Shintaro Makino

Effect of steroid administration and plasmapheresis to prevent fetal congenital heart block in patients with systemic lupus erythematosus and/or Sjögren's syndrome

Congenital heart block (CHB) is the most serious manifestation of neonatal lupus syndrome (NLS), and maternal antibodies directed against the 52-kd SSA/Ro and 48-kd SSB/La antigens have been reported to be more strongly associated with CHB than those directed against the 60-kd SSA/Ro antigen alone (1). The most important treatment strategy for CHB is preventive, based on therapy with a fluorinated steroid and plasmapheresis during pregnancy (2). We treated both patients who were seropositive for anti-52-kd SSA/Ro and anti-48-kd SSB/La antibodies or had high titers of only anti-SSA/Ro antibody ( 1:512) measured by ELISA and Western blot analysis, as high-risk cases for CHB in their offspring, with a fluorinated oral steroid (prednisolone) and plasmapheresis. The aim of our study was to investigate whether treatment with a flurionated steroid and plasmapheresis of pregnant women with systemic lupus erythematosus (SLE) and/or Sjögren’s syndrome (SjS) may be effective in preventing CHB.

National survey of fibrinogen concentrate usage for post‐partum hemorrhage in Japan: Investigated by the Perinatology Committee, Japan Society of Obstetrics and Gynecology

The aim of this study was to provide basic documents applicable to studying the usefulness of administering fibrinogen concentrate to patients with massive post‐partum hemorrhage. We investigated the usage of fibrinogen concentrate at training institutions for specialist physicians of the Japan Society of Obstetrics and Gynecology.

Double vertical compression sutures: A novel conservative approach to managing post-partum haemorrhage due to placenta praevia and atonic bleeding

Compression has been regarded as the main haemostatic mechanism of compression sutures; however, we suggest that reduced uterine blood flow may be another important action. We suggest that our ‘double vertical compression sutures’ may have dual actions: haemostatic compression of the bleeding surface and reduced uterine blood flow.

The effect of progesterone on genes involved in preterm labor

The decidua is known to be a major source of intrauterine PGF2α during late gestation and labor, and inflammatory cytokines, including IL-1β, IL-6, and IL-8, are elevated in spontaneous preterm deliveries. In the present study, to elucidate how progesterone blocks the pathways associated with preterm birth, we determined the effects of P4 on the expression of PTGS-2 and PTGFR mRNA in human decidua fibroblast cells, as well as the genes, using microarray analysis. Senescence was induced in primary cultured human decidual cells treated with IL-1β. The IL-1β treatment implicated by microarray analysis increased gene expression levels of PTGS-2, PTGFR, NFκ-B p65, IL-17, and IL-8. In contrast, P4+IL-1β decreased the expression levels of all of these genes in comparison to treatment with IL-1β alone (p<0.05). IL-1β also increased the proportion of SA-β-gal-positive cells. Treatment with IL-1β also increased the p21 protein level in comparison to cells treated either with the vehicle or P4. Neither the p21 protein level nor the number of SA-β-gal-positive cells was increased in normal endometrial glandular cells by IL-1β (p<0.05). Our studies demonstrated that P4 changes the level of gene expression in a manner that favors an anti-inflammatory milieu. Because IL-8 appears to be the cytokine whose expression is most significantly modulated by P4, further studies evaluating IL-8 as a therapeutic target are needed.

Spontaneous uterine rupture at 32 weeks of gestation after previous uterine artery embolization

Uterine artery embolization (UAE) is a common treatment for post‐partum hemorrhage and uterine fibroids. However, the effects of UAE on subsequent pregnancies have not been established. Here, we present a case of spontaneous uterine rupture after previous UAE. A 31‐year‐old woman underwent UAE for a cervical ectopic pregnancy. Contrast‐enhanced magnetic resonance imaging (MRI) at days 5 and 25 post‐UAE suggested a regionally decreased blood supply in the mid‐posterior wall of the uterine fundus. During a subsequent pregnancy at age 35 years, she underwent an emergency cesarean delivery due to spontaneous uterine rupture at the mid‐posterior wall of the uterus at 32 weeks of gestation. Obstetricians should be attentive to the possibility of spontaneous uterine rupture in pregnant women who have previously undergone UAE. Detection of ischemic uterine muscle on MRI may predict potential for uterine rupture in a subsequent pregnancy.

Prospective comparison of delivery outcomes of vaginal births after cesarean section versus laparoscopic myomectomy

Aim:  This study was designed to assess the delivery outcomes of vaginal birth after cesarean section in comparison with delivery after laparoscopic myomectomy.

Heparin/heparan sulfate/CD44-v3 enhances cell migration in term placenta-derived immortalized human trophoblast cells.

ABSTRACT The function of CD44-v3 and heparin/heparan sulfate (HS) signaling was investigated during trophoblast cell migration to identify their role in the renewal of syncytial layer damage caused by increased hemodynamic turbulence in the intervillous space and maintenance of syncytial integrity in pre-eclampsia. We evaluated the effect of heparin/HS/CD44-v3-mediated processes during scratch wound closure in monolayer immortalized human trophoblast cells derived from term placenta (TCL-1 cells). Western blot analysis showed that these cultured human trophoblast cells express the epidermal growth factor receptor and CD44-v3 but do not express syndecan 4. An in vitro scratch wound healing assay showed enhanced migration of trophoblast cells in a dose-dependent manner in the presence of heparin compared with controls when cultured under serum-free conditions. Conversely, an anti-CD44 function-blocking antibody and CD44 siRNA suppressed the migration of trophoblast cells in the presence of heparin in a similar scratch assay. Furthermore, both heparin treatment and in vitro scratch wounding induced the phosphorylation of p21-activated kinase 1 (PAK1), whereas the anti-CD44-v3 antibody suppressed the heparin-induced phosphorylation of PAK1 in trophoblast cells. These results indicate that heparin/HS/CD44-v3-mediated signaling, in the absence of growth factor networks, enhances the direct repair of the damaged trophoblast layer through the migration of trophoblast cells. This renewed cell coverage may lead to the maintenance of syncytiotrophoblast cell function and an associated reduction in pathogenic soluble factors derived from the damaged trophoblast cells.

Factors associated with adverse pregnancy outcomes in women with antiphospholipid syndrome: A multicenter study

The aim of this study was to understand the clinical features of antiphospholipid syndrome (APS)-complicated pregnancies and evaluate risk factors for the adverse pregnancy outcomes. This multicenter study evaluated live-birth rates according to therapy modality for APS and risk factors of pregnancy loss in 81 pregnancies. Risk factors for pregnancy complications, including premature delivery before 34 gestational weeks, hypertensive disorders of pregnancy, thrombocytopenia, and light-for-date neonate, were evaluated in 51 women who received low dose aspirin (LDA) plus unfractionated heparin (UFH) and delivered after 24 GW. The live-birth rate in APS pregnancies with LDA+UFH therapy was 92.6%. A multiple logistic regression analysis demonstrated that LDA+UFH therapy decreased the risk of pregnancy loss (OR 0.13, 95%CI 0.03-0.62), and that a history of pregnancy loss despite LDA+UFH therapy increased the risk of pregnancy loss (OR 8.74, 95%CI 1.69-45.2). LDA therapy prior to pregnancy decreased the risk of premature delivery (OR 0.14, 95%CI 0.03-0.69). Positive tests for two or more anti-phospholipid antibodies increased the risks of premature delivery (OR 9.61, 95%CI 1.78-51.8) and thrombocytopenia (OR 4.90, 95%CI 1.11-21.7). Laboratory findings of low complements increased the risk of hypertensive disorders of pregnancy (OR 12.1, 95%CI 1.61-91.0). Standard therapy yielded high live-birth rates. Positive tests for two or more anti-phospholipid antibodies and low complements were associated with adverse pregnancy outcomes. These results have important implications for clinicians.

Relationship between maternal thyroid-stimulating hormone (TSH) elevation during pregnancy and low birth weight: A longitudinal study of apparently healthy urban Japanese women at very low risk

OBJECTIVE Thyroid hormones cross the placenta and promote fetal development and growth. The present study investigated whether an increase in maternal thyroid-stimulating hormone (TSH) concentration between the first and third trimesters is a determinant of birth weight during normal pregnancy. METHODS Maternal thyroid hormones and TSH were longitudinally measured at 12, 25, and 36weeks of pregnancy in 163 healthy pregnant women. Low birth weight (LBW) was defined as less than 2500g. ∆TSH12-36W was calculated as the difference in TSH concentrations between 12 and 36weeks of pregnancy. RESULTS Of the 163 neonates, 10 (6.1%) were LBW neonates. Free triiodothyronine and free thyroxine levels were similar at all gestational ages in the normal birth weight (Normal) and LBW groups. However, the median ∆TSH12-36W value was higher in the LBW than the Normal group (1.67 vs. 0.54mIU/L, P=0.008). Multivariate linear regression analysis showed that ∆TSH12-36 was inversely correlated with birth weight (β=-0.179, P=0.008). CONCLUSION An increase in maternal TSH concentration between the first and third trimesters is an independent determinant of birth weight in normal pregnancy.

Time spatial labeling inversion pulse magnetic resonance angiography in pregnancy with adenomyosis.

Time spatial labeling inversion pulse (Time‐SLIP) is a non‐contrast magnetic resonance angiography (MRA) technique. No cases in which this technique was used during pregnancy have been reported. We report herein two cases with adenomyosis of the same size and location that underwent Time‐SLIP MRA during pregnancy. In case 1, the blood flow within the adenomyosis was poor, and the uterine blood flow toward the placenta was normal, resulting in no fetal growth restriction (FGR). In case 2, the blood flow within the adenomyosis was quite rich, and placental blood flow seemed decreased, resulting in severe FGR. As well as the Doppler ultrasonography, Time‐SLIP MRA was useful for evaluating uterine blood flow during pregnancy. This is the first report of the use of Time‐SLIP MRA during pregnancy.