Katharina Klein

Vaginal progesterone in women with an asymptomatic sonographic short cervix in the midtrimester decreases preterm delivery and neonatal morbidity: a systematic review and metaanalysis of individual patient data

OBJECTIVE To determine whether the use of vaginal progesterone in asymptomatic women with a sonographic short cervix (≤ 25 mm) in the midtrimester reduces the risk of preterm birth and improves neonatal morbidity and mortality. STUDY DESIGN Individual patient data metaanalysis of randomized controlled trials. RESULTS Five trials of high quality were included with a total of 775 women and 827 infants. Treatment with vaginal progesterone was associated with a significant reduction in the rate of preterm birth <33 weeks (relative risk [RR], 0.58; 95% confidence interval [CI], 0.42-0.80), <35 weeks (RR, 0.69; 95% CI, 0.55-0.88), and <28 weeks (RR, 0.50; 95% CI, 0.30-0.81); respiratory distress syndrome (RR, 0.48; 95% CI, 0.30-0.76); composite neonatal morbidity and mortality (RR, 0.57; 95% CI, 0.40-0.81); birthweight <1500 g (RR, 0.55; 95% CI, 0.38-0.80); admission to neonatal intensive care unit (RR, 0.75; 95% CI, 0.59-0.94); and requirement for mechanical ventilation (RR, 0.66; 95% CI, 0.44-0.98). There were no significant differences between the vaginal progesterone and placebo groups in the rate of adverse maternal events or congenital anomalies. CONCLUSION Vaginal progesterone administration to asymptomatic women with a sonographic short cervix reduces the risk of preterm birth and neonatal morbidity and mortality.

Prevention of preterm delivery in twin gestations (PREDICT): a multicenter, randomized, placebo‐controlled trial on the effect of vaginal micronized progesterone

Studies on high‐risk singleton gestations have shown a preventive effect of progesterone treatment on preterm delivery. This study was conducted to investigate the preventive effect of vaginal micronized progesterone in a large population of twin gestations.

Posterior reversible encephalopathy syndrome: do predisposing risk factors make a difference in MRI appearance?

IntroductionPosterior reversible encephalopathy syndrome (PRES) is a clinico-neuroradiological entity, characterized by typical neurological deficits, distinctive magnetic resonance imaging (MRI) features, and a usually benign clinical course. Although frequently seen in association with hypertensive conditions, many other predisposing factors, notably cytotoxic and immunosuppressant drugs have been associated with PRES. The aim of this study was to determine differences in the MR appearance of PRES according to various risk factors.MethodsThirty consecutive patients with clinical and MRI findings consistent with PRES were included. We identified 24 patients with hypertension-related conditions, including 14 patients with preeclampsia–eclampsia, and six patients without hypertension, in whom PRES was associated with exposition to neurotoxic substances. Lesion distribution, extent of disease, and number of affected brain regions were compared between patients with PRES with and without hypertension, and patients with PRES with and without preeclampsia–eclampsia, respectively.ResultsNo statistically significant differences in distribution of lesions and extent of disease were observed between patients with PRES with or without hypertension, and patients with or without preeclampsia–eclampsia, respectively. The number of affected brain regions was significantly higher in patients with preeclampsia–eclampsia (p = 0.046), and the basal ganglia region was more frequently involved in these patients (p = 0.066).ConclusionApart from a significant higher number of involved brain regions and a tendency for basal ganglia involvement in patients with PRES associated with preeclampsia–eclampsia, the MRI appearance of patients with PRES does not seem to be influenced by predisposing risk factors.

Does the mode of delivery influence sexual function after childbirth

OBJECTIVE The aim of the study was to evaluate the influence of the mode of delivery on female sexuality 12-18 months after childbirth. METHODS Fifty-five primiparae who delivered vaginally without complication and 44 who underwent elective cesarean section after 37 weeks of gestation were included. Sexual function was assessed by a validated self-reported questionnaire, the Female Sexual Function Index (FSFI), 12 months after birth and compared between groups. Additionally, we have analyzed subjective stress variables recorded after birth between the two groups. RESULTS Women with cesarean section were older (p = 0.002) and had a higher body mass index (BMI) (p =0.02). The total score of the FSFI was not significantly different between the groups. Patients recall of dyspareunia at 3 months after childbirth was higher in those who underwent vaginal delivery (p < 0.001). CONCLUSIONS We suggest that there is no significant difference in sexual function 12-18 months after childbirth between women who delivered vaginally without episiotomy, heavy perineal laceration, or secondary operative interventions and women who underwent elective cesarean section.

Osteocalcin Is Related to Enhanced Insulin Secretion in Gestational Diabetes Mellitus

OBJECTIVE There is growing evidence that osteocalcin, an osteoblast-derived protein locally acting on bone formation, can increase insulin secretion as well as insulin sensitivity and thus prevent the development of obesity and diabetes in experimental animals. In humans, osteocalcin has been reported to be decreased in patients with type 2 diabetes. Because gestational diabetes mellitus (GDM) can serve as a model of pre–type 2 diabetes, the aim of this study was to investigate osteocalcin in GDM. RESEARCH DESIGN AND METHODS Osteocalcin measurement and an oral glucose tolerance test were performed in 78 pregnant women (26 women had GDM and 52 women had normal glucose tolerance [NGT] during pregnancy; women were matched for age and BMI) and in 34 women postpartum. RESULTS During pregnancy osteocalcin was significantly higher in the women with GDM than in the women with NGT (15.6 ± 6.4 vs. 12.6 ± 4.0 ng/ml; P < 0.015), whereas no difference was observed between the two groups at 12 weeks postpartum (36.2 ± 10.2 vs. 36.2 ± 13.0 ng/ml), when osteocalcin was found to be increased compared with the level in the pregnant state in all women (+145 ± 102% in GDM vs. +187 ± 119% in NGT; P < 0.0001). Moreover, osteocalcin showed a significant correlation with basal and total insulin secretion in the whole study group (R = 0.3, P < 0.01). CONCLUSIONS In GDM osteocalcin was higher and thus less restrained than in women with NGT during pregnancy and furthermore correlated with insulin secretion parameters. Therefore, it could be hypothesized that osteocalcin can enhance insulin secretion in insulin-resistant states; alternatively an effect of hyperinsulinemia on osteocalcin secretion cannot be excluded.

Vaginal micronized progesterone and risk of preterm delivery in high-risk twin pregnancies: secondary analysis of a placebo-controlled randomized trial and meta-analysis

Progesterone treatment reduces the risk of preterm delivery in high‐risk singleton pregnancies. Our aim was to evaluate the preventive effect of vaginal progesterone in high‐risk twins.

Prenatal sonography can predict degree of placental invasion

To evaluate whether the maximum degree of placental invasion (placenta accreta, increta or percreta) can be predicted with ultrasound imaging, using criteria developed in our department.

Prediction of spontaneous preterm delivery in twin pregnancies by cervical length at mid-gestation.

The objective of our study was to evaluate the correlation of the cervical length at 20-25 weeks of gestation with the incidence of spontaneous preterm delivery in twins in a country with a high incidence of preterm delivery compared to other European countries. Cervical length was measured in 262 consecutive patients. Previous preterm delivery before 34 weeks of gestation, chorionicity, maternal age, body-mass-index, smoking habit and parity were recorded as risk factors for preterm delivery. Women who were symptomatic at 20-25 weeks and who delivered because of other reasons than spontaneous labour and preterm rupture of membranes or at term were excluded. The primary outcome was incidence of preterm birth before 34 weeks. Two hundred and twenty-three patients were analyzed. Thirty-two (14%) delivered before 34 weeks. There was a significant correlation between cervical length of less than 25 mm and spontaneous delivery before 34 weeks (50% vs. 13%, p = .007). In addition, logistic regression analysis found cervical length to be the only significant predictor of spontaneous delivery before 34 weeks (OR 1.084; 95% CI 1.015; 1.159; p = .017). We conclude that the risk of severe preterm delivery in twins is high. Cervical length at mid-gestation was the only predictor of delivery before 34 weeks.

Identification of Oncostatin M as a STAT5-Dependent Mediator of Bone Marrow Remodeling in KIT D816V-Positive Systemic Mastocytosis

Systemic mastocytosis is a neoplastic disease of mast cells harboring the activating KIT mutation D816V. In most patients, mast cell infiltration in the bone marrow is accompanied by marked microenvironment alterations, including increased angiogenesis, osteosclerosis, and sometimes fibrosis. Little is known about the mast cell-derived molecules contributing to these bone marrow alterations. We show here that neoplastic mast cells in patients with systemic mastocytosis express oncostatin M (OSM), a profibrogenic and angiogenic modulator. To study the regulation of OSM expression, KIT D816V was inducibly expressed in Ba/F3 cells and was found to up-regulate OSM mRNA and protein levels, suggesting that OSM is a KIT D816V-dependent mediator. Correspondingly, KIT D816V(+) HMC-1.2 cells expressed significantly higher amounts of OSM than the KIT D816V(-) HMC-1.1 subclone. RNA interference-induced knockdown of STAT5, a key transcription factor in KIT D816V(+) mast cells, inhibited OSM expression in HMC-1 cells, whereas a constitutively activated STAT5 mutant induced OSM expression. Finally, OSM secreted from KIT D816V(+) mast cells stimulated growth of endothelial cells, fibroblasts, and osteoblasts, suggesting that mast cell-derived OSM may serve as a key modulator of the marrow microenvironment and thus contribute to the pathology of systemic mastocytosis.

Risk Factor Profile and Pregnancy Outcome in Women with Type 1 and Type 2 Diabetes Mellitus

OBJECTIVE To assess differences in congenital anomalies, infant mortality, and obstetrical complications as well as risk factors associated with an adverse pregnancy outcome in women with type 1 (T1DM) and type 2 diabetes mellitus (T2DM). METHODS This observational study was performed at a university clinic and included a total of 200 singleton pregnancies between January 1995 and December 2006. Outcome measures comprise the prevalence of major congenital malformations, fetal losses, stillbirths, and neonatal deaths as well as the combined end point, adverse pregnancy outcome, and obstetrical complications. RESULTS Despite changes in prevailing risk factors, the rate of congenital anomalies and embryonic as well as perinatal death was comparable in type 1 diabetic women over time as well as between women with T1DM and T2DM. Outcome measures and risk factor profile were similar in women with preconception and newly diagnosed T2DM. Glycemic control and increased body mass index (BMI) during the first trimester were the strongest predictors of an adverse pregnancy outcome. Hemoglobin A1c (HbA1c) was higher in T1DM than in T2DM but similar in women with T1DM over time. BMI was highest in women with T2DM, followed by T1DM women of the most recent time period. CONCLUSIONS In addition to HbA1c, other risk factors, especially high BMI, strongly influence pregnancy outcome. The higher prevalence of these risk factors in T2DM might compensate for the better glycemic control, resulting in a pregnancy outcome comparable to that of T1DM. Pregnancy outcome in T1DM remained unchanged over time, possibly because of the missing amelioration of HbA1c levels and the increasing BMI.