Hiromi Hayakawa

Placenta previa increta/percreta in Japan: A retrospective study of ultrasound findings, management and clinical course

Aim:  Placenta accreta is an abnormally firm attachment of placental villi to the uterine wall, which may cause postpartum hemorrhage resulting in maternal morbidity and mortality. The purpose of the present study was to clarify the incidence, clinical background and prognosis of placenta previa increta/percreta treated with different modalities in Japan.

Methods for myometrium closure and other factors impacting effects on cesarean section scars of the uterine segment detected by the ultrasonography

Objective. Ultrasound examination is an objective method for assessment of uterine scar defects. The present study was conducted to compare single‐layer interrupted sutures (Group A) with double‐layer interrupted sutures (Group B) and our new method (Group C) as well as other perioperative parameters in relation to risk of wedge defects in scars. Methods. We have introduced a new myometrium closure procedure consisting of continuous suture with decidual closure followed by interrupted myometrium suture. In this prospective study, women undergoing cesarean operation (n=137) were examined by transvaginal ultrasound one month after surgery to assess the appearance of lower uterine scars. Multivariate logistic regression analysis was performed to identify associations of perioperative parameters and methods for lower myometrium closure with abnormal wedge formation. Results. Wedge defects were observed in a total of 27 patients (19.7%). The analysis revealed Groups B and C to have reduced risks with odds ratios of 0.28 and 0.077, respectively, as compared to Group A. Furthermore, increasing gestational week at delivery, plural fetal pregnancies, premature rupture of membranes and pre‐eclampsia were also linked with an increased risk, with odds ratios of 1.4–8.9. Conclusion. The incidence of uterine scar defects 1 month after cesarean sections varies with the method applied for myometrial suture and perioperative variables. The data suggest that methods for myometrium closure as well as other factors influence the condition of myometrial healing.

Activator Protein-2 Impairs the Invasion of a Human Extravillous Trophoblast Cell Line

The reduced migration/invasion of extravillous trophoblasts (EVTs) is a key feature of the genesis of preeclampsia. We and others previously reported that transcriptional factors activator protein-2 (AP-2) alpha and AP-2gamma act as suppressors of tumor invasion. The present study examined the expressions of AP-2alpha and AP-2gamma in preeclamptic placenta vs. control placenta and investigated their effect on the function of EVTs. The expressions of AP-2alpha and AP-2gamma were elevated in the preeclamptic placentas in comparison with the gestational age-matched control placentas. Their expressions also increased in EVTs of the preeclamptic placentas. Thereafter, we transfected AP-2alpha or AP-2gamma into human EVT cell line, HTR-8/SVneo. The overexpression of AP-2alpha or AP-2gamma decreased the migratory and invasive abilities in HTR-8/SVneo cells. This was followed by the reduction of protease activated receptor-1 and matrix metalloproteinases and a significant induction of plasminogen activator inhibitor-1 and the tissue inhibitor of metalloproteinase-1. AP-2alpha and AP-2gamma were weakly expressed in the cultured EVTs and HTR-8/SVneo cells, whereas they were induced by TNF-alpha, which increases in preeclamptic placenta and impairs trophoblast invasion. In the presence of TNF-alpha, the invasion of the HTR-8/SVneo cells was partially restored by a blocking of AP-2 induction using small interfering RNA of AP-2. The present data suggest that AP-2 may suppress trophoblast migration and invasion, thus leading to a shallow placentation in preeclampsia.

The MRI findings of the right-sided fetal lung can be used to predict postnatal mortality and the requirement for extracorporeal membrane oxygenation in isolated left-sided congenital diaphragmatic hernia.

We evaluated whether a correlation existed between fetal pulmonary magnetic resonance imaging (MRI) findings and postnatal mortality, as well as the requirements for extracorporeal membrane oxygenation (ECMO) in infants with prenatally diagnosed, isolated left-sided congenital diaphragmatic hernia (CDH). Twenty-one pregnant women carrying fetuses with CDH underwent 30 MRI scans, and the right-sided fetal lung volume (FLV) was measured. In the control, a regression analysis was performed to associate FLV with gestational age. This yielded a formula that enabled the calculation of the expected right fetal lung volume (ERFLV). In cases with CDH, the right-sided observed FLV/ERFLV (= %RFLV) was compared with both the postnatal mortality and whether ECMO was required. Additionally, we investigated the relationship between the lung shape on MRI (whether there was a complete pulmonary baseline present) and postnatal mortality. The %RFLV was significantly lower in nonsurvivors compared with survivors. Among survivors, the %RFLV was significantly lower in infants who required ECMO compared with those who did not. The pulmonary baseline was completely present in 3 (38%) and 13 (100%) of the nonsurvivors and survivors, respectively. In isolated left-sided CDH, the %RFLV is a good predictor not only of postnatal mortality but also of the requirement for ECMO.

Uterine sutures at prior caesarean section and placenta accreta in subsequent pregnancy: a case–control study

To clarify the effects of uterine myometrial suture techniques at prior caesarean section on the incidence of pathologically diagnosed placenta accreta in placenta praevia with prior caesarean section (PPPC).

Maternal mental disorders and pregnancy outcomes: A clinical study in a Japanese population

Aim:  To assess the maternal and neonatal outcomes of pregnant women with mental disorders in Japan.

Tocilizumab Inhibits Interleukin-6-Mediated Matrix Metalloproteinase-2 and -9 Secretions from Human Amnion Cells in Preterm Premature Rupture of Membranes

Background/Aims: In the present study, we investigated the participation of inflammatory cytokine-induced mediated matrix metalloproteinase (MMP) expressions and inhibition of interleukin (IL)-6-induced MMP secretion in amniotic epithelial cells by tocilizumab. Methods: To investigate the role of MMP expressions, immunohistochemical staining was performed using membranes obtained from 10 patients with preterm premature rupture of membranes (PPROM) and from 10 patients who underwent a nonlabor cesarean section. We also investigated the regulation of MMP expression by inflammatory cytokines in human amnion cells. Results: Immunohistochemical staining showed a significantly higher expression of MMP-2 and -9 in PPROM. Treatment of cultured WISH and primary amniotic epithelial cells with 10–8 or 10–7M IL-6 or tumor necrosis factor (TNF)-α clearly increased the secretion of MMP-2 and -9. Treatment with 10–8M TNF-α or IL-6 significantly increased the invasion of WISH or primary amniotic epithelial cells, respectively, compared with the control. At a low concentration of 1 μg/ml, tocilizumab (anti-human IL-6 receptor monoclonal antibody) inhibited the IL-6-induced MMP secretion. Conclusions: This paper is the 1st report of tocilizumab inhibiting IL-6-induced MMP-2 and MMP-9 secretions from human amnion cells in PPROM.

Amniotic lamellar body counts can predict the occurrence of respiratory distress syndrome as well as transient tachypnea of the newborn (TTN)

Abstract Aims: The purpose of this study is to predict the occurrence of transient tachypnea of the newborn (TTN) using amniotic lamellar body count (LBC) and compare the LBCs in neonates with TTN with the LBCs in neonates with respiratory distress syndrome (RDS) and controls. Methods: Three hundred and eighty-one amniotic fluid samples were obtained at cesarean section from 27 to 40 weeks of gestation. Samples were analyzed immediately without centrifugation and the number of lamellar bodies was counted. Results: The LBC in amniotic fluid ranged from 1,000 to 577,000/μL. An LBC cut-off value of 48,500/μL resulted in 84.7% sensitivity, 76.2% specificity, and 98.1% negative predictive value for predicting TTN. The LBC in neonates with TTN was significantly lower than that in controls (50,000 vs. 122,000; P<0.001) and significantly higher than that in neonates with RDS (50,000 vs. 21,000; P=0.042). Conclusions: We established a cut-off value of LBC for predicting the occurrence of TTN. The LBC in neonates with TTN was significantly lower than that in controls. Amniotic LBC can be a useful marker to predict if neonatal respiratory management is required.

A case report of placental mesenchymal dysplasia with an increased VEGF-D expression

The pathogenesis of placental mesenchymal dysplasia (PMD) remains unclear. This report presents a case of PMD with a female fetus complicated with intrauterine growth restriction (IUGR). The ultrasound findings were similar to molar pregnancies, but PMD was suspected based on the presence of low β-hCG levels and a normal karyotype. After delivery, pathological examination of the placenta showed dilated villi and thick-walled vessels lacking trophoblast proliferation, which thus led to a diagnosis of PMD. The VEGF-D (Xp22.31) mRNA expression was found to have increased in the abnormal villi. Whether this is an incidental or X-linked gene specific event in, IUGR complicated, PMD pathogenesis warrants further investigation of VEGF-D expression in PMD.

Intra-amniotic infection increases amniotic lamellar body count before 34 weeks of gestation.

Objective. To examine the lamellar body count (LBC) value in intra-amniotic infection cases and evaluate its association with the incidence of respiratory distress syndrome (RDS). Methods. Three hundred sixty-five amniotic fluid (AF) samples were obtained at caesarean section from 27 to 38 weeks of gestation. LBC and glucose concentrations in AF were measured with no centrifugation. We defined AF glucose concentrations <0.8 mmol/L and positive C-reactive protein (CRP) of the neonates as intra-amniotic infection. Results. An LBC cutoff value of 29,500/μL resulted in 94.0% sensitivity, 82.4% specificity, and 99.1% negative predictive value (NPV) for RDS. Neonates with glucose concentrations <0.8 mmol/L in AF and positive CRP had no RDS and significantly higher LBC values than controls before 34 weeks of gestation (17.0 vs. 4.3, p < 0.05 and 25.5 vs. 5.0, p < 0.05, respectively), but there were no significant differences after 34 weeks of gestation. Conclusions. LBC is an accurate predictor of foetal lung maturity and our LBC cutoff value had a high NPV for predicting RDS. We showed that intra-amniotic infection was associated with significantly higher LBC values than the value in controls before 34 weeks of gestation, which correlated with a low incidence of RDS.