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The latest treatments do not sufficiently prevent miscarriage and fetal growth restriction (FGR) in pregnant women. Here, we assessed the effects of a human protein, CTRP6, that specifically inhibits the activation of the alternative complement pathway on miscarriage, fetal and placental development.Pregnant CBA/J mice mated with DBA/2 male mice as a model of spontaneous abortion and FGR were randomly divided into the control and CTRP6 groups. In the CTRP6 group, the mice were intravenously administered CTRP6 on days 4.5 and 6.5 post-conception (dpc). The abortion rate and fetal and placental weights on 14.5 dpc were examined. Remodeling of the spiral artery was also assessed.The abortion rate in the CTRP6 group (13%) was reduced compared to the control group (21%), but there was no statistical difference. The placental and fetal weights in the CTRP6 group were also heavier than those in the control (P 0.05). Moreover, the thickness of the blood vessel wall in the CTRP6 group was significantly thinner than that in the control (P 0.05) and comparable to that in the non-abortion model (CBA/J x BALB). The ratio of the inner-per-the-outer diameter of the spiral artery increased more in the CTRP6 group than that in the control (P 0.05). As well, the Th1/Th2 cytokine ratio was significantly reduced by CTRP6 treatment.Taken together, the supplementation with a protein that regulates the alternative complement pathway in vivo improves FGR and promotes spiral artery remodeling in a mouse model of miscarriage and FGR.

Background The aims of this study were to evaluate the time intervals of flow velocity waveforms (FVW) of ductus venosus (DV) and cardiac cycles, as well as the pulsatility index of DV-FVW (DV-PI), in correlation with umbilical artery (UA) pH at birth in fetal growth restriction (FGR) complicated with placental insufficiency. Methods Data were retrospectively retrieved from pregnancies complicated by FGR. FGR was defined as an estimated fetal weight below − 2.0 S.D. with an elevated UA-PI. Time interval assessments of DV-FVW were as follows: the duration of systolic wave was divided by the duration of diastolic wave and defined as DV-S/D. We also measured the following time intervals of ventricular inflow through tricuspid valve (TV) and mitral valve (MV): (iii), from the second peak of ventricular inflow caused by atrial contraction (A-wave) to the opening of atrio-ventricular valves and: (iv), from the opening of atrio-ventricular valves to the peak of A-wave. (iii)/(iv) was expressed as TV-S/D and MV-S/D, for TV and MV, respectively. The time interval data were transformed into z-scores. Results Thirty-one FGR fetuses were included in this study. Both DV-PI and DV-S/D showed significant correlation with UA-pH (r = − 0.677, p = r = 0.489, p = 0.005 for DV-PI and z-score of DV-S/D, respectively) and more significances were observed in FGR ≤ 28 + 6 gestational weeks (r = − 0.819, p r = 0.726, p = 0.005, for DV-PI and z-score of DV-S/D, respectively) than in FGR > 28 + 6 gestational weeks (r = − 0.634, p = 0.007 and r = 0.635, p = 0.020, for DV-PI and z-score of DV-S/D, respectively). On the other hand, TV-S/D and MV-S/D showed no significant correlation with UA-pH, although these z-scores indicated significant decreases compared with normal references. Conclusions Time interval analysis of DV-FVW might be a valuable parameter, as well as DV-PI, for the antenatal prediction of fetal acidemia in the management of FGR fetuses.

Pelvic organ prolapse (POP) in women is associated with deficiency of elastic fibers, and fibulin-5 is known to be a critical protein in the synthesis of elastin. The purpose of this study is to investigate the related pathway for the synthesis of elastin via fibulin-5 using fibulin-5 knockout mice. Fibulin-5 knockout mice were generated using the CRISPR/Cas9 system, and vaginal dilatation was used to mimic vaginal delivery. We divided the mice into three groups: Fbln5+/+ mice immediately after dilatation (Fbln5+/+ day0), Fbln5+/+ mice 3 days after dilatation (Fbln5+/+ day3) and Fbln5−/− mice 3 days after dilatation (Fbln5−/− day3). Proteins related to elastogenesis in the vaginal wall were measured by liquid chromatography mass spectrometry (LC-MS/MS) analysis, and differences in the expression of these proteins between the Fbln5−/− mice and the Fbln5+/+ mice were analyzed using western blotting. In the LC-MS/MS analysis, protein tyrosine kinase 7 (PTK7) was not detected in the Fbln5−/− day3 group, although the expression increased by > 1.5 times between the Fbln5+/+ day0 and day3 groups. PTK7 and β-catenin are known to act in the Wnt/β-catenin pathway, and both were upregulated after dilatation in the Fbln5+/+ mice, though not in the Fbln5−/− mice. Our findings suggest that these proteins are involved in elastogenesis via fibulin-5, and the impairment of these proteins might be the underlying cause of POP manifestation.

Background and Objectives: There are no reports showing the hematopoietic effect of TJ-108 on pregnant women. The aim of this study was to investigate the effect of TJ-108 on the hemoglobin and hematocrit levels, and white blood cell and platelet counts of pregnant women complicated with placenta previa who were managed with autologous blood storage for cesarean section. Materials and Methods: We studied two groups of patients who were complicated with placenta previa and who underwent cesarean delivery. Group A consisted of women who were treated with oral iron medication (100 mg/day), and Group B consisted of women who were treated with TJ-108 at a dose of 9.0 g per day, in addition to oral iron medication, from the first day of blood storage until the day before cesarean delivery. To evaluate the effect of TJ-108, the patients’ red blood cell (RBC); Hb; hematocrit (Ht); white blood cell (WBC); and platelet count (PLT) levels were measured 7 days after storage and at postoperative days (POD) 1 and 5. Results: The study included 65 individuals, 38 in group A and 27 in group B. At the initial storage, a 0.2 g/dL reduction in Hb levels was observed, as compared to the initial Hb levels, in the TJ-108 treated patients, whereas a 0.6 g/dL reduction in Hb levels was observed in the non-TJ-108 treated group. On the other hand, regarding the second and subsequent storages, no significant difference was found in the decrease in the Hb levels of both groups. Conclusions: This study is the first report showing the effect of TJ-108 on improving anemia in pregnant women, presumably by its boosting effect on myelohematopoiesis. Therefore, the combined administration of both iron and TJ-108 is effective as a strategy for pregnant women at a high risk of PPH due to complications such as placenta previa.

Objectives To evaluate the safety and efficacy of transvaginal mesh surgery using a polytetrafluoroethylene mesh to treat pelvic organ prolapse. Methods This prospective observational study included women undergoing transvaginal mesh surgery for pelvic organ prolapse that used new polytetrafluoroethylene mesh cut into a shape similar to that of Elevate. We evaluated the subjective and objective outcomes at 3 and 12 months, as well as postoperative complication rates. Results This study included 55 patients. The pelvic organ prolapse quantification scores improved significantly at 3 and 12 months after surgery compared with scores before surgery. In four patients (7.3%), a pelvic examination showed stage 2 objective recurrence without subjective symptoms. Clavien-Dindo grades 2 and 3 perioperative complications were observed in 9.1% and 1.8% of the patients, respectively. Vaginal mesh exposure occurred in one patient (1.8%) at the time of the 3-month follow-up evaluation. The mesh was exposed at the proximal midline of the anterior vaginal wall. Conclusions These findings show the safe and effective use of the polytetrafluoroethylene mesh for transvaginal mesh surgery.

Since it is extremely difficult to establish an animal model for human chromosomal abnormalities, induced pluripotent stem cells (iPSCs) provide a powerful alternative to study underlying mechanisms of these disorders and identify potential therapeutic interventions. In this study we established iPSCs from a young girl with a hemizygous deletion of Xq27.3-q28 who exhibited global developmental delay and intellectual disability from early in infancy. The deletion site on the X chromosome includes Fragile X Mental Retardation 1 (FMR1), the gene responsible for fragile X syndrome, which likely contributes to the patient's neurodevelopmental abnormalities. The FMR1 gene was expressed in approximately half of the iPSC clones we generated while it was absent in the other half due to the random inactivation of normal and abnormal X chromosomes. The normal or absent expression pattern of the FMR1 gene was not altered when the iPSCs were differentiated into neural progenitor cells (NPCs). Moreover, chromosome reactivating reagents such as 5-aza-2-deoxycytidine, trichostatin A, and UNC0638, were tested in an attempt to reactivate the suppressed FMR1 gene in affected iPSC-NPCs. The affected and control isogenic iPSCs developed in this study are ideal models with which to identify downstream consequences caused by the Xq27.3-q28 deletion and also to provide tools for high-throughput screening to identify compounds potentially improving the well-being of this patient population.

Background: Pregnant women are in the highest priority group for receiving influenza vaccination. However, they may be reluctant to receive the vaccination due to concerns about the influence of vaccination on the fetuses. Methods: This prospective cohort study of 10 330 pregnant women examined the safety of influenza vaccination in terms of adverse birth outcomes. Influenza vaccination during pregnancy was determined from questionnaires before and after the 2013/2014 influenza season. All subjects were followed until the end of their pregnancy. Adverse birth outcomes, including miscarriage, stillbirth, preterm birth, low birth weight, and malformation, were assessed by obstetrician reports. Results: Adverse birth outcomes were reported for 641 (10%) of the 6387 unvaccinated pregnant women and 356 (9%) of the 3943 vaccinated pregnant women. Even after adjusting for potential confounders, vaccination during pregnancy showed no association with the risk of adverse birth outcomes (odds ratio 0.90, 95% confidence interval 0.76–1.07). Vaccination during the first or second trimester displayed no association with adverse birth outcomes, whereas vaccination during the third trimester was associated with a decreased risk of adverse birth outcomes (odds ratio 0.70, 95% confidence interval 0.51–0.98). Conclusions: Influenza vaccination during pregnancy did not increase the risk of adverse birth outcomes, regardless of the trimester in which vaccination was performed, when compared to unvaccinated pregnant women. Keywords: Adverse birth outcomes, Influenza vaccine, Pregnant women, Prospective cohort study, Vaccine safety

We assessed the effects of feeding regimen (ad libitum vs. time-restricted food access) and type of food (normal chow (NC: 12% fat) vs. moderately high calorie diet (mHCD: 31% fat)) on fertility competence of female mice. Mice fed mHCD had higher number of oocytes than mice fed NC. On the other hand, when mice were fed NC under time-restricted access to food (NT), the developmental rate to the blastocyst per number of normally fertilized ova was significantly decreased compared to others. The reactive oxygen species (ROS) level in oocytes increased in time-restricted food access and NC group. Transcriptome analysis of whole ovarian tissues from these mice showed a change in the cholesterol metabolism among the four groups. Time-restricted food access decreased serum LDL cholesterol level in both NC and mHCD groups. Moreover, the number of atretic follicles increased in NT mice compared to ad libitum food access mice. The present study shows that mHCD feeding increases the number of ovulated oocytes and that time-restricted feeding of NC impairs the developmental competence of oocytes after fertilization, probably due to the changes in serum cholesterol levels and an increase in the ROS content in oocytes.

Aim Tension-free vaginal mesh (TVM) surgery using synthetic polypropylene (PP) soft mesh had spread rapidly. However, the frequency of mesh-related postoperative complications had increased, and PP was banned in April 2019. In Japan, however, transvaginal surgery using polytetrafluoroethylene (PTFE) mesh had been approved. In this study, we evaluated the clinical outcome and quality of life (QOL) of the postoperative course using PP mesh and PTFE mesh (named "ORIHIME™" ) in a combination surgery for utero-sacral ligament suspension and anterior vaginal support using anterior TVM. Methods The vaginal hysterectomy and utero-sacral ligament colpopexy augmented by anterior vaginal mesh implants using PP mesh and PTFE mesh were performed on patients with stage III to IV cystocele and uterine prolapse. The clinical outcome and QOL changes in their postoperative course were evaluated by comparing 15 cases of PP mesh and 13 cases of PTFE mesh. Results There was no difference between the PP group and PTFE group in characteristics. No mesh-related complications occurred during the follow-up period. With regard to the pelvic organ prolapse quantification (POP-Q) score, no significant difference was found between the two groups. Comparing the postoperative QOL of both groups, the PTFE group had significantly higher values in two domains than PP group (SF-12v2 questionnaire). Conclusions We used the world's first PTFE mesh to compare PP mesh with postoperative POP-Q and QOL after the same surgery, with the same operator, and at the same institution. The results showed no significant difference between both mesh materials in the short-term.

Amniotic fluid embolism (AFE) is a catastrophic condition in the peripartum period and still remains as a leading cause of maternal death. Although over 80% of cases of AFE cases are accompanied by coagulopathy, the pathology of disseminated intravascular coagulation is not well understood not only because of its rarity but also because of the limited availability of laboratory testing in emergent clinical settings. We describe a case of AFE whose characteristic data for coagulation and fibrinolysis were timely depicted with sequential thromboelastography. We believe that the point-of-care, which provides information for both coagulopathy and fibrinolysis, may provide crucial data not only for the treatment of postpartum hemorrhage in daily clinical practice but also for the elucidation of AFE pathophysiology.

Pelvic organ prolapse (POP) is a multifactorial disorder that impairs the quality of life (QoL) of older women in particular. The purpose of this study was to elucidate the pathogenesis of POP by focusing on the extracellular matrix (ECM). Patients were classified into two groups—with or without cervical elongation—using the POP quantification system. Specimens were obtained from 29 women with POP during hysterectomy. The expression of fibulin-5, elastin, integrin β1 (ITGβ1), lysyl oxidase-like protein-1 (LOXL1) and collagen in the vagina, uterosacral ligament, and uterine cervix was investigated by quantitative real-time polymerase chain reaction (RT-PCR) and correlation between gene levels and severity of POP examined. The location of proteins was analyzed using immunohistochemical staining and expression of fibulin-5 protein analyzed by Western blotting. Fibulin-5 and elastin were mainly expressed in lamina propria and fibromuscular layers of the vagina and uterosacral ligament. Gene levels of fibulin-5 and ITGβ1 in uterosacral ligaments increased with severity of POP in women with cervical elongation, while no correlation was observed in women with a normal cervix. In women with uterine cervical elongation, each ECM-related gene significantly increased with POP staging. Furthermore, fibulin-5 protein also increased in the uterosacral ligament and uterine cervix. The severity of POP and gene expression of ECM-related proteins were inversely correlated in vaginal tissue in a normal and elongated cervix. These results suggested that the differing progression of the two types of POP have a relationship with ECM-related protein.

Purpose To study the outcomes of mouse preimplantation embryos irradiated with low doses of X-rays (≤ 1 Gy) and investigate apoptosis and pluripotency of the irradiated embryos. Methods Mouse embryos at the 2-cell stage were collected for in vitro culture. After reaching the 8-cell stage, embryos were irradiated with various low doses of X-rays (0–1 Gy). Blastocysts with a normal appearance were transferred into a pseudopregnant uterus. The developmental rate to blastocysts and the survival rate following embryo transfer were examined. Expression levels of p21, Smad2, Foxo1, Cdx2, Oct4, and Nanog genes were measured by RT-PCR. Apoptotic cells in mouse blastocysts were examined immunofluorescently by staining for cleaved caspase-3. Results More than 90% of non-irradiated and low-dose X-ray-irradiated preimplantation embryos developed to morphologically normal blastocysts that could be implanted and survive in the uterus. However, embryos irradiated with X-rays had more apoptotic cells in a dose-dependent manner. Expression of p21, Smad2, and Foxo1 genes in X-ray-irradiated embryos was increased significantly, while expression of Cdx2, Oct4, and Nanog genes was maintained in comparison with non-irradiated embryos. Conclusions Although irradiated embryos contained apoptotic cells, the low doses of irradiation did not disturb development of 8-cell stage embryos to blastocysts or their survival in utero. The underlying mechanisms might involve anti-apoptotic systems, including the Smad-p21 pathway, and preservation of pluripotency. Electronic supplementary material The online version of this article (10.1007/s10815-018-1156-y) contains supplementary material, which is available to authorized users.

This prospective cohort study showed that the effectiveness of prenatal and postpartum influenza vaccination of mothers in preventing influenza among their infants was 61% and 53%, respectively. Maternal influenza vaccination during the prenatal or postpartum periods had beneficial effects in protecting infants from influenza., Background Infants

Toll-like receptors (TLRs) are important components of the innate immune system, but how neonatal TLR-mediated immune responses differ from those of adults is unknown. We aimed to clarify the TLR-mediated expression profiles of cell surface antigens related to antigen presentation in neonates. CD14-positive monocytes were isolated from human cord blood and adult peripheral blood and then stimulated with lipopolysaccharide (LPS; TLR4 agonist) or zymosan (TLR2/6 agonist) or left unstimulated. Expression levels of the surface antigens major histocompatibility (MHC)-class II, CD80, CD86, CD11b, CD11c, CD14, and CD16 were then evaluated by flow cytometry. Cord blood CD14+CD16high monocytes (CBM) showed significantly lower basal levels of MHC-class II, CD80, and CD11b than adult blood CD14+CD16intermediate monocytes (ABM) (P

To evaluate influenza disease burden among pregnant women, an epidemiological study using the self-control method was conducted. Study subjects were 12,838 pregnant women who visited collaborating maternity hospitals and clinics in Osaka Prefecture, Japan, before the 2013/14 influenza season. As a study outcome, hospitalization due to respiratory illnesses between the 2010/11 and 2013/14 seasons was collected from each study subject through a baseline survey at the time of recruitment and a second survey after the 2013/14 season. The hospitalization rates during pregnancy and non-pregnancy periods was calculated separately. To compare the hospitalization rate during pregnancy with that during non-pregnancy within the same single study subject, Mantel-Haenzel rate ratios (RRMH) were calculated. During the four seasons examined in this study, nine and 17 subjects were hospitalized due to respiratory illnesses during pregnancy and non-pregnancy periods, respectively. The hospitalization rate was 2.54 per 10,000 woman-months during pregnancy and 1.08 per 10,000 woman-months during non-pregnancy. The RRMH for the hospitalization rate during pregnancy compared with that during non-pregnancy was 4.30 (95% confidence interval, 1.96-9.41). Our results suggest that during the influenza season, pregnant women have a higher risk than non-pregnant women for hospitalization due to respiratory illnesses. The self-control method appears to be an appropriate epidemiological method for evaluating the disease burden of influenza among pregnant women.

Objective The aims of this study were to investigate the time intervals of each component of cardiac flow velocity waveforms (FVWs) in fetuses with fetal growth restriction (FGR) and to compare these with those of normal fetuses using reference ranges. Methods The durations of atrioventricular (AV) valve opening (AVVO), AV valve closure (AVVC), total E- (total-E) and A- (total-A) waves, total ejection time (total-ET), acceleration time (acc-E for E-wave, acc-A for A-wave, and acc-ET for ejection time), and deceleration time (dec-E for E-wave, dec-A for A-wave, and dec-ET for ejection time) were measured in fetuses with FGR. All variables were analyzed using z -scores. Results Measurements of 17 growth-restricted fetuses were obtained. The time intervals between the last Doppler examination and delivery ranged from 0 to 6 days, with a median of 1 day. Significant increases were observed in AVVO, total-E, dec-E, and acc-A of the left heart. acc-E, acc-ET and AVVC of the left heart were significantly decreased. In the right heart, AVVO, total-E and dec-E were significantly increased. Conclusion A prolonged time interval between early ventricular inflow and atrial contraction, as well as increased duration of AV valve opening, may reflect hemodynamic alterations in FGR fetuses.

Very-long-chain acyl-coenzyme A dehydrogenase deficiency (VLCADD) is a rare and life-threatening disease characterized by an enzymatic defect in the fatty acid β-oxidation pathway. A nulliparous woman with VLCADD showed improvements in serum levels of the long-chain acylcarnitine moiety (C14:1) during pregnancy and successfully delivered a healthy infant vaginally. Pregnancy and vaginal delivery can be successfully completed in patients with VLCADD with careful management.

Objective To investigate time intervals of the ductus venosus (DV) flow velocity waveform (FVW) and those of the cardiac cycle that correspond with each DV-FVW component in fetuses with intrauterine growth restriction (IUGR) due to placental insufficiency. Methods Women with a pregnancy complicated by IUGR were recruited into the study, as was a normal control group. Time intervals for systolic (S) and diastolic (D) components were measured in DV-FVW as follows: SDV, from the nadir of the a-wave during atrial contraction to the nadir between the S-wave and D-wave; DDV, from the nadir between S-wave and D-wave to the nadir of the a-wave. Regarding cardiac cycles, the following variables were measured from ventricular inflow through the tricuspid valve (TV) and mitral valve (MV): STV and SMV, from the second peak of ventricular inflow caused by atrial contraction (A-wave) to the opening of the atrioventricular valve; DTV and DMV, from the opening of the atrioventricular valve to the peak of the A-wave. In the IUGR group, only the last examination performed within 1 week of delivery was used for analysis. All variables were analyzed statistically using Z-scores. Results Data were obtained from 249 normal fetuses and 26 fetuses with IUGR. Compared to normal fetuses, SDV showed a significant decrease (P

We aimed to construct reference ranges for time intervals of each component of cardiac flow velocity waveforms in normal fetuses, comparing those variables between right and left ventricles.In 359 fetuses at the gestational age of 17-38 weeks, the durations of atrioventricular (AV) valve opening (AVVO), AV valve closure (AVVC), total E- (total-E) and A- (total-A) waves, total ejection time (total-ET), acceleration time (acc-E for E-wave, acc-A for A-wave, and acc-ET for ejection time), and deceleration time (dec-E for E-wave, dec-A for A-wave, and dec-ET for ejection time) were studied cross sectionally.Both right and left acc-E showed the strongest correlations with gestational age (r = 0.478 and r = 0.519, respectively). Left AVVO showed a stronger correlation (r = 0.474) than right AVVO (r = 0.282) and, conversely, right AVVC showed a stronger correlation (r = 0.399) than left AVVC (r = 0.195) with gestational age. Significant differences (all P values0.001) were observed for all right and left parameters other than total-A and acc-E.Characteristic differences between right and left ventricles were found in the reference ranges, suggesting the developmental properties of the fetal heart. © 2014 John WileySons, Ltd.

A national survey of pregnancy outcomes after living donor liver transplantation (LDLT) was performed in Japan. Thirty-eight pregnancies in 30 recipients resulted in 31 live births (25 recipients), 3 artificial abortions in the first trimester (3 recipients), 1 spontaneous abortion (1 recipient), and 3 fetal deaths (3 recipients). After the exclusion of the 3 artificial abortions, there were 35 pregnancies in 27 recipients: pregnancy-induced hypertension developed during 6 pregnancies (5 recipients), fetal growth restriction developed during 7 pregnancies (6 recipients), acute rejection developed during 2 pregnancies (2 recipients), and ileus developed during 1 pregnancy (1 recipient). Preterm delivery (37 weeks) occurred for 10 pregnancies (10 recipients), and cesarean delivery was performed for 12 pregnancies (12 recipients). After delivery, acute rejection developed in 3 recipients. Twelve neonates were born with low birth weights (2500 g), and 4 of these 12 neonates had extremely low birth weights (1500 g). Two neonates had congenital malformations. The pregnancy outcomes after LDLT were similar to those reported for cadaveric liver transplantation (LT). The incidence of pregnancy-induced hypertension in recipients who were 33 years old or older at the diagnosis of pregnancy was significantly higher than the incidence in recipients who were less than 33 years old at the diagnosis of pregnancy. The incidences of fetal growth restriction, pregnancy-induced hypertension, and extremely low birth weight were significantly higher in the early group (3 years after transplantation) versus the late group (≥3 years after transplantation). In conclusion, it is necessary to pay careful attention to complications during pregnancy in recipients who become pregnant within 3 years of LT, particularly if the age at the diagnosis of pregnancy is ≥33 years.

To investigate time intervals of ductus venosus (DV) flow velocity waveforms (FVW) in correlation to fetal heart rate and gestational age and to construct reference ranges for the second and third trimester. Furthermore, we investigate time intervals of FVW through the tricuspid valve.Flow velocity waveforms of the DV and through the tricuspid valve were recorded in 135 normal singleton fetuses between 17 and 38 weeks' gestation. Time intervals for systolic (S) and early diastolic (D) peaks were analyzed regarding acceleration time (acc-S for S, acc-D for D) and deceleration time (dec-S for S, dec-D for D), respectively. Similarly, time intervals for both peaks of right ventricular inflow were analyzed regarding acceleration time (acc-E for E-wave, acc-A for A-wave) and deceleration time (dec-E for E-wave, dec-A for A-wave), respectively.In the DV, acc-D and dec-D increased significantly with gestational age. In tricuspid valve, acc-E and acc-A showed a significant increase with gestational age. All parameters except acc-S showed significant negative correlations with fetal heart rate.With advancing gestational age, prolongation of the diastolic phase of DV-FVW and of the E-wave of tricuspid flow was observed, suggesting maturation of ventricular diastolic function. Time-related analysis of Doppler signals of DV-FVW may provide detailed insights into fetal cardiac function.

Protein S is an antithrombotic cofactor for protein C that also has multifunctional anti-inflammatory, cellular protective, apoptotic and mitogenic properties. Protein S levels are thought to decrease during pregnancy, but the underlying mechanism remains unknown. We compared protein S concentrations throughout normal pregnancy with those of nonpregnant women and measured plasma C4b-binding protein levels in nonpregnant women and in pregnant women at the 40th gestational week. We also examined protein S and C4b-binding protein in the placenta by immunohistochemical staining at early (20th gestational week) and late (40th gestational week) stages of pregnancy. Plasma protein S activity and free protein S-antigen levels significantly decreased from the 10th gestational week and total protein S antigen decreased from the 20th. C4b-binding protein levels between pregnant and nonpregnant women did not significantly differ. The stainable portion of protein S was located at the fetomaternal interface, particularly at degenerative villi. C4b-binding protein was weakly stained at the same areas as protein S. Neither protein S nor C4b-binding protein were stained at normal villi. These results indicated that protein S can protect or restore damaged villi via a physiological effect in addition to its anticoagulation properties.

Widespread use of fetal aortic blood flow velocity measurements for assessment of fetal circulatory status has been precluded by difficulties in achieving an adequate Doppler insonation angle at particular sampling points. The goal of this study was to evaluate the differences in resistance index (RI) and systolic peak velocity (Vmax) of fetal aortic blood flow velocity waveforms throughout gestation among various Doppler sampling points.A total of 551 normal women between 18-41 weeks of pregnancy participated in this study. Pulsed Doppler flow velocity waveforms were acquired from three different aortic sampling points (thoracic portion, beneath the diaphragm, and abdominal portion) of the fetal descending aorta. The Vmax and RI were calculated at the respective sampling points.The Vmax were significantly lower in abdominal portion than those in thoracic portion at every time point (from 69 +/- 11 cm/second in thoracic to 49 +/- 8 cm/second in abdominal portion at 18-19 gestational weeks, p0.0001), and RI were also lower (from 0.84 +/- 0.05 in thoracic portion to 0.76 +/- 0.05 in abdominal portion at 18-19 gestational weeks, p0.0001). Significant increase in the Vmax was seen until third trimester (from 58+/-10 cm/second at 18-19 gestational weeks to 113 +/- 13 cm/second at 38-39 gestational weeks beneath the diaphragm, p0.0001), while the RI remained stable (0.79 +/- 0.04 at 18-19 gestational weeks; 0.80 +/- 0.05 at 38-39 gestational weeks beneath the diaphragm).In measuring the fetal circulatory status, these data demonstrate that the sampling point should be considered when evaluating the maximum systolic velocity and the resistance index of the fetal descending aorta.

Tetrahydrobiopterin (BH 4 ) is an essential co-factor for nitric oxide (NO) synthase (NOS) and regulates the production of NO, or endothelium derived relaxation factor. Although NOS is highly expressed in the placenta and NO plays a critical role in the regulation of feto-placental circulation, the mechanism maintaining the level of BH 4 is not known. To investigate the de novo synthesis of BH 4 in the human placenta, the activity of guanosine triphosphate cyclo-hydrolase I (GTPCH), 6-pyruvoyltetrahydropterin synthase (PTPS), and sepiapterin reductase (SR) in the chorionic tissue during the first, second and third trimester of pregnancy was analyzed. GTPCH activity was the lowest of the three enzymes and became negligible after the second trimester. There was no significant change in PTPS activity throughout pregnancy. Although SR activity decreased significantly after the second trimester, the levels remained abundant throughout pregnancy. These results showed that GTPCH is a rate-limiting enzyme and the total activity of the de novo synthesis of BH 4 is negligible in the mature placenta after the second trimester when fetal growth is accelerated. The present study suggests that the level of BH 4 in the placenta depends principally on the system other than de novo synthesis. The salvage pathway is considered the most potent system, which is formed by the transfer of the substrates from the fetus and their enzymatic conversion to BH 4 in the placenta.

Tetrahydrobiopterin (BH4) is an essential cofactor of nitric oxide synthase as well as a cofactor of aromatic amino acid hydroxylases. However, its role in pregnancy is not yet understood. We evaluated the concentrations of BH4 throughout normal pregnancy and puerperium, and compared them with those of non-pregnant women by measuring its oxidation product biopterin. In addition, we also measured 6-pyruvoyl tetrahydropterin synthase (PTPS) activities, the rate-limiting enzyme in synthesizing BH4, in pregnant women at the 30th gestational week and non-pregnant women. Although the urinary biopterin levels did not remarkably change, plasma biopterin levels significantly decreased from the 10th gestational week to the 1st day of postpartum compared with those of non-pregnant women. There was no significant difference in PTPS activities between pregnant and non-pregnant women. However, the proportion of reticulocytes, which have been shown to possess high PTPS activity, is significantly higher in pregnant women than in non-pregnant women. Our results suggest that decreased plasma BH4 levels in pregnancy is caused by impaired PTPS activity.

The small neutrophil reserve and exaggerated release of stored neutrophils are factors which predispose neonates to neutrophil reserve exhaustion during bacterial sepsis. Our objective is to try to improve in utero the myelopoietic function of the fetus before delivery. In the first series, recombinant human (rh) granulocyte colony-stimulating factor (G-CSF) (rhG-CSF; 100 μg/kg) was injected subcutaneously into rat fetuses at the indicated times to assess drug absorption and fetal response. In the second series, rhG-CSF (100 μg/kg) or saline (control) was injected into the fetuses once every other day to investigate the effect of repeated injections of rhG-CSF on enhancing fetal myelopoiesis preceding birth. Delivery was performed by cesarean section on embryonic day 21. The plasma concentration of G-CSF was determined by ELISA. The effect of rhG-CSF injection on granulopoiesis was assessed by measurement of the neutrophil count in the fetal peripheral blood and by histological examination of the fetal bone marrow, spleen, and liver. Fetally administered rhG-CSF enhanced fetal myelopoiesis preceding birth.

EDITORIAL COMMENT: We accepted this case for publication to remind readers that although uterine rupture during labour in a primigravida is extremely uncommon it does occur, or at any rate nulliparas can develop abdominal pain and shock in labour with a haemoperitoneum resulting from a tear in a vein in the lower posterior uterine wall. When one sees the hugely dilated uterine and ovarian venous plexuses at Caesarean section it is easy to believe that bleeding from such a vessel during labour could be prodigious. This case suggests that a dilated vein with blood flow derangements may be the cause. Nonetheless, as the authors warn us, the necessary response is not a precise diagnosis, but rapid laparotomy. See also Editorial Comment to Chin MMS, Harvey JA, Duffy BL. Uterine rupture during labour in a primigravida. Aust NZ J Obstet Gynaecol 1996; 36: 210.