Vasa previa in singleton pregnancies: diagnosis and clinical management based on an international expert consensus.

BACKGROUND: There are limited data to guide the diagnosis and management of vasa previa. Currently, what is known is largely based on case reports or series and cohort studies. OBJECTIVE: This study aimed to systematically collect and classify expert opinions and achieve consensus on the diagnosis and clinical management of vasa previa using focus group discussions and a Delphi technique. STUDY DESIGN: A 4-round focus group discussion and a 3-round Delphi survey of an international panel of experts on vasa previa were conducted. Experts were selected on the basis of their publication record on vasa previa. First, we convened a focus group discussion panel of 20 experts and agreed on which issues were unresolved in the diagnosis and management of vasa previa. A 3-round anonymous electronic survey was then sent to the full expert panel. Survey questions were presented on the diagnosis and management of vasa previa, which the experts were asked to rate on a 5-point Likert scale (from "strongly disagree"=1 to "strongly agree"=5). Consensus was defined as a median score of 5. Following responses to each round, any statements that had median scores of ≤3 were deemed to have had no consensus and were excluded. Statements with a median score of 4 were revised and re-presented to the experts in the next round. Consensus and nonconsensus statements were then aggregated. RESULTS: A total of 68 international experts were invited to participate in the study, of which 57 participated. Experts were from 13 countries on 5 continents and have contributed to >80% of published cohort studies on vasa previa, as well as national and international society guidelines. Completion rates were 84%, 93%, and 91% for the first, second, and third rounds, respectively, and 71% completed all 3 rounds. The panel reached a consensus on 26 statements regarding the diagnosis and key points of management of vasa previa, including the following: (1) although there is no agreement on the distance between the fetal vessels and the cervical internal os to define vasa previa, the definition should not be limited to a 2-cm distance; (2) all pregnancies should be screened for vasa previa with routine examination for placental cord insertion and a color Doppler sweep of the region over the cervix at the second-trimester anatomy scan; (3) when a low-lying placenta or placenta previa is found in the second trimester, a transvaginal ultrasound with Doppler should be performed at approximately 32 weeks to rule out vasa previa; (4) outpatient management of asymptomatic patients without risk factors for preterm birth is reasonable; (5) asymptomatic patients with vasa previa should be delivered by scheduled cesarean delivery between 35 and 37 weeks of gestation; and (6) there was no agreement on routine hospitalization, avoidance of intercourse, or use of 3-dimensional ultrasound for diagnosis of vasa previa. CONCLUSION: Through focus group discussion and a Delphi process, an international expert panel reached consensus on the definition, screening, clinical management, and timing of delivery in vasa previa, which could inform the development of new clinical guidelines.

Exploring the Impact of Endometrioma Aspiration and Dienogest Combination Therapy on Cyst Size, Inflammatory Cytokines in Follicular Fluid and Fertility Outcomes.

Endometriomas (chocolate cysts) are cystic lesions that can develop on ovaries, and are characterized by the presence of ectopic endometrial tissue or similar tissue. Such lesions can cause a decline in the number and quality of oocytes, and lead to implantation failure. In this study, we retrospectively assessed the efficacy of repeated endometrioma aspiration and dienogest combination therapy in patients suffering endometriosis-associated infertility with endometriomas. A comparison was made between a treated group that underwent combination therapy followed by controlled ovarian hyperstimulation (COH) (n = 30) and a control group that did not undergo treatment (n = 40), at the IVF Osaka Clinic from September 2019 to September 2021. There were no differences in patient background between the two groups. A reduction in endometrioma size continued for 12 months after treatment. The numbers of follicles that developed to 15 mm or greater in size following COH and mature oocytes were significantly lower in the treated group compared to those in the control group. The levels of inflammatory cytokines in the follicular fluid significantly decreased in the treated group (p < 0.05). In patients in the treated group who underwent a second ova retrieval, the results were compared between those in the first ova retrieval (immediately after the end of treatment) and those in the second ova retrieval (four months after the first retrieval). The numbers of follicles following COH, retrieved, mature and fertilized ova were significantly increased in the second ova retrieval.

The Impact of Assisted Reproductive Technology on Umbilical Cord Insertion: Increased Risk of Velamentous Cord Insertion in Singleton Pregnancies Conceived through ICSI.

Background and Objectives: Vasa previa (VP) is a significant perinatal complication that can have serious consequences for the fetus/neonate. Velamentous cord insertion (VCI) is a crucial finding in prenatal placental morphology surveillance as it is indicative of comorbid VP. Assisted reproductive technology (ART) has been identified as a risk factor for VCI, so identifying risk factors for VCI in ART could improve VP recognition. This study aims to evaluate the displacement of umbilical cord insertion (CI) from the placental center and to examine the relationship between the modes of conception. Materials and Methods: We conducted a retrospective study at the Obstetrics Department of Osaka Metropolitan University Hospital in Japan between May 2020 and June 2022. The study included a total of 1102 patients who delivered after 22 weeks of gestation. They were divided into three groups: spontaneous pregnancy, conventional in vitro fertilization (cIVF), and in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). We recorded patient background information, perinatal complications, perinatal outcomes, and a numerical "displacement score", indicating the degree of separation between umbilical CI and the placental center. Results: The displacement score was significantly higher in the cIVF and IVF/ICSI groups compared with the spontaneous conception group. Additionally, the IVF/ICSI group showed a significantly higher displacement score than the cIVF group. Conclusions: Our study provides the first evidence that the methods of ART can affect the location of umbilical CI on the placental surface. Furthermore, we found that IVF/ICSI may contribute to greater displacement of CI from the placental center.

Long-term follow up in two cases of pelvic reconstruction using a combined VRAM flap-sacrocolpopexy for severe perineal hernia after abdominoperineal resection.

Perineal hernia is an infrequent complication of abdominoperineal resection (APR) and, currently, there is no consensus as to the optimal operative technique. Surgical repair can be achieved by either cerclage or the use of mesh or autologous tissue, and it has been reported that the recurrence rate after repair using autologous tissue is 33%. We present two post-APR cases of severe perineal hernia with pelvic organ prolapse (POP) which did not improve after repair using mesh. We regenerated the pelvic floor using a vertical rectus abdominis myocutaneous (VRAM) flap and performed a concomitant sacrocolpopexy to fix the POP. Drooping of the perineum and pelvic floor was greatly improved, and the patients have not experienced any recurrence for 6 years. This dual procedure has not been previously mentioned in the literature, and we consider this the first report of its kind.

Prevention of intrauterine fetal growth restriction by administrating C1q/TNF-related protein 6, a specific inhibitor of the alternative complement pathway.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The Hematopoietic Effect of Ninjinyoeito (TJ-108), a Traditional Japanese Herbal Medicine, in Pregnant Women Preparing for Autologous Blood Storage.

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.

Upregulation of PTK7 and ß-catenin after vaginal mechanical dilatation: an examination of fibulin-5 knockout mice.

INTRODUCTION AND HYPOTHESIS: 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. METHODS: 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. RESULTS: 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 ß-catenin are known to act in the Wnt/ß-catenin pathway, and both were upregulated after dilatation in the Fbln5+/+ mice, though not in the Fbln5-/- mice. CONCLUSION: 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.

Time interval analysis of ductus venosus and cardiac cycles in relation with umbilical artery pH at birth in fetal growth restriction.

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 = < 0.001 and 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 < 0.001 and 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.

Preliminary evaluation of the short-term outcomes of polytetrafluoroethylene mesh for pelvic organ prolapse.

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.

Transvaginal polytetrafluoroethylene mesh surgery for pelvic organ prolapse: 1-year clinical outcomes.

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.

Differential gene expression of extracellular-matrix-related proteins in the vaginal apical compartment of women with pelvic organ prolapse.

INTRODUCTION AND HYPOTHESIS: 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). METHODS: 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 ß1 (ITGß1), 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. RESULTS: 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 ITGß1 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. CONCLUSIONS: 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.

Protective Effect of Maternal Influenza Vaccination on Influenza in Their Infants: A Prospective Cohort Study.

Background: Infants <6 months of age are too young to receive influenza vaccine, despite being at high risk for severe influenza-related complications. Methods: To examine the effectiveness of maternal influenza vaccination in preventing influenza in their infants, we conducted a prospective cohort study of 3441 infants born at participating hospitals before the 2013-2014 influenza season. At the time of recruitment, their mothers completed a questionnaire about influenza vaccination status for the 2013-2014 season. A follow-up survey was conducted after the end of the 2013-2014 season to collect information regarding influenza diagnosis and hospitalization among infants. Results: During the 2013-2014 influenza season, 71 infants (2%) had influenza diagnosed, and 13 infants (0.4%) were hospitalized with influenza. Maternal influenza vaccination (especially prenatal vaccination) decreased the odds of influenza among infants. The effectiveness of prenatal vaccination was 61% (95% confidence interval, 16%-81%), whereas that of postpartum vaccination was 53% (-28%-83%). Although maternal influenza vaccination was also associated with a decreased odds of influenza-related hospitalization among infants, vaccine effectiveness (73%) did not reach statistical significance, owing to the limited number of infants hospitalized because of influenza. Conclusions: The present findings indicated that pregnant women and postpartum women should receive influenza vaccination to protect their infants.

Low-dose irradiation of mouse embryos increases Smad-p21 pathway activity and preserves pluripotency.

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.

Zymosan Induces Immune Responses Comparable with Those of Adults in Monocytes, Dendritic Cells, and Monocyte-Derived Dendritic Cells from Cord Blood.

OBJECTIVE: To investigate the differences in toll-like receptor (TLR)-mediated immune responses between human neonates and adults, focusing on the cytokine profiles of monocytes, dendritic cells (DCs), and monocyte-derived DCs (MoDCs) in cord and adult blood. STUDY DESIGN: Purified monocytes, DCs, and MoDCs were stimulated with the following TLR ligands: lipopolysaccharide (TLR4), Pam3CSK4 (TLR1/2), flagellin (TLR5), zymosan (TLR2), polyinosinic:polycytidylic acid (TLR3), imiquimod (TLR7), and CpG (TLR9). Interleukin (IL)-8, IL-6, tumor necrosis factor, IL-1ß, and IL-10 concentrations were analyzed in culture supernatants. RESULTS: Compared with the effects in adult blood, lipopolysaccharide-, Pam3CSK4-, flagellin-, and polyinosinic:polycytidylic acid-stimulated inflammatory cytokine production in cord blood was generally weak in monocytes, comparable in DCs, and elevated in MoDCs. CpG- and imiquimod-stimulated cytokine production in DCs was comparable in cord blood and adult blood, but cytokine production was almost absent in monocytes and MoDCs in both cord blood and adult blood. In contrast, zymosan stimulation produced comparable inflammatory cytokine profiles in the monocytes, DCs, and MoDCs of cord blood and adult blood. CONCLUSION: The immaturity of TLR-mediated innate immunity in neonates depends on monocytes rather than on DCs. Our results indicate that zymosan-mediated TLR2 signaling may be useful for developing a neonatal vaccine adjuvant.

Characteristic differences and reference ranges for mitral, tricuspid, aortic, and pulmonary Doppler velocity waveforms during fetal life.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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 values <0.001) were observed for all right and left parameters other than total-A and acc-E. CONCLUSIONS: Characteristic differences between right and left ventricles were found in the reference ranges, suggesting the developmental properties of the fetal heart. © 2014 John Wiley & Sons, Ltd.

Successful management of pregnancy with very-long-chain acyl-coenzyme A dehydrogenase deficiency.

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 ß-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.

Pregnancy outcomes after living donor liver transplantation: results from a Japanese survey.

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.

Increased annexin A2 expression in the placenta of women with acute worsening of preeclampsia.

BACKGROUND: The aims of present study were to investigate the expression of Annexin A2 in the placenta of patients with preeclampsia (PE) and correlate these data with acute worsening of clinical symptoms. METHODS: Placentas were collected from uncomplicated normal pregnancies (n = 9), PE cases without emergency termination of pregnancy (group 1, n = 6), and PE cases with acute worsening of symptoms necessitating immediate pregnancy termination (group 2, n = 7). Immunohistochemistry data were analyzed quantitatively, and placental mRNA expression was measured by Real-time PCR. RESULTS: Group 2 had a significantly shorter interval between diagnosis and pregnancy termination compared with group 1 (p = 0.002). Birth weight and placental weight in group 2 were significantly lower compared with the normal group (p = 0.006 and p = 0.03, birth weight and placental weight, respectively), whereas there were no differences in gestational age at delivery between the three groups or the severity of high blood pressure and proteinuria between the PE groups. Placental expression of Annexin A2 as determined by immunohistochemistry was significantly higher in both PE groups compared with the uncomplicated pregnancy group (p < 0.001 and p < 0.001, groups 1 and 2, respectively). Placental Annexin A2 mRNA expression was significantly elevated in group 2 compared with the normal group (p = 0.002) but did not change in group 1. CONCLUSIONS: This study is the first to demonstrate increased placental Annexin A2 mRNA expression during the acute phase of PE. Immunohistochemical staining of placental Annexin A2 was high, regardless of PE phase. These findings suggest that worsening of PE might alter Annexin A2 expression at the transcription level.