Mervi Väisänen-Tommiska

Cervical nitric oxide release in women postterm.

OBJECTIVE: Nitric oxide may be a factor in cervical ripening. We compared the nitric oxide metabolite levels in cervical fluid in women going beyond term and in women delivering spontaneously at term. METHODS: We studied a total of 208 women with singleton pregnancies: 108 women who went beyond term (294 days or longer), and 100 women who went spontaneously into labor at term. Cervical fluid samples, collected well before the initiation of labor, were assessed for nitric oxide metabolites using an assay with a detection limit of 3.8 μmol/L. RESULTS: Women going beyond term had detectable levels of nitric oxide metabolites in their cervical fluid (60%) less often (P = .001) than women delivering at term (87%). The nitric oxide metabolite concentration in cervical fluid in women going beyond term (median 23.5 μmol/L; 95% confidence interval less than 3.8, 31.8) was 4.5 times lower (P < .001) than that in women delivering at term (median 106.0 μmol/L; 95% confidence interval 81.8, 135.0). Such a difference (14.0 versus 106.0 μmol/L) also existed when only the 66 women going into spontaneous postterm labor were included in the comparison. Both nulliparous (median less than 3.8 μmol/L) and parous (median 31.3 μmol/L) women going beyond term had lower (P < .01) cervical fluid nitric oxide metabolite levels than nulliparous and parous women delivering at term (medians 76.1 and 101.3 μmol/L, respectively). In the postterm group, women with cervical fluid nitric oxide metabolite concentrations at or below the median failed more often (P < .001) to progress in labor and had longer (P = .02) duration of labor than those with cervical fluid nitric oxide metabolite concentrations above the median. CONCLUSION: Reduced cervical nitric oxide release may contribute to prolonged pregnancy. LEVEL OF EVIDENCE: II-2

Serum cholesterol efflux potential in postmenopausal women treated with isolated isoflavones.

Objective:Based on the low cardiovascular risk in Asian populations, phytoestrogens are believed to provide vascular benefits. To elucidate the mechanisms behind the possible cardiovascular effects of phytoestrogens, we evaluated reverse cholesterol transport by assessing the capacity of serum to promote cholesterol efflux in postmenopausal women treated with isolated isoflavones. Design:Thirty postmenopausal women were treated in a randomized, placebo-controlled, crossover trial with isoflavones or placebo for 3 months interrupted by a 2-month washout period. Serum samples were collected before and after each treatment period, and the cholesterol efflux potential was investigated by using 3H-cholesterol--labeled Fu5AH cells in culture. Results:Serum promoted 20.2% ± 3.0% and 19.9% ± 3.4% (mean ± SD) cholesterol efflux after isoflavonoid treatment and after placebo treatment, respectively. Thus, the isoflavone treatment did not affect serum cholesterol efflux. We also studied separately women who produced high concentrations of the isoflavone metabolite equol into serum because some studies suggest that equol could exert favorable vascular effects. However, there was no difference in serum cholesterol efflux capacity between the equol producers (n = 15) and non-equol producers (n = 15). Conclusions:In conclusion, isoflavone treatment did not affect serum cholesterol efflux potential in postmenopausal women. Based on our findings, isolated isoflavones do not provide vascular benefits by improving cholesterol efflux.

Association between high risk papillomavirus DNA and nitric oxide release in the human uterine cervix

OBJECTIVE Local cervical factors may determine the outcome of human papillomavirus (HPV) infection. Nitric oxide (NO) may be one such factor, since it is produced by uterine cervical cells and it takes part in both immunological and carcinogenic reactions. We studied the association between the presence of cervical high risk (hr) HPV DNA and NO in the cervical canal in women. METHODS High risk HPV DNA status was assessed from 328 women by using a specific DNA test and the release of cervical NO was assessed as nitrate/nitrite in cervical fluid. Cervical NO was then compared between women showing different status of hr HPV DNA and different cytological and histological findings. RESULTS High risk HPV DNA was present in 175/328 (53%) women. The cervical NO release in women with hr HPV DNA was 90% higher compared to hr HPV DNA negative women (p<0.001) (median 45.2 micromol/L; 95% CI 35.2-53.1 vs. 23.8 micromol/L; 95% CI 21.0-26.1). This elevation was not affected by parity, use of oral contraception, intrauterine devices, or signs of bacterial vaginosis or candida infection. Cytologically healthy epithelium and epithelium with mild cytological or histological changes showed elevated NO release if hr HPV DNA was present. CONCLUSIONS The presence of hr HPV DNA is associated with an increased release of NO in the human uterine cervix. The clinical significance of this phenomenon remains open.

Nitric oxide in the human uterine cervix: Endogenous ripening factor

The human uterine cervix can produce nitric oxide (NO), a free radical with an ultra‐short half‐life. The release of NO changes during pregnancy and is increased in early nonviable pregnancies compared to normal uncomplicated pregnancies. This review concentrates on the role of NO release in cervical ripening in pregnant women. Also some suggestions on future aspects are discussed.

Risk factors and outcomes in “well-selected” vaginal breech deliveries: a retrospective observational study

Abstract Objective: To assess risk factors for adverse perinatal and neonatal outcomes in “well-selected” singleton vaginal breech deliveries at term. Methods: During the time span from January 2008 up to April 2015 a total of 786 singleton term breech deliveries with a planned vaginal delivery were identified in a retrospective observational study at Helsinki University Central Hospital, Finland. The study’s end point was a composite of adverse perinatal and neonatal outcomes. Infants with an adverse outcome were compared to all spontaneous singleton vaginal breech deliveries with normal perinatal and neonatal outcomes. A multivariate logistic regression model was used to analyze associations between adverse neonatal outcomes and several variables. The secondary outcome was the severe morbidity rate according to the criteria of the term breech trial. Results: An adverse neonatal outcome was recorded for 38 (4.8%) infants. According to the study the second delivery stage lasting <40 min [adjusted odds ratio (aOR): 0.34, 95% confidence interval (95% CI): 0.15–0.79] was associated with lower odds and had a protective effect against adverse outcomes. Epidural anesthesia (aOR: 2.88, 95% CI: 1.08–7.70) was associated with higher adverse outcomes. The incidence rate of severe morbidity was 1.3% (10/787). Conclusion: Adverse neonatal outcomes in well-selected breech deliveries are associated with a prolonged second delivery stage lasting >40 min and with epidural anesthesia.

Breech presentation at term and associated obstetric risks factors-a nationwide population based cohort study

PurposeThe aim of this study was to estimate whether breech presentation at term was associated with known individual obstetric risk factors for adverse fetal outcome.MethodsThis was a retrospective, nationwide Finnish population-based cohort study. Obstetric risks in all breech and vertex singleton deliveries at term were compared between the years 2005 and 2014. A multivariable logistic regression model was used to determine significant risk factors.ResultsThe breech presentation rate at term for singleton pregnancies was 2.4%. The stillbirth rate in term breech presentation was significantly higher compared to cephalic presentation (0.2 vs 0.1%). The odds ratios (95% CIs) for fetal growth restriction, oligohydramnios, gestational diabetes, a history of cesarean section and congenital fetal abnormalities were 1.19 CI (1.07–1.32), 1.42 CI (1.27–1.57), 1.06 CI (1.00–1.13), 2.13 (1.98–2.29) and 2.01 CI (1.92–2.11).ConclusionsThe study showed that breech presentation at term on its own was significantly associated with antenatal stillbirth and a number of individual obstetric risk factors for adverse perinatal outcomes. The risk factors included oligohydramnios, fetal growth restriction, gestational diabetes, history of caesarean section and congenital anomalies.

Neurodevelopmental outcome at the age of 4 years according to the planned mode of delivery in term breech presentation: a nationwide, population-based record linkage study

Abstract Purpose: To evaluate whether a trial of planned vaginal breech labor affects neurologic development in children. Methods: This is a nationwide, Finnish, population-based record linkage study. An odds ratio with 95% confidence intervals was used to estimate the relative risk that a child delivered by planned vaginal breech labor would be diagnosed with adverse neurodevelopmental outcome (cerebral palsy, epilepsy, intellectual disability, sensor neural developmental outcome, hyperactivity, speech and language problems) at the age of 4 years. The reference group were children born by planned cesarean section. Results: During a study period of 7 years, 8374 infants were delivered in breech position. Among them, 3907 (46.7%) had an attempted labor and 4467 (53.3%) infants were delivered by planned cesarean section. There were no differences in the neurodevelopmental outcome. In the planned vaginal labor group, 133 (3.4%) children had an abnormal neurodevelopmental outcome at the age of 4 years compared to 142 (3.2%) in the planned cesarean section group. Conclusion: The absolute risk of abnormal neurological outcome in breech deliveries at term was low, regardless of planned mode of birth. Planned vaginal breech labor did not increase the risk for abnormal neurological outcome compared to planned cesarean section.

High-risk human papillomavirus-induced expression of endothelial and inducible nitric oxide synthase in human uterine cervix

Introduction. Levels of nitric oxide metabolites are elevated in the cervical fluid of women with high-risk human papillomavirus (hrHPV). To elucidate the origin of this elevation we studied the cervical expression and localization of endothelial and inducible nitric oxide synthases (eNOS, iNOS) in women. Material and methods. Expression of eNOS and iNOS was studied by Western blotting in the uterine cervixes of 86 women with (n = 41) and without (n = 45) hrHPV infection. The localization of eNOS and iNOS in cervical cells was studied by immunohistochemistry in 32 randomly selected women. Results. Expression of eNOS and iNOS (in mean [95% CI] density units relative to actin) was higher in women with hrHPV versus those without (eNOS: 33.8 [22.5–45.1] versus 20.2 [6.1–34.3], P = 0.007; iNOS: 12.0 [7.1–16.9]) versus 5.6 [2.0–9.2], P = 0.003). Smoking reduced 64% eNOS (P = 0.001) and 68% iNOS (P = 0.008) in women with hrHPV. Endothelial NOS was localized in the vascular endothelium, while iNOS was present in basal squamous epithelial cells. Low-grade histological lesions were accompanied by elevated expression of both eNOS and iNOS. Conclusions. High-risk HPV-associated elevation in cervical fluid nitric oxide metabolites results from both eNOS and iNOS stimulation. However, smoking seems to suppress this stimulation in hrHPV-infected women.

Cervical nitric oxide release in Chlamydia trachomatis and high-risk human papillomavirus infection

Objective. To compare cervical fluid nitric oxide release in women with and without Chlamydia trachomatis and high‐risk human papillomavirus infection (hrHPV). Design. An open clinical study. Setting. University Hospital of Helsinki. Population. Thirty‐nine women with (n=21) and without C. trachomatis (n=18). Methods. Chlamydia trachomatis and/or hrHPV were studied by using specific RNA‐ and DNA‐based tests. Levels of cervical fluid nitric oxide metabolite (NOx) were assessed by the Griess reaction. Main Outcome Measures. The difference in cervical fluid NOx between women with and without C. trachomatis and hrHPV. Results. Fourteen (67%) C. trachomatis‐infected women and three (17%) noninfected women had concomitant hrHPV. The level of cervical fluid NOx in women with C. trachomatis (median 37.5μmol/l, 95% confidence interval 26.1–50.9) was higher (p=0.02) than that in C. trachomatis‐noninfected women (median 19.7μmol/L, 95% confidence interval 5.6–30.0). The presence of hrHPV did not associate with any difference in NOx levels between C. trachomatis‐infected or ‐noninfected women. Conclusions. Chlamydia trachomatis was associated with increased release of nitric oxide metabolites in the uterine cervix. This stimulus was stronger than that of hrHPV, because no additional rise in NOx was seen in women with concomitant C. trachomatis and hrHPV infection.

Abnormal cervical cytology is associated with increased nitric oxide release in the uterine cervix

Objective. The human uterine cervix is capable of producing nitric oxide (NO). We studied the impact of cytological changes on the release of cervical NO. Design. Population‐based case–control study. Setting. City of Helsinki, Finland. Population. Cervical cytology tests and cervical fluid samples were collected in 297 women. Methods. Cervical cytology tests, classified according to Bethesda criteria, were specifically analyzed for changes typically seen in human papillomavirus (HPV) infection, and the level of NO metabolites (NOx) in cervical fluid was assessed by Griess reaction. Main outcome measures. The difference in cervical fluid NOx between normal and abnormal cytology. Results. Cervical cytology was normal in 219 women and abnormal in 78 women. Among women with abnormal cytology there was both a higher detection rate (89% vs. 71%) and a higher concentration of NOx (median 22.5 μmol/l, 95% CI 14.6–31.9 vs. 11.0 μmol/l, 95% CI 8.0–16.7) compared to women with normal cytology. Age, parity, use of oral contraceptives, phase of the menstrual cycle, or history of miscarriage or termination of early pregnancy were not linked to an increased cervical NOx level. Conclusions. Cervical cell changes (suggestive of HPV infection) are accompanied by an increased release of NO in the human cervix. The significance of this finding remains uncertain, but in theory, increased release of NO could modify the outcome of cervical infection.