Effects of maternal and fetal choline concentrations on the fetal growth and placental DNA methylation of 12 target genes related to fetal growth, adipogenesis, and energy metabolism.

AIM: We performed a birth cohort study involving 124 mother-infant pairs to investigate whether placental DNA methylation is associated with maternal choline status and fetal development. METHODS: Plasma choline concentration was assayed longitudinally in the 1st and 3rd trimesters and at term-pregnancy in mothers and cord blood. Placental DNA methylation was measured for 12 target candidate genes that are related to fetal growth, adipogenesis, lipid and energy metabolism, or long interspersed nuclear elements. RESULTS: Higher maternal plasma and cord blood choline levels at term tended to associate with lower birthweight (r = -0.246, P < 0.013; r = -0.290, P < 0.002) and body mass index (BMI) at birth (r = 0.344, P < 1E-3; r = -0.360, P < 1E-3). The correlation between maternal plasma choline level and cord blood choline level was relatively modest (r = 0.049, P = 0.639). There was an inverse correlation between placental DNA methylation at the retinoid X receptor alpha (RXRA) gene and maternal plasma choline level (r = -0.188 to r = -0.452, P = 0.043 to P < 1E-3 at three points). RXRA methylation level was positively associated with birthweight and BMI at birth (r = 0.306, P = 0.001; r = 0.390, P < 1E-3). Further, RXRA methylation was inversely correlated with RXRA gene expression level (r = 0.333, P < 1E-3). CONCLUSION: Our results suggest that the association between maternal choline status and placental RXRA methylation represents a potential fetal programing mechanism contributing to fetal growth.

Multiple pregnancy, short cervix, part-time worker, steroid use, low educational level and male fetus are risk factors for preterm birth in Japan: a multicenter, prospective study.

AIM: To examine the relationship between preterm birth and socioeconomic factors, past history, cervical length, cervical interleukin-8, bacterial vaginosis, underlying diseases, use of medication, employment status, sex of the fetus and multiple pregnancy. METHODS: In a multicenter, prospective, observational study, 1810 Japanese women registering their future delivery were enrolled at 8⁺° to 12⁺6 weeks of gestation. Data on cervical length and delivery were obtained from 1365 pregnant women. Multivariate logistic regression analysis was performed. RESULTS: Short cervical length, steroid use, multiple pregnancy and male fetus were risk factors for preterm birth before 34 weeks of gestation. Multiple pregnancy, low educational level, short cervical length and part-timer were risk factors for preterm birth before 37 weeks of gestation. CONCLUSION: Multiple pregnancy and cervical shortening at 20-24 weeks of gestation was a stronger risk factor for preterm birth. Any pregnant woman being part-time employee or low educational level, having a male fetus and requiring steroid treatment should be watched for the development of preterm birth.

Severely fluctuating blood glucose levels associated with a somatostatin-producing ovarian neuroendocrine tumor.

CONTEXT: Somatostatin-producing tumors are a rare type of neuroendocrine tumor. Their effects on blood glucose levels have been variously reported, and detailed reports have been scarce. OBJECTIVE: The aim of this study was to identify the reasons for the extraordinary blood glucose fluctuations in a case with no previous history of diabetes. PATIENTS AND METHODS: A 68-yr-old nondiabetic woman with an ovarian tumor was suffering from hyper- and hypoglycemia. Based on the results of an oral glucose tolerance test and continuous glucose monitoring, we speculated that the fluctuating blood glucose level was accompanied not only by a low insulin level but also by low counter-regulatory hormones levels, and that those broad hormonal suppressions were caused by a high somatostatin level produced in the ovarian tumor. We performed an oophorectomy and assessed the pathology of the tumor and changes in the blood glucose profile as well as hormonal levels postoperatively. RESULTS: The blood glucose level was completely normalized after the oophorectomy. Insulin secretion was also normalized. Histological examination showed that the tumor comprised a mature cystic teratoma and a stromal carcinoid. Immunohistochemically, the stromal carcinoid component was positive for somatostatin. The somatostatin level was 8505 pmol/liter preoperatively, which dropped down to 71.5 pmol/liter postoperatively. We found two previous reports of somatostatin-producing ovarian neuroendocrine tumors. Somatostatin levels among cases of ovarian origin were much higher than those among cases of gastrointestinal origins, and cases of ovarian origin all experienced blood glucose fluctuations. CONCLUSION: Extremely high somatostatin levels and blood glucose fluctuations may be characteristics of somatostatin-producing ovarian neuroendocrine tumors.

Vaginal evisceration 3 years after abdominal hysterectomy and bilateral salpingo-oophorectomy.

Vaginal evisceration after a pelvic operation is a rare gynecological emergency. When intercourse is the cause, most cases occur within 1 year of surgery. A 53-year-old woman presented to the emergency room for vaginal evisceration half a day after the first postoperative occurrence of intercourse 3 years after an abdominal hysterectomy and bilateral salpingo-oophorectomy. In an emergency laparotomy, the protruding small bowel was replaced within the abdominal cavity. The avulsed vaginal cuff, which measured 6 cm in length and had atrophic but non-necrotic margins, was sutured. Women who go for long periods without intercourse after a hysterectomy, especially post-menopausal women, should be made aware of unrecognized vaginal atrophy that could, in some cases, lead to rupture and evisceration during the next occurrence of intercourse.

Effect of Social Service Prenatal Care Utilization on Perinatal Outcomes among Women with Socioeconomic Problems in the Tokyo Metropolitan Area.

Background. To investigate the effect of social service prenatal care (PNC) utilization on perinatal outcomes among women with socioeconomic problems in the Tokyo metropolitan area. Methods. Retrospective study. The study enrolled all women at our hospital who either attended PNC utilizing social services (attenders) or who did not attend PNC (nonattenders) between January 1, 2007, and December 31, 2010. We compared the maternal characteristics and perinatal outcome of attenders with those of nonattenders. Results. A total of 83 attenders and 45 nonattenders were enrolled. The mean gestational age at the first PNC visit was 31.1 weeks in the attenders. Attenders were found to have a lower incidence of preterm delivery, pregnancy-induced hypertension, emergency cesarean section, low birth weight, and the NICU admission than nonattenders (P < 0.05). Conclusions. The utilization of social service PNC greatly improved perinatal outcomes among women with socioeconomic problems problems in the Tokyo metropolitan area.

Prolonged fetal bradycardia as the presenting clinical sign in congenital syphilis complicated by necrotizing funisitis: a case report.

Syphilis remains a serious cause of neonatal morbidity and mortality worldwide. In this paper, we describe a case of congenital syphilis that was fully supported by abnormal fetal heart rate patterns and placental histopathological evidence. A 24-year-old para 4 woman, who did not attend antenatal care, was admitted to our hospital with a complaint of abdominal discomfort at an estimated 31-week gestation. Fetal heart rate monitoring showed prolonged bradycardia. A neonate weighting 1,423 g with severe birth asphyxia was immediately delivered by cesarean section. Following delivery, the mother and the neonate were diagnosed with syphilis. Histopathological examination confirmed severe chorioamnionitis and necrotizing funisitis with numerous Treponema pallidum. Conclusions. Challenges in establishing the diagnosis of necrotizing funisitis are essential for optimal management of a fetus with a systemic inflammatory response in utero.

Postpartum maternal pneumococcal meningitis complicated by endocarditis.

Bacterial meningitis is associated with high morbidity and mortality. Few cases of pneumococcal meningitis during pregnancy and the postpartum period have been reported. We describe a case of postpartum pneumococcal meningitis complicated by endocarditis. A 26-year-old para-2 woman who had had a normal vaginal delivery at 38 weeks at a maternity home was transported to our hospital with a 39.5°C fever 11 days postpartum. Eight hours after her arrival, her state of consciousness deteriorated rapidly. Lumbar puncture revealed Gram-positive cocci consistent with Streptococcus pneumoniae. She was immediately treated with antibiotics and subsequently diagnosed with endocarditis. Final culture results from the blood and cerebrospinal fluid confirmed the presence of S. pneumoniae. She recovered completely with no evidence of neurological damage. Maintaining a high clinical suspicion and initiating appropriate diagnostic testing and therapeutic interventions promptly are essential to reducing the morbidity and mortality associated with bacterial meningitis.

Antepartum intracranial hemorrhage due to unrecognized unilateral moyamoya disease: a case report.

PURPOSE: Moyamoya (meaning a "hazy puff of smoke" in Japanese) disease is a rare cerebrovascular occlusive disease. Moyamoya disease may become symptomatic for the first time during pregnancy. We report a case of antepartum intracranial hemorrhage due to unrecognized unilateral moyamoya disease, which was subsequently diagnosed as HELLP syndrome during the postpartum period. STUDY DESIGN: A case report of a 29-year-old Japanese primigravida who was transported to our hospital at 39 weeks of gestation because of sudden loss of consciousness and left hemiplegia. On arrival, her blood pressure was 143/94 mmHg with 1+ proteinuria by dipstick. Brain computed tomography revealed a right putaminal hemorrhage with intraventricular hemorrhage. The patient delivered a neonate by emergency cesarean section, and an intracranial hematoma was subsequently evacuated. Approximately 3 h postoperatively, she was diagnosed with HELLP syndrome and the following were initiated: IV magnesium sulfate, antihypertensive agents, and transfusion of 10 units of platelets. Angiographic findings were consistent with unilateral moyamoya disease. CONCLUSIONS: Moyamoya disease is a rare entity that must be considered in the differential diagnosis of hemorrhagic stroke during pregnancy. It is important to perform careful monitoring and adequate management with cooperation between obstetricians and other specialists when serious complications arise.

Habitual use of warm-water cleaning toilets is related to the aggravation of vaginal microflora.

AIM: Warm-water cleaning toilets, or 'bidet toilets', are one of the most popular household goods in Japan. However, a recent large-scale survey raised questions about the relationship between bidet toilet use and bacterial vaginitis as reflecting bacterial vaginosis with inflammation. Recently, gynecologists have expressed concerns about the increase in aggravated vaginal microflora in habitual bidet users. Therefore, the present study was designed to clarify the possible relevancy of bidet usage to changes in vaginal microflora. METHODS: Two hundred and sixty-eight non-pregnant women of reproductive age, with an increase in vaginal discharge, consented to enter the study. On outpatient visit, an aliquot of cervicovaginal secretion was obtained by a sterilized cotton swab and cultured using standard culture systems. RESULTS: Normal microflora (Lactobacillus species) was not present in 42.86% of bidet toilet users, compared to 8.77% of non-users. Fecal bacteria were detected in 50 of the 268 cases (18.66%), 46 cases in users (92%) and only 4 cases in non-users (8%). Contamination by other pathogens was 4 to 6 times higher in users than in non-users. CONCLUSION: Habitual use of bidet toilets aggravates vaginal microflora, either by depriving normal microflora or facilitating opportunistic infection of fecal bacteria and other microorganisms.

Noninvasive monitoring of placental oxygenation by near-infrared spectroscopy.

We evaluated the clinical usefulness of near-infrared spectroscopic quantitative measurement of placental oxygenation for the noninvasive estimation of uteroplacental function in pregnant women. We performed a prospective, observational clinical study. Women without complications (N = 15), women with threatened preterm delivery (TPD; N = 6), and women with intrauterine fetal growth restriction (IUGR; N = 6) were enrolled. Measurements of placental tissue oxygenation index (TOI) using the NIRO-300 (Hamamatsu Photonics, Hamamatsu City, Japan) were recorded. Mean TOI was 72.3 +/- 5.3% in women without complications, 72.9 +/- 5.6% in pregnant women with TPD, and 78.7 +/- 3.0% in pregnant women with IUGR. Mean TOI in pregnant women with IUGR was significantly higher than that of the other two groups (P < 0.05). In the IUGR group, although gestational age at measurement on admission was less than that made during hospitalization (P < 0.05), there were no differences in the TOI in relation to gestational age at measurement. Higher TOIs in pregnant women suggest decreased placental function. Monitoring the TOI by near-infrared spectroscopic quantitative measurement may have a high potential for clinical application, particularly in prenatal management.

Transabdominal measurement of placental oxygenation by near-infrared spectroscopy.

We evaluated the clinical usefulness of near-infrared spectroscopic quantitative measurement of placental tissue oxygenation for noninvasive estimation of uteroplacental function in pregnant women. We performed a prospective observational clinical study. Women without complications (N = 15) and women with pregnancy-induced hypertension (PIH; N = 6) were enrolled. Measurements of placental tissue oxygenation index (TOI) using NIRO-300 (Hamamatsu Photonics, Hamamatsu City, Japan) were recorded. The mean TOI in women without complications was 72.36 +/- 5.36% and 80.28 +/- 2.78% in pregnant women with PIH. The mean TOI in pregnant women with PIH was higher than that of pregnant women without complications. There were no differences in the TOI in relation to gestational age at onset of PIH, forms of PIH, or severity of hypertension. Higher TOIs in pregnant women suggest the reduced ability of the placental function. Monitoring the TOI by near-infrared spectroscopic quantitative measurement may have a high potential for clinical application, particularly in prenatal management.

Establishment of a prediction method for premature rupture of membranes in term pregnancy using active ceruloplasmin in cervicovaginal secretion as a clinical marker.

AIM: Term pregnancy complicated by premature rupture of membranes (PROM) is thought to be associated in part with subclinical infection, and places mothers and neonates at an increased risk for several complications. Therefore, perinatal care would be greatly helped if a reliable clinical measure were available for predicting the incidence of PROM. METHODS: One hundred and ninety-six pregnant women who consented to enter this study were screened using a method developed to assess active ceruloplasmin in cervicovaginal secretion as a clinical marker for predicting the incidence of PROM. Cervicovaginal secretions were obtained from the cervical canal at about 36 weeks of pregnancy. The active ceruloplasmin level in the cervicovaginal secretion was measured using an original enzyme-linked immunoabsorbent assay. RESULTS: Of 196 women, 27 women (13.8%) developed PROM and 169 women (86.2%) did not develop PROM. Active ceruloplasmin in the cervicovaginal secretion was significantly higher in the PROM group than in the non-PROM group (P < 0.001). Analysis using receiver-operating characteristic curves showed that the active ceruloplasmin level (1420.0 ng/mL) proved to be the proper cut-off value to best predict the incidence of PROM. CONCLUSION: Active ceruloplasmin in the cervicovaginal secretion might be a reliable clinical marker for term PROM.

Hyalinizing spindle cell tumor with giant rosettes of the omentum.

We report the first case of a hyalinizing spindle cell tumor with giant rosettes of the omentum. The mesenchymal tumor arises from a multiplication of fibroblastic cells containing large rosette-like structures composed of a central collagen core surrounded by plump oval to spindle tumor cells. A 38-year-old woman exhibited the symptom of abdominal pain in the right side, with a correlated sensation of a mass in the same area. A tumor consisting of both solid and cystic cytologic features was subsequently diagnosed, on the right side of the uterus. Her serum level of CA-125 was only slightly elevated. Surgical intervention indicated that the tumor originated from lower pole of the omentum and the histological diagnosis was hyalinizing spindle cell tumor with giant rosettes. The metastatic potential of this type of tumor is considered similar to that of the metastatic low-grade fibromyxoid sarcoma, which indicated the need for careful clinical follow up of this case.

[Management of tuberculosis during pregnancy and puerperium].

We reported 22 cases with tuberculosis in pregnancy and puerperium, who were treated in our hospital from 1993 to 2001. Nine out of 22 cases were foreign women and the onset of tuberculosis was not clear and the diagnosis tended to be delayed in most cases. In the reports from industrial countries, most of those patients are foreign bone and the delay in diagnosis is common because symptoms are apt to be mixed up those for pregnancy and puerperium. In 10 of 22 cases, extrapulmonary lesions were noted. Most of our cases were treated with INH, RFP and EB, and in some severer cases PZA was added. WHO and BTS recommend standard therapy with PZA but ATS recommends INH, RFP and EB without PZA. Generally SM is contraindicated because of adverse effect of hearing loss for all pregnant periods, and the data for PZA and other second line drugs are insufficient. Our cases and their neonates showed normal course and no malformation nor congenital tuberculosis. 2 cases could not keep adherence for drugs and 2 babies got active tuberculosis. Precaution for infection is one of most important problem to deal with cases with tuberculosis during pregnancy and postpartum in the hospital. If she is still infectious on delivery, we should consider prevention for transmission and manage her in isolated manner. CDC recommends not to treat for latent tuberculosis during pregnancy because of high frequency of hepatic damage due to INH. It is the best way to check and treat latent tuberculosis before gestation if she is at high risk with tuberculosis.