Related Factors for Abnormal Umbilical Cord Insertion: A Preliminary Study Based on Two Regional Tertiary Hospitals in Japan.

OBJECTIVE: We elucidated maternal background, perinatal complications and outcomes as potential related factors for abnormal umbilical cord insertion (ACI) -velamentous and marginal- based on data from two tertiary perinatal hospitals in Japan. MATERIALS AND METHODS: The subjects were 3,741 women with singleton pregnancies who delivered at ≥ 22 weeks' gestation in Kurume University Hospital and St. Mary's Hospital, Kurume, Japan from January 2013 to December 2015. They were divided into two groups, with and without ACI. Related factors were extracted from the medical registry database of the perinatal committee in the Japan Society of Obstetrics and Gynecology. Random Forest and stepwise logistic regression models were employed to evaluate their impact on ACI. RESULTS: Related factors for ACI in terms of maternal background and perinatal complications and outcomes were: pre-pregnancy smoking habit (adjusted odds ratio, OR, 3.38; 95% confidence interval, CI, 2.20-5.20; P < 0.0001); conception using assisted reproductive technology (adjusted OR, 2.00; 95% CI, 1.11-3.60; P = 0.021); placenta previa (adjusted OR, 4.74; 95% CI, 2.06-10.90; P < 0.0001); fetal growth restriction (adjusted OR, 2.43; 95% CI, 1.49-3.97; P < 0.0001); and non-reassuring fetal status during labor (adjusted OR, 2.74; 95% CI, 1.71-4.38; P < 0.0001). CONCLUSION: This was a preliminary study attempting to elucidate related factors for ACI in a Japanese population. However, further large-scale studies are needed in Japan.

Pathophysiology of gestational diabetes mellitus in lean Japanese pregnant women in relation to insulin secretion or insulin resistance.

To determine the pathophysiology of gestational diabetes (GDM) in lean Japanese pregnant women in relation to insulin secretion or insulin resistance. The 75-g oral glucose tolerance test (OGTT) was performed in case of positive results of universal screening of a 50-g glucose challenge test at 24-28 weeks' gestation in Japanese pregnant women. These women were treated in our hospital between 2012 and 2016. Among these women, 30 with a body mass index of < 18.5 kg/m2 were selected as lean subjects. Nine women were diagnosed with GDM (GDM group) and the remaining 21 had normal glucose tolerance (control group). For evaluating insulin secretion or resistance, the following parameters were compared between the two groups together with a family history of diabetes mellitus (DM) among first-degree relatives: (1) plasma glucose and immnunoreactive insulin (IRI) levels after glucose loading, (2) insulinogenic index (I.I), (3) homeostasis model assessment of ß-cell function (HOMA-ß), (4) homeostasis model assessment of insulin resistance (HOMA-IR), and (5) insulin sensitivity index (ISI) composite. The percentage of having a family history of DM was significantly higher in the GDM group (3/9, 33.3%) than in the control group (0/21, 0.0%, P < 0.001). Serum glucose levels at 30, 60, and 120 min after glucose loading were significantly higher in the GDM group than in the control group (all P < 0.05). IRI levels at 60 and 120 min were significantly higher in the GDM group than in the control group (both P < 0.05), and they showed persistent insulin secretion patterns. Values of the I.I. and ISI composite were significantly lower in the GDM group than in the control group (both P < 0.05), with no differences in HOMA-ß, HOMA-IR and HbA1c levels between the groups. Lean Japanese pregnant women with GDM have impaired ß-cell function, which is in part associated with hereditary traits.

Prediction of histological chorioamnionitis and neonatal and infantile outcomes using procalcitonin in the umbilical cord blood and amniotic fluid at birth.

AIM: We aimed to clarify the usefulness of procalcitonin (PCT) in the evaluation of histological chorioamnionitis (CAM) and in the prediction of neonatal and infantile outcomes as a reference of interleukin-6 (IL-6). METHODS: Subjects were 36 singleton pregnant women delivered at 22-37 weeks' gestation due to threatened premature delivery and/or preterm premature rupture of membranes. Cases were classified into the CAM and non-CAM groups, according to Blanc's criteria. Comparisons were made on umbilical venous and amniotic fluid PCT levels among the groups. The relations between umbilical venous PCT and IL-6 levels and neonatal and infantile outcomes were also analyzed. RESULTS: The umbilical venous PCT level in the CAM group (240.2 pg/mL, 125.4-350.3 pg/mL: median, first quartile-third quartile) was higher than that in the non-CAM group (105.1, 50.2-137.5 pg/mL; P = 0.0006). There were no differences in the amniotic fluid PCT levels between the groups. There was a strong correlation between umbilical venous PCT and IL-6 levels (correlation coefficient: 0.793). Among 10 cases with an umbilical venous PCT level of ≥170.0 pg/mL and six cases with IL-6 ≥ 11.0 pg/mL, six (60.0%) and five cases (83.3%), respectively, had adverse neonatal and infantile outcomes. Among seven cases with adverse neonatal and infantile outcomes, six (85.7%) and five (71.4%) cases showed umbilical venous PCT levels of ≥170.0 pg/mL and IL-6 levels of ≥11.0 pg/mL, respectively. CONCLUSION: Similar to IL-6, the umbilical venous PCT level is a promising parameter for predicting histological CAM and adverse neonatal and infantile outcomes related to in utero inflammatory status.

Predictors of Abnormal Glucose Tolerance in the Early Postpartum Period in Patients with Gestational Diabetes.

This study was designed to investigate the clinical predictors of abnormal glucose tolerance 5-7 weeks after delivery. Subjects were 155 women diagnosed with gestational diabetes mellitus (GDM) between October 2005 and September 2013 whose pregnancy and delivery were managed at our center. Subjects were divided into a normal glucose tolerance group (NGT; n = 113), or abnormal glucose tolerance group (AGT; n = 42) with borderline or overt diabetes mellitus, based on 75-g oral glucose tolerance test (75 gOGTT) results 5-7 weeks after delivery. We extracted profiles by which abnormal glucose tolerance levels 5-7 weeks after delivery were predicted using a classification and regression tree (CART) from parameters measured at the time of GDM diagnosis. Logistic regression analysis was used to determine prediction accuracy. Subjects with fasting plasma glucose (FPG) ≥92 mg/dL and immuno-reactive insulin level <100 µU/mL 60 min after load (IRI60min) at time of diagnosis showed a significantly higher risk of developing abnormal glucose tolerance 5-7 weeks after delivery than subjects with FPG <92 mg/dL (p < 0.0001). Subjects with FPG ≥92 mg/dL and IRI60min ≥ 100 µU/mL had the same risk as those with FPG of <92 mg/dL. Patients with gestational diabetes who met the criteria specified above at diagnosis were at a higher risk of developing diabetes mellitus in the future. By explaining this issue to patients, we expect to improve the rate of postpartum follow-up. This should facilitate early detection of diabetes, and help prevent associated complications.

Prognosis of Pregnant Women with One Abnormal Value on 75g OGTT.

The aim of this study was to identify risk factors to allow us to detect patients at high risk of requiring insulin therapy, among Japanese pregnant women with one abnormal value (OAV) on a 75-g oral glucose tolerance test (75-g OGTT). A total of 118 pregnant women with OAV on a previous 75-g OGTT between 1997 and 2010 were studied. We identified the factors which can predict patients at high risk of requiring insulin therapy among Japanese pregnant women with OAV, by comparing severe abnormal glucose tolerance (insulin treatment; n=17) with mild glucose tolerance patients (diet only; n=101). The following factors were examined; plasma level of glucose (PG) and immunoreactive insulin (IRI) at fasting, 0.5, 1 and 2 hours after loading glucose, insulinogenic index, homeostasis model assessment insulin resistance (HOMA-IR), insulin sensitivity index-composite (ISI composite), and HbA1c at the time of the 75-g OGTT. Univariate analysis showed a positive correlation between insulin therapy and 2-h PG value, 0.5-h and 1-h IRI values, AUC-IRI and insulinogenic index (p<0.05). Multivariate analysis showed that the PG 2-h value and insulinogenic index were independent predictive factors of insulin therapy. A 2-h PG ≥153 mg / dl and an insulinogenic index of <0.42 had a sensitivity of 81.8%, a specificity of 83.8%, a positive predictive value of 60.0% and a negative predictive value of 93.9% for the prediction of patients who required insulin therapy among pregnant women with OAV. These results suggest that a level of 2-h PG ≥153 mg/dl and an insulinogenic index of <0.42 on 75-g OGTT are predictive factors for insulin therapy in Japanese pregnant women with OAV.

Changes in the nitric oxide-soluble guanylate cyclase system and natriuretic peptide receptor system in placentas of pregnant Dahl salt-sensitive rats.

AIM: Diminished vasodilator activity during pregnancy, which augments vascular responses to vasoconstrictors, is one reason for the onset of pre-eclampsia and superimposed pre-eclampsia. It is known that Dahl salt-sensitive (Dahl-S) rats develop salt-sensitive hypertension like African-Americans. The present study attempted to assess the changes and the interactions of the NOS-NO-sGC-cGMP and NP-NPR-cGMP systems in the hypertensive placenta using Dahl-S rats as an animal model of superimposed pre-eclampsia. MATERIAL AND METHODS: Pregnant Dahl-S rats were fed a high-salt diet to induce the development of hypertension and fetal growth restriction. Using these rats, we investigated the regulation of these two vasodilatation systems, including the kinetics of cyclic guanosine monophosphate (cGMP), soluble guanylate cyclase (sGC), endothelial nitric oxide synthase (NOS), cytokine-inducible NOS, natriuretic peptides (NP) (atrial NP, brain NP and C-type NP), and NP receptors (NPR) (NPR-A, NPR-B, NPR-C). RESULTS: Dahl-S rats fed a high-salt diet exhibited hypertension, fetal growth restriction and thickening of the walls in decidual vessels. The placental cGMP level in the rats fed the high-salt diet was significantly decreased compared with that in controls. The expression levels of endothelial NOS and cytokine-inducible NOS mRNA increased significantly, while that of sGCα2-sunbnit declined significantly. Messenger RNA levels of NPR-C, a clearance-type receptor of NP, declined significantly, whereas those of NP and their functional receptors NPR-A and NPR-B were unchanged. CONCLUSIONS: As Dahl-S rats with excess salt-loading during pregnancy exhibited pathological changes similar to those observed in female humans with pre-eclampsia/superimposed pre-eclampsia, this rat could be useful as an animal model of superimposed pre-eclampsia. In the placentas of hypertensive Dahl-S rats, vasodilatation seemed to be disturbed by the deregulation of both the NO-sGC-cGMP and NP-NPR-cGMP systems.

Fetomaternal hemorrhage with intraplacental chorioangioma.

A 37-year-old Asian woman, gravid 0 para 0, was admitted to our hospital at 34 weeks and 5 days of her pregnancy for management of preeclampsia. A few days after admission, she recognized diminished fetal movement, and a non-stress test revealed a non-reassuring fetal heart rate pattern with decreased variability. A female baby weighing 1840 g was delivered by emergency cesarean section with Apgar scores of 5 and 5 at 1 and 5 min, respectively. Significant neonatal anemia with a hemoglobin level of 4.3 g/dL was observed. The elevated level of hemoglobin F (HbF) in the maternal blood accounted for 4.6% (normal≦0.5%), and was indicative of the presence of fetomaternal hemorrhage (FMH). Microscopic examination of the placenta revealed chorioangioma. We report here a rare case of FMH with intraplacental chorioangioma, and discuss the relationship between these two pathologies.

Desmoplastic small round cell tumor in the ovary: Report of two cases and literature review.

Desmoplastic small round cell tumor (DSRCT) is a rare intra-abdominal tumor of uncertain histogenesis that occurs predominantly in young males. We report two cases of DSRCT in young women that presented clinically as ovarian tumor with extensive pelvic and abdominal dissemination. Both patients underwent debulking surgery and combined chemotherapy. After primary therapy, the tumors recurred and both women died of the disease. The clinical presentation and differential diagnosis, as well as the treatment, including surgical debulking and combined chemotherapy are discussed.

Stanford type B aortic dissection associated with pregnancy in patients with Marfan syndrome-A case report and review of the literature.

A 36-year-old female patient known to have Marfan syndrome (MFS) presented with Stanford type B aortic dissection (type B-AD) 3 days after delivery although she had taken oral ß-blocker and underwent prophylactic cesarean section at 34 weeks when she showed 42 mm of the ascending aorta. She was successfully treated medically without further progression of the dissection. A review of the literature revealed an additional 19 patients with MFS who suffered from type B-AD associated with pregnancy. Of 20 patients, 1 (5%) died but the remaining 19 patients were successfully treated either medically (n = 9) or surgically (n = 10). Of 13 patients whose aortic diameter was known, 5 showed <40 mm of the ascending aorta. Pregnancy in MFS can be complicated by type B-AD with a peak around term delivery irrespective of the size of ascending aorta and even with ß-blocker.

Fetal arrhythmia: prenatal diagnosis and perinatal management.

The importance of managing fetal arrhythmia has increased over the past three decades. Although most fetal arrhythmias are benign, some types cause fetal hydrops and can lead to fetal death. With the aim of improving the outcome in such cases, various studies for prenatal diagnosis and perinatal management have been published. Detailed analysis of the type of arrhythmia in utero is possible using M-mode and Doppler echocardiography. In particular, a simultaneous record of Doppler waveform at the superior venous cava and the ascending aorta has become an important and useful method of assessing the interval between atrial and ventricular contractions. Common causes of fetal tachycardia (ventricular heart rate faster than 180 bpm), are paroxysmal supraventricular tachycardia (SVT) with 1:1 atrioventricular (AV) relation and atrial flutter with 2:1 AV relation. Of fetal SVT, short ventriculo-atrial (VA) interval tachycardia due to atrioventricular reentrant tachycardia is more common than long VA interval. Most fetuses with tachycardia are successfully treated in utero by transplacental administration of antiarrhythmic drugs. Digoxin is widely accepted as a first-line antiarrhythmic drug. Sotalol, flecainide and amiodarone are used as second-line drugs when digoxin fails to achieve conversion to sinus rhythm. Fetal bradycardia is diagnosed when the fetal ventricular heart rate is slower than 100 bpm, mainly due to AV block. Approximately half of all cases are caused by associated congenital heart disease, and the remaining cases that have normal cardiac structure are often caused by maternal SS-A antibody. The efficacy of prenatal treatment for fetal AV block is limited compared with treatment for fetal tachycardia. Beta stimulants and steroids have been reported as effective transplacental treatments for fetal AV block. Perinatal management based on prospective clinical study protocol rather than individual experience is crucial for further improvement of outcome in fetuses with tachycardia and bradycardia.