研究者詳細 - 池ノ上　学

論文 - 池ノ上　学

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Virtual telehealth visits for prenatal checkups during the COVID- 19 pandemic in Japan: a nationwide survey and feasibility study

Kobayashi M., Nakagawa S., Kamei Y., Maenaka T., Hiramatsu K., Mimura K., Kimura T., Ueda Y., Fujii M., Endo M., Adachi K., Kurokawa S., Maeda T., Ikenoue S., Tanaka M., Kimura T.

BMC Pregnancy and Childbirth 25 （ 1 ） 476 2025年12月

Background: We investigated the use of virtual telehealth visits (VV) for prenatal checkups in Japan during the coronavirus disease (COVID-19) pandemic, identified challenges associated with their use, and assessed the feasibility of future VV implementation for prenatal care. Methods: Surveys were conducted at birthing facilities across Japan and with pregnant women attending Osaka and Keio University hospitals. To assess the feasibility of VV, we compared the self-measured blood pressure, fundal height, urinary test results, and fetal heart rate of pregnant women with those measured by healthcare providers. Results: We received responses from 1,096 birthing facilities (49.5% response rate) and 96 women. Only 1.6% of birthing facilities implemented VV, mainly due toto a lack of human resources, costs, and low demand from both patients and healthcare providers. In contrast, 60.2% of pregnant women expressed anxiety about in-person visits during the pandemic, and 36.6% preferred the introduction of VV. The Pearson correlation coefficients between self-measured and provider-measured values systolic and diastolic blood pressure and fundal height were 0.68, 0.58, and 0.87, respectively. The concordance rates for proteinuria and urinary glucose were 91.6% and 98.9%, respectively. However, the correlation for fetal heart rate measurements was poor (-0.04). Bland–Altman analysis revealed 95% limits of agreement ranging from -42.6 to 65.6 bpm, indicating the need for methodological improvement. Conclusion: Despite maternal interest, VV has been limitedly implemented in Japan. Our study found that self-measured values, except for fetal heart rate, were highly correlated with those measured by healthcare providers. These findings are important for healthcare providers and government agencies when considering future prenatal checkups.

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Maternal Serum 25-Hydroxyvitamin D as a Possible Modulator of Fetal Adiposity: A Prospective Longitudinal Study

Akita K., Ikenoue S., Tamai J., Otani T., Fukutake M., Kasuga Y., Tanaka M.

International Journal of Molecular Sciences 26 （ 9 ） 2025年05月

ISSN 16616596

25-hydroxyvitamin D (25(OH)D) regulates lipid metabolism, and its decrease is proposed as a pathogenesis of metabolic syndrome, gestational diabetes mellitus (GDM), and eventually fetal adiposity. Decreased 25(OH)D is also linked with the development of gestational diabetes mellitus (GDM), which is associated with increased fetal adiposity. Fetuses are dependent on the supply of 25(OH)D from maternal circulation. However, the influence of maternal serum 25(OH)D on fetal adiposity remains unclear. This study aimed to investigate the association between maternal serum 25(OH)D and fetal adiposity. A prospective longitudinal study was conducted in a cohort of 89 (including 21 GDM) singleton pregnancies. Maternal blood samples were obtained at 10, 24, 30, and 36 weeks, and fetal ultrasonography was performed at 24, 30, and 36 weeks of gestation. Estimated fetal adiposity (EFA) was calculated as the average z-score of cross-sectional arm and thigh percentage fat area and anterior abdominal wall thickness as previously reported. The multiple linear regression analyses indicated that maternal 25(OH)D levels across gestation were not associated with EFA at 24 and 30 weeks, while maternal 25(OH)D at 24 weeks was inversely correlated with EFA at 36 weeks. Particularly, in the GDM group, maternal 25(OH)D levels at 10, 24, 30, and 36 weeks all showed a significant negative correlation with EFA at 36 weeks. Decreased maternal serum 25(OH)D level could be an early biomarker of increased fetal adiposity in late gestation, especially in diabetic pregnancies.

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The Association Between Glucose Variability and Insulin Parameters in Gestational Diabetes Diagnosed After 24 Gestational Weeks

Kasuga Y., Kajikawa K., Ishikawa N., Ogata Y., Takahashi M., Akita K., Tamai J., Fukuma Y., Tanaka Y., Otani T., Fukutake M., Ikenoue S., Tanaka M.

Nutrients 17 （ 3 ） 2025年02月

Background/Objectives: Recently, it was reported that glucose variability (GV) calculated using the 75 g oral glucose tolerance test (OGTT) is associated with adverse perinatal outcomes. However, its role in gestational diabetes mellitus (GDM) remains unclear. We investigated the association between GV and insulin parameters in Japanese women diagnosed with GDM after 24 weeks of gestation (late GDM). Methods: A total of 280 mothers with late GDM cared for at Keio University Hospital were included in this study. Using 75 g OGTT, the initial increase and subsequent decrease were calculated as the GV. Results: The initial increase was significantly positively associated with 1 h plasma glucose level (PG) and 2 h PG with 75 g OGTT (p < 0.001), but fasting PG, insulinogenic index (IGI), and homeostasis model assessment—insulin resistance were negatively associated with the initial increase (all p < 0.001). The subsequent decrease was significantly positively correlated with 1 h PG (p < 0.001) but negatively correlated with 2 h PG (p < 0.001), IGI (p = 0.009), and the whole-body insulin sensitivity index derived from the OGTT (p = 0.02). Insulin Secretion-Sensitivity Index-2 was not associated with an initial increase or subsequent decrease. Conclusions: Since the initial increase might reflect insulin secretion and the subsequent decrease might reflect insulin sensitivity in Japanese women with late GDM, GV could alter several insulin parameters. Further studies are required to investigate the usefulness of GV in the management of GDM.

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Origins of obesity in the womb: Fetal adiposity and its determinants

Ikenoue S., Tamai J., Akita K., Otani T., Kasuga Y., Tanaka M.

Journal of Obstetrics and Gynaecology Research 50 （ 12 ） 2178 - 2182 2024年12月

ISSN 13418076

Birth weight is an important predictor of perinatal complications and long-term health outcomes of offspring. Fetal programming influenced by maternal obesity, overnutrition, and hyperglycemia has been proposed as the fuel overload hypothesis. Recent investigations related with fetal body composition have revealed that neonatal adiposity can be predicted by fetal fat mass, and that maternal insulin resistance and serum leptin level are indicators of fetal adiposity. Based on the current evidence, the origins of obesity can partly be traced back into the fetal life. Further clarification of the determinants of fetal fat mass may lead to the clinical interventions and treatment strategies for fetal growth and development. This effort potentially leads to the elucidation of pathological conditions related with long-term health outcomes and the primary prevention of childhood obesity and early onset metabolic syndrome.

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Multiple positive points during the 75 g oral glucose tolerance test are good predictors for early insulin therapy in gestational diabetes mellitus diagnosed before 24 gestational weeks

Kasuga Y., Takahashi M., Kajikawa K., Akita K., Tamai J., Fukuma Y., Tanaka Y., Hasegawa K., Otani T., Ikenoue S., Tanaka M.

Journal of Diabetes Investigation 15 （ 12 ） 1803 - 1808 2024年12月

ISSN 20401116

Aims/Introduction: This study evaluated the risk factors for insulin therapy before 24 gestational weeks (early insulin therapy) in pregnant women with gestational diabetes diagnosed before 24 gestational weeks (E-GDM). Materials and Methods: This study included 530 singleton mothers with E-GDM who underwent a 75 g oral glucose tolerance test (OGTT) in the first trimester at Keio University Hospital between January 2013 and December 2021. E-GDM can be classified according to its management into only diet therapy until delivery (Diet E-GDM), insulin therapy started before 24 gestational weeks (EarlyIns E-GDM), and insulin therapy started after 24 gestational weeks (LateIns E-GDM). We analyzed the risk factors for EarlyIns E-GDM. Results: Patients with EarlyIns E-GDM had a significantly higher maternal age at delivery, pre-pregnancy BMI, first trimester hemoglobin A1c, 1 h plasma glucose levels (1 h-PG), and 2 h-PG, as well as a more pronounced initial increase and subsequent decrease, compared with those in the Diet E-GDM group. However, the Apgar scores at both 1 and 5 min were significantly lower in patients with EarlyIns E-GDM than in those with Diet E-GDM. The number of abnormal values in the OGTT showed the largest area under the receiver operating characteristic curve (AUC) for predicting EarlyIns E-GDM (0.83, 95% confidence interval [CI]: 0.79–0.86), followed by the 1 h-PG value (AUC: 0.81, 95% CI: 0.77–0.85). The initial increase showed the third largest AUC (0.78, 95% CI: 0.74–0.82). Conclusions: Although further research is needed, our data suggest the importance of early insulin therapy in cases of E-GDM with multiple abnormal OGTT values, especially with high 1 h-PG levels and initial increase.

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Efficacy of controlled-release dinoprostone vaginal insert for elective induction of labor before due date

Tamai J., Ikenoue S., Akita K., Fukuma Y., Tanaka Y., Hasegawa K., Otani T., Kasuga Y., Tanaka M.

Journal of Obstetrics and Gynaecology Research 50 （ 12 ） 2226 - 2230 2024年12月

ISSN 13418076

Aim: The induction of labor before due date has recently been proved to reduce the rate of cesarean sections and is not associated with increased risk of adverse perinatal outcomes as compared to expectant management. Controlled-release dinoprostone (PGE2) vaginal insert has recently been approved for use in Japan. However, evidence regarding its efficacy in cervical ripening and labor induction before due date remains limited. We aimed to compare the efficacy of PGE2 vaginal inserts and mechanical dilation for labor induction before due date. Methods: This retrospective cohort study included 206 mothers at 37, 38, and 39 weeks' gestation delivered at our institution between January 2021 and October 2022. Perinatal outcomes, including the success rate of vaginal delivery, were compared between the PGE2 (n = 46) and metreurynter/laminaria tent (non-PGE2) (n = 160) groups. The success rate of vaginal delivery was defined as the proportion of women who delivered vaginally within 48 h of initiating oxytocin augmentation. Results: The success rate of vaginal delivery was significantly higher in the PGE2 group (37/49, 80.4%) than in the non-PGE2 group (106/177, 66.2%). Emergency cesarean section related to non-reassuring fetal status was performed with none in the PGE2 group and with eight (5.0%) in the non-PGE2 group. Conclusions: The rate of vaginal delivery was significantly higher in the PGE2 group for elective labor induction between 37 and 39 weeks. The PGE2 vaginal insert could increase the success rate of vaginal delivery for elective induction of labor at 39 weeks.

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Perinatal Outcomes of Diet Therapy in Gestational Diabetes Mellitus Diagnosed before 24 Gestational Weeks

Kasuga Y., Takahashi M., Kajikawa K., Akita K., Otani T., Ikenoue S., Tanaka M.

Nutrients 16 （ 11 ） 2024年05月

To evaluate perinatal outcomes and risk factors for large for gestational age (LGA; birth weight over 90 percentile) in gestational diabetes diagnosed before 24 gestational weeks and treated with diet therapy alone until delivery (Diet Early gestational diabetes mellitus (Diet Early GDM)), we assessed the maternal characteristics and perinatal outcomes of patients with early GDM (n = 309) and normal glucose tolerance (NGT; n = 309) at Keio University Hospital. The gestational weight gain (GWG) expected at 40 weeks was significantly lower in the Diet Early GDM group than in the NGT group. The Diet Early GDM group exhibited a significantly lower incidence of low birth weight (<2500 g) and higher Apgar score at 5 min than the NGT group. Multiple logistic regression analysis revealed that the pre-pregnancy body mass index and GWG expected at 40 weeks were significantly associated with LGA for Diet Early GDM. No differences were observed in random plasma glucose levels in the first trimester, 75 g oral glucose tolerance test values, and initial increase or subsequent decrease between the two groups. Dietary early GDM did not exhibit a worse prognosis than NGT. To prevent LGA, it might be important to control maternal body weight not only during pregnancy but also before conception.

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Association of maternal obesity with growth of fetal fractional limb volume

Ikenoue S., Akiba Y., Ishii R., Otani T., Kasuga Y., Tanaka M.

Early Human Development 191 105990 2024年04月

ISSN 03783782

Background: Maternal obesity influences birth weight and newborn adiposity. Fetal fractional limb volume has recently been introduced as a useful parameter for the proxy of fetal adiposity. However, the association between maternal adiposity and the growth of fetal fractional limb volume has not been examined. Aims: To investigate the association of maternal pre-pregnancy BMI with the growth of fetal fractional limb volume. Study design: Prospective cohort study. Subjects: Women with singleton uncomplicated pregnancies enrolled between July 2017 and June 2020. Outcome measures: Fetal fractional limb volume was assessed between 20 and 40 weeks' gestation, measured as cylindrical limb volume based on 50 % of the total diaphysis length. The measured fractional limb volume at each gestational week were converted to z-scores based on a previous report. The association between pre-pregnancy BMI and fetal fractional limb volume was examined. Maternal age, parity, gestational weight gain and fetal sex were considered as potential confounding variables. Results: Ultrasound scans of 455 fractional arm volume and thigh volume were obtained. Fractional limb volume increased linearly until the second trimester of gestation, then increased exponentially in the third trimester. Maternal pre-pregnancy BMI was significantly correlated with z-scores of fractional arm volume and thigh volume across gestation. The post-hoc analysis showed the association between pre-pregnancy BMI and fractional arm volume was significant especially between 34 and 40 weeks. Conclusions: Maternal obesity influences the growth pattern of fetal fractional limb volume. Fractional arm volume may potentially provide a useful surrogate marker of fetal nutritional status in late gestation.

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Sonographic changes in uterine vein thrombosis during pregnancy on transvaginal ultrasound

Sato A., Tanaka K., Sakuma M., Ikenoue S., Kasuga Y., Tanaka M.

Journal of Medical Ultrasonics 51 （ 2 ） 369 - 370 2024年04月

ISSN 13464523

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Perinatal care at periviable age　妊娠22週・23週の分娩における産科管理

池ノ上学

日本周産期・新生児医学会雑誌（(一社)日本周産期・新生児医学会） 59 （ 4 ） 475 - 477 2024年04月

ISSN 1348-964X

当院で2013～2020年に妊娠22週0日～23週6日で分娩となった単胎妊娠17例を対象とし、「分娩様式」「帝王切開時のニトログリセリン投与の有無」「新生児合併症」「1歳時死亡率」などについて後方視的に調査した。分娩様式は経腟分娩2例(12%)、帝王切開15例(88%)で、経腟分娩例はいずれも当院へ母体搬送時に子宮口が全開大で頭位であったため経腟分娩となった。帝王切開例のうち子宮筋層切開時にグリセリンが投与されたのは4例(27%)であった。新生児合併症は慢性肺疾患を12例(71%)、脳室内出血を2例(12%)、壊死性腸炎を2例(12%)に認め、脳室内出血を認めた2例はいずれも帝王切開時にニトログリセリン投与が行われていなかった。1歳未満の死亡が2例(12%)あり、いずれもHELLP症候群と胎児発育不全のため帝王切開で出生し、生後に慢性肺疾患と肺炎をきたしていた。

周産期の栄養と代謝を考える:妊娠中の栄養と代謝を考える　Fetal Origins of Obesity　超音波を用いた胎児脂肪量の評価とその規定因子の解明

池ノ上学

周産期学シンポジウム（(一社)日本周産期・新生児医学会）（ 42 ） 101 - 103 2024年

ISSN 1342-0526

Fetal Origins of Obesity:超音波を用いた胎児脂肪量の評価とその規定因子の解明を試みた。超音波パラメータを用い、新生児体脂肪率の予測因子や胎児脂肪量の規定因子の探索目的に以下の検討を行った。(1)胎児脂肪量と新生児体脂肪率の関連、(2)母体インスリン抵抗性と胎児脂肪量の関連、(3)母体血清アディポカインと胎児脂肪量の関連。その結果、妊娠後期の胎児脂肪量と新生児体脂肪率との関連を認め、妊娠中期の母体インスリン抵抗性や血清レプチン濃度は妊娠後期の胎児脂肪量の指標となることが判明した。以上より、胎児脂肪量から新生児体脂肪率の予測が可能で、母体のインスリン抵抗性や血清レプチン濃度は胎児脂肪量の指標となる。

染色体異常を伴わない胎児臍帯ヘルニアの2例

木村由実子, 玉井順子, 春日義史, 秋田啓介, 田中邦生, 葉室明香, 福間優花, 長谷川慶太, 大谷利光, 池ノ上学, 青木大輔, 田中守

東京産科婦人科学会会誌（(一社)東京産科婦人科学会） 72 （ 2 ） 327 - 331 2023年04月

ISSN 2186-0599

緒言:今回我々は染色体異常を伴わない胎児臍帯ヘルニアの2例の周産期管理を行ったので報告する.症例1は41歳,1妊0産.体外受精-胚移植により妊娠成立し,妊娠13週に臍帯ヘルニアを指摘された.症例2は40歳,1妊0産.自然妊娠にて妊娠成立し,妊娠12週に胎児腹部腫瘤を指摘された.いずれも妊娠16週の羊水検査で正常核型であり,超音波断層法では肝脱出型臍帯ヘルニアと単一臍帯動脈以外の形態異常は指摘されなかった.出生後の精査にて症例1は食道閉鎖,鎖肛,軟口蓋裂,左多合指症等を認めたためVATER連合,症例2は耳介の形態や高インスリン血症からBeckwith-Wiedemann症候群が疑われた.結論:染色体異常を伴っていない臍帯ヘルニアでは,他の症候群の1症候であり出生後に判明する場合があることを念頭に胎児の慎重な観察と家族への十分な説明を行うことが望ましいと考えられた.(著者抄録)

Ultrasonographic Prediction of Placental Invasion in Placenta Previa by Placenta Accreta Index

Hasegawa K., Ikenoue S., Tanaka Y., Oishi M., Endo T., Sato Y., Ishii R., Kasuga Y., Ochiai D., Tanaka M.

Journal of Clinical Medicine （Journal of Clinical Medicine） 12 （ 3 ） 2023年02月

ISSN 2077-0383

This study aimed to investigate the diagnostic accuracy of the placenta accreta index (PAI) for predicting placenta accreta spectrum (PAS) in women with placenta previa. We analyzed 33 pregnancies with placenta previa at Keio University Hospital. The PAI was assessed in the early third trimester, and PAS was diagnosed histologically or clinically defined as retained placenta after manual removal attempts. The PAI and incidence of PAS were analyzed. Ten women (30%) were diagnosed with PAS and had higher volumes of perioperative bleeding (p = 0.016), higher rate of requiring uterine artery embolization (p = 0.005), and peripartum hysterectomy (p = 0.0002) than women without PAS. A PAI > 2 was the most useful cut-off point for predicting PAS and was more sensitive than prediction values using traditional evaluation (history of cesarean section and placental location). Post-hoc analysis revealed a higher rate of previous history of cesarean delivery (30% vs. 4.4%, p = 0.038), severe placental lacunae (≥grade2) (70% vs. 8.7%, p = 0.0003), thin myometrial thickness (90% vs. 22%, p = 0.0003), anterior placenta (100% vs. 30%, p = 0.0002), and presence of bridging vessels (30% vs. 0%, p = 0.0059) in PAS women. PAI could help predict the outcomes of women with placenta previa with and without a history of cesarean delivery to reduce PAS-induced perinatal complications.

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Obstetric outcomes after medroxyprogesterone acetate treatment for early stage endometrial cancer or atypical endometrial hyperplasia: a single hospital-based study.

Oishi M, Kasuga Y, Fukuma Y, Hamuro A, Tamai J, Tanaka Y, Hasegawa K, Yoshimura T, Ikenoue S, Ochiai D, Yamagami W, Tanaka M

International journal of clinical oncology （International Journal of Clinical Oncology） 28 （ 4 ） 587 - 591 2023年01月

ISSN 1341-9625

Background: To investigate perinatal outcomes in pregnancy after high-dose medroxyprogesterone acetate (MPA) therapy for early stage endometrial cancer (EC) and atypical endometrial hyperplasia (AEH) and to determine whether pregnancy after MPA therapy is at a higher risk of placenta accreta. Methods: Data of 51 pregnancies in 46 women who received MPA therapy for EC or AEH and delivered after 22 weeks of gestation at Keio University Hospital were reviewed. A retrospective matched case–control study was performed to determine the risk of placenta accreta in pregnancy after MPA therapy compared with singleton pregnancies without any history of maternal malignancy treatments. Results: The incidence of placenta accreta was higher in the MPA group than in the control group (15.7 vs. 0%, p = 0.0058). However, no differences in other perinatal outcomes were observed between groups. While gestational weeks at delivery in the MPA group were later than those in the control group (p = 0.0058), no difference in the incidence of preterm delivery was recorded between groups. In the MPA therapy group, the number of patients who underwent ≥ 6 dilation and curettage (D&C) was higher in the placenta accreta group than in the non-placenta accreta group (50.0 vs. 14.0%, p = 0.018). Patients with ≥ 6 D&Cs demonstrated a 6.0-fold increased risk of placenta accreta (p = 0.043, 95% CI 1.05–34.1) than those receiving ≤ 3 D&Cs. Conclusion: Pregnancy after MPA therapy is associated with a high risk of placenta accreta. In cases in which the frequency of D&C is high, placenta accreta should be considered.

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Pregnancy outcomes and vaccine effectiveness during the period of omicron as the variant of concern, INTERCOVID-2022: a multinational, observational study.

Villar J, Soto Conti CP, Gunier RB, Ariff S, Craik R, Cavoretto PI, Rauch S, Gandino S, Nieto R, Winsey A, Menis C, Rodriguez GB, Savasi V, Tug N, Deantoni S, Fabre M, Martinez de Tejada B, Rodriguez-Sibaja MJ, Livio S, Napolitano R, Maiz N, Sobrero H, Peterson A, Deruelle P, Giudice C, Teji JS, Casale RA, Salomon LJ, Prefumo F, Cheikh Ismail L, Gravett MG, Vale M, Hernández V, Sentilhes L, Easter SR, Capelli C, Marler E, Cáceres DM, Albornoz Crespo G, Ernawati E, Lipschuetz M, Takahashi K, Vecchiarelli C, Hubka T, Ikenoue S, Tavchioska G, Bako B, Ayede AI, Eskenazi B, Thornton JG, Bhutta ZA, Kennedy SH, Papageorghiou AT, INTERCOVID-2022 International Consortium

Lancet (London, England) （The Lancet） 401 （ 10375 ） 447 - 457 2023年01月

ISSN 0140-6736

Background: In 2021, we showed an increased risk associated with COVID-19 in pregnancy. Since then, the SARS-CoV-2 virus has undergone genetic mutations. We aimed to examine the effects on maternal and perinatal outcomes of COVID-19 during pregnancy, and evaluate vaccine effectiveness, when omicron (B.1.1.529) was the variant of concern. Methods: INTERCOVID-2022 is a large, prospective, observational study, involving 41 hospitals across 18 countries. Each woman with real-time PCR or rapid test, laboratory-confirmed COVID-19 in pregnancy was compared with two unmatched women without a COVID-19 diagnosis who were recruited concomitantly and consecutively in pregnancy or at delivery. Mother and neonate dyads were followed until hospital discharge. Primary outcomes were maternal morbidity and mortality index (MMMI), severe neonatal morbidity index (SNMI), and severe perinatal morbidity and mortality index (SPMMI). Vaccine effectiveness was estimated, adjusted by maternal risk profile. Findings: We enrolled 4618 pregnant women from Nov 27, 2021 (the day after WHO declared omicron a variant of concern), to June 30, 2022: 1545 (33%) women had a COVID-19 diagnosis (median gestation 36·7 weeks [IQR 29·0–38·9]) and 3073 (67%) women, with similar demographic characteristics, did not have a COVID-19 diagnosis. Overall, women with a diagnosis had an increased risk for MMMI (relative risk [RR] 1·16 [95% CI 1·03–1·31]) and SPMMI (RR 1·21 [95% CI 1·00–1·46]). Women with a diagnosis, compared with those without a diagnosis, also had increased risks of SNMI (RR 1·23 [95% CI 0·88–1·71]), although the lower bounds of the 95% CI crossed unity. Unvaccinated women with a COVID-19 diagnosis had a greater risk of MMMI (RR 1·36 [95% CI 1·12–1·65]). Severe COVID-19 symptoms in the total sample increased the risk of severe maternal complications (RR 2·51 [95% CI 1·84–3·43]), perinatal complications (RR 1·84 [95% CI 1·02–3·34]), and referral, intensive care unit (ICU) admission, or death (RR 11·83 [95% CI 6·67–20·97]). Severe COVID-19 symptoms in unvaccinated women increased the risk of MMMI (RR 2·88 [95% CI 2·02–4·12]) and referral, ICU admission, or death (RR 20·82 [95% CI 10·44–41·54]). 2886 (63%) of 4618 total participants had at least a single dose of any vaccine, and 2476 (54%) of 4618 had either complete or booster doses. Vaccine effectiveness (all vaccines combined) for severe complications of COVID-19 for all women with a complete regimen was 48% (95% CI 22–65) and 76% (47–89) after a booster dose. For women with a COVID-19 diagnosis, vaccine effectiveness of all vaccines combined for women with a complete regimen was 74% (95% CI 48–87) and 91% (65–98) after a booster dose. Interpretation: COVID-19 in pregnancy, during the first 6 months of omicron as the variant of concern, was associated with increased risk of severe maternal morbidity and mortality, especially among symptomatic and unvaccinated women. Women with complete or boosted vaccine doses had reduced risk for severe symptoms, complications, and death. Vaccination coverage among pregnant women remains a priority. Funding: None.

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Pregnancy outcomes following radical trachelectomy for early-stage cervical cancer: A retrospective observational study in the Kanto area, Japan

Kasuga Y., Hasegawa K., Hamuro A., Fukuma Y., Tamai J., Tanaka Y., Ikenoue S., Tanaka M.

International Journal of Gynecology and Obstetrics （International Journal of Gynecology and Obstetrics） 164 （ 1 ） 108 - 114 2023年

ISSN 00207292

Objective: The authors aimed to investigate the prevalence of pregnancy and obstetric outcomes in patients who underwent radical trachelectomy (RT) for early-stage cervical cancer in the Kanto area, Japan. Method: A survey among 113 perinatal centers affiliated with the Kanto Society of Obstetrics and Gynecology was conducted to investigate their experience in managing pregnancies following RT, between 2010 and 2020. The association between preterm delivery (before 34 gestational weeks) and a midtrimester short cervix (<13 mm) was evaluated. Results: The authors retrospectively collected maternal and perinatal data from 13 hospitals. There were 135 pregnancies among 115 women following RT. Of the 135 pregnancies, 32 were miscarriages (<12 gestational weeks: n = 22; >12 gestational weeks: n = 10), and 103 were delivered after 22 gestational weeks. The incidences of preterm delivery before 28 and 34 gestational weeks were 8.7% and 30.1%, respectively. A midtrimester short residual cervix was associated with preterm delivery (P = 0.046). Conclusion: Since more than 100 pregnancies were recorded after RT in the Kanto area, many physicians had more opportunities to manage pregnancy after RT. Pregnancy following RT is associated with increased risk of preterm delivery, and midtrimester short residual cervix is a good predictor of preterm delivery.

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Risk factors of neonatal hypoglycemia in neonates born to mothers with gestational diabetes

Arimitsu T., Kasuga Y., Ikenoue S., Saisho Y., Hida M., Yoshino J., Itoh H., Tanaka M., Ochiai D.

Endocrine Journal （Endocrine Journal） 70 （ 5 ） 511 - 517 2023年

ISSN 09188959

Hypoglycemia is one of the most significant problems in neonates born to mothers with gestational diabetes (GDM). This study aimed to identify novel predictors of hypoglycemia in neonates born to mothers with GDM. A total of 443 term singleton infants from mothers diagnosed with GDM and cared for at Keio University Hospital between January 2013 and December 2019 were included in this study. Neonatal hypoglycemia was defined as hypoglycemia of less than 47 mg/dL at 1 or 2 or 4 h after birth, according to previous studies. Among 443 full-term singleton neonates born to mothers with GDM, 200 developed hypoglycemia (45%). Gestational weight gain (GWG), HbA1c at 1st trimester, HbA1c at GDM diagnosis, and the incidence of insulin therapy in the neonatal hypoglycemia group were significantly higher than those in the non-neonatal hypoglycemia group (p = 0.016, p = 0.032, p = 0.011, and p = 0.017, respectively). Regarding the multiple regression analysis adjusted for nulliparity, GWG, and gestational weeks at delivery, the odds ratio for maternal HbA1c ≥5.2% at 1st trimester was 1.63 (p = 0.034), and maternal insulin therapy during pregnancy was 1.72 (p = 0.015). In conclusion, HbA1c in the 1st trimester and insulin therapy during pregnancy were good predictors of hypoglycemia in neonates born to GDM mothers, especially when their HbA1c was 5.2% or more. Further research will be necessary to improve the perinatal management of hypoglycemia.

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Factors associated with low birthweight among late preterm singletons in Japan using pregnancy birth registry data

Kasuga Y., Tanaka K., Akita K., Tamai J., Hamuro A., Fukuma Y., Hasegawa K., Ikenoue S., Tanaka M.

Journal of Developmental Origins of Health and Disease （Journal of Developmental Origins of Health and Disease） 14 （ 5 ） 1 - 7 2023年

ISSN 20401744

Late preterm (LP, born between 34 0/7 and 36 6/7 weeks of gestation) infants may experience several adverse outcomes, similar to those experienced by low birthweight (LBW, birthweight <2500 g) infants. However, while LP infants are often born with LBW, the association between LP and LBW remains unknown. This study aimed to investigate LBW rate and independent risk factors for LBW in LP singleton neonates. We retrospectively analyzed data of LP singleton neonates, born between 2013 and 2017, from the Japan Society of Obstetrics and Gynecology Successive Pregnancy Birth Registry System. The exclusion criteria included stillbirths and infants with missing data. Logistic regression analyses were performed to investigate maternal and perinatal factors associated with LBW in LP singletons. LBW was observed in 62.5% (n = 35,113) of 56,160 LP singleton births. In the multiple logistic regression analysis, LBW in LP neonates was independently associated with modifiable maternal factors, including pre-pregnancy underweight, inadequate gestational weight gain, and smoking during pregnancy, as well as non-modifiable factors, including younger maternal age, nulliparity, hypertensive disorder of pregnancy, preeclampsia, cesarean section delivery, and female offspring. According to the Japanese pregnancy birth registry data, more than half of LP neonates were LBW. We previously discussed the issue of LBW regarding infants with different backgrounds, as there are many different causes of LBW. Several risk factors should be subdivided and considered for the risk of LP and LBW.

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Fetal growth restriction and a single umbilical artery are independent predictors of hypospadias during pregnancy

Endo T., Iida M., Ichihashi Y., Oishi M., Ikenoue S., Kasuga Y., Sato T., Hida M., Ishii T., Asanuma H., Hasegawa T., Tanaka M., Ochiai D.

Placenta （Placenta） 130 53 - 59 2022年12月

ISSN 01434004

Introduction: Little is known about the association between hypospadias and small fetuses, as well as the pathological implications of fetal growth restriction (FGR). Thus, we aimed to investigate the association between hypospadias and small fetuses using a database of fetal ultrasound and obstetric events. Methods: A cohort of male singleton infants delivered after 22 weeks of gestation at Keio University Hospital between 2013 and 2019 was retrospectively reviewed. FGR was defined according to the Delphi criteria. Logistic regression analysis was performed to identify the significant predictors of hypospadias. Placental pathology was reviewed in cases with hypospadias. Results: Of the 2,040 male infants included in the present study, 23 had hypospadias. The prevalences of a single umbilical artery (SUA), small for gestational age, maternal hypertensive disorders of pregnancy, and a small placenta, were significantly higher in infants with hypospadias. Multiple logistic regression analysis revealed that FGR (odds ratio [OR] = 9.39; 95% confidence interval [CI], 2.50–35.3) and the presence of a SUA (OR = 33.4; 95% CI, 8.00–139.5) were independently and significantly associated with hypospadias. When FGR was stratified by the time of onset, its association with hypospadias was significant regardless of the time of onset. Moreover, placental histological findings suggested that fetal vascular malperfusion might play a role in hypospadias. Discussion: FGR and SUAs are independent prenatal predictors of the development of hypospadias, and fetal vascular malperfusion of the placenta may be involved in the etiology of hypospadias.

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Exponential increase of the gestational-age-specific incidence of preeclampsia onset (COPE study): a multicenter retrospective cohort study in women with maternal check-ups at <20 weeks of gestation in Japan

Ohkuchi A., Suzuki H., Matsubara K., Watanabe K., Saitou T., Oda H., Obata S., Kondo S., Noda K., Miyoshi J., Ikenoue S., Nomiyama M., Seki H., Sukegawa S., Ichigo S., Ando H., Fuseya C., Shimomura T., Suzuki R., Mimura K., Yasuhi I., Fukuda M., Hara S., Kurashina R., Shiozaki A., Matsubara S., Saito S.

Hypertension Research （Hypertension Research） 45 （ 11 ） 1679 - 1689 2022年11月

ISSN 09169636

According to the 2004 Japanese definition, early-onset (EO) preeclampsia (PE) is defined as PE occurring at <32 weeks of gestation. This was based on the presence of “dual peaks” (30–31 and 34–35 weeks) in the prevalence of severe forms of hypertension. In contrast, the international definition adopted a cutoff of 34 weeks based on the consensus. Our aim was to investigate whether there were “dual peaks” in the gestational-age-specific incidence or prevalence of PE onset in pregnant women who underwent maternal check-ups at <20 weeks of gestation in a multicenter retrospective cohort study. Diagnoses of PE and superimposed preeclampsia (SPE) were based on the new Japanese definition. A total of 26,567 pregnant women with singleton pregnancy were investigated. The best fitting equations for the distribution of the onset of gestational-age-specific incidence (hazard) rates of PE/SPE, PE, and PE with severe hypertension (a systolic blood pressure ≥160 and/or a diastolic blood pressure ≥110 mmHg) were investigated using the curve estimation function in SPSS. PE/SPE occurred in 1.83% of the patients. EO-PE/SPE with onset at <32 and <34 weeks of gestation and preterm PE/SPE occurred in 0.38, 0.56, and 1.07% of the patients, respectively. Gestational-age-specific incidence rates of PE/SPE, PE, and PE with severe hypertension showed exponential increases, with very high R2 values (0.975, 0.976, and 0.964, respectively). There were no “dual peaks” in the prevalence rates of women with SPE/PE, PE, and PE with severe hypertension. In conclusion, the absence of “dual peaks” refutes the previous rationale of EO-PE being defined as PE at <32 weeks of gestation. Further studies to determine an appropriate definition of EO-PE/SPE are needed.

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