Screening of gestational diabetes mellitus in early pregnancy by oral glucose tolerance test and glycosylated fibronectin: study protocol for an international, prospective, multicentre cohort trial.

INTRODUCTION: As the accurate diagnosis and treatment of gestational diabetes mellitus (GDM) is of increasing importance; new diagnostic approaches for the assessment of GDM in early pregnancy were recently suggested. We evaluate the diagnostic power of an 'early' oral glucose tolerance test (OGTT) 75 g and glycosylated fibronectin (glyFn) for GDM screening in a normal cohort. METHODS AND ANALYSIS: In a prospective cohort study, 748 singleton pregnancies are recruited in 6 centres in Switzerland, Austria and Germany. Women are screened for pre-existing diabetes mellitus and GDM by an 'early' OGTT 75 g and/or the new biomarker, glyFn, at 12-15 weeks of gestation. Different screening strategies are compared to evaluate the impact on detection of GDM by an OGTT 75 g at 24-28 weeks of gestation as recommended by the International Association of Diabetes and Pregnancy Study Groups (IADPSG). A new screening algorithm is created by using multivariable risk estimation based on 'early' OGTT 75 g and/or glyFn results, incorporating maternal risk factors. Recruitment began in May 2014. ETHICS AND DISSEMINATION: This study received ethical approval from the ethics committees in Basel, Zurich, Vienna, Salzburg and Freiburg. It was registered under http://www.ClinicalTrials.gov (NCT02035059) on 12 January 2014. Data will be presented at international conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT02035059.

Lumbar neuraxial anatomical changes throughout pregnancy: a longitudinal study using serial ultrasound scans.

This observational study was designed to investigate the anatomical changes of the lumbar spine over the course of pregnancy using serial ultrasound scans. We performed paramedian scans on 58 women at the L2-3, L3-4 and L4-5 levels; these were done at four periods of 11+0-13+6, 19+0-23+0, 28+0-32+0 and 38+0-40+0 weeks gestation. At each intervertebral level, the length of the interlaminar space, length of the visible intervertebral posterior dura and depth of the posterior dura mater from the skin were measured. The length of the interlaminar space and length of the visible intervertebral posterior dura mater were longer, and the depth of the posterior dura mater was shallower, with ascending spinal interspace. The depth of the posterior dura mater increased during pregnancy, although it plateaued between the third and fourth measurement periods. The other spinal measurements were not affected by gestation. These findings indicate that the L2-3 level is the most appropriate puncture site for epidural anaesthesia in pregnant women. Our results ought to be embraced as a departure point towards developing neuraxial insertion techniques guided or aided by ultrasound.

Age intrinsic loss of telomere protection via TRF1 reduction in endothelial cells.

Aging is a major factor predisposing for multiple diseases. Telomeres at the ends of chromosomes protect the integrity of chromosomal DNA. A specialized six-protein complex termed shelterin protects the telomere from unwanted interaction with DNA damage pathways. The aim of our study was to evaluate the integrity of telomeres and the stability of telomere protection during aging in endothelial cells (EC). We describe that aging EC can be characterized by an increased cell size (40%, p=0.02) and increased expression of PAI 1 (4 fold, p=0.02), MCP1 (10 fold, p=0.001) and GMCSF (15 fold, p=0.004). Telomeric state in aging cells is defined by an increased telomere oxidation (27%, p=0.01), reduced telomere length (62%, p=0.02), and increased DNA damage foci formation (5% in young EC versus 16% in aged EC, p=0.003). This telomeric dysfunction is accompanied by a reduction in the shelterin component TRF1 (33% mRNA, p=0.001; 24% protein, p=0.007). Overexpression of TRF1 in aging EC reduced telomere-associated DNA damage foci to 5% (p=0.02) and reduced expression levels of MCP1 (18% reduction, p=0.008). Aged EC have increased telomere damage and an intrinsic loss of telomere protection. Reestablishing telomere integrity could therefore be a target for rejuvenating endothelial cell function.

Sequential cervical length screening in pregnancies after loop excision of the transformation zone conisation: a retrospective analysis.

OBJECTIVE: To review our experience with a screening programme that included four sequential cervical length (CL) measurements from 16 to 22( ) weeks of gestation. DESIGN: Historical cohort study. SETTING: Tertiary-care centre in a university hospital. POPULATION: There were 312 singleton pregnancies in 321 women with a previous large loop excision of the transformation zone (LLETZ), and 62 pregnancies after a second-trimester miscarriage in a previous pregnancy. METHODS: The CL measurements were performed by transvaginal ultrasound at 16, 18, 20, and 22 completed weeks of gestation. MAIN OUTCOME MEASURES: Early preterm delivery before 34 completed weeks of gestation. RESULTS: Early preterm delivery was found in 7.4%. The CL at 16 completed weeks of gestation was smaller in the LLETZ group (36 mm, interquartile range 30-40 mm) compared with the control group (38 mm, interquartile range 32-42 mm; P = 0.040). For the analysis of risk factors for early preterm delivery after LLETZ, only cases with a complete data set were included (n = 145). In a multivariate analysis, two parameters remained significantly predictive, with CL at 16 completed weeks of gestation being the most significant measure (P < 0.001, OR 0.90, 95% CI 0.83-0.98), followed by conception using IVF treatment (P = 0.031, OR 0.64, 95% CI 1.54-34.80). CONCLUSIONS: Even as early as 16 weeks of gestation, women with early preterm delivery reveal a significantly lower CL than those without. Dynamics in the CL do not add to this information.

A pilot study of hormone replacement therapy with tibolone in women with mastopathic breasts.

OBJECTIVE: Our purpose was to investigate the effect of tibolone in a prospective randomized, double-blind pilot study in postmenopausal women with clinically palpable mastopathic changes. METHODS: Twenty postmenopausal non-users of hormone replacement therapy undergoing mammography were randomly allocated to receive either 2.5 mg tibolone (Livial, Organon) or placebo (2 mg lactose). Mammographic density according to the Wolfe classification, severity of breast discomfort, parity, smoking habits, body weight and follicle-stimulating hormone (FSH) and estradiol (E(2)) levels were documented at baseline and after 6 months of treatment. RESULTS: There were no statistically significant differences between the two treatment groups in terms of parity, smoking, body weight and FSH and E(2) levels. At 6 months, four patients in the tibolone group showed reduced breast density, compared with one patient in the placebo group. Whereas no significant differences were found between the two treatment groups when the categories 'minimal reduction' and 'reduction' in mammographic density were combined, combination of the categories 'no change' and 'minimal reduction' showed a significant difference (P<0.036). Also, women in the tibolone group showed a statistically significant improvement in breast discomfort (P<0.019). CONCLUSION: This pilot study showed decreases in breast density as well as an attendant significant alleviation of breast discomfort in women with baseline mastopathic changes treated with tibolone for 6 months, which may be due to the inhibitory effect of tibolone on the enzymes involved in the biosynthesis of estradiol demonstrated in previous trials and should be further evaluated in long-term studies.

[Prenatal diagnosis of full, non mosaic trisomy 22 in the third trimester]. / Zur pränatalen Ultraschall-Diagnostik des Vollbildes der Trisomie 22 im III. Trimenon.

A 31-year-old Caucasian women was referred to our department after IUGR was suspected by her gynaecologist at 29 weeks' amenorrhea in her second pregnancy. Multiple anomalies were detected by prenatal ultrasound in the 29th week of gestation. Chordocentesis was performed and revealed a Trisomy 22 in all fetal blood cells. The pregnancy was terminated. Post-mortem investigations excluded chromosomal mosaicism. Prenatal ultrasound findings and post-mortem features are presented.

Three- versus two-dimensional ultrasound for nuchal translucency thickness measurements: comparison of feasibility and levels of agreement.

We have determined feasibility and levels of agreement for visualizing the nuchal translucency within a time limit with three-dimensional (3D) and two-dimensional (2D) transvaginal ultrasound. A total of 213 women of median gestational age 13 weeks (range 11-14 weeks) undergoing first-trimester nuchal translucency (NT) thickness measurements with 2D transabdominal ultrasound were included in the study. Additionally all women underwent 2D and 3D transvaginal NT examination within a time limit of 90 s. These two methods were compared with each other and with our standard method (2D transabdominal ultrasound) with respect to visualization of fetal nuchal fold and to the levels of agreement. The nuchal fold was visualized by 3D and 2D transvaginal ultrasound in 85.9% (95% CI: 80.5%, 90.3%) and 25.8% (95% CI: 20.1%, 32.2%), respectively (p<0.001). There was a statistically significant underestimation of the NT by 2D transabdominal as compared with 3D transvaginal ultrasound of 0.1 mm (p<0.001), and by 3D transvaginal as compared with 2D transvaginal ultrasound of even 0.1 mm (p<0.001). 3D transvaginal ultrasound of the nuchal fold has increased feasibility to 2D transvaginal ultrasound within a short examination time and with minimal, but significant, measurement differences.

Influence of acupuncture on Doppler ultrasound in pregnant women.

OBJECTIVE: To evaluate the influence of acupuncture on the blood flow in the umbilical artery (UA), fetal aorta and uterine artery and on the fetal heart rate using two different acupuncture points (SP-6 (Sanyinjiao) and LI-4 (Hegu)). METHODS: In group A (n = 50), measurements (Doppler ultrasound and fetal heart rate) were performed at term after an uneventful pregnancy (#1) followed by acupuncture treatment using the acupuncture-point SP-6 bilaterally. The treatment time lasted 15 min after which the next measurement (#2) was carried out. The needles were then inserted into the LI-4 acupuncture point for a further 15 min. A third measurement at the end of acupuncture treatment (#3) completed the session. In group B (n = 25), measurements were made before (#1) and after (#4) acupuncture at LI-4 acupuncture points only. RESULTS: In group A, the mean systolic/diastolic (S/D) ratios of UA #1, UA #2 and UA #3 were 2.45, 2.38 and 2.22, respectively (P = 0.0012). The difference in mean S/D ratios between UA #1 and UA #3 as well as that between UA #2 and UA#3 were statistically significant (P = 0.0002 and P = 0.008, respectively). There was no difference between the mean S/D ratios of the uterine artery and between the mean resistance indices of the fetal aorta. In group B, the only significant difference between measurements following acupuncture treatment was in fetal heart rate (139 vs. 143 bpm, P = 0.02). CONCLUSION: Our study indicates a positive influence of acupuncture treatment on umbilical artery waveforms when using a combination of SP-6 (Sanyinjiao) and LI-4 (Hegu) acupuncture points. Acupuncture performed at these sites either individually or in combination does not seem to affect blood flow in the fetal aorta or uterine artery.

High levels of reticulated platelets and thrombopoietin characterize fetal thrombopoiesis.

To characterize fetal thrombopoiesis, we determined plasma thrombopoietin (TPO) and glycocalicin levels, platelet counts and reticulated platelets (RP) of fetuses and compared them with the respective values of their mothers. Percutaneous umbilical vein sampling in abnormal pregnancies revealed twofold higher thrombopoietin levels and 20-fold higher reticulated platelet counts, but lower levels of glycocalicin in fetuses compared with their mothers (P < 0.05). Neither the expression of platelet glycoprotein Ib and IIb on platelets nor the platelet counts were different between mothers and their fetuses. These data indicate enhanced thrombopoiesis and/or increased platelet turnover in fetuses.

The influence of cotinine on interleukin 6 expression in smokers with cervical preneoplasia.

BACKGROUND: Several epidemiological investigations have shown that cigarette smoking leads to increased serum IL-6 levels and is a risk factor for cervical cancer. METHODS: We examined the levels of interleukin 6 (IL-6) and the amount of cotinine in the cervical fluid of 78 women and compared the presence of human papillomavirus (HPV) in smokers and nonsmokers. RESULTS: The results of our study showed that IL-6 levels were higher in the cervical mucus of smokers than in nonsmokers. Fourteen percent of smokers were in the category with highest IL-6 levels compared to 6% of nonsmokers. However, our IL-6 results were not significant as they were probably influenced by the higher rates of HPV infection in smokers (17 cases) than in nonsmokers (4 cases). Significant findings showed that smokers had a higher prevalence of squamous intraepithelial lesions (SILs) than nonsmokers. Smokers' cotinine levels also exceeded those of nonsmokers: 13.95 ng/ml compared with 5.00 ng/ml. However, less IL-6 activity was evident in smokers with high-grade SILs and HPV infection of high-risk types. CONCLUSION: Our results suggest that smoking has a stimulatory effect on the production of IL-6 in the cervix. Furthermore, smokers show a higher genital HPV infection rate and a higher prevalence of SILs.

Human papillomavirus in the cervix and placenta.

OBJECTIVE: To determine the prevalence and association of human papillomavirus (HPV) infection in the cervices and placentas of pregnant women. METHODS: Cervical samples were taken from 179 of 226 women who had placental biopsies because of abnormal ultrasound findings or were older than 35 years, to detect HPV infections with hybrid capture II tests. Polymerase chain reaction (PCR) was done on placental tissue of 147 of the 226 women to detect HPV DNA. RESULTS: We found 44 of 179 women (24.6%, 95% confidence interval 18.3, 31.0) to test positive for HPV in their cervices. Logistic regression analyses showed decreased prevalence of HPV infection with increased maternal age (P =.039). The HPV DNA E6 PCR from the villus tissue was negative in the 147 cases examined. However, a significant contingency coefficient between low-risk HPV infection and elevated risk of chromosome aberration was found (φ = V = 0.15, P =.050). CONCLUSION: The infection rate of 24.6% in women without clinical symptoms of HPV infection was high, but there seemed to be no virus transmission to the placenta in women with subclinical infections. Low-risk cervical HPV infection might be associated with a slightly higher risk of abnormal fetal karyotype.

Ultrasound imaging of Bartholin's cysts.

In a prospective, randomized study, Bartholin's cysts were depicted in 36 patients by means of ultrasound imaging. Patients were requested to return for a follow-up US examination after surgery. We were able to show that Bartholin's cysts can easily be expressed with ultrasonographic techniques. In clinical practice, this approach may not only help to improve diagnostics, but may also make therapy measurable and, for the first time, objectifiable.

Relationship of serum levels of endogenous relaxin to cervical size in the second trimester and to cervical ripening at term.

OBJECTIVE: To assess whether cervical size in the early second trimester and cervical ripening at term may be related to serum levels of endogenous relaxin, 17beta-oestradiol or progesterone. DESIGN: A cross-sectional study investigating the relationship between hormone concentrations and cervical parameters as measured by ultrasound and Bishop score, respectively. PARTICIPANTS: Uncomplicated human pregnancies with normal fetal outcome, 72 women in the second trimester and 40 women at term. METHODS: Vaginal ultrasound and palpation were used to estimate cervical parameters. Hormones were analysed either by dissociation-enhanced fluoroimmunoassay (relaxin) or by automated electrochemiluminescent immunoassays. RESULTS: Cervical length and diameter correlated positively during mid-gestation and negatively at term. During mid-gestation, but not at term, relaxin was significantly associated with cervical length and volume, and with progesterone. Bishop score only correlated inversely with progesterone at term. CONCLUSION: Corpus luteum function is reflected by progesterone and relaxin in the early second trimester. An impact of relaxin on cervical growth, previously demonstrated by animal models and in vitro experiments, was confirmed during human mid-gestation. In contrast to many other species, human cervical ripening was not associated with endogenous relaxin at term, but with decreased progesterone.

Cystic adenomatoid malformation of the lung: prenatal diagnosis, prognostic factors and fetal outcome.

AIM: To evaluate 14 cases of cystic adenomatoid malformation (CAM) of the lung with regard to antenatal management and fetal outcome. RESULTS: Intrauterine shunts were placed in 3 fetuses to avoid pulmonary hypoplasia. Prenatal sonography showed that the lesions had a tendency to resolve in 4 cases. Of the 9 infants who survived, 5 were treated surgically (lobectomy). CONCLUSIONS: The antenatal evolution of these lesions is highly variable; the lesions may even resolve spontaneously, therefore the diagnosis of CAM types II and III should be followed by a period of observation. Intrauterine drainage is recommended in cases of CAM type I if unfavorable prognostic factors are encountered.

Intrauterine device localization by three-dimensional transvaginal sonography.

Our objective was to investigate the possible role of three-dimensional transvaginal ultrasound in the visualization of an intrauterine device (IUD) for routine follow-up after insertion. A total of 96 women were examined after insertion of a TCu380A IUD. Three-dimensional ultrasonographic imaging was carried out using a special vaginal probe and a commercially available ultrasound machine at a mean interval of 22 days after insertion. Complete simultaneous imaging of all parts of the IUD was possible in 95% of cases. In the three-plane mode, all parts of the IUD could be visualized in 64% and in a further 30 cases this was possible only after volume rendering. In two women, incomplete opening of the two arms of the device was demonstrated. In one of these cases, the entire IUD was displaced into the cervical canal. In another case, an intrauterine pregnancy was found together with an IUD in the correct position. Three-dimensional ultrasound provides useful information on the location of the IUD following insertion. It enables imaging of the entire IUD, i.e. the shaft and the arms, simultaneously. Additionally, the examination time can be kept to a minimum with this new technique.

[Measuring amniochorionic membrane thickness with high frequency ultrasound]. / Die Messung der Eihautdicke mittels Hochfrequenzultraschall.

The postpartal thickness of the amniochorionic membrane was measured by means of 20 MHz ultrasound after 28 inconspicuous deliveries in the course of a prospective study. The aim of our investigation was to determine the thickness of the amniochorionic membrane using high frequency ultrasound and to evaluate the results for a statistical correlation with fetal and maternal parameters. The data obtained were compared with histological sections for measurement accuracy using a linear regression analysis method. Membrane thickness of the total study group was 0.83 +/- 0.11 mm (0.72-1.08 mm). Based on a statistical comparison with the histological sections, the high frequency ultrasonographic examination was shown to be highly reliable with a correlation coefficient of r = 0.96 (p < 0.0001). Results obtained by ultrasonography were correlated with maternal (gestational age, patient age, parity) and neonatal (size and weight at birth, sex, placental weight, Apgar 1/5/10) parameters by means of linear regression analysis. There was a statistically significant correlation between parity and membrane thickness (r = 0.485, p < 0.05). There was also a correlation of Apgar scores at 5 minutes post partum (r = 0.485, p < 0.05). We were able to demonstrate that the measurement of membrane thickness by ultrasound is an objective and reliable method and may be a gain to prenatal diagnostics when used in vivo.

Measurement of amniochorionic membrane thickness using high-frequency ultrasound.

Premature rupture of the membranes (PROM) accounts for approximately 30 per cent of all preterm deliveries. PROM is thought to be mainly due to a decrease in membrane integrity. The aim of our investigation was to determine, post-partum after 28 normal deliveries, the thickness of the amniochorionic membrane using a 20 MHz high-frequency ultrasound. The data obtained were compared with histological sections for measurement accuracy using a linear regression analysis method. The membrane thickness of the total study group was 0.83 +/- 0.11 mm (0.72-1.08 mm). Based on a statistical comparison with the histological sections, the high-frequency ultrasound examination was shown to be highly reliable, with a correlation coefficient of r = 0.96 (P < 0.0001). High-frequency ultrasonographic examinations of membrane thickness are an objective and reliable method and may be a gain to prenatal diagnostics once this method can be used in vivo.

[Efficacy of various methods for preoperative vaginal antisepsis]. / Zur Effizienz von Verfahren für die präoperative Vaginalantiseptik.

In a prospective clinical study we investigated 115 patients prior to vaginal surgical interventions to determine the antimicrobial efficacy of six different procedures for vaginal antisepsis. To sample the microorganisms we used a cotton swab moistened with a neutralising fluid. Immediately after the time of action of the antiseptic procedures (3 minutes), providone-iodine solution, applied undiluted or diluted 1:10, yielded the strongest median reduction of the vaginal flora (log RF 3.60 and 2.68, respectively). Of three detergents with antiseptic efficacy, octenidine 0.1% was the most efficient formula (log RF 2.32). After 30 minutes the log reduction factors (log RF) of almost all procedures (log RF 2.79-3.25) were in a fairly close range, excepting chlorohexidine 0.05% (log RF 2.07). Overall, the antiseptic detergents showed a marked residual effect, which was less pronounced, if at all, with providone-iodine solutions. A germ-reducing effect of povidone-iodine vaginal suppositories, applied 2 to 3 hrs prior to surgery, was not confirmed, while additional findings indicated that providone-iodine solution applied with the help of a vaginal douche yields a similarly strong germ reduction as the application by means of a ball swabs.