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Cytokine storm is recognized as one of the factors contributing to organ failures and mortality in patients with COVID-19. Due to chronic inflammation, COVID-19 patients with diabetes mellitus (DM) or renal disease (RD) have more severe symptoms and higher mortality. However, the factors that contribute to severe outcomes of COVID-19 patients with DM and RD have received little attention. In an effort to investigate potential treatments for COVID-19, recent research has focused on the immunomodulation functions of mesenchymal stem cells (MSCs). In this study, the correlation between DM and RD and the severity of COVID-19 was examined by a combined approach with a meta-analysis and experimental research. The results of a systematic review and meta-analysis suggested that the odd of mortality in patients with both DM and RD was increased in comparison to those with a single comorbidity. In addition, in the experimental research, the data showed that high glucose and uremic toxins contributed to the induction of cytokine storm in human lung adenocarcinoma epithelial cells (Calu-3 cells) in response to SARS-CoV Peptide Pools. Of note, the incorporation of Wharton's jelly MSC-derived extracellular vesicles (WJ-EVs) into SARS-CoV peptide-induced Calu-3 resulted in a significant decrease in nuclear NF-κB p65 and the downregulation of the cytokine storm under high concentrations of glucose and uremic toxins. This clearly suggests the potential for WJ-EVs to reduce cytokine storm reactions in patients with both chronic inflammation diseases and viral infection.

Combustible cigarette smoking impacts fetal growth during pregnancy. However, the risk associated with heated tobacco products (HTPs) remains unclear. This nationwide cross-sectional study investigated whether HTP use during pregnancy is associated with small for gestational age (SGA) outcomes among 5647 post-delivery women with singleton pregnancies, which were divided into four groups: lifetime never-smokers, former smokers before pregnancy, and current smokers for each of the tobacco products during pregnancy (sole HTP and sole combustion smokers). Information on the prevalence of SGA, defined as birth weight and height below the 10th percentile, was retrieved from the Maternal and Child Health Handbooks of post-delivery women. Using logistic regression, the association between sole HTP smokers during pregnancy and SGA, adjusted for covariates, with lifetime never-smokers as reference, was investigated. The prevalence was: current sole HTP smokers during pregnancy, 1.8% (102/5647); and SGA, 2.9% (164/5647). Sole HTP smokers during pregnancy had a higher prevalence of SGA (5.9% [6/102] vs. 2.7% [111/4144]) with an adjusted odds ratio (OR) of 2.50 (95% confidence interval [CI], 1.03–6.05) than lifetime never-smokers. Among sole combustion smokers, the adjusted OR for SGA was 1.95 (95% CI, 0.81–4.67). In Japan, HTP smoking during pregnancy may be associated with an increased risk for SGA.

Pulmonary embolism remains a leading cause of maternal mortality in developed countries despite developments in venous thromboembolism prophylaxis strategies. This study aimed to evaluate the effectiveness of our approach involving risk-scoring, D-dimer level assessment, and ultrasonography for obstetric venous thromboembolism.This retrospective cohort study included women who delivered at 22-41 weeks of gestation in The University of Tsukuba Hospital, Japan between January and December 2020. Venous thromboembolism risk (determined according to Japanese guidelines) and D-dimer levels were evaluated within 20 weeks of gestation, 30-34 weeks of gestation, and during the pre-delivery period (36 weeks of gestation or any time before preterm delivery). Compression and color Doppler ultrasonography for lower extremity deep vein thrombosis were performed if D-dimer levels were ≥3.2 μg/mL (for those undergoing cesarean delivery, 1.0 μg/mL).Of 1026 women, 6 women had deep vein thrombosis during pregnancy and 1 during the puerperium period. Pulmonary embolism was not observed. The D-dimer screening result was positive for 8 women (2%) within 20 weeks of gestation (deep vein thrombosis was confirmed in 3 of them), 87 women (10%) (no deep vein thrombosis) at 30-34 weeks of gestation, and 367 women (36%) during the pre-delivery period (asymptomatic deep vein thrombosis in one). Based on the Japanese guidelines, 1%, 11%, 33%, and 55% of women had high, intermediate, low, and no postpartum risk factors, respectively.Our approach appears useful for antenatal venous thromboembolism screening in the first trimester. For postpartum prophylaxis, more cost-effective strategies are needed.

A 28-year-old woman was admitted during the eighth week of her pregnancy because her clinical course was consistent with rapid progressive glomerulonephritis (RPGN). Anti-glomerular basement membrane antibody (anti-GBM Ab) and myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) were positive, and the anti-GBM Ab titer being extremely high. She was treated with hemodialysis, plasma exchange and prednisolone. She survived the illness; however, neither the fetus nor her kidney function could be rescued. She had human leukocyte antigen (HLA)-DRB1*1502:01, which differs from the DRB1*1501 associated with anti-GBM GN. When patients have particular symptoms, we should check the urine and serum creatinine to exclude RPGN, even in cases of pregnancy.

The incidence of chromosomal abnormalities in twin pregnancies is not well-studied. In this retrospective study, we investigated the frequency of chromosomal abnormalities in twin pregnancies and compared the incidence of chromosomal abnormalities in dichorionic diamniotic (DD) and monochorionic diamniotic (MD) twins. We used data from 57 clinical facilities across Japan. Twin pregnancies of more than 12 weeks of gestation managed between January 2016 and December 2018 were included in the study. A total of 2899 and 1908 cases of DD and MD twins, respectively, were reported, and the incidence of chromosomal abnormalities in one or both fetuses was 0.9% (25/2899) and 0.2% (4/1908) in each group (p = 0.004). In this study, the most common chromosomal abnormality was trisomy 21 (51.7% [15/29]), followed by trisomy 18 (13.8% [4/29]) and trisomy 13 (6.9% [2/29]). The incidence of trisomy 21 in MD twins was lower than that in DD twins (0.05% vs. 0.5%, p = 0.007). Trisomy 21 was less common in MD twins, even when compared with the expected incidence in singletons (0.05% vs. 0.3%, RR 0.15 [95% CI 0.04–0.68]). The risk of chromosomal abnormality decreases in twin pregnancies, especially in MD twins.

Maternal glucocorticoid exposure increases the risk of preterm delivery; however, the association between glucocorticoids and preterm premature rupture of membranes (pPROM)-a direct cause of preterm delivery-has rarely been investigated.To examine this association, we evaluated the clinical data of patients with systemic lupus erythematosus (SLE). Mechanism analysis was performed in both human amnion-derived mesenchymal cells (as a model for fetal membranes) and the amnion from SLE patients. We characterized the effects of glucocorticoids on the amnion in both models through comprehensive gene expression profiling and by electric cell-substrate impedance sensing in the mesenchymal cells.The average glucocorticoid dose in cases with pPROM (13.3 mg/day, n = 10) was significantly higher than in those without pPROM (8.5 mg/day, n = 65; P 0.01) among pregnant patients with well-controlled SLE (SLEDAI4, n = 75); however, we did not observe a statistically significant difference in it between cases with or without chorioamnionitis. Glucocorticoid-treated human amnion mesenchymal cells showed decreased electric resistance between cells, indicating increased permeability. Differentially expressed genes upon glucocorticoid treatment were significantly enriched with cell adhesion-related genes. Among them, ITGA8 was strikingly induced in both the amnion mesenchymal cells and in amnion derived from patients with SLE.We observed an association between glucocorticoids and pPROM with non-infectious etiology. Our findings indicate that glucocorticoids increase amnion permeability and modulate cell-adhesion related genes. ITGA8 represents a primary molecule that triggers pPROM through fibrotic remodeling and preventing resealing of the rupture site in fetal amnion.

Aim We aimed to evaluate the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of noninvasive prenatal testing (NIPT) in high-risk pregnant women. Methods Pregnant women who underwent GeneTech NIPT, the most commonly used NIPT in Japan, between January 2015 and March 2019, at Japan NIPT Consortium medical sites were recruited for this study. The exclusion criteria were as follows: pregnant women with missing survey items, multiple pregnancy/vanishing twins, chromosomal abnormalities in the fetus other than the NIPT target disease, and nonreportable NIPT results. Sensitivity and specificity were calculated from the obtained data, and maternal age-specific PPV and NPV were estimated. Results Of the 45 504 cases, 44 263 cases fulfilling the study criteria were included. The mean maternal age and gestational weeks at the time of procedure were 38.5 years and 13.1 weeks, respectively. Sensitivities were 99.78% (95% confidence interval [95% CI]: 98.78-99.96), 99.12% (95% CI: 96.83-99.76), and 100% (95% CI: 88.30-100) for trisomies 21, 18, and 13, respectively. Specificities were more than 99.9% for trisomies 21, 18, and 13, respectively. Maternal age-specific PPVs were more than 93%, 77%, and 43% at the age of 35 years for trisomies 21, 18, and 13, respectively. Conclusion The GeneTech NIPT data showed high sensitivity and specificity in the detection of fetal trisomies 21, 18, and 13 in high-risk pregnant women, and maternal age-specific PPVs were obtained. These results could provide more accurate and improved information regarding NIPT for genetic counseling in Japan.

Background The human-to-rat hematopoietic stem cell transplantation (HSCT) model is rare, unlike its human-to-mouse counterpart. The rat models are desired, especially in areas of physiology, toxicology, and pharmacology. In addition to lymphocytes, macrophages are also considered to be important for xenotransplantation. We generated a rat xenotransplantation model to prove the role of macrophages as a xenotransplantation barrier. Methods Immunodeficiency in SRG rats, which are Sprague-Dawley (SD) rats lacking Rag2 and Il2rg, was confirmed by flow cytometry and spleen immunostaining. Human umbilical cord blood was collected after scheduled cesarean section at the University of Tsukuba Hospital. Cord blood mononuclear cells (CB-MNCs) were transplanted into the SRG rats administered several injections of clodronate liposome (CL), which cause macrophage depletion. Survival of human cells was observed by flow cytometry. Rat macrophage phagocytosis assay was performed to check the species-specific effects of rat macrophages on injected human/rat blood cells. Results SRG rats were deficient in T/B/NK cells. Without CL pretreatment, human CB-MNCs were removed from SRG rats within 7 hours after transplantation. The rats pretreated with CL could survive after transplantation. Prolonged survival for more than 4 weeks was observed only following a one-time CL injection. Rat macrophages had a species-specific potential for the phagocytosis of human blood cells in vivo. Conclusion In human-to-rat HSCT, the short period of early macrophage control, leading to macrophage immunotolerance, is important for engraftment. The generated model can be useful for the creation of future xenotransplantation models or other clinical research.

There is a paucity of data on the risk of preterm birth subcategorized by gestational age in pregnancies after the pre-pregnancy excisional treatment for cervical lesions. In addition, little is known about the effect of prophylactic cerclage on the risk of preterm birth. The aim of this study was to investigate the risk of preterm birth stratified by gestational period and its reduction by the prophylactic cerclage in women with prior excisional surgery.We retrospectively analyzed a cohort of singleton pregnancies in the Japan Perinatal Registry Network Database (2013-2014,In the propensity-score matched population (cases,Pre-pregnancy excisional cervical surgery was associated with the increased risk of preterm birth, especially before 32 weeks of gestation. The prophylactic cerclage did not reduce the risk of preterm birth.

Objective To examine the association between the risk of postpartum hemorrhage (PPH) and poor uterine contractility, which is suggested by the characteristics of labor. Methods This case-control study used cases recorded in the Japan Perinatal Registry database during the period 2013-2016. After exclusion of women with specified known risk factors for PPH, we enrolled 174 082 primiparas who had a full-term live singleton vaginal birth. Participants were classified into four classes according to the diagnosis of abnormal labor patterns and use of uterotonics. χ2 tests were used to compare PPH cases with controls, and odds ratios (OR) were calculated by univariate and multivariate analyses. Results Among the enrolled women, 10 508 (6.0%) had PPH. Abnormal labor patterns were significantly associated with an increased risk of PPH. Compared with women without any abnormal labor patterns who had not used uterotonics, women with abnormal labor patterns were at a significantly increased risk for PPH regardless of whether they had used uterotonics (adjusted OR 1.23, 95% confidence interval [CI] 1.10-1.37) or not (adjusted OR 1.30, 95% CI 1.23-1.37). Conclusion Our study suggests that among low-risk women with PPH, poor uterine contractility in labor could be a significant predisposing risk factor for PPH.

Aim To evaluate the efficacy and safety of dinoprostone vaginal insert (PROPESS) in pregnant post‐term Japanese women requiring cervical ripening. Methods This randomized, double‐blind, placebo‐controlled study included 114 pregnant Japanese women at term (41 weeks of gestation) requiring cervical ripening (baseline Bishop score (BS) ≤ 4). The primary end‐point was the proportion of subjects with successful cervical ripening defined as BS ≥ 7 or vaginal delivery in 12 h. The secondary end‐points were changes in BS, proportion of women with vaginal delivery, proportion of women receiving mechanical cervical ripening procedure and use of oxytocic drugs. Results PROPESS administration for a maximum of 12 h showed significantly higher successful cervical ripening rate (47.4% vs 14.3%, respectively; treatment contrast [TC]: 33.1%; P = 0.0002). The median time from administration to vaginal delivery was significantly shorter in the PROPESS group than in the placebo group (26.18 h vs 33.02 h; OR 2.51; 95% CI [1.60–3.92]; P

This study aimed to assess characteristics of pregnant women taking antiepileptic drugs with inadequate folic acid intake. This cross-sectional study examined pregnant women taking antiepileptic drugs who were registered in the Japanese Drug Information Institute in Pregnancy (JDIIP) database between October 2005 and December 2016. Participants were classified into two groups according to when they started folic acid supplementation (before pregnancy: 'adequate', after pregnancy or never: 'inadequate'). Logistic regression analysis was performed to investigate factors associated with inadequate folic acid intake. Of 12,794 registrants, 468 pregnant women were taking antiepileptics during the first trimester. Of these, we analysed data from 456 women who had no missing data. As a result, inadequate folic acid intake was noted among 83.3% of them, suggesting that the current level of folic acid intake is insufficient overall. Younger age, smoking, alcohol drinking, multiparity, unplanned pregnancy, and being prescribed AEDs by paediatric or psychiatric departments were independent factors associated with inadequate folic acid intake. As planned pregnancy was the strongest factor, healthcare professionals should ensure that childbearing women taking antiepileptics are informed of the importance of planned pregnancy. In addition, healthcare professionals must gain a better understanding of folic acid intake, as the prevalence of adequate intake differed according to which departments prescribed antiepileptic drugs.

To compare the prevalence of enlarged ovarian and intrapelvic parasitic arteries to the gravid uterus between cases of placenta accreta spectrum (PAS) and those with normal placentation using unenhanced magnetic resonance (MR) angiography.Unenhanced time-of-flight MR angiography was performed in 12 consecutive women with PAS (mean age, 34 years; range, 23-42 years) and 24 women with normal placentation (mean age, 31 years; range, 24-42 years) in their third trimester and reviewed by two independent observers. The consensus reading served as the reference standard. Findings of pelvic arteriography performed at cesarean hysterectomy were reviewed in all cases of PAS. The prevalence of enlarged ovarian and intrapelvic parasitic arteries was compared using Fisher's exact test. The interobserver agreement was assessed with Kappa statistics.The prevalence of enlarged ovarian arteries was not significantly different between cases of PAS and normal placentation (17% [4/24 pelvic sides] vs. 4% [2/48 pelvic sides], P = .091). The prevalence of intrapelvic parasitic arteries was significantly higher in cases of PAS than in those with normal placentation (67% [16/24 pelvic sides] vs. 0% [0/48 pelvic sides], P .0001). On a patient-by-patient basis, the intrapelvic parasitic artery was frequently present in women with PAS (92% [11/12 patients]). The Kappa values were 0.915 and 0.852 for detecting enlarged ovarian and intrapelvic parasitic arteries, respectively, indicating excellent interobserver agreement.The development of intrapelvic parasitic arteries was an anomalous phenomenon observed on unenhanced MR angiography in the majority of women with PAS but was not observed in those with normal placentation.

Aims The objective of this study was to determine how many pregnant Japanese women with diabetes mellitus (DM)/gestational diabetes mellitus (GDM) experience perinatal mortality in the presence of fetal anomalies. Methods Our investigation included data from 205 secondary/tertiary obstetric facilities located widely in Japan. The Japan Ministry of Health, Labour and Welfare Vital Statistics of Japan was used for comparison. Results Of 237 941 women giving birth at 205 hospitals, 1796 (0.8%) and 13 037 (5.5%) had DM and GDM, respectively. The perinatal mortality rates (per 1000 births) were 10.6 (19/1796) for women with DM, 5.2 (68/13037) for women with GDM, and 3.7 (7612/2039504) for the general Japanese population. Detailed information was available for 63 (72%) of the 87 perinatal deaths occurring in women with diabetes including DM and GDM; fetal anomalies were associated with 40% (25/63) of perinatal deaths, exceeding 16% (1211/7612) in the general Japanese population (P

This study aimed to assess characteristics of pregnant women taking antiepileptic drugs with inadequate folic acid intake. This cross-sectional study examined pregnant women taking antiepileptic drugs who were registered in the Japanese Drug Information Institute in Pregnancy (JDIIP) database between October 2005 and December 2016. Participants were classified into two groups according to when they started folic acid supplementation (before pregnancy: ‘adequate’, after pregnancy or never: ‘inadequate’). Logistic regression analysis was performed to investigate factors associated with inadequate folic acid intake. Of 12,794 registrants, 468 pregnant women were taking antiepileptics during the first trimester. Of these, we analysed data from 456 women who had no missing data. As a result, inadequate folic acid intake was noted among 83.3% of them, suggesting that the current level of folic acid intake is insufficient overall. Younger age, smoking, alcohol drinking, multiparity, unplanned pregnancy, and being prescribed AEDs by paediatric or psychiatric departments were independent factors associated with inadequate folic acid intake. As unplanned pregnancy was the strongest factor, healthcare professionals should ensure that childbearing women taking antiepileptics are informed of the importance of planned pregnancy. In addition, healthcare professionals must gain a better understanding of folic acid intake, as the prevalence of adequate intake differed according to which departments prescribed antiepileptic drugs.

Introduction Some pregnant women develop significant proteinuria in the absence of hypertension. However, clinical significance of isolated gestational proteinuria (IGP) is not well understood. This study aimed to determine the prevalence of IGP in singleton pregnancies and the proportion of women with IGP who subsequently developed preeclampsia (IGP-PE) among all PE cases. Material and methods This was an observational study of 6819 women with singleton pregnancies at 12 centers, including 938 women with at least once determination of protein-to-creatinine ratio (P/Cr). Significant proteinuria in pregnancy (SPIP) was defined as P/Cr (mg/mg) level >0.27. IGP was defined as SPIP in the absence of hypertension. Gestational hypertension (GH) preceding preeclampsia (GH-PE) was defined as preeclampsia (PE) in which GH preceded SPIP. Simultaneous PE (S-PE) was defined as PE in which both SPIP and hypertension occurred simultaneously. Results IGP and PE were diagnosed in 130 (1.9%) and 158 (2.3%) of 6819 women, respectively. Of 130 women with IGP, 32 (25%) progressed to PE and accounted for 20% of all women with PE. Hence, women with IGP had a relative risk of 13.1 (95% CI; 9.2–18.5) for developing PE compared with those without IGP [25% (32/130) vs. 1.9% (126/6689)]. At diagnosis of SPIP, P/Cr levels already exceeded 1.0 more often in women with S-PE than in those with IGP-PE [67% (33/49) vs. 44% (14/32), respectively, p = 0.031]. Conclusions IGP is a risk factor for PE, and IGP-PE accounts for a considerable proportion (20%) of all PE.

Perinatal care in Japan has progressed rapidly in recent decades, remarkably reducing maternal, perinatal and neonatal mortality rates. This is attributable not only to the sustained efforts and dedication of past obstetricians and midwives, but also to the collective results achieved by the Japan Society of Obstetrics and Gynecology and healthcare administration, including research on advanced medical care, education, medical care improvements and establishing perinatal care centers. Although the maternal mortality rate was in steady decline until 2007 (3.1/100 000 births), it repeatedly fluctuated thereafter, plateauing at 3.4 per 100 000 births in 2013 and 2.7 per 100 000 births in 2014. Thus, the Perinatology Committee has analyzed the current situation of maternal deaths and has proposed countermeasures to reduce such death. The items deliberated upon by related subcommittees in 2015 are presented herein. The addition of indications for ‘fibrinogen concentrate’, ‘eptacog alfa’ and approval of the PGE2 vaginal tablet for cervical ripening were discussed in the subcommittee for unapproved drug review. Thus, a request for approval for health insurance coverage was submitted to the ‘Evaluation committee on unapproved or off-label drugs with high medical needs’ of the Ministry of Health, Labour and Welfare. Maternal and late-maternal deaths from suicide during the 10 years from 2005 to 2014 in Tokyo's 23 wards were jointly examined with the Tokyo Medical Examiner's Office. The suicide rate in the 23 wards is very high, at 8.7 per 100 000 births. Thus, the subcommittee for the reduction of maternal death discussed countermeasures for the eradication of maternal death and maternal suicide and the revision of death certificates.

Aim Post-partum hematomas are a serious obstetrical complication. Choosing treatments for post-partum hematomas is difficult, and the application of transcatheter arterial embolization remains unclear. We aimed to clarify the clinical characteristics, identify the treatment indications and create a treatment algorithm for post-partum hematomas. Methods Fifty-four patients with post-partum hematomas were enrolled. Hematomas were categorized according to location: upper vaginal, lower vaginal and vulvar. Blood loss, treatment methods and other clinical data were collected from the patients' medical records and analyzed retrospectively. Results Five, 19 and 30 patients had upper vaginal wall, lower vaginal wall and vulvar hematomas, respectively. All upper vaginal wall hematomas required transcatheter arterial embolization to control bleeding, and the average blood loss was 2473 ± 1689 mL. Most lower vaginal wall hematomas were treated surgically; however, two patients required transcatheter arterial embolization, and the average blood loss in these patients was much higher (2010 ± 1145 mL) than that in patients with lower vaginal wall hematomas (395 ± 316 mL). No patient with vulvar hematomas was treated with transcatheter arterial embolization. Two and four patients with vulvar and lower vaginal wall hematomas, respectively, were managed with observation. Conclusion We created an algorithm for post-partum hematoma management. Post-partum hematoma location should guide treatment selection. Transcatheter arterial embolization should be selected for upper vaginal wall hematomas. Most lower vaginal wall hematomas are treatable with surgery, but transcatheter arterial embolization should be considered for hemostasis in difficult cases. Management with observation may also be possible for lower vaginal wall and vulvar hematomas.

Objective To report a case of gas gangrene in a fetus at term, which was diagnosed by antenatal computed tomography (CT) imaging. Case Report A 23-year-old primiparous woman, who did not undergo any prenatal health checks until term, developed hypertension, proteinuria, and clouding of consciousness, and experienced intrauterine fetal death. A single, mature fetus with voluminous gas bubbles was observed on CT, which was consistent with a diagnosis of fetal gas gangrene. Following the induction of labor, a dead, malodorous infant was delivered, along with foul-smelling and frothy amniotic fluid. The patient's condition deteriorated, and intensive care support was required to treat the patient for septic shock and disseminated intravascular coagulation during the postpartum period. She died on the 2 nd postpartum day. Conclusion Fetal gas gangrene is a very rare and potentially lethal event in pregnant women. To our knowledge, this is the first report on the antenatal diagnosis of fetal gas gangrene in a term pregnancy through CT. CT was useful for evaluating the extent of emphysematous change in the fetal and maternal organs.

To clarify the effect of starvation due to hyperemesis gravidarum on the screening of gestational diabetes mellitus (GDM).A retrospective study was undertaken of pregnant women who delivered at Tsukuba University Hospital, Japan, between October 1, 2010, and September 30, 2013. GDM screening was performed in the first trimester using the random blood glucose test with a cutoff value of 5.2mmol/L and in the second trimester using a 50-g glucose challenge test with a cutoff value of 7.8mmol/L. If the screening was positive, a 75-g oral glucose tolerance test was performed for a definite diagnosis.Among 2112 eligible women, 33 (1.6%) required hospitalization for hyperemesis; the remaining 2079 women formed the control group. In the first trimester, the positive GDM screening rate was significantly higher in the hyperemesis group than in the control group (13 [39.4%] vs 115 [5.5%]; P0.001). Additionally, the positive predictive value was significantly lower in the hyperemesis group (23.1% vs 73.9%; P0.001). In the second trimester, no significant differences were observed between groups.Hyperemesis gravidarum affects the positive GDM screening rate in the first trimester.

Study objectives In humans and other mammals, sleep is altered during pregnancy. However, no studies have been conducted on sleep/wakefulness during pregnancy in mice. In this study, we examined sleep/wakefulness in female C57BL/6 mice during pregnancy. We also examined sleep/wake behaviors in an animal model of preeclampsia, pregnancy-associated hypertensive (PAH) mice, in which increased angiotensin causes hypertension. Methods Sleep/wake behaviors of female C57BL/6 and PAH mice were examined based on electroencephalogram (EEG) or electromyogram recordings before, during, and after pregnancy. To examine whether high blood pressure disrupts the integrity of the blood-brain barrier in PAH mice, Evans blue dye was injected intravenously. Angiotensin II receptor blocker (olmesartan)-administered PAH mice and female Tsukuba hypertensive mice were also examined. Results C57BL/6 mice showed a decreased total wake time and increased nonrapid eye movement (NREM) sleep time during late pregnancy. Rapid eye movement (REM) sleep time did not change during the course of pregnancy. PAH mice exhibited a general slowing of EEG during late pregnancy and subsequently returned to apparently normal sleep/wakefulness after delivery. All PAH mice exhibited multiple focal leakages of Evans blue dye in the brain. Spike-and-wave discharges were observed in 50% of PAH mice. Olmesartan-administered PAH mice did not show general slowing of EEG. Tsukuba hypertensive mice showed a normal time spent in wakefulness and NREM sleep and a decreased total REM sleep time. Conclusions This study showed pregnant-stage-specific changes in sleep/wakefulness in C57BL/6 mice. Furthermore, PAH mice may be useful as an animal model for eclampsia.

The objective of this study was to determine how many pregnant Japanese women with diabetes mellitus (DM)/gestational diabetes mellitus (GDM) experience perinatal mortality in the presence of fetal anomalies.Our investigation included data from 205 secondary/tertiary obstetric facilities located widely in Japan. The Japan Ministry of Health, Labour and Welfare Vital Statistics of Japan was used for comparison.Of 237 941 women giving birth at 205 hospitals, 1796 (0.8%) and 13 037 (5.5%) had DM and GDM, respectively. The perinatal mortality rates (per 1000 births) were 10.6 (19/1796) for women with DM, 5.2 (68/13037) for women with GDM, and 3.7 (7612/2039504) for the general Japanese population. Detailed information was available for 63 (72%) of the 87 perinatal deaths occurring in women with diabetes including DM and GDM; fetal anomalies were associated with 40% (25/63) of perinatal deaths, exceeding 16% (1211/7612) in the general Japanese population (P0.0001). The leading four fetal anomalies associated with perinatal mortality in women with diabetes were fetal trisomy (6 cases: 1 of trisomy-13 and 5 of trisomy-18), non-immune hydrops fetalis (5 cases), cardiac deformities (3 cases) and holoprosencephaly (2 cases).Perinatal mortality was more likely to occur in women with glucose intolerance. In the Japanese infants that succumbed to perinatal mortality, fetal anomaly was more prevalent in those born to women with a glucose intolerance than in those born to the general population.

The original publication is available at www.springerlink.com, This questionnaire survey was conducted at 11 hospitals in Japan to determine vaccination coverage against seasonal influenza and the prevalence rate of influenza among pregnant Japanese women. Of 2,808 postpartum women who gave birth at the 11 hospitals during the study period from March 1, 2014, to July 31, 2014, 1,713 (61 %) participated in this study and 876 (51 %) reported having received vaccination against influenza in or after October 2013. Women aged < 25 years had a significantly lower vaccination rate than those aged a parts per thousand yen25 years (31 % vs. 53 %, respectively; p = 0.0000). Eighty-seven (5.1 %) and 1,626 (94.9 %) women did and did not contract influenza, respectively. Although prior birth did not affect overall vaccination coverage (50 % for primiparous vs. 53 % for multiparous), multiparous women had a significantly higher rate of contracting influenza than primiparous women, irrespective of vaccination status (5.6 % vs. 2.2 % [p = 0.0216] and 9.7 % vs. 3.5 % [p = 0.0003] for women with and without vaccination, respectively). The 2013-2014 vaccination program significantly reduced the influenza infection rate by 35 % (3.9 % vs. 6.3 % for women with and without vaccination, respectively; p = 0.0272). Seventy-two (83 %) of the 87 women took antiviral agents for the treatment of influenza and two (2.3 %) required hospitalization. These results suggested that pregnant Japanese women had a high level of concern regarding seasonal influenza. However, campaigns targeting young pregnant Japanese women, as well as multiparous women, for vaccination are needed in order to further reduce the incidence of influenza among pregnant Japanese women.

We evaluated the postnatal outcomes of patients with prenatally diagnosed agenesis of the corpus callosum (ACC), in conjunction with ventriculomegaly, as a tool for parental counseling. Through a retrospective review of maternal and infant records, we evaluated the postnatal outcomes of 21 patients with prenatally diagnosed ACC and fetal ventriculomegaly. Ten of the 21 patients (48 %) were diagnosed with isolated ACC. Among these 10 patients, neurodevelopmental outcomes were normal in four, uncertain in one, and five demonstrated mild or moderate disabilities. The remaining 11 patients had ACC associated with either central nervous system (CNS) anomalies (7 of 11) or chromosomal abnormalities (4 of 11). The outcomes were estimated in nine of the 11 children; all nine had severe disabilities. The mortality rate of ACC, associated with other anomalies, was 29 % (2 of 7) in children with CNS anomalies and 75 % (3 of 4) for those with chromosomal abnormalities. If ACC with fetal ventriculomegaly is associated with other malformations, a poor outcome is highly likely. Although the outcome of isolated ACC with fetal ventriculomegaly was generally better, >50 % of the patients had mild or moderate neurodevelopmental disabilities. These findings provide useful information for parental counseling.

Purpose To investigate whether planning of pregnancy in women with epilepsy affects seizure control during pregnancy and to compare the maternal and neonatal outcomes in planned and unplanned pregnancies. Methods This was a retrospective cohort study of 153 pregnant women with epilepsy who were treated at the University of Tsukuba Hospital and Hokkaido University Hospital between 2003 and 2011. Twenty-one pregnancies were excluded due to insufficient data. Data of patients followed by neurologists during their planned pregnancies (planned-pregnancy group, n =51) were compared to those of patients referred to neurologists after conception for managing epilepsy during pregnancy (unplanned-pregnancy group, n =81). The treatment profile for epilepsy, seizure control, and maternal and neonatal outcomes in both groups were compared using Chi-square test or Fisher's exact test and Mann–Whitney U test. Results Compared to the unplanned-pregnancy group, the planned-pregnancy group showed a significantly greater proportion of patients receiving monotherapy with antiepileptic drugs (80% vs. 61%: planned vs. unplanned, P =0.049) and those not requiring valproic acid (77% vs. 56%, P =0.031). Furthermore, the frequency of epileptic seizures (16% vs. 35%, P =0.018) and changes in antiepileptic drugs (24% vs. 41%, P =0.042) were significantly lower in the planned-pregnancy group than in the unplanned-pregnancy group. No significant intergroup differences were noted in the obstetric complications and neonatal outcomes, including congenital malformations. Conclusion For women with epilepsy, planning of pregnancy is associated with good seizure control during pregnancy and less fetal exposure to antiepileptic drugs.

Liver dysfunction with decreased antithrombin (AT) activity and/or thrombocytopenia is life threatening in pregnant women. Whether AT is clinically useful for prediction of liver dysfunction remains unclear.A total of 541 women were registered prospectively at gestational week 34.7 (20.0-41.4) with available data on antenatal AT and platelet count (PLC).Liver dysfunction defined as serum aspartate aminotransferase 45 IU/L concomitant with lactate dehydrogenase 400 IU/L occurred in five women antenatally (≤ 2 weeks before delivery) and in 17 women post-partum (within 1 week post-partum). Median (5th-95th) antenatal value was 85 (62-110)% for AT and 202 (118-315) × 10Reduced AT not accompanied by thrombocytopenia can precede liver dysfunction. Clinical introduction of AT may enhance the safety of pregnant women.

Background: The dipstick test is widely used as a primary screening test for detection of significant proteinuria in pregnancy (SPIP). However, it often shows a false positive test result. This study was performed to determine which pregnant women should be recommended to undergo determination of urinary protein-to-creatinine ratio (mg/mg, P/Cr test) after dipstick test for confirmation of SPIP. Methods: This was a multicenter, prospective, and observational study of 2212 urine specimens from 1033 pregnant women who underwent simultaneous dipstick and P/Cr tests in the same spot urine samples at least once. SPIP was defined as P/Cr > 0.27. Preeclampsia was diagnosed in women with both hypertension and SPIP. Results: Preeclampsia, hypertension alone, and SPIP alone developed in 202 (20 %), 73 (7.1 %), and 120 (12 %) women, respectively. Creatinine concentration [Cr] varied greatly, ranging from 8.1 to 831 mg/dL in the 2212 urine samples. Rate of positive dipstick test results increased with increasing [Cr], while SPIP prevalence rate was lower in urine samples with higher [Cr], yielding higher false positive rates in samples with higher [Cr]. Postpartum urine samples had significantly lower [Cr] compared to those obtained antepartum (60 [8.7-297] vs. 100 [10-401] mg/dL, respectively). At the first P/Cr test among women with similar dipstick test results, the risk of having SPIP was consistently and significantly higher for hypertensive women than for normotensive women at any dipstick test result: 18 % (14/77) vs. 3.2 % (8/251), 47 % (26/55) vs. 8.7 % (37/425), 91 % (82/90) vs. 59 % (44/75) for negative/equivocal, 1+, and >= 2+ test results, respectively. The risk of SPIP was 16 % (9/55) for normotensive women when two successive antenatal urine samples showed a dipstick test result of 1 +. Conclusions: For prediction of SPIP, the dipstick test was more likely to show a false positive result in concentrated urine samples with higher [Cr]. Hypertensive women with >= 1+ as well as normotensive women with >= 2+ on dipstick test should be advised to undergo the P/Cr test.

Clinical guidelines for obstetrical practice were first published by the Japan Society of Obstetrics and Gynecology (JSOG) and the Japan Association of Obstetricians and Gynecologists (JAOG) in 2008, and a revised version was published in 2011. The aims of this publication include the determination of current standard care practices for pregnant women in Japan, the widespread use of standard care practices, the enhancement of safety in obstetrical practice, the reduction in burdens associated with medico-legal and medico-economical problems, and a better understanding between pregnant women and maternity-service providers. These guidelines include a total of 87 Clinical Questions followed by several Answers (CQ&A), a Discussion, a List of References, and some Tables and Figures covering common problems and questions encountered in obstetrical practice. Each answer with a recommendation level of A, B or C has been prepared based principally on "evidence" or a consensus among Japanese obstetricians in situations where "evidence" is weak or lacking. Answers with a recommendation level of A or B represent current standard care practices in Japan. All 87 CQ&As are presented herein to promote a better understanding of the current standard care practices for pregnant women in Japan.

A diamniotic-monochorionic pregnancy of twins was revealed by transvaginal ultrasonography: one fetus with holoprosencephaly was diagnosed at 11 weeks of gestation. This is the first case of holoprosencephaly diagnosed in the first trimester. Prenatal diagnosis of this anomaly in the first trimester is now possible by transvaginal ultrasonography.

A case of a 37-year-old pregnant patient with antiphospholipid syndrome (APS), who has a medical history of both thrombosis and recurrent fetal loss, is presented. She was treated with predonisolone and fixed-dose unfractionated heparin (UFH) infusion, followed by plasmaphereses and fixed-dose low-molecular-weight heparin infusion during her fourth pregnancy. Unfortunately, this treatment did not have beneficial effects, resulting in intrauterine growth restriction and finally neonatal death. Continuous intravenous UFH infusion and low-dose aspirin were administrated under the monitoring of the activated partial thromboplastin time to achieve a target level of 120 s during her fifth pregnancy. A healthy baby weighing 1818 g at birth was delivered by Cesarean section at the 34th week of pregnancy. High-dose UFH infusion may be considered to be one of the preferable options to manage pregnant patients with refractory APS.

Background Fetal growth restriction (FGR) and low birth weight(LBW) are serious public health problems. In developing countries, the incidence of low birth weight is predominantly the result of FGR, and both low birth weight and FGR are associated with neonatal death and later growth and development. Fetal growth charts are important for assessing the size of the fetus during pregnancy. The aims of this study were to describe the fetal growth pattern of a population in rural Bangladesh where maternal undernutrition is prevalent and to compare the timing of FGR in that population with WHO and INTERGROWTH- 21st international reference values. Methods From November 2001 to October 2003, pregnant women were recruited in Matlab, a sub district of Bangladesh, and underwent three follow-up ultrasound examinations during pregnancy for measurement of the parameters of the fetal head, abdomen, and femur. The data were fitted to a linear-cubic model, and the derived values were compared with international reference values. Results A total of 2678 singleton pregnancies were included in the analyses. The mean (SD) maternal age was 25.9 (5.8) years (range, 14–47 years). The mean (SD) early pregnancy BMI was 20.1 (2.6) kg/m2, and 27.6% of the women were underweight (BMI

Objective: To clarify the impact of a mild form of gestational diabetes mellitus (GDM) on neonatal birth size, and on insulin-related hormones and adiponectin (AdipoQ) in cord blood. Methods: Two hundred and sixteen Japanese pregnant women diagnosed as having normal glucose tolerance according to the JSOG criteria were enrolled. Of the 216 women, 38 women were reclassified into a mild GDM (mGDM) group according to the IADPSG criteria. Of the remaining 178 women, 135 women with normal 50-g glucose challenge test were reclassified into a normal glucose tolerance (NGT) group. Cord blood insulin-like growth factor (IGF)-1, IGF-binding proteins (IGFBPs) and AdipoQ were measured in the offspring of the two groups. Results: Birth weight and its SD scores were larger in the mGDM group than in the NGT group. The incidence of large-for-gestational age (LGA) newborns was higher in the mGDM than in the NGT group. No differences in cord blood free IGF-1, IGFBP-1, IGFBP-2 or AdipoQ levels were observed between the mGDM and NGT groups. Conclusions: Our study suggests that mild GDM reclassified according to the IADPSG criteria influences neonatal birth size, but neither the IGF-IGFBP axis nor AdipoQ can account for the changes of birth size in offspring of women with mild GDM.

Aims: This study aimed to determine effective predictive factors for primary postpartum hemorrhage (PPH) among clinical blood parameters associated with coagulation and fibrinolysis and demographic characteristics. Methods: We retrospectively studied 1032 women who underwent determinations of clinical blood parameters at gestational week (GW) 29–32 and GW 35–37 and gave birth to singleton infants at our hospital between January 2011 and December 2013. PPH was defined as estimated blood loss ≥700 mL. Multivariate logistic regression analyses were used to determine independent risk factors and odds ratios (OR) for PPH. Results: PPH occurred in 104 of 1032 women (10%). Three blood variables, fibrinogen level 2.7 μg/mL (2.03 [1.29–3.19]) at GW 35–37, and three demographic characteristics, maternal age ≥35 years (1.75 [1.15–2.68]), BMI >28.2 kg/m2 on admission for childbirth (1.95 [1.20–3.16]), and previous cesarean delivery (2.77 [1.31–5.83]), were identified as independent risk factors for PPH. Conclusion: Among blood parameters, higher D-dimer levels and lower levels of antithrombin activity and fibrinogen in late gestation were independent risk factors for PPH.

Fetal magnetocardiography (fMCG) is useful for analysis of fetal cardiac events. However, fetal presentation and movement affect the fMCG waveform, making it difficult to standardize the waveform. The aim of this study was to investigate whether the use of vector magnetometers can compensate for these limitations. We studied 59 fetuses (gestational age, 22-40 wk, median, 32), including 41 with uncomplicated pregnancies and 18 with fetal cardiac disease. fMCG was recorded twice in each case, and the two waveforms were compared with each other in uncomplicated subjects to investigate the effects of fetal presentation. The superconducting quantum interference device (SQUID) system used in this study was a 12-channel vector magnetometer, by which the three components of the magnetic field (Bx, By, Bz) could be detected simultaneously at four recording points. By constructing the three components, a composite waveform (Bxyz) was obtained. The configuration of the composite waveforms was similar among normal fetuses always with positive polarity, independent of fetal presentation and movement. The difference in the time intervals (PR, QRS, and ventricular activation time [VAT]) between the first and second measurements was minimal in the composite waveforms (Bxyz) compared with that in each channel (Bx, By, Bz). Even before signal averaging, waveforms with high time resolution were recorded in at least one of the three components, making it possible to analyze fetal arrhythmias precisely. Our results indicate that vector magnetocardiography is potentially useful for standardization of the fMCG waveforms and to provide a more complete and accurate analysis of fetal arrhythmias.

The successful establishment of human embryonic stem cell (hESC) lines has inaugurated a new era in regenerative medicine by facilitating the transplantation of differentiated ESCs to specific organs. However, problems with the safety and efficacy of hESC therapy in vivo remain to be resolved. Preclinical studies using animal model systems, including nonhuman primates, are essential to evaluate the safety and efficacy of hESC therapies. Previously, we demonstrated that common marmosets are suitable laboratory animal models for preclinical studies of hematopoietic stem cell therapies. As this animal model is also applicable to preclinical trials of ESC therapies, we have established novel common marmoset ESC (CMESC) lines. To obtain marmoset embryos, we developed a new embryo collection system, in which blastocysts can be obtained every 3 weeks from each marmoset pair. The inner cell mass was isolated by immunosurgery and plated on a mouse embryonic feeder layer. Some of the CMESC lines were cultured continuously for more than 1 year. These CMESC lines showed alkaline phosphatase activity and expressed stage-specific embryonic antigen (SSEA)-3, SSEA-4, TRA-1-60, and TRA-1-81. On the other hand, SSEA-1 was not detected. Furthermore, our novel CMESCs are pluripotent, as evidenced by in vivo teratoma formation in immunodeficient mice and in vitro differentiation experiments. Our established CMESC lines and the common marmoset provide an excellent experimental model system for understanding differentiation mechanisms, as well as the development of regenerative therapies using hESCs.

We report a fetus at 33 weeks of gestation with supraventricular tachycardia, which was successfully managed by transplacental administration of an antiarrhythmic agent. Fetal magnetocardiography (fMCG) revealed supraventricular tachycardia of the long RP’ tachycardia type. Transplacental administration of sotalol, instead of digoxin, was selected as the first-line drug, and it successfully converted supraventricular tachycardia to sinus rhythm. The diagnosis of the type of supraventricular tachycardia was confirmed by electrocardiography after birth. Sotalol was also effective after birth to maintain sinus rhythm. This case demonstrates that fMCG is potentially useful for prenatal differentiation of the type of supraventricular tachycardia and for prenatal treatment of fetal tachyarrhythmias.

We here report the first case of discordant Pena-Shokeir phenotype observed in monoamniotic twins. A 34-year-old woman, pregnant with twins, was referred at 10 weeks' gestation because one of the twins had increased nuchal translucency. Serial ultrasonographic examinations suggested that twin A may have had several other abnormalities, including pleural effusion at 21 weeks' gestation, decreased movement and contracted limbs at 24 weeks, and fetal growth restriction at 26 weeks. No abnormalities were observed in twin B. At 34 weeks of gestation, the twins were delivered by cesarean section. There were cord entanglements, and although the resuscitation of twin A was attempted, it proved difficult due to lockjaw. Twin A died during the second hour of life, and autopsy findings were consistent with the diagnosis of Pena-Shokeir phenotype. We suggest that cord entanglement during early gestation is a possible cause for the occurrence of Pena-Shokeir phenotype through an anoxic-ischemic mechanism.

The Leiden mutation in the coagulation factor V (F5) gene associated with preeclampsia in Caucasians has not been found in Japanese populations. We examined the association of 20 missense polymorphisms in the F5 gene in 133 pregnant Japanese women with preeclampsia and in 224 unrelated, healthy, pregnant Japanese women. Among nine polymorphisms identified in the subjects, the M385T and R485K polymorphisms were associated with preeclampsia (P = 0.05 and P = 0.02, respectively). Haplotype analysis indicated that the R485K polymorphism is truly associated with preeclampsia, whereas the association of the M385T polymorphism is due to linkage disequilibrium. Taken together with reports that the R485 allele yields poor factor V function in comparison with that of the K485 allele and that the F5 Leiden mutation is associated with preeclampsia in Caucasian populations, the findings of the present study suggest that the F5 gene is associated with preeclampsia in pregnant Japanese women.

Toxoplasma gondii is an obligate intracellular protozoan pathogen that can cross the placenta, resulting in congenital toxoplasmosis with severe fetal brain abnormalities. The molecular mechanisms of immune responses against T. gondii infection in the placenta have largely remained unclear. An analytical method for characterizing phenotypes of immune cells in the placenta by flow cytometry was established and it was found that numbers of CD11b(+) Gr-1(+) cells in the placenta increased significantly after T. gondii infection. These results suggest that innate immune responses play an important role in immunity against T. gondii infection via the feto-maternal interface.

The 'Clinical Guidelines for Obstetrical Practice, 2011 edition' were revised and published as a 2014 edition (in Japanese) in April 2014 by the Japan Society of Obstetrics and Gynecology and the Japan Association of Obstetricians and Gynecologists. The aims of this publication include the determination of current standard care practices for pregnant women in Japan, the widespread use of standard care practices, the enhancement of safety in obstetrical practice, the reduction of burdens associated with medico-legal and medico-economical problems, and a better understanding between pregnant women and maternity-service providers. The number of Clinical Questions and Answers items increased from 87 in the 2011 edition to 104 in the 2014 edition. The Japanese 2014 version included a Discussion, a List of References, and some Tables and Figures following the Answers to the 104 Clinical Questions; these additional sections covered common problems and questions encountered in obstetrical practice, helping Japanese readers to achieve a comprehensive understanding. Each answer with a recommendation level of A, B or C was prepared based principally on 'evidence' or a consensus among Japanese obstetricians in situations where 'evidence' was weak or lacking. Answers with a recommendation level of A or B represent current standard care practices in Japan. All 104 Clinical Questions and Answers items, with the omission of the Discussion, List of References, and Tables and Figures, are presented herein to promote a better understanding among English readers of the current standard care practices for pregnant women in Japan.

Beckwith-Wiedemann syndrome is an inherited disorder most commonly characterized by prenatal or postnatal overgrowth, macroglossia, omphalocele, unusual earlobe creases, and increased risk of neoplasia. Several reported cases of this syndrome have been prenatally diagnosed, but no report has described the occurrence of this syndrome in association with a single umbilical artery. We report a case in which prenatal sonographic examination demonstrated fetal overgrowth, macroglossia, and omphalocele together with a single umbilical artery; our prenatal diagnosis of Beckwith-Wiedemann syndrome was confirmed after birth of the infant. The possibility of this syndrome should be considered when performing a detailed sonographic examination of a fetus with a single umbilical artery.

Preeclampsia is associated with thrombosis of the intervillous or spiral artery. A deletion/insertion polymorphism (4G or 5G) in the promoter of the plasminogen activator inhibitor type 1 (PAI-1) gene is suggested to be involved in regulating the synthesis of the inhibitor, 4G allele, being associated with the enhanced gene expression and plasma PAI-1 levels. We assessed the association between preeclampsia and the 4G/5G polymorphism of the PAI-1 gene in 115 preeclamptic patients, 210 pregnant controls, and 298 healthy volunteer controls. The frequency of the homozygotes for the 4G allele was significantly higher in the patients than in the control pregnant women (P = 0.04) or in the healthy volunteers (P = 0.02). The 4G allele frequency was also significantly higher in the patients than in the control group of pregnant women (P = 0.03) and in the healthy volunteers (P = 0.02). These results suggest that the presence of the 4G/4G genotype of the PAI-1 gene is one of the risk factors for preeclampsia.

Visual disturbances occur more frequently during preeclampsia than during pregnancy in general, but visual disturbances due to cranial nerve palsy are rare. We present the case of a 35-year-old preeclamptic woman with left third nerve palsy and left serous retinal detachment. The patient complained of visual disturbance and double vision soon after cesarean section. Left third nerve palsy and left serous retinal detachment were diagnosed by urgent ophthalmologic evaluation. Aneurysm and organic brain lesion were ruled out by diagnostic imaging. By 2 months postpartum, the visual disturbance had improved spontaneously.

The purpose of this study was to determine the proportion of fetal nucleated red blood cells (NRBCs) among enriched NRBCs and to evaluate the effectiveness of enriching NRBCs in maternal blood using fluorescence-activated cell sorting (FACS) to separate NRBCs. The origin of enriched NRBCs was determined using fluorescence in situ hybridization (FISH) methods. Y-specific signals were observed in 4.6 +/- 1.5 per cent of the enriched cells from 14 of 16 (87.5 per cent) pregnant women who gave birth to boys. In this series, the specificity of the fetal sex diagnosis was 100 per cent, the sensitivity 88 per cent, and the negative predictive value 86 per cent. Fetal NRBCs are present in maternal blood and FACS has the potential to enrich fetal NRBCs. Fetal cells were estimated to be enriched more than 10,000-fold in the first trimester and more than 100-fold in the third trimester. Average frequencies of fetal cells in maternal blood were 8.1 x 10(-5) and 1.6 x 10(-5) in the first trimester and the second/third trimesters. However, most of the NRBCs in maternal blood are maternal in origin.

We present the first report on the use of helical computed tomography (CT), a new, non-invasive diagnostic technique that produces three-dimensional (3-D) images, in prenatal diagnosis. This technique was used to construct 3-D images in the prenatal diagnosis of two anomalous fetuses. The 3-D images provided clear information about the anomalies: trisomy 18 in one case and cystic hygroma in the other. In one case, rapid intervention after a planned Caesarean section prevented respiratory distress. Surgery to correct the anomaly was performed 2 days postnatally; the infant recovered uneventfully.

We present a 28-year-old pregnant woman who exhibited intolerance to lysinuric protein. However, she gave birth to a normal child without serious maternal complications. Since four of seven similar patients reported previously developed serious complications such as hemorrhage and eclampsia, patients with lysinuric protein intolerance are considered to be at high risk during pregnancy. A successful outcome can be achieved, provided that the anemia, thrombocytopenia, toxemia and hyperammonemia are well controlled.

OBJECTIVE: The purpose of this study was to determine the frequency of fetal nucleated cells and their serial changes in maternal peripheral blood after delivery. STUDY DESIGN: A total of 135 blood samples were investigated by means of fluorescence in situ hybridization by observing cells with Y chromosomes. Polymerase chain reaction amplifying two different Y-specific fragments were also carried out for genomic deoxyribonucleic acid from the same samples. RESULTS: The mean frequency of the Y-positive cells detected by fluorescence in situ hybridization in mothers who gave birth to male children was about 1 in 17,500 1 day after delivery. The frequency of these cells decreased with time, dropping below detectable levels 3 months after delivery. The frequency estimated by polymerase chain reaction experiments was significant and positively correlated with those found by fluorescence in situ hybridization. CONCLUSION: Fetal nucleated cells in maternal peripheral blood decrease in frequency with time after delivery. These cells disappear from maternal circulation 3 months after delivery in most, if not all, mothers. (AM J OBSTET GYNECOL 1994;170:1188-93.)

Few reports of fetal cystic lymphangioma have described assessment in utero by magnetic resonance imaging (MRI). We evaluated a fetus with cystic lymphangioma by this method. Complementing the characteristic features of cystic lymphangioma in ultrasonographic images, prenatal MRI provided a detailed view of anatomic relationships of cysts to surrounding tissues in this case. This anatomic evaluation facilitated planning of perinatal management and choice of manner of delivery. We found MRI very helpful in antepartum assessment of fetal cystic lymphangioma.