Published papers

There is a paucity of information on perinatal data regarding gestational diabetes mellitus (GDM) by the new criteria from a real experience because the number of health care associations implementing the new criteria is still limited. The aim of this study is to investigate perinatal features of the new criteria-defined GDM. We reviewed a total of 995 women with singleton pregnancy that underwent GDM screening followed by a diagnostic oral glucose tolerance test (OGTT). All women found to have GDM underwent self-monitoring of blood glucose measurements as well as dietary management. Insulin treatment was initiated when dietary treatment did not achieve the glycemic goal. Of the 995 women, 141 had GDM (14.2%): 104 with one, 27 with two, and 10 with three abnormal OGTT values. Women with two or three abnormal OGTT values (2/3-AV) needed insulin treatment more frequently than those with one abnormal OGTT value (1-AV) (70.3% vs 23.1%, P < 0.0001). After adjustment for age, pregravid overweight, gestational weeks at diagnosis, a first-degree family history of diabetes was correlated with the implementation of insulin treatment in women with 1-AV (adjusted odds ratio 3.9; 95% Confidence Interval 1.7-9.2; P = 0.001). When compared perinatal outcomes between women with normal glucose tolerance and GDM, fetal growth and the occurrence of pregnancy-induced hypertension were comparable between the two groups. Our data suggest that the IADPSG-defined GDM with 1-AV show less severe glucose intolerance, but might be at risk of insulin requirement when a first-degree family history of diabetes exists.

Calcium and nutrients are transferred from mothers to fetuses or infants during pregnancy or lactation, respectively, promoting metabolic changes in the mother, many uncharacterized. To evaluate these changes, we undertook two parallel studies. In one we analyzed fourteen clinical cases of vertebral fragility fractures, at or before three months after partum, in mothers who breastfed their infants. In the other, we enrolled 79 additional pregnant subjects, some who chose to breastfeed and others who did not, and analyzed changes in bone metabolic status starting between 34 and 36 weeks of gestation and ending one month after partum. In the larger group, bone-resorbing and bone-forming parameters such as serum TRACP5b and osteocalcin, respectively, significantly increased after partum. Among parameters that changed after partum, serum PTH and the bone-resorbing markers serum TRACP5b and urine NTX were significantly higher in mothers who only breastfed infants compared to mothers who fed infants formula or a mix of both. However, bone-forming parameters were comparable between breastfeeding and non-breast-feeding groups after partum, suggesting that elevated bone-resorption occurs only in the breastfeeding group. Radiographic analysis after partum demonstrated that no subject among the 79 analyzed showed vertebral fractures, even those who breastfed exclusively. Among fracture cases analyzed, subjects exhibited significantly lower bone mineral density than did non-fracture cases in breastfeeding-only subjects. We conclude that bone metabolic status significantly changes over the period between pregnancy and post-partum lactation, and that low bone mineral density seen in a small subset of breastfeeding-only cases likely causes post-partum vertebral fragility fractures.

OBJECTIVE: Pregnancy after conization is associated with a high risk of preterm delivery. However, because risk factors for preterm delivery after conization remain unknown, we conducted a multicenter observational study to investigate risk factors associated with preterm delivery. METHODS: We selected patients who had previously undergone conization and reviewed medical records from 18 hospitals in cooperation with Keio University School of Medicine between January 2013 and December 2019. Women were classified as nulliparous and primiparous, and a multiple logistic regression analysis was performed to evaluate the relative contributions of the various maternal risk factors for preterm delivery (i.e. delivery before 37 gestational weeks). RESULTS: Among 409 pregnant women after conization, 68 women delivered preterm (17%). The incidence of nulliparity (p = .014) was higher and a history of preterm delivery (p = .0010) was more common in the preterm delivery group than in the term delivery group. Furthermore, the proportion of women diagnosed with adenocarcinoma in situ (AIS) and cervical cancer in the preterm delivery group was higher than that in the term delivery group (p = .0099 and .0004, respectively). In multiple regression models in nulliparous women, cervical cancer or AIS (Odds ratio [OR]: 4.16, 95% CI: 1.26-13.68, p = .019) and a short cervix in the second trimester (OR: 13.41, 95% CI: 3.88-46.42, p < .0001) increased the risk of preterm delivery. Furthermore, a history of preterm delivery (OR: 7.35, 95% CI: 1.55-34.86, p = .012), cervical cancer or AIS (OR: 5.07, 95% CI: 1.24-20.73, p = .024), and a short cervix in the second trimester (OR: 4.29, 95% CI: 1.11-16.62, p = .035) increased the risk of preterm delivery in the multiple regression models in primiparous women. CONCLUSION: Pregnant women who previously underwent conization are at risk for preterm delivery. The histological type of AIS and cervical cancer was evaluated as a risk factor for preterm delivery. KEY MESSAGESPrior preterm delivery, presence of a short cervix, and cervical cancer or AIS were predictors of preterm delivery after conization.The depth of conization in cervical cancer or AIS group was significantly larger than that in the CIN group.

Fetal fractional limb volume is a useful measure for predicting birth weight and newborn adiposity; however, a normal growth curve has been reported solely in the United States. As the birth weight of neonates in Japan is significantly lower than that in the US, fetal fractional limb volume is likely to be smaller in the Japanese population. This study aimed to define the normal growth curve of fractional arm volume (AVol) and thigh volume (TVol) in the Japanese population. Ultrasound scans of 453 AVol and TVol pairs were obtained; each AVol and TVol percentile at each gestational age was calculated. The measured AVol and TVol at each gestational week were also converted to z-scores based on a previous report. The growth curves increased linearly until the second trimester and exponentially in the third trimester. Linear regression showed a significant negative correlation between gestational age and AVol and TVol z-scores. The growth pattern of fetal fractional limb volume in the Japanese population is consistent with, but smaller than, that reported in the US; this difference becomes greater as the gestational age progresses.

BACKGROUND: Among nonpregnant individuals, diabetes mellitus and high body mass index increase the risk of COVID-19 and its severity. OBJECTIVE: This study aimed to determine whether diabetes mellitus and high body mass index are risk factors for COVID-19 in pregnancy and whether gestational diabetes mellitus is associated with COVID-19 diagnosis. STUDY DESIGN: INTERCOVID was a multinational study conducted between March 2020 and February 2021 in 43 institutions from 18 countries, enrolling 2184 pregnant women aged ≥18 years; a total of 2071 women were included in the analyses. For each woman diagnosed with COVID-19, 2 nondiagnosed women delivering or initiating antenatal care at the same institution were also enrolled. The main exposures were preexisting diabetes mellitus, high body mass index (overweight or obesity was defined as a body mass index ≥25 kg/m2), and gestational diabetes mellitus in pregnancy. The main outcome was a confirmed diagnosis of COVID-19 based on a real-time polymerase chain reaction test, antigen test, antibody test, radiological pulmonary findings, or ≥2 predefined COVID-19 symptoms at any time during pregnancy or delivery. Relationships of exposures and COVID-19 diagnosis were assessed using generalized linear models with a Poisson distribution and log link function, with robust standard errors to account for model misspecification. Furthermore, we conducted sensitivity analyses: (1) restricted to those with a real-time polymerase chain reaction test or an antigen test in the last week of pregnancy, (2) restricted to those with a real-time polymerase chain reaction test or an antigen test during the entire pregnancy, (3) generating values for missing data using multiple imputation, and (4) analyses controlling for month of enrollment. In addition, among women who were diagnosed with COVID-19, we examined whether having gestational diabetes mellitus, diabetes mellitus, or high body mass index increased the risk of having symptomatic vs asymptomatic COVID-19. RESULTS: COVID-19 was associated with preexisting diabetes mellitus (risk ratio, 1.94; 95% confidence interval, 1.55-2.42), overweight or obesity (risk ratio, 1.20; 95% confidence interval, 1.06-1.37), and gestational diabetes mellitus (risk ratio, 1.21; 95% confidence interval, 0.99-1.46). The gestational diabetes mellitus association was specifically among women requiring insulin, whether they were of normal weight (risk ratio, 1.79; 95% confidence interval, 1.06-3.01) or overweight or obese (risk ratio, 1.77; 95% confidence interval, 1.28-2.45). A somewhat stronger association with COVID-19 diagnosis was observed among women with preexisting diabetes mellitus, whether they were of normal weight (risk ratio, 1.93; 95% confidence interval, 1.18-3.17) or overweight or obese (risk ratio, 2.32; 95% confidence interval, 1.82-2.97). When the sample was restricted to those with a real-time polymerase chain reaction test or an antigen test in the week before delivery or during the entire pregnancy, including missing variables using imputation or controlling for month of enrollment, the observed associations were comparable. CONCLUSION: Diabetes mellitus and overweight or obesity were risk factors for COVID-19 diagnosis in pregnancy, and insulin-dependent gestational diabetes mellitus was associated with the disease. Therefore, it is essential that women with these comorbidities are vaccinated.

BACKGROUND: The effect of COVID-19 in pregnancy on maternal outcomes and its association with preeclampsia and gestational diabetes has been reported; however, a detailed understanding of the effect of maternal positivity, delivery mode and perinatal practices on fetal and neonatal outcomes is urgently needed. OBJECTIVE: To evaluate the impact of COVID-19 on fetal and neonatal outcomes and the role of the mode of delivery, breastfeeding and early neonatal care practices on the risk of mother-to-child transmission. STUDY DESIGN: In this cohort study that took place from March 2020 to March 2021, involving 43 institutions in 18 countries, 2 unmatched, consecutive, not-exposed women were concomitantly enrolled immediately after each infected woman was identified, at any stage of pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed up until hospital discharge. COVID-19 in pregnancy was determined by laboratory confirmation of COVID-19 and/or radiological pulmonary findings or 2 or more predefined COVID-19 symptoms. The outcome measures were indices of neonatal and perinatal morbidity and mortality, neonatal positivity and its correlation with mode of delivery, breastfeeding and hospital neonatal care practices. RESULTS: A total of 586 neonates born to women with COVID-19 diagnosis and 1535 neonates born to women without COVID-19 diagnosis were enrolled. Women with COVID-19 diagnosis had a higher rate of cesarean section (52.8% compared to 38.5% for those without COVID-19 diagnosis, p<0.01) and pregnancy related complications such as hypertensive disorders of pregnancy and fetal distress, all with p-value < 0.001, compared to women without COVID-19 diagnosis. Maternal diagnosis of COVID-19 carried an increased rate of preterm birth (p ≤0.001) and lower neonatal weight (p ≤0.001), length, and head circumference at birth. In mothers with COVID-19 diagnosis, the length of in-utero exposure was significantly correlated to the risk of the neonate testing positive (OR, 4.5; 95% CI 2.2-9.4 for length of in-utero exposure > 14 days). Among neonates born to mothers with COVID-19 diagnosis, birth via cesarean section was a risk factor for them testing positive for COVID-19 (OR 2.4, 95% CI 1.2-4.7), even when severity of maternal conditions was considered and after multivariable logistic analysis. In the subgroup of neonates born to women with COVID-19 diagnosis, the outcomes worsened when the neonate also tested positive, with higher rates of Intensive Care Unit admission, fever, gastrointestinal and respiratory symptoms and death, even after adjusting for prematurity. Breastfeeding by mothers with COVID-19 diagnosis, as well as hospital neonatal care practices including immediate skin-to-skin contact and rooming-in, were not associated with an increased risk of newborn positivity. CONCLUSIONS: In this multinational cohort study, COVID-19 in pregnancy was associated with increased maternal and neonatal complications. Cesarean section was significantly associated with newborn COVID-19 diagnosis. Vaginal delivery should be considered the safest mode of delivery if obstetrical and health conditions allow it. Mother to child skin-to-skin contact, rooming-in and direct breastfeeding did not represent risk factors for newborn COVID-19 diagnosis, thus well-established best practices can be continued among women with COVID-19 diagnosis.

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.

緒言:脳動脈解離は若年発症脳梗塞の原因となり、リスク因子としては片頭痛や高血圧が挙げられるが、妊婦における初発例は稀である。今回我々は妊娠中に発症した脳動脈解離による脳梗塞の1例を経験したので報告する。症例:31歳、3妊1産。既往歴として片頭痛を認めた。妊娠26週0日に激しい頭痛が出現し、その1週間後に右側半盲を認めた。頭部MRI/MRA検査で左後大脳動脈の狭小化と左後頭葉の虚血性変化が認められ、脳動脈解離による脳梗塞の診断となった。神経学的症状の増悪や血圧の変動なく経過し、妊娠37週5日に経腟分娩に至った。児は2926gの女児でApgar score 8/10点(1/5分値)であった。分娩中や分娩後に血圧の変動や新規の神経学的異常所見の出現は認めなかった。結論:神経学的異常所見を伴う頭痛を認める際には脳動脈解離を含めた脳血管障害を念頭に頭蓋内病変精査を行う必要があると考えられた。(著者抄録)

胎児巨大肝血管腫は動静脈シャントによって高拍出性心不全を呈し,胎盤循環も悪化する.そのため胎盤循環を含めた胎児循環の評価を行い適切な娩出時期を決定する必要があるが,いまだ確立した評価方法がない.臍静脈血流量(UVFV)の総心拍出量(CCO)における割合(UVFV/CCO)は胎盤循環の指標となることが報告されており,この指標を含めた心循環機能評価を行うことで早期に病状の変化をとらえた胎児巨大肝血管腫の症例を報告する.妊娠27週に心胸郭断面積比(CTAR)48.5%の心拡大と軽度の僧帽弁・三尖弁逆流を認めた.CCO 1,214ml/min,UVFV 350ml/minと増加を認めたが,UVFV/CCOは28.9%と保たれ,羊水量は正常で胎児水腫を認めなかった.しかし,妊娠30週1日にCTAR 62.9%と増悪,CCO 1,620ml/min,UVFV 236ml/minとなり,UVFV/CCOは14.6%に低下した.胎児水腫は認めなかったが羊水過少となり,Biophysical profiling score 2/10点と低値であった.妊娠30週4日に胎児心拍数陣痛図において基線細変動の減少が出現し,胎児機能不全と診断,緊急帝王切開術を施行した.児は2,340g,Apgar score 1点(1分値),5点(5分値),臍帯動脈血pH 7.254で出生した.日齢1.5に肝血管腫に対してコイル塞栓術を行ったが原病のコントロールがつかず,グラム陽性球菌による敗血症で日齢70に永眠した.UVFV/CCOの減少が巨大肝血管腫による胎児胎盤循環の悪化を反映すると思われた.(著者抄録)

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)

日本人妊娠糖尿病(Gestational Diabetes Mellitus:GDM)既往女性における産後糖代謝異常(Postpartum Abnormal Glucose Tolerance:pAGT)発症予測因子を検討した。対象は日本人GDM合併単胎妊婦のうち、分娩後1年以内に75gOGTTを受けた女性である(pAGT[n=59]、正常耐糖能型[n=154])。GDM診断時OGTT血糖値ならびに遺伝因子とpAGTとの関連解析を行ったところ、OGTT2時間値のpAGT発症予測能が高かった(AUC=0.72)。遺伝因子では4遺伝子がpAGT群においてリスクアレルを多く持つ傾向にあり、検出された4遺伝子中、3遺伝子はインスリン分泌関連遺伝子であった。日本人GDM既往女性において、GDM診断時OGTT 2時間値がpAGT発症予測に有用であり、遺伝学的にインスリン分泌不全の関与が示唆された。(著者抄録)

既報の新基準妊娠糖尿病(GDM)の臨床像は、旧基準でのデータベース解析をもとに推測されたものが多く、基準改定後の実際の臨床像に関して十分な知見は得られていない。そこでわれわれは、基準改定後に当院にて妊娠初期から周産期管理を行った単胎妊婦853例を対象に、GDMの臨床像について後方視的検討を行った。853例中GDM例は101例(11.8%)、overt diabetesは3例(0.3%)であった。さらに経口糖負荷試験(OGTT)陽性ポイント数に関して、OGTT 1点陽性例は69例(68%)、2点/3点陽性例は32例(2点陽性例:24例、3点陽性例:8例)であった。また101例中55例は妊娠初期スクリーニングにて検出された。分娩までの血糖コントロールに関して、OGTT 1点陽性例に比べてOGTT 2点/3点陽性例のインスリン導入率は有意に高値であった(20%vs.84%、p<0.05)。なお、OGTT 1点陽性例のなかでは、糖尿病家族歴を有する場合にインスリン療法を要する頻度が高率であった。本検討により、OGTT 1点陽性例はGDMの過半数を占めることが示され、糖尿病家族歴を有するOGTT 1点陽性例では、インスリン療法を要する可能性を念頭においた周産期管理が必要と考えられた。(著者抄録)

産科領域における腹部コンパートメント症候群(abdominal compartment syndrome:ACS)の報告は稀である。今回我々は、帝王切開術後に腹腔内出血を認め、ACSに準じて加療した症例を経験した。症例は43歳、妊娠39週0日に分娩中に児の持続徐脈を認め、超緊急帝王切開術を施行し常位胎盤早期剥離と診断した。帰室1時間後、出血性ショック状態のため産科危機的出血を宣言し子宮動脈塞栓術を施行した。術後1日目、著明な腹部膨隆を認め、ACSを疑い腹部造影CT検査を行ったが臓器血流障害は認めなかった。また、膀胱内圧は14mmHgと上昇しており、約4Lの血性腹水を経腹的にドレナージしたところ呼吸状態が劇的に改善した。そして、その後の経過は順調で術後7日目に退院した。ACS疑いの症例では、腹腔内圧の推定には膀胱内圧が有用であり、早期の治療介入が病態改善に寄与する可能性が示唆された。(著者抄録)