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Biomedical subjects

Peter Husslein

Publications and source records attributed to Peter Husslein.

At least 19 recordsLinked to original sources

Induction of labor at term using isosorbide mononitrate simultaneously with dinoprostone compared to dinoprostone treatment alone: a randomized, controlled trial.

OBJECTIVE: We aimed to determine whether isosorbide mononitrate (IMN) given simultaneously with dinoprostone in term pregnancies is superior to dinoprostone alone to promote delivery. STUDY DESIGN: One hundred and twenty nulliparous women at term were randomly assigned to receive per vaginam IMN 40 mg or placebo in addition to 3 mg dinoprostone 2 times daily for up to 2 days. Analysis was by intention to treat. RESULTS: Baseline characteristics of both groups were comparable. The induction to delivery intervals did not differ between the IMN and the placebo group (26.4 +/- 14.4 vs 23.4 +/- 14.8 hours, P = .408). IMN resulted in more headache compared to placebo (32/55 [58.2%] vs 2/55 [3.6%], P < .001). CONCLUSION: Vaginally administered IMN does not play a role in promoting delivery in term pregnancy if given at the same time as dinoprostone. This might reflect its relaxant effect on the uterine fundus, which may overcome its cervical softening effect.

Administration, Intravaginal↗

Preeclampsia and pregnancy loss in women with a history of venous thromboembolism and prophylactic low-molecular-weight heparin (LMWH) during pregnancy.

Limited data are available regarding complications of pregnancy and pregnancy outcome under prophylaxis with low-molecular-weight heparin (LMWH) in women with a history of thromboembolism (TE). We retrospectively evaluated pregnancy complications in a cohort of 80 women. All had a history of TE (76 venous, two arterial and two venous and arterial) and received prophylactic LMWH during 86 pregnancies. The rate of preeclampsia and stillbirth in these women was compared to that of a control group of 313 women without a history of TE and LMWH. Prophylaxis was started at a median of 10 weeks of gestation and usually continued until six weeks post partum. In 94% of the cases the outcome of pregnancy was favourable with a live birth. Four pregnancies (4.7%) ended in miscarriage. Two (2.3%) pregnancies were complicated by a thromboembolic event (one deep leg vein thrombosis and PRIND, respectively). One patient developed HELLP-syndrome. Severe preeclampsia occurred in three (3.8%) and stillbirth in one (1.3%) of the patients (n = 80), whereas this was the case in four (1.3%, odds ratio 3.01; 95% confidence interval (CI) 0.66-13.73, p = 0.15) and 10 (3.2%, OR = 0.38; 95% CI 0.05-3.04, p = 0.72) control women. Mean birth weight and standard deviation of infants was 3,160 +/- 930 g in patients and 3,300 +/- 540 g in controls (p = 0.11). We conclude that a favourable pregnancy outcome in women with a history of thromboembolism who use prophylactic LMWH during pregnancy can be expected. There was a trend towards a higher risk of preeclampsia, and these women should be carefully monitored for this complication.

Abortion, Spontaneous↗

Activation of the canonical wingless/T-cell factor signaling pathway promotes invasive differentiation of human trophoblast.

The molecular mechanisms governing invasive differentiation of human trophoblasts remain largely elusive. Here, we investigated the role of Wnt-beta-catenin-T-cell factor (TCF) signaling in this process. Reverse transcriptase-polymerase chain reaction and Western blot analyses demonstrated expression of Wnt ligands, frizzled receptors, LRP-6, and TCF-3/4 transcription factors in total placenta and different trophoblast cell models. Immunohistochemistry of placental tissues and differentiating villous explant cultures showed that expression of TCF-3/4 strongly increased in invading trophoblasts. Some of these cells also accumulated dephosphorylated beta-catenin in the nucleus. Wnt3A treatment of primary cytotrophoblasts and SGHPL-5 cells induced activity of TCF-luciferase reporters. Accordingly, the ligand provoked interaction of TCF-3/4 with beta-catenin as assessed in electrophoretic mobility shift assays (EMSAs) and up-regulation of Wnt/TCF target genes as observed by Western blot analyses. Wnt3A stimulated trophoblast migration and invasion through Matrigel, which could be blocked by addition of Dickkopf-1, mediating in-hibition of canonical Wnt signaling. Dickkopf-1 also reduced basal migration, invasion, and proliferation of cytotrophoblasts, suggesting expression of endogenous Wnt ligand(s). Immunohistochemistry revealed that the percentage of extravillous trophoblasts containing nuclear beta-catenin was significantly higher in placentas of complete hydatidiform mole pregnancies as compared to normal placentas. Thus, canonical Wnt signaling may promote invasive trophoblast differentiation, and exaggerated activation of the path-way could contribute to trophoblastic hyperplasia and local invasion.

Cell Differentiation↗

Polymorphisms of the Nos3 gene and unexplained late intrauterine fetal death.

OBJECTIVE: Genetic polymorphisms associated with vascular diseases have been proposed to be involved in the pathogenesis of late unexplained intrauterine fetal death (IUFD). The Nos3 gene is known to regulate vascular tone via the endothelial nitric oxide synthase/nitric oxide pathway. STUDY DESIGN: In a multicenter case-control study, we evaluated two Nos3 polymorphisms (exon 7 Glu298Asp and a 27bp-repeat in intron 4) in 92 women with IUFD and 92 healthy control women. RESULTS: The investigated Nos3 polymorphisms were not associated with the occurrence of IUFD. In the subgroup of pregnancies affected by IUFD, women with at least one mutant allele of the Nos3 intron 4 polymorphism were diagnosed with IUFD at a significantly earlier gestational age (31.8 [standard deviation (S.D.) = 4.9] weeks versus 34.6 [S.D. = 4.8] weeks, p = 0.02) and showed a significantly reduced birth weight (2113 g [S.D. = 1028] versus 1571 g [S.D. = 568], p = 0.03). CONCLUSION: We are the first to report on Nos3 polymorphisms and IUFD. While not being associated with the incidence of IUFD overall, the intron 4 Nos3 polymorphism might modulate the timing of IUFD in affected pregnancies.

Adult↗

First-trimester nuchal translucency screening in pregnant women who subsequently developed gestational diabetes.

OBJECTIVE: To compare the nuchal translucency (NT) thickness at 11-14 weeks of gestation in women who will later develop gestational diabetes mellitus (GDM) with that of women with normal glucose tolerance (NGT) in the second trimester of pregnancy. METHODS: Four hundred sixty-four women underwent NT screening at 11-14 weeks of gestation according to the standards of the Fetal Medicine Foundation. They all underwent an oral glucose tolerance test (OGTT) between 24 and 28 weeks. RESULTS: Women with GDM (n = 135) were significantly older (34.0 years [+/-4.8] vs 29.4 years [+/-5.2]; P < .001), had a significantly higher body mass index (BMI) (28.2 kg/m2 [+/-6.0] vs 24.4 [+/-5.0]; P < .001), and had a significantly higher serum concentration of hemoglobin A1c (HbA1c) at the time of the NT measurement (5.38% [+/-0.6] vs 4.95% [+/-0.4]; P < .001] than women with NGT (n = 329). There is no significant difference in the NT measurement at 11 to 14 weeks of gestation between women with GDM and NGT after correction for crown rump length (CRL) (r = -.08, P = .45). We performed multiple linear regression analysis with NT as the dependent variable, and BMI, maternal age, CRL, and GDM/NGT as independent variables. CRL (P < .001) was significantly related to the NT measurement, whereas GDM/NGT, BMI, and maternal age were not. CONCLUSION: As no significant difference in the NT measurement between women with GDM and NGT was observed, the risk estimation for chromosomal abnormality derived from the maternal age and NT measurement can also be used in women with glucose disorders.

Adult↗

Influence of labor induction on obstetric outcomes in patients with prolonged pregnancy: a comparison between elective labor induction and spontaneous onset of labor beyond term.

BACKGROUND: Prolonged pregnancy is the most frequent reason for induction of labor. This study aims to determine the effects of labor induction on delivery outcome and to quantify the risks of cesarean delivery associated with labor induction in post-date pregnancies. PATIENTS AND METHODS: This retrospective case-control study included a total of 205 women who reached 42 weeks' gestation (41 weeks and 3 days) between January 2002 and April 2004 and who were scheduled for induction of labor with vaginal prostaglandins. These cases were matched for age and parity with controls in spontaneous labor beyond 41 weeks' gestation. Women with any additional medical or obstetric risk factors were excluded from the study. Maternal, neonatal and delivery outcomes were the main variables of interest. RESULTS: During the study period the data of 410 women were available for analysis. Our data revealed that the use of amniotomy (p=0.02), oxytocin (p=0.006) and epidural analgesia (p=0.001) was increased significantly in the induction group compared with the control group of women with spontaneous onset of labor beyond term. The frequency of cesarean delivery and vacuum extraction was also significantly higher in the induction group (p=0.0001). The Bishop score before induction was an important factor that affected the delivery outcome, resulting in significantly higher rates of cesarean section and vacuum extraction when the score was unfavorable (p=0.0001). A univariate regression model revealed induction per se (p=0.0001), primiparity (p= 0.0001), increased maternal age (p=0.006) and an unfavorable Bishop score (p=0.0001) as statistically significant risk factors for cesarean section. In a multivariate logistic regression model, primiparity (p=0.03), increased maternal age (p=0.02) and an unfavorable Bishop score (p=0.01) remained independent risk factors for cesarean section. High infant birth weight was also an independent risk factor (p=0.03). CONCLUSIONS: Our data suggest that women undergoing labor induction because of prolonged pregnancy should be sufficiently informed regarding the risks of a cesarean section or a vacuum extraction. Furthermore, the option of elective cesarean section should be considered, particularly in primiparous women with an unfavorable cervix, higher age, and high estimated infant birth weight.

Adolescent↗

Increased intrauterine frequency of Ureaplasma urealyticum in women with preterm labor and preterm premature rupture of the membranes and subsequent cesarean delivery.

OBJECTIVE: The purpose of this study was to evaluate the prevalence of microbial invasion of the amniotic cavity at the time of preterm cesarean delivery for therapy-resistant preterm labor or preterm premature rupture of membranes, which are events that commonly are induced by infection, and to compare this group of patients with a group of patients who underwent preterm cesarean delivery for indications other than preterm labor or preterm premature rupture of membranes. STUDY DESIGN: We studied 207 consecutive women between 23 and 34 weeks of gestation who underwent cesarean delivery. These patients were divided into 3 groups according to the indication for cesarean delivery: patients with preterm labor (group 1), patients with preterm premature rupture of membranes (group 2), and patients with other indications (group 3). In the course of the surgical procedure, amniotic fluid, amniotic membrane, and placental tissue specimens were collected for the detection of pathogens. RESULTS: Ureaplasma urealyticum was detected in 43.9% (58/132) of the patients of groups 1 and 2, with no significant difference between these 2 subgroups. In group 3, which served as the comparison group, Ureaplasma urealyticum was isolated in only 2.7% (2/75) of the patients. Ureaplasma urealyticum as a single pathogen was more frequent than all obligate pathogens together (43.9% vs 39.3%). CONCLUSION: Our results provide evidence for an association between intrauterine colonization with Ureaplasma urealyticum and both therapy-resistant preterm labor and preterm premature rupture of membranes.

Adult↗

An Angiopoietin-2 gene polymorphism in unexplained intrauterine fetal death: a multi-center study.

OBJECTIVE: Angiopoietin-2 (Ang-2) is a potent regulator of angiogenesis and vascular tone. As vascular processes have been proposed to be involved in the pathogenesis of pregnancy associated complications such as late unexplained intrauterine fetal death (IUFD), we determined whether a common G/A polymorphism of the Ang-2 gene (ANGPT2) is associated with this condition. METHODS: In a multicenter case-control study, we evaluated the common G/A polymorphism within exon 4 of the ANGPT2 gene using PCR in 90 women with IUFD and 90 healthy women with at least one uncomplicated full term pregnancy and no history of IUFD. RESULTS: Genotype (p=0.2; OR=1.4 [0.8-2.6]) and allele frequencies (p=0.1; OR=1.4 [0.9-2.1]) of the ANGPT2 polymorphism did not differ between women with IUFD and healthy women. A multivariate regression analysis with smoking habits and preexisting diabetes as covariates did not change the results. CONCLUSIONS: We are the first to report on a common polymorphism of the ANGPT2 gene in patients with late IUFD. The investigated ANGPT2 poylmorphism does not seem to be a candidate gene for IUFD in Caucasian women.

Adult↗

An interleukin-6 gene promoter polymorphism and unexplained late intrauterine fetal death: a multicenter study.

OBJECTIVE: Interleukin-6 (IL-6)-mediated inflammatory processes have been proposed to be involved in the pathogenesis of pregnancy-associated complications such as late unexplained intrauterine fetal death (IUFD). Therefore we determined whether a common guanine/cytosine polymorphism at position -174 of the promoter of the IL-6 gene (IL6) known to affect in vivo protein activity can serve as candidate gene for this condition. METHODS: In a multicenter case-control study, we evaluated the IL6 promoter polymorphism by pyrosequencing in 92 women with IUFD. Ninety-four healthy women with at least one uncomplicated full-term pregnancy and no history of IUFD served as the control group. RESULTS: No significant association was found between the presence of at least one mutant allele of the IL6 promoter polymorphism (P = .2; odds ratio = 1.5 [95% confidence interval, 0.8-2.7]) and the incidence of IUFD. In women with IUFD, the presence of at least one mutant allele of the IL6 promoter polymorphism did not influence timing of fetal death (33.9 [5.1] gestational weeks vs 34.1 [4.9] gestational weeks, P = .8) or birth weight (2055 [1119] g vs 1963 [992] g, P = .7). CONCLUSION: To our knowledge, we are the first to report on a common polymorphism of the IL6 promoter gene in women with late IUFD. The investigated IL6 promoter polymorphism can not be seen as candidate gene for IUFD in Caucasian women.

Adult↗

Gene expression profiling of cervical tissue during physiological cervical effacement.

OBJECTIVE: The softening and dilation of cervical tissue during parturition requires a rapid reorganization of extracellular matrix and cellular interactions. The purpose of this study was to gain insight into the complex transformational changes in gene expression that lead to cervical effacement. METHODS: Cervical biopsies from effaced cervices of 10 women undergoing spontaneous vaginal delivery and from competent cervices of 10 women undergoing primary cesarean delivery were collected at 37-41 weeks of gestation and subjected to differential complementary DNA (cDNA) microarray analysis. Gene expression results were validated by real-time polymerase chain reaction (PCR). RESULTS: In a cDNA array that enables the analysis of the differential gene expression of more than 600 genes, the messenger (m)RNA expression of 40 genes increased more than 2.5-fold during cervical ripening. The majority of these genes encode cytokines, transcription factors, and cell-matrix-associated proteins. The mRNA expression of 6 genes decreased to less than 0.5-fold. The remaining 556 genes were not significantly altered. Real-time PCR analysis performed for selected, highly up-regulated genes confirmed our cDNA array findings. CONCLUSION: Complete cervical effacement is associated with a characteristic and profound alteration in the gene expression profile of cervical cells. We hypothesize that an understanding of the molecular events that accompany physiological cervical dilation is pivotal to an understanding of pathological conditions such as premature delivery and postterm pregnancy.

Biopsy↗

Polymorphisms within the interleukin-1 gene family and unexplained late intrauterine fetal death: a multi-center study.

PROBLEM: Interleukin-1 (IL-1) mediated inflammatory processes have been proposed to be involved in the pathogenesis of late unexplained intrauterine fetal death (IUFD). We determined whether common polymorphisms within the IL-1 gene locus can serve as candidate genes for this condition. METHOD OF STUDY: In a multi-center case-control study, we evaluated the -889 C/T polymorphism of the IL-1alpha gene (IL1A), the -511 C/T polymorphism of the IL-1beta promoter (IL1B promoter), the +3953 C/T polymorphism of IL-1beta exon 5 (IL1B exon 5), and a 86 base pair repeat in intron 2 of the IL-1 receptor antagonist gene (IL1RN) in 94 women with IUFD and 94 healthy controls using pyrosequencing. RESULTS: No significant associations were found between the presence of polymorphic alleles of IL1A (P = 0.9), IL1B promoter (P = 0.3), IL1B exon 5 (P = 0.9), and IL1RN intron 2 (P = 0.7) and the incidence of IUFD. In women with IUFD, polymorphisms were not associated with the timing of fetal death and birth weight. CONCLUSIONS: Polymorphisms within the IL1 gene family are not associated with the occurrence of IUFD overall and do not modulate the clinical characteristics of affected pregnancies in a large series of Caucasian women.

Female↗

IL-8 concentrations in maternal serum, amniotic fluid and cord blood in relation to different pathogens within the amniotic cavity.

OBJECTIVE: The association between elevated interleukin (IL)-8 concentrations in amniotic fluid and preterm delivery is well described. Little consideration has been given to the impact of different groups of microorganisms within the amniotic cavity on IL-8 concentration. METHODS: We collected amniotic fluid, placental tissue and amniotic membranes during preterm cesarean sections for bacterial culture. In addition, we determined IL-8 concentrations in maternal serum, amniotic fluid and cord blood and correlated them with the various intra-amniotic pathogens isolated by bacterial culture. RESULTS: IL-8 concentrations were determined in amniotic fluid in 107 cases, in cord blood in 185 cases and in maternal blood in 158 cases. Women with intra-amniotic Ureaplasma urealyticum infection had significantly higher amniotic fluid concentrations of IL-8 than those without (P< 0.001). In cord blood, we found significantly elevated IL-8 concentrations due to intra-amniotic infection with U. urealyticum (P=0.045) and other pathogens (P=0.04). In maternal sera, we found no significant elevation of maternal IL-8 in any of the groups. CONCLUSION: Intrauterine infection with U. urealyticum seems to play a profound role in the cascade of inflammation and increases IL-8 concentrations in amniotic fluid and cord blood.

Adult↗

Prospective randomised controlled trial of an infection screening programme to reduce the rate of preterm delivery.

OBJECTIVE: To evaluate whether a screening strategy in pregnancy lowers the rate of preterm delivery in a general population of pregnant women. DESIGN: Multicentre, prospective, randomised controlled trial. SETTING: Non-hospital based antenatal clinics. PARTICIPANTS: 4429 pregnant women presenting for their routine prenatal visits early in the second trimester were screened by Gram stain for asymptomatic vaginal infection. In the intervention group, the women's obstetricians received the test results and women received standard treatment and follow up for any detected infection. In the control group, the results of the vaginal smears were not revealed to the caregivers. MAIN OUTCOME MEASURES: The primary outcome variable was preterm delivery at less than 37 weeks. Secondary outcome variables were preterm delivery at less than 37 weeks combined with different birth weight categories equal to or below 2500 g and the rate of late miscarriage. RESULTS: Outcome data were available for 2058 women in the intervention group and 2097 women in the control group. In the intervention group, the number of preterm births was significantly lower than in the control group (3.0% v 5.3%, 95% confidence interval 1.2 to 3.6; P = 0.0001). Preterm births were also significantly reduced in lower weight categories at less than 37 weeks and <or= 2500 g. Eight late miscarriages occurred in the intervention group and 15 in the control group. CONCLUSION: Integrating a simple infection screening programme into routine antenatal care leads to a significant reduction in preterm births and reduces the rate of late miscarriage in a general population of pregnant women.

Adult↗

Influence of the birth attendant on maternal and neonatal outcomes during normal vaginal delivery: a comparison between midwife and physician management.

BACKGROUND: The purpose of this study was to compare the obstetric outcome of low-risk maternity patients attended by certified midwives with that of low-risk maternity patients attended by obstetricians. PATIENTS AND METHODS: Obstetric outcome of 1352 midwife patients was compared with that of 1352 age- and parity-matched physician patients with normal spontaneous vaginal delivery at the Department of Obstetrics and Gynecology of the University Hospital Vienna during the period from January 1997 to July 2002. Our analysis was restricted to a sample of low-risk pregnant women. Women with medical or obstetric risk factors were excluded. RESULTS: A significant decrease in the use of oxytocin (p=0.0001) was observed in women who selected a midwife as their primary birth attendant compared with women in the physician group. In both groups most women gave birth in a supine position; however, significantly more alternative birth positions were used by midwife patients (p = 0.0001). Concerning perineal trauma, a significantly lower rate of episiotomies (p = 0.0001) and perineal tears of all degrees (p=0.006) were found in midwife patients. When analyzing severe postpartum hemorrhage and postpartum infections, there were no significant differences between the two groups (p > 0.05). Concerning neonatal outcome, there were no significant differences in APGAR score < 7 at 5 minutes (p > 0.05). Our data clearly show the ability of certified midwives to successfully provide prenatal care and delivery to low-risk maternity patients, with neonatal outcomes comparable to those of physician patients. The use of certified midwives supervised by obstetricians may provide the optimum model for perinatal care, particularly for those women who are low-risk maternity patients, leaving physicians free to attend to the high-risk elements of care.

Austria↗