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AIM: This study aimed to investigate the current status of progestogen treatment for pregnant women at a high risk for preterm birth (PTB) in childbirth healthcare facilities in Japan. METHODS: A web-based nationwide questionnaire survey regarding progestogen use for prevention of PTB was conducted among childbirth healthcare facilities from 2019 to 2021. RESULTS: Valid responses were obtained from 528 facilities (25.2% of those surveyed), including 155 tertiary perinatal facilities (making up 92.3% of all tertiary perinatal care facilities). In the survey period, progestogen treatment was implemented in 207 facilities (39.2%) for PTB prevention. Regarding types of progestogens, 17α-hydroxyprogesterone caproate was used in 170 facilities (82.1%), with a low dose (125 mg/week) administered in 62.9% of the facilities to comply with the regulations of the national health insurance system, although 250 mg/week is considered the best dose. Vaginal progesterone was used in 36 facilities (17.4%), although the cost of vaginal progesterone was not covered by health insurance. Of the facilities not administering progestogen treatment, approximately 40% expressed that vaginal progesterone would be their first choice for PTB prevention in daily practice if it would be covered by health insurance in the future. CONCLUSIONS: Due to the current regulations of the Japanese health insurance system, 17α-hydroxyprogesterone caproate, rather than vaginal progesterone, was mainly used for PTB prevention. Despite global evidence supporting vaginal progesterone as the approach with the highest efficacy, only a limited number of facilities have utilized it due to the current drug use regulations in Japan.

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A pregnant woman with severe aplastic anemia was managed using biweekly red blood cell transfusion and oral eltrombopag olamine administration during pregnancy. She was diagnosed with preeclampsia at 35 weeks of gestation. The severity of aplastic anemia is very important for predicting the course of pregnancy.

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In the near future, hypertensive disorders of pregnancy (HDP) have been diagnosed by home blood pressure monitoring (HBPM) instead of clinic BP monitoring. A multicenter study of HBPM was performed in pregnant Japanese women in the non-high risk group for HDP. Participants were women (n = 218), uncomplicated pregnancy who self-measured and recorded their HBP daily. Twelve women developed HDP. HBP was appropriate (100 mmHg in systole and 63 mmHg in diastole), bottoming out at 17 to 21 weeks of gestation. It increased after 24 weeks of gestation and returned to non-pregnant levels by 4 weeks of postpartum. The upper limit of normal HBP was defined as the mean value +3 SD for systolic and mean +2 SD for diastolic with reference to the criteria for non-pregnant women. Using the polynomial equation, the hypertensive cut-off of systolic HBP was 125 mmHg at 15 weeks and 132 mmHg at 30 weeks of gestation, while it for diastolic HBP was 79 mmHg at 15 weeks and 81 mmHg at 30 weeks of gestation. Systolic HBP in women who developed HDP was higher after 24 weeks of gestation, and diastolic HBP was higher during most of the pregnancy compared to normal pregnancy. When the variability of individual HBP in women developed HDP compared to normal pregnant women was examined using the coefficient of variation (CV), the CV was lower in HDP before the onset of HDP. HBPM can be used not only for HDP determination, but also for early detection of HDP.

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BACKGROUND: Noninvasive prenatal testing (NIPT) is used to screen for fetal chromosomal abnormalities, such as fetal aneuploidy, and has been offered at our hospital since 2013. We analyzed data from our center to determine if NIPT screenees could be given more-accurate information on NIPT outcomes. METHODS: This retrospective observational study included 819 pregnant women who requested NIPT at Nippon Medical School Hospital from November 2013 to October 2021. We examined medical records for data on NIPT results and clinical outcomes. RESULTS: Of the 819 women, 764 (93.2%) underwent NIPT, and 55 (6.7%) did not. Of the 764 women who underwent NIPT, 17 received a positive result (2.2%), of whom 2 (11.8%), 4 (23.5%), and 11 (64.7%) received a positive result for trisomy 13, 18, and 21, respectively. The true-positive rates after definitive diagnoses of trisomy 13, 18, and 21 were 1 (50%), 3 (75%), and 11 (100%), respectively. Of the 17 positive results, there were two false-positive results (11.8%) (for trisomy 13 and trisomy 18). Eleven women with fetal aneuploidy terminated their pregnancies, and four cases resulted in intrauterine fetal death. Five neonates with negative NIPT results had congenital disease without chromosomal abnormality. Two patients had indeterminate results from the first blood sampling, possibly because of treatment with unfractionated heparin. The results of repeat testing after heparin cessation were negative. CONCLUSIONS: Our results were generally similar to nationwide data for Japan. NIPT providers can provide more detailed and individualized genetic counseling for each situation by understanding their own medical facility's data in detail.

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AIM: The fetal sample used for embryonic chromosome analysis is often contaminated with maternal cells, making it difficult to evaluate the fetal chromosomes. We examined on the rate of maternal cell contamination and its relationship with maternal information in the embryonic chromosome analysis of missed abortions using the Giemsabanding method. METHODS: Chromosome analysis was performed in 200 cases of delayed miscarriages in first trimester between July 1, 2000 and May 31, 2019. Chorionic villi were collected and were analyzed using the Giemsa banding method. Among the 20 cells for which chromosomal examination was performed, cells wherein 46,XX chromosomes were found together with normal male karyotype or abnormal chromosomes were defined as maternal cell contamination. RESULTS: Of the 200 cases analyzed, 136 had abnormal chromosomes. The normal female karyotype (n = 52) was four times more prevalent than the normal male karyotype (n = 12). Maternal cell contamination was seen in 15.4% of the abnormal chromosome cases and 8.3% of the normal male karyotype cases. There was no significant difference in the gestational age between the contaminated and noncontaminated groups at the time of miscarriage diagnosis. However, miscarriage before fetal heartbeat confirmation was significantly associated with higher maternal cell contamination. CONCLUSION: We found maternal cell contamination in 15% of all the cases. Moreover, in many cases of the normal female karyotype, it was suspected that only maternal chromosomes were cultured. When performing embryonic chromosome analysis in recurrent miscarriages, we should pay attention to maternal cell contamination and interpret the results accordingly.

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BACKGROUND: Miscarriage occurs in 10-15% of pregnancies and recurrent pregnancy loss (RPL) occurs in 1% of couples hoping for a child. Various risk factors, such as thrombophilia, uterine malformation, and embryonic chromosomal aberration cause RPL. We hypothesized that antithrombotic therapy for RPL patients with thrombophilia would reduce miscarriage due to thrombophilia, which would reduce the total miscarriages and result in a relative increase in miscarriage due to embryonic chromosomal aberrations. In this study, we investigated the incidence of chromosomal aberrations in products of conception in RPL patients with and without antithrombotic therapy. METHODS: We performed a single-center, retrospective review of cases diagnosed as miscarriage with embryo chromosome analysis between July 1, 2000, and May 31, 2019. Rates of chromosomal aberration were compared between RPL patients with and without thrombophilia or antithrombotic therapy. RESULTS: One hundred and-ninety RPL cases were analyzed. The average age was 37.4 ± 4.3 years, and the average number of previous pregnancy losses was 2.2 ± 1.1. The overall chromosomal aberration rate was 67.4% (128/190). There was no difference in the chromosomal aberration rate between the factors for RPL, with or without thrombophilia, and antithrombotic therapy. Only advancing maternal age had significant correlation to increased embryo chromosomal aberration rates. CONCLUSIONS: With or without antithrombotic therapy, miscarriage was caused by embryonic chromosome abnormalities at a certain rate. Antithrombotic therapy in RPL patients with thrombophilia may reduce abortions due to thrombophilia, which may also normalize the rate of embryonic chromosome aberrations in the subsequent miscarriages.

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Objective: To examine whether the presence of amniotic fluid sludge (AFS) could increase the risk of preterm delivery in women with a cervical length (CL) of less than 25 mm.Materials and methods: This is a retrospective cohort study of 110 women who were 14-30 weeks pregnant with a singleton gestation and a CL of less than 25 mm. The primary outcomes were defined as preterm delivery before 34 weeks and preterm delivery before 37 weeks. The secondary outcome was defined as preterm premature rupture of membranes (PPROM) prior to preterm delivery. Risk factors for preterm delivery were defined as AFS, subchorionic hematoma (SCH), history of preterm delivery, CL of less than 20 mm, and CL of less than 15 mm. A univariate analysis was performed to assess the primary and secondary outcomes according to the presence or absence of each risk factor. A multiple logistic regression analysis was performed to evaluate the parameters, using a significance of p < .05 on the univariate analysis to examine whether they were independent risk factors.Results: A significantly increased risk of preterm delivery was found in the group of women with AFS who actually did deliver prior to 34 weeks (p < .001; odds ratio [OR] 6.44; 95% confidence interval [CI] 2.51-16.5), prior to 37 weeks (p = .001; OR 4.46; 95% CI 1.76-11.3), and who had PPROM (p < .001; OR 4.96; 95% CI 2.00-12.3). A multivariate logistic regression analysis was performed in the women with AFS who experienced preterm delivery before 34 weeks, in the women with a CL less than 20 mm, and in the women with a CL less than 15 mm. The results showed that AFS was an independent risk factor for preterm delivery before 34 weeks (p = .001; OR 5.86; 95% CI 2.11-16.3).Conclusion: The presence of AFS was an independent risk factor for preterm delivery before 34 weeks in women with a CL less than 25 mm.

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AIM: To assess the preventive effect on preterm birth of intravaginal ulinastatin (urinary trypsin inhibitor; UTI) administration during the mid-trimester in women with singleton pregnancy and both cervical shortening and lower genital infections. METHODS: Pregnant women with a short cervical length < 25 mm between 16 and 26 weeks of gestation and who had been diagnosed with a lower genital infection were randomly assigned for intravaginal UTI administration or placebo. All of the women were screened for infection or inflammation of the lower genital tract, and women with negative results were excluded. RESULTS: Of the 92 patients with a short cervical length who were assessed for eligibility for this study, 86 singleton patients were enrolled. All patients were randomized to one of two treatment groups: patients administered UTI (n = 35) and placebo (n = 35). There were no differences between the two groups in the incidence of preterm delivery before 28, 30, 32, 34 and 37 weeks of gestation and in perinatal outcomes. CONCLUSION: For women diagnosed with a short cervical length < 25 mm) between 16 and 26 weeks of gestation and lower genital infection, who were at risk of preterm birth, administration of transvaginal UTI with vaginal irrigation showed no apparent benefit. Future research on the efficacy of UTI should evaluate modified modes of UTI application.

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OBJECTIVE: To clarify whether distinguishing between the uterine isthmus and cervix can improve the accuracy of diagnosing placenta previa at term. METHODS: A multicenter prospective observational study was conducted among pregnant women with suspected placenta previa at 20-24 weeks' gestation. Subjects were divided into the open isthmus group and closed isthmus group. The accuracy of diagnosing placenta previa at term was compared between the 2 groups. RESULTS: We screened 9,341 patients, and 53 (0.6%) met the inclusion criteria. Nineteen cases with an open isthmus and 34 with a closed isthmus were followed. The accuracy for diagnosing placenta previa or a low-lying placenta at term was 94.7% in the open isthmus group and 26.5% in the closed isthmus group (p < 0.001). Elective or emergency Cesarean section was required in 100% of cases in the open isthmus group and 20.6% in the closed isthmus group (p < 0.001). CONCLUSION: A high prediction rate of placenta previa was obtained by using transvaginal ultrasound at 20-24 weeks' gestation after the isthmus opened by carefully distinguishing between the cervix and isthmus.

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AIM: This is the first report of a randomized trial of cerclage on pure cervical shortening without vaginosis or cervicitis. The objective of our multicenter randomized controlled trial was to assess the benefits of ultrasound-indicated cervical cerclage in the mid-trimester to prevent preterm birth in women who have no signs of infection or inflammation of the lower genital tract. MATERIAL AND METHODS: Women with a short cervical length < 25 mm between 16 and 26 weeks of gestation were randomly assigned to receive a Shirodkar cerclage, McDonald cerclage, or bedrest (no cerclage). Before being randomly assigned to one of the three groups, all women were screened for infection/inflammation of the lower genital tract; those with positive results were excluded from the study. The ratio of preterm delivery as a primary end-point was evaluated in the groups. RESULTS: A total of 106 singleton patients with a short cervical length were assessed for study eligibility; 106 patients were randomized to the three treatment options. Ultimately, 98 patients (in the Shirodkar [n = 34], McDonald [n = 34] and bedrest [n = 30] groups) were analyzed. No differences in preterm delivery or perinatal outcomes were found between the three groups. Significantly fewer patients in the Shirodkar group required hospitalization for treatment of threatened preterm labor when compared to patients in the bedrest group. CONCLUSION: For women with a short cervical length < 25 mm between 16 and 26 weeks of gestation, Shirodkar cerclage might be considered to reduce the occurrence of threatened preterm labor.

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PURPOSE: To evaluate whether type and location of placenta previa affect risk of antepartum hemorrhage-related preterm delivery. METHODS: We retrospectively studied 162 women with singleton pregnancies presenting placenta previa. Through observation using transvaginal ultrasound the women were categorized into complete or incomplete placenta previa, and then assigned to anterior and posterior groups. Complete placenta previa was defined as a placenta that completely covered the internal cervical os, with the placental margin >2 cm from the os. Incomplete placenta previa comprised marginal placenta previa whose margin adjacent to the internal os and partial placenta previa which covered the os but the margin situated within 2 cm of the os. Maternal characteristics and perinatal outcomes in complete and incomplete placenta previa were compared, and the differences between the anterior and the posterior groups were evaluated. RESULTS: Antepartum hemorrhage was more prevalent in women with complete placenta previa than in those with incomplete placenta previa (59.1% versus 17.6%), resulting in the higher incidence of preterm delivery in women with complete than in those with incomplete placenta previa [45.1% versus 8.8%; odds ratio (OR) 8.51; 95% confidence interval (CI) 3.59-20.18; p < 0.001]. In complete placenta previa, incidence of antepartum hemorrhage did not significantly differ between the anterior and the posterior groups. However, gestational age at bleeding onset was lower in the anterior group than in the posterior group, and the incidence of preterm delivery was higher in the anterior group than in the posterior group (76.2% versus 32.0%; OR 6.8; 95% CI 2.12-21.84; p = 0.002). In incomplete placenta previa, gestational age at delivery did not significantly differ between the anterior and posterior groups. CONCLUSION: Obstetricians should be aware of the increased risk of preterm delivery related to antepartum hemorrhage in women with complete placenta previa, particularly when the placenta is located on the anterior wall.

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Cesarean scar pregnancy is one of the rare types of ectopic pregnancy. Ultrasonography enables early diagnosis and the successful preservation of the uterus. However, the correct diagnosis of cesarean scar pregnancy can be difficult in some cases. We describe a case of cesarean scar pregnancy that was initially misdiagnosed on the basis of current ultrasonographic criteria. Ultrasonographic images at 9 weeks' gestation demonstrated no gestational sac but did show a bulging mass in uterine wall with irregularly shaped hypoechoic areas, which resembled the lacunae in placenta previa. Color Doppler imaging demonstrated that the lacunae-like areas were richly perfused. Cesarean scar pregnancy was finally diagnosed with magnetic resonance imaging, which showed a lack of myometrium in the lower anterior uterine wall with placental invasion. Histological examination of the uterus after hysterectomy revealed the direct invasion of trophoblasts into the mural zone which had resulted in a deficit of myometrium at the previous cesarean scar. A mass in the myometrium with richly perfused lacunae-like areas should be considered as one of the important ultrasonographic findings indicating cesarean scar pregnancy.

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We illustrate three cases of isolated congenital lymphangioma (CL). Fetal ultrasound (US) demonstrated uniloculated cystic masses that changed to multiloculated, subcutaneous, hypoechoic, avascular cystic masses with thin septations without solid components. Case 1: CL of the right forearm; Case 2: CL of the right hypochondrium; and Case 3: CL of the left upper posterior back. Postnatal US detected multiloculated, subcutaneous, hypoechoic, avascular cystic masses with thin septations without solid components or invasive developments. We prenatally and postnatally diagnosed them as isolated CL cases due to focal, soft, bulging masses with unclear margins. Due to our correct diagnosis and precise evaluation of sizes and locations, no perinatal complications occurred. In this case series, uniloculated features changed to multiloculated features and the largest macrocyst size decreased, whereas the sizes of the smaller microcysts increased. These morphological changes observed via fetal US represent intermittent CL growing processes.

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The aim of our study was to use brachial-ankle pulse wave velocity (baPWV) measurements to noninvasively assess the effect of exercise training on arterial stiffness in normal pregnant women. Arterial stiffness was assessed at the beginning of the early second trimester of pregnancy and 1 month after delivery in 17 women with normal singleton pregnancies who exercised regularly throughout pregnancy: 81 matched controls were used for comparison. No significant differences were observed in baPWV between the exercise and control groups at the beginning of the second trimester. BaPWV 1 month after delivery (1160.2 ± 109.1 cm·second(-1)) was signifi-cantly higher than that in the early second trimester (1116.7 ± 87.9 cm·second(-1)) in the control group (indicating increased arterial stiffness), but not in the exercise group (1145.9 ± 88.1 cm/second vs 1122.7 ± 100.2 cm·second(-1), respectively: not significant). The results indicated that regular maternal exercise training decreased arterial stiffness in normal pregnant women, which suggests that regular exercise may help prevent hypertensive disorders during pregnancy. Key pointsRegular maternal exercise training decreased arterial stiffness in normal pregnant women, which suggests that regular exercise may help prevent hypertensive disorders during pregnancy.Maternal exercise suggests that disturbances in arterial function during pregnancy may be prevented by regular exercise.

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OBJECTIVE: The objective of this study was to explore factors influencing the accuracy of transvaginal digital examination for determining fetal head position during the first stage of labor. MATERIALS AND METHODS: Fetal head position was assessed in 87 women in the first stage of labor at term with normal singleton cephalic presentation. Transvaginal digital examinations were performed by attending midwives and were followed immediately by transabdominal ultrasound assessments performed by a single sonographer. Accuracy was defined as agreement of the results of each examination. Multivariate logistic regression analysis was performed to determine the independent factors influencing accuracy. RESULTS: In only 40.3% of patients (n = 35) were transvaginal digital examinations consistent with ultrasound assessments. Multivariate logistic regression analysis showed that the accuracy of digital examinations was significantly associated with cervical dilatation more than 7 cm (odds ratio, 3.01; 95% confidence interval [CI], 1.03-9.4), birth weight less than 2,500 g (odds ratio, 8.68; 95% CI, 1.08-86.28), and the anterior occiput position group (odds ratio, 4.73; 95% CI, 1.76-13.49). CONCLUSIONS: The present study demonstrates that transvaginal digital examination is less accurate than ultrasonography for determining fetal head position during the first stage of labor. The results suggest that ultrasound assessments should be routinely performed in patients with a cervical dilatation less than 7 cm, an estimated fetal body weight more than 2,500 g, the occiput posterior position, or the occiput transverse position.

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BACKGROUND: The incidence of placenta previa has been increasing. It is of a great importance to determine the clinical risk factors for peripartum blood transfusion in women with placenta previa in an effort to anticipate cases of severe hemorrhage. METHODS: A total of 129 consecutive cases of placenta previa (64 cases of complete placenta previa and 65 cases of marginal placenta previa), including 43 cases requiring blood transfusion, were retrospectively analyzed. Maternal and neonatal clinical data were examined with univariate and multivariate logistic regression analyses for potential risk factors for peripartum blood transfusion. RESULTS: The independent risk factors for blood transfusion were maternal age greater than 34 years (adjusted odds ratio [OR]=3.7; 95% confidence interval [CI]=1.5-7.5, p<0.05), history of having undergone dilatation and curettage more than once (adjusted OR=4.8; 95% CI=1.1-26.2, p<0.05), and complete placenta previa (adjusted OR=2.6, 95% CI=1.2-5.9, p<0.05). Body mass index, gravidity, parity, previous cesarean section, antepartum hemorrhage, use of tocolytic agents, gestational age at delivery, preoperative anemia, emergent surgery, birth weight, and Apgar score were not associated with the incidence of blood transfusion. CONCLUSION: Risk factors for blood transfusion in women with placenta previa are advanced maternal age, repeat dilatation and curettage, and complete placenta previa. Women with placenta previa who are at risk for blood transfusion should be carefully managed with sufficient preparation for blood transfusion.

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OBJECTIVE: The aims of this study were to assess the frequency of inpatient falls and to evaluate potential risk factors in an academic hospital. METHODS: An electronic audit of the inpatient database at the Tama-Nagayama Hospital of Nippon Medical School from April 2004 through March 2005 was performed. Inpatient falls were registered regularly with incident reports submitted by nurses and other hospital employees discovering the fall. All inpatients were analyzed for potential risk factors using univariate and multivariate logistic regression analysis. RESULTS: Of the 8,537 patients, 109 (1.3%) fell. Multivariate logistic regression analysis showed that inpatient falls were significantly associated with a patient age of 51 to 70 years (odds ratio, 2.4; 95% CI, 1.3 - 4.7) or of 71 to 90 years (odds ratio, 4.2; 95% CI, 2.4 - 8.1); with a hospital stay of 15 to 21 days (odds ratio, 3.4; 95% CI, 1.6 - 7.0), 22 to 28 days (odds ratio, 4.3; 95% CI, 1.8 - 9.5), or 29 days or longer (odds ratio, 13.8; 95% CI, 8.3 - 24.1); with admission to the surgery (odds ratio, 2.0; 95% CI, 1.1 - 3.5), orthopedics (odds ratio, 2.5; 95% CI, 1.1 - 4.9), neurosurgery (odds ratio, 3.0; 95% CI, 1.5 - 5.9), or urology service (odds ratio, 3.9; 95% CI, 1.8 - 8.2); and with no surgical procedure (odds ratio, 1.6; 95% CI, 1.0 - 2.6). CONCLUSIONS: The present study demonstrates that patient-related factors, such as age and length of stay, and treatment-related factors, such as no surgical procedure and admission to the surgery, orthopedics, neurosurgery, or urology service, are independent risk factors for inpatient falls. The results suggest that fall-prevention programs should target patients with these risk factors.

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OBJECTIVE: Early structural and functional changes in the systemic vasculature have been proposed to play a major pathogenetic role in HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. Our objective was to assess whether the evaluation of maternal hepatic blood supply is instructive to the prediction of onset of HELLP syndrome. DESIGN: Prospective observation study. POPULATION: Fifty-eight women with severe preeclampsia and 60 healthy pregnant controls at 25-36 weeks gestation. METHODS: Angle-corrected time-averaged flow velocity and the cross-sectional area of common hepatic artery and portal vein were measured by using Doppler ultrasonography in 58 women with severe preeclampsia and in 60 healthy pregnant controls at 25-36 weeks gestation. Intravascular flow volumes were calculated from the product of the time-averaged velocity and the cross-sectional area. The total liver blood flow was taken as the sum of flow volumes in the hepatic artery and portal vein. RESULTS: The total liver blood flow decreased significantly to about 40% of control in 9 women with severe preeclampsia who developed HELLP syndrome within 4 days after the examination, but not in 49 women with severe preeclampsia without HELLP syndrome. CONCLUSION: The results indicated that the decrease in dual hepatic blood supply preceded the onset of HELLP syndrome.

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OBJECTIVE: The aim of this study was to assess the frequency of severe perineal lacerations defined as either third- or fourth-degree lacerations during normal spontaneous vaginal delivery and to evaluate potential risk factors in Japanese patients. MATERIALS AND METHODS: An electronic audit of the perinatal database at the Tama-Nagayama Hospital of Nippon Medical School and Yamaguchi Hospital from 1997 through 2004 was completed. Singleton vaginal vertex deliveries were analyzed for potential risk factors using univariate and multivariate logistic regression analysis. RESULTS: From the database, 7,946 deliveries were identified, with 135 deliveries resulting in severe lacerations (1.7%). In the multivariate logistic regression analysis, severe lacerations were associated significantly with primiparous (odds ratio, 4.36; 95% CI, 2.17-9.57), oxytocin use (odds ratio, 2.19; 95% CI, 1.27-3.73), midline episiotomy (odds ratio, 4.68; 95% CI, 2.09-11.55), forceps-assisted delivery (odds ratio, 7.11; 95% CI, 1.95-20.59), vacuum-assisted delivery (odds ratio, 5.93; 95% CI, 3.38-10.36), and shorter attendant experience (odds ratio, 2.88; 95% CI, 1.12-9.81). CONCLUSIONS: The present study demonstrated that operator factors, such as midline episiotomy, oxytocin use, assisted delivery and attendant experience, are independent risk for severe perineal lacerations after vaginal delivery in Japanese patients. The results suggest that midline episiotomy and assisted vaginal delivery, especially forceps-assisted delivery should be avoided in patients who are being delivered of a first child whenever possible.

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