinatal outcomes, and little is known about the impact of the fetal movement count on maternal behavior after the perception of decreased fetal movement. We investigated the impact of the daily fetal movement count on maternal behavior after the perception of decreased fetal movement and on the stillbirth rate in this prospective population-based study. Pregnant women in Shiga prefecture of Japan were asked to count the time of 10 fetal movements from 34 weeks of gestation. We analyzed 101 stillbirths after the intervention compared to 121 stillbirths before the intervention. In multivariable analysis, maternal delayed visit to a health care provider after the perception of decreased fetal movement significantly reduced after the intervention (aOR 0.31, 95% CI 0.11-0.83). Our regional stillbirth rates in the pre-intervention and post-intervention periods were 3.06 and 2.70 per 1000 births, respectively. Informing pregnant women about the fetal movement count was associated with a reduction in delayed maternal reaction after the perception of decreased fetal movement, which might reduce stillbirths

Insufficient antenatal identification of fetal growth restriction leading to intrauterine fetal death: a regional population-based study in Japan.

Objective:Fetal growth restriction (FGR) is associated with perinatal adverse outcomes including intrauterine fetal death. Antenatally unidentified FGR has a higher risk of intrauterine fetal death than that identified antenatally. We, therefore, investigated the antenatal identification of FGR among intrauterine fetal deaths, and assessed the perinatal factors associated with the identification of FGR.Methods:This retrospective and population-based study reviewed all stillbirths in Shiga Prefecture, Japan, from 2007 to 2016 with exclusion criteria of multiple births, births at unidentified gestational weeks or < 22 gestational weeks, and lethal disorders. We analyzed cases of FGR, using the Japanese clinical definition: Z-score of estimated fetal weight for gestational age <-1.5 standard deviations (SD).Results:We identified 94 stillbirths with FGR among 429 stillbirths. Thirty-seven cases were antenatally identified during pregnancy management (39%). Dividing cases by a Z-score of -2.5 SD, 51 cases were classified as ≤-2.5 SD. Twenty-eight of the 51 cases (55%) with a Z-score <-2.5 SD were antenatally identified as having FGR, whereas 9 of the 43 cases (21%) with a Z-score ≥-2.5 SD were antenatally identified as having FGR (p = .002). Among cases with a Z-Score <-2.5 SD, 16 of 21 (76%) beyond 28 weeks\u27 gestation and 12 of 30 (40%) before 28weeks\u27 gestation were antenatally identified as having FGR (p = .023).Conclusion:Fetal growth restriction leading to intrauterine fetal death in Japan was antenatally identified in less than half of cases. Antenatal identification of FGR was associated with the severity of growth restriction

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Study for effectively utilizing of limited resources for improvement of perinatal medical system in Shiga Prefecture

科学研究費補助金研究成果報告書研究種目: 基盤研究(C)研究期間: 2011～2014課題番号: 23590594研究代表者: 高橋 健太郎（滋賀医科大学・医学部・特任教授）研究分担者: 越田 繁樹（滋賀医科大学・医学部・特任講師

Bifidobacterium bifidum OLB6378 Simultaneously Enhances Systemic and Mucosal Humoral Immunity in Low Birth Weight Infants: A Non-Randomized Study

Probiotic supplementation has been part of the discussion on methods to enhance humoral immunity. Administration of Bifidobacterium bifidum OLB6378 (OLB6378) reduced the incidence of late-onset sepsis in infants. In this non-randomized study, we aimed to determine the effect of administration of live OLB6378 on infants’ humoral immunity. Secondly, we tried to elucidate whether similar effects would be observed with administration of non-live OLB6378. Low birth weight (LBW) infants weighing 1500–2500 g were divided into three groups: Group N (no intervention), Group L (administered live OLB6378 concentrate), and Group H (administered non-live OLB6378 concentrate). The interventions were started within 48 h after birth and continued until six months of age. Serum immunoglobulin G (IgG) levels (IgG at one month/IgG at birth) were significantly higher in Group L than in Group N (p &lt; 0.01). Group H exhibited significantly higher serum IgG levels (p &lt; 0.01) at one month of age and significantly higher intestinal secretory immunoglobulin A (SIgA) levels (p &lt; 0.05) at one and two months of age than Group N. No difference was observed in the mortality or morbidity between groups. Thus, OLB6378 administration in LBW infants enhanced humoral immunity, and non-live OLB6378, which is more useful as a food ingredient, showed a more marked effect than the viable bacteria

Study for effectively utilizing of limited resources for improvement of perinatal medical system in Shiga Prefecture

科学研究費補助金研究成果報告書研究種目: 基盤研究(C)研究期間: 2011～2014課題番号: 23590594研究代表者: 高橋 健太郎（滋賀医科大学・医学部・特任教授）研究分担者: 越田 繁樹（滋賀医科大学・医学部・特任講師）死亡小票を用いて過去5年間（2007年～2011年）の滋賀県における後期死産188症例および新生児死亡102症例の検討を行った結果、死産症例や新生児死亡症例を回避するためには、出生後の新生児管理改善のみならず妊娠管理能力の向上、妊娠中の異常を早期に発見する出生前診断技術の向上およびハイリスク症例は早期の高次医療機関への紹介等に関する医療従事者への提言と、胎動減少自覚時の速やかな受診等の社会への啓発が重要であることが判明した。このように、死亡症例の25%は周産期医療従事者の技量アップ対策と住民の妊娠・分娩に対する意識改革で、死亡を回避できる可能性があることが判明した。We aimed to examine backgrounds of both stillbirths and neonatal deaths, and the possibilities of prevention in a region of Japan. The 188 stillbirths and 102 neonatal deaths in Shiga prefecture between 2007 and 2011 were included. We evaluated the possibilities of preventable stillbirth and neonatal death, determining specific recommendations for its prevention. The audit conference judged that 25% of them were determined to have had some possibility of prevention. We identified major causes of preventable stillbirths and neonatal death, including substandard obstetrical management, delayed referral of high-risk women from primary obstetrical clinics to higher perinatal centers, and delayed visits of pregnant women with decreased fetal movements to clinics or hospitals. Based on the results of this study, we conclude that education for pregnant women is required as well as the necessity of improving obstetric care to prevent stillbirths