Reiko Neki

Placental interleukin-6 production is enhanced in intrauterine infection but not in labor

OBJECTIVE Because interleukin-6 is an important mediator in the host defense mechanism against infection and tissue damage, we studied the capacity of placentas with or without either labor or chorioamnionitis in the third trimester to produce interleukin-6. STUDY DESIGN The placental blocks were cultured, and their interleukin-6 titers were measured by a bioassay. RESULTS Placentas with labor produced a similar amount of interleukin-6 to placentas without labor. In contrast, placentas with chorioamnionitis produced much more interleukin-6 than the placentas with or without labor (p < 0.0001). CONCLUSION Placental interleukin-6 is thus surmised to participate in potentiation of the placental and fetomaternal defense mechanisms together with placental interleukin-1 during chorioamnionitis.

Fetal mononuclear cells show a comparable capacity with maternal mononuclear cells to produce IL-8 in response to lipopolysaccharide in chorioamnionitis

IL-8 is a chemotactic and activating cytokine for neutrophils which eliminate invading bacteria by releasing bactericidal metabolites. Cord blood mononuclear cells (CBMCs) obtained from neonates born to mothers with chorioamnionitis actively produced a significantly higher amount of IL-8 than those of neonates without chorioamnionitis, suggesting that the mononuclear cells of fetuses with chorioamnionitis had been activated in utero. As lipopolysaccharide (LPS) can often be detected in the uteroplacental space in chorioamnionitis, the LPS-mediated activation mechanism of neonatal mononuclear cells was analyzed in vitro to produce IL-8. Neonatal mononuclear cells stimulated with LPS increased IL-8 production in a time- and dose-dependent manner. The ability of term or preterm neonatal mononuclear cells to produce IL-8 was comparable with that of adult (maternal) mononuclear cells, suggesting functional maturity of the neonatal or fetal mononuclear cells to produce IL-8. However, IL-8 production by neonatal CBMCs was down-regulated by dexamethasone, a glucocorticoid which is clinically administered to mothers to promote fetal lung maturity in preterm delivery. Our present study revealed a regulatory mechanism of fetal IL-8 production, suggesting that functionally mature fetal mononuclear cells produce IL-8 in response to LPS in chorioamnionitis and activate the fetal defense mechanism against infection.

The use of serum TA-4 in monitoring patients with malignant transformation of ovarian mature cystic teratoma

The development of cancer in mature cystic teratomas of the ovary is rare and sometimes difficult to detect because of sampling errors. Six cases of squamous cell carcinoma arising in ovarian mature cystic teratomas were studied, five of which showed an elevated level of a squamous cell carcinoma‐associated antigen, TA‐4, in the sera obtained preoperatively; the preoperative determination was not performed in the sixth case. However, no elevated TA‐4 level was detected in the sera of 28 patients with mature cystic teratomas of the ovary. Moreover, serial determination of the serum TA‐4 level showed a good correlation between the clinical course and the serum TA‐4 level. Interestingly, an abnormal TA‐4 level preceded the clinical detection of recurrence by 2 months in two patients. Thus, determination of the serum TA‐4 concentration may be useful for diagnosing and monitoring patients with squamous cell carcinoma arising in mature cystic teratomas of the ovary.

Risk factors for maternal and fetal outcome in pregnancy complicated by Ebstein anomaly

OBJECTIVE The goal of the study was to examine risks in pregnancy in patients with Ebstein anomaly. STUDY DESIGN Data were examined retrospectively for 13 patients (27 pregnancies, 21 live births) with Ebstein anomaly during pregnancy who were treated at our institution from 1985 to 2011. The associated anomalies in these patients were atrial septal defect (ASD) (n = 4) and the Wolff-Parkinson-White syndrome (n = 6). RESULTS Before pregnancy, 2 patients underwent ASD closure and 1 received tricuspid valve replacement (TVR). In all patients, the cardiothoracic ratio increased from 55.1 at conception to 57.0 during pregnancy and 58.0 postpartum (P < .05). Cesarean sections were performed in 3 cases: 1 with ventricular tachycardia and orthopnea (New York Heart Association [NYHA] III) preterm; at full term, and the third in a patient with a mechanical tricuspid valve who developed maternal cerebellum hemorrhage at 27 weeks. The baby died of prematurity in the third case. In all other cases (20 of 21), neonatal prognoses were good without congenital heart diseases. There were 6 spontaneous abortions. Recurrent paroxysmal supraventricular tachycardia occurred during pregnancy in 2 cases and was treated with adenosine triphosphate or verapamil. In 17 pregnancies, NYHA remained in class I and all had full-term vaginal delivery. CONCLUSION Maternal and fetal outcomes are good in patients with Ebstein anomaly and NYHA class I. However, pregnancy in Ebstein anomaly can be complicated with tachyarrhythmia or cardiac failure. In post-TVR cases, meticulous care is required for these complications during pregnancy and delivery.

Intrapartum fetal heart rate monitoring in cases of congenital heart disease

OBJECTIVE We evaluated the intrapartum fetal heart rate (FHR) patterns in fetuses with congenital heart disease (CHD). STUDY DESIGN One hundred sixteen cases of fetal CHD were identified at our institute between 2000-2007; 464 fetuses without CHD were used as controls. The incidences of abnormal FHR patterns and umbilical blood gases were compared. RESULTS More fetuses with CHD showed variant FHR than did control fetuses (46.6% vs 17.7%; P < .01). Cesarean section deliveries that were based on fetal indications were performed more frequently in fetuses with CHD than in control fetuses (12.9% vs 3.2%; P < .01). Isomerism and tetralogy of Fallot were observed frequently with variant FHR. When chromosomal abnormalities and intrauterine growth restriction were excluded, the fetuses with CHD showed more variant FHR than did the control fetuses. CONCLUSION Fetuses with CHD are more likely to show abnormal FHR patterns than are control fetuses. We suggest that cardiac abnormalities are associated with abnormalities in FHR patterns.

Retrospective Review of Thoracoamniotic Shunting Using a Double-Basket Catheter for Fetal Chylothorax

Objective: From a single-center retrospective cohort with fetal chylothorax, we evaluated the factors related to the decision to use shunting, poor prognostic factors, and reported shunting outcomes with a new double basket-catheter device. Methods: A retrospective single-center study was performed in 35 cases of fetal chylothorax. Results: There were 35 cases of chylothorax: 23 with hydrops and 12 without hydrops. Twenty-one procedures were performed on 15 fetuses (11 with hydrops) with a single shunt in 11, two shunts in 3 and four shunts in 1. All 12 nonhydropic cases survived. In 23 hydropic cases, overall survival rates with and without thoracoamniotic shunting were 46 and 33%, respectively. The mortality rates of fetal hydropic cases with and without ascites were 93 and 11%, respectively. Fetal ascites, progression of fetal hydrops, and premature delivery at <33 weeks were significant risk factors for a poor prognosis. Progression of polyhydramnios after shunting was also associated with a poor prognosis. Obstruction of the catheter was observed in 38%. There were no direct fetal deaths associated with shunting. Conclusion: Thoracoamniotic shunting should be considered for pleural effusion before development of fetal hydrops, or at least before the appearance of fetal ascites. A double-basket catheter tends to be obstructive, but may be less invasive for fetuses.

Genetic analysis of patients with deep vein thrombosis during pregnancy and postpartum

Deep vein thrombosis (DVT) is a serious pregnancy-related complication. Recent studies indicate that the genetic background for DVT differs with ethnicity. In our study, we enrolled 18 consecutive Japanese patients who had developed DVT during pregnancy and postpartum. We performed a genetic analysis of three candidate genes for DVT, protein S, protein C and antithrombin, in these patients. We found that four patients had missense mutations in the protein S gene, including the K196E mutation in two patients, the L446P mutation in one patient, and the D79Y and T630I mutations in one patient, as well as one patient with the C147Y mutation in the protein C gene. All five patients with genetic mutations had DVT in their first two trimesters. Nine of the patients without genetic mutations developed DVT in the first two trimesters, and four in the postpartum period. Thus, genetic mutations in the protein S gene were predominant in pregnant Japanese DVT women, and DVT in pregnant women with genetic mutations occurred more frequently at the early stage of pregnancy than postpartum. Considering the rapid decrease in protein S activity during pregnancy, we may need to assess thrombophilia in women before pregnancy.

Nonsynonymous mutations in three anticoagulant genes in Japanese patients with adverse pregnancy outcomes

BACKGROUND Hereditary thrombophilias may associate with uteroplacental thrombosis leading to adverse pregnancy outcomes. The present study was conducted to reveal the frequency of the low-frequency thrombophilic protein S K196E mutation, as well as the frequency of very rare nonsynonymous mutations in protein S, protein C, and antithrombin genes, in patients with adverse pregnancy outcomes. PATIENTS AND METHODS We enrolled 330 Japanese patients with adverse pregnancy outcomes and divided them into 233 patients with two or more miscarriages and 114 patients with fetal growth restriction (FGR) and/or intrauterine fetal death (IUFD); 17 patients belonged to both groups. We sequenced the entire coding regions of three anticoagulant genes in all 330 patients. RESULTS We found that protein S K196E mutation was identified in 4 out of 233 patients with recurrent miscarriage and in 2 out of 114 patients with FGR and/or IUFD. The frequencies of this mutation in these patient groups were not different from that in a Japanese general population. Very rare nonsynonymous mutations were identified in 3.3% (11 out of 330) of patients with adverse pregnancy outcomes. CONCLUSIONS Although the low-frequency protein S K196E mutation can increase the risk for venous thromboembolism, it did not increase the risk for adverse pregnancy outcomes even in Japanese.

Vaginal delivery in pregnancy with Moyamoya disease: Experience at a single institute

Cesarean section is commonly selected in pregnancy with Moyamoya disease. We consider vaginal delivery with epidural anesthesia a viable alternative in such cases.

Acute aortic dissection (Stanford type B) during pregnancy.

We report a case of acute aortic dissection (Stanford type B) that occurred in pregnant woman at 34-week gestation. She had no systemic characteristics of Marfan syndrome, however she exhibited a mutation of FBN1, Arg 545 Cys, which has been found to correlate with ectopia lentis but not with aortic dissection.