Cervical pessary versus vaginal progesterone in women with a singleton pregnancy, a short cervix, and no history of spontaneous preterm birth at less than 34 weeks' gestation: open label, multicentre, randomised, controlled trial.

OBJECTIVE: To compare the effectiveness of cervical pessary and vaginal progesterone in the prevention of adverse perinatal outcomes and preterm birth in pregnant women of singletons with no prior spontaneous preterm birth at less than 34 weeks' gestation and who have a short cervix of 35 mm or less. DESIGN: Open label, multicentre, randomised, controlled trial. SETTING: 20 hospitals and five obstetric ultrasound practices in the Netherlands. PARTICIPANTS: Women with a healthy singleton pregnancy and an asymptomatic short cervix of 35 mm or less between 18 and 22 weeks' gestation were eligible. Exclusion criteria were prior spontaneous preterm birth at less than 34 weeks, a cerclage in situ, maternal age of younger than 18 years, major congenital abnormalities, prior participation in this trial, vaginal blood loss, contractions, cervical length of less than 2 mm or cervical dilatation of 3 cm or more. Sample size was set at 628 participants. INTERVENTIONS: 1:1 randomisation to an Arabin cervical pessary or vaginal progesterone 200 mg daily up to 36 weeks' of gestation or earlier in case of ruptured membranes, signs of infection, or preterm labour besides routine obstetric care. MAIN OUTCOME MEASURES: Primary outcome was a composite adverse perinatal outcome. Secondary outcomes were rates of (spontaneous) preterm birth at less than 28, 32, 34, and 37 weeks. A predefined subgroup analysis was planned for cervical length of 25 mm or less. RESULTS: From 1 July 2014 to 31 March 2022, 635 participants were randomly assigned to pessary (n=315) or to progesterone (n=320). 612 were included in the intention to treat analysis. The composite adverse perinatal outcome occurred in 19 (6%) of 303 participants with a pessary versus 17 (6%) of 309 in the progesterone group (crude relative risk 1.1 (95% confidence interval (CI) 0.60 to 2.2)). The rates of spontaneous preterm birth were not significantly different between groups. In the subgroup of cervical length of 25 mm or less, spontaneous preterm birth at less than 28 weeks occurred more often after pessary than after progesterone (10/62 (16%) v 3/69 (4%), relative risk 3.7 (95% CI 1.1 to 12.9)) and adverse perinatal outcomes seemed more frequent in the pessary group (15/62 (24%) v 8/69 (12%), relative risk 2.1 (0.95 to 4.6)). CONCLUSIONS: In women with a singleton pregnancy with no prior spontaneous preterm birth at less than 34 weeks' gestation and with a midtrimester short cervix of 35 mm or less, pessary is not better than vaginal progesterone. In the subgroup of a cervical length of 25 mm or less, a pessary seemed less effective in preventing adverse outcomes. Overall, for women with single baby pregnancies, a short cervix, and no prior spontaneous preterm birth less than 34 weeks' gestation, superiority of a cervical pessary compared with vaginal progesterone to prevent preterm birth and consecutive adverse outcomes could not be proven. TRIAL REGISTRATION: International Clinical Trial Registry Platform (ICTRP, EUCTR2013-002884-24-NL).

Pessary or Progesterone to Prevent Preterm delivery in women with short cervical length: the Quadruple P randomised controlled trial.

BACKGROUND: Preterm birth is in quantity and in severity the most important topic in obstetric care in the developed world. Progestogens and cervical pessaries have been studied as potential preventive treatments with conflicting results. So far, no study has compared both treatments. METHODS/DESIGN: The Quadruple P study aims to compare the efficacy of vaginal progesterone and cervical pessary in the prevention of adverse perinatal outcome associated with preterm birth in asymptomatic women with a short cervix, in singleton and multiple pregnancies separately. It is a nationwide open-label multicentre randomized clinical trial (RCT) with a superiority design and will be accompanied by an economic analysis. Pregnant women undergoing the routine anomaly scan will be offered cervical length measurement between 18 and 22 weeks in a singleton and at 16-22 weeks in a multiple pregnancy. Women with a short cervix, defined as less than, or equal to 35 mm in a singleton and less than 38 mm in a multiple pregnancy, will be invited to participate in the study. Eligible women will be randomly allocated to receive either progesterone or a cervical pessary. Following randomization, the silicone cervical pessary will be placed during vaginal examination or 200 mg progesterone capsules will be daily self-administered vaginally. Both interventions will be continued until 36 weeks gestation or until delivery, whichever comes first. Primary outcome will be composite adverse perinatal outcome of perinatal mortality and perinatal morbidity including bronchopulmonary dysplasia, intraventricular haemorrhage grade III and IV, periventricular leukomalacia higher than grade I, necrotizing enterocolitis higher than stage I, Retinopathy of prematurity (ROP) or culture proven sepsis. These outcomes will be measured up until 10 weeks after the expected due date. Secondary outcomes will be, among others, time to delivery, preterm birth rate before 28, 32, 34 and 37 weeks, admission to neonatal intensive care unit, maternal morbidity, maternal admission days for threatened preterm labour and costs. DISCUSSION: This trial will provide evidence on whether vaginal progesterone or a cervical pessary is more effective in decreasing adverse perinatal outcome in both singletons and multiples. TRIAL REGISTRATION: Trial registration number: NTR 4414 . Date of registration January 29th 2014.

Atosiban versus fenoterol as a uterine relaxant for external cephalic version: randomised controlled trial.

OBJECTIVE:  To compare the effectiveness of the oxytocin receptor antagonist atosiban with the beta mimetic fenoterol as uterine relaxants in women undergoing external cephalic version (ECV) for breech presentation. DESIGN:  Multicentre, open label, randomised controlled trial. SETTING:  Eight hospitals in the Netherlands, August 2009 to May 2014. PARTICIPANTS:  830 women with a singleton fetus in breech presentation and a gestational age of more than 34 weeks were randomly allocated in a 1:1 ratio to either 6.75 mg atosiban (n=416) or 40 µg fenoterol (n=414) intravenously for uterine relaxation before ECV. MAIN OUTCOME MEASURES:  The primary outcome measures were a fetus in cephalic position 30 minutes after the procedure and cephalic presentation at delivery. Secondary outcome measures were mode of delivery, incidence of fetal and maternal complications, and drug related adverse events. All analyses were done on an intention-to-treat basis. RESULTS:  Cephalic position 30 minutes after ECV occurred significantly less in the atosiban group than in the fenoterol group (34% v 40%, relative risk 0.73, 95% confidence interval 0.55 to 0.93). Presentation at birth was cephalic in 35% (n=139) of the atosiban group and 40% (n=166) of the fenoterol group (0.86, 0.72 to 1.03), and caesarean delivery was performed in 60% (n=240) of women in the atosiban group and 55% (n=218) in the fenoterol group (1.09, 0.96 to 1.20). No significant differences were found in neonatal outcomes or drug related adverse events. CONCLUSIONS:  In women undergoing ECV for breech presentation, uterine relaxation with fenoterol increases the rate of cephalic presentation 30 minutes after the procedure. No statistically significant difference was found for cephalic presentation at delivery. TRIAL REGISTRATION:  Dutch Trial Register, NTR 1877.

Maternal lipid profile during early pregnancy and pregnancy complications and outcomes: the ABCD study.

CONTEXT: Elevated lipid levels during late pregnancy are associated with complications and adverse outcome for both mother and newborn. However, it is inconclusive whether a disturbed lipid profile during early pregnancy has similar negative associations. OBJECTIVE: Our objective was to investigate whether nonfasting maternal total cholesterol and triglyceride levels during early pregnancy are associated with six major adverse pregnancy outcomes. METHODS: Data were derived from the Amsterdam Born Children and Their Development (ABCD) cohort study. Random blood samples of nonfasting total cholesterol and triglyceride levels were determined during early gestation (median = 13, interquartile range = 12-14 wk). Outcome measures were pregnancy-induced hypertension (PIH), preeclampsia, preterm birth, small/large for gestational age (SGA/LGA), and child loss. Only nondiabetic women with singleton deliveries were included; the baseline sample consisted of 4008 women. Analysis for PIH and preeclampsia were performed in nulliparous women only (n = 2037). RESULTS: Mean (sd) triglyceride and total cholesterol levels were 1.33 (0.55) and 4.98 (0.87) mmol/liter, respectively. The incidence of pregnancy complications and perinatal outcomes were as follows: PIH, 4.9%; preeclampsia, 3.7%; preterm birth, 5.3%; SGA, 9.3%; LGA, 9.3%; and child loss, 1.4%. After adjustments, every unit increase in triglycerides was linearly associated with an increased risk of PIH [odds ratio (OR) = 1.60, P = 0.021], preeclampsia (OR = 1.69, P = 0.018), LGA (OR = 1.48, P < 0.001), and induced preterm delivery (OR = 1.69, P = 0.006). No associations were found for SGA or child loss. Total cholesterol was not associated with any of the outcome measures. CONCLUSIONS: Elevated maternal triglyceride levels measured during early pregnancy are associated with pregnancy complications and adverse pregnancy outcomes. These results suggest that future lifestyle programs in women of reproductive age with a focus on lowering triglyceride levels (i.e. diet, weight reduction, and physical activity) may help to prevent hypertensive complications during pregnancy and adverse birth outcomes.

Does physical activity in leisure time early in pregnancy reduce the incidence of preeclampsia or gestational hypertension?

OBJECTIVE: Assessment of the association of physical activity in leisure time with preeclampsia and gestational hypertension in nulliparous women. DESIGN: Population based prospective cohort study. SETTING: Amsterdam, The Netherlands. POPULATION: All pregnant women in Amsterdam between January 2003 and March 2004 who were nulliparous with a singleton pregnancy and who delivered after 24 weeks. DESIGN: At their first prenatal care visit, women were invited to fill out a questionnaire with sociodemographic and psychosocial variables. Physical activity in leisure time in the past week was measured using questions about walking, cycling, playing sports and other activities in leisure time. The amount of minutes and intensity of each activity was studied using four categories: no, low, moderate or high activity. By using multivariate logistic regression, we adjusted for sociodemographic and medical confounders. MAIN OUTCOME MEASURES: Incidence of preeclampsia and gestational hypertension. Results. A total of 12,377 women were invited with a response rate of 67%; 3,679 nulliparous women were included. The incidence of preeclampsia and gestational hypertension was 3.5% and 4.4%, respectively. The amount of time or intensity of physical activity in leisure time was not associated with a difference in risk of preeclampsia or gestational hypertension. CONCLUSION: Physical activity in leisure time early in pregnancy does not reduce the incidence of preeclampsia or gestational hypertension in an unselected population of nulliparous women.

Accuracy of mean arterial pressure and blood pressure measurements in predicting pre-eclampsia: systematic review and meta-analysis.

OBJECTIVE: To determine the accuracy of using systolic and diastolic blood pressure, mean arterial pressure, and increase of blood pressure to predict pre-eclampsia. DESIGN: Systematic review with meta-analysis of data on test accuracy. DATA SOURCES: Medline, Embase, Cochrane Library, Medion, checking reference lists of included articles and reviews, contact with authors. Review methods Without language restrictions, two reviewers independently selected the articles in which the accuracy of blood pressure measurement during pregnancy was evaluated to predict pre-eclampsia. Data were extracted on study characteristics, quality, and results to construct 2x2 tables. Summary receiver operating characteristic curves and likelihood ratios were generated for the various levels and their thresholds. RESULTS: 34 studies, testing 60 599 women (3341 cases of pre-eclampsia), were included. In women at low risk for pre-eclampsia, the areas under the summary receiver operating characteristic curves for blood pressure measurement in the second trimester were 0.68 (95% confidence interval 0.64 to 0.72) for systolic blood pressure, 0.66 (0.59 to 0.72) for diastolic blood pressure, and 0.76 (0.70 to 0.82) for mean arterial pressure. Findings for the first trimester showed a similar pattern. Second trimester mean arterial pressure of 90 mm Hg or more showed a positive likelihood ratio of 3.5 (95% confidence interval 2.0 to 5.0) and a negative likelihood ratio of 0.46 (0.16 to 0.75). In women deemed to be at high risk, a diastolic blood pressure of 75 mm Hg or more at 13 to 20 weeks' gestation best predicted pre-eclampsia: positive likelihood ratio 2.8 (1.8 to 3.6), negative likelihood ratio 0.39 (0.18 to 0.71). Additional subgroup analyses did not show improved predictive accuracy. CONCLUSION: When blood pressure is measured in the first or second trimester of pregnancy, the mean arterial pressure is a better predictor for pre-eclampsia than systolic blood pressure, diastolic blood pressure, or an increase of blood pressure.

Sensitivity of spontaneous baroreflex control of the heart and hemodynamic parameters are not influenced by the menstrual cycle.

OBJECTIVE: The purpose of this study was to evaluate if hemodynamic parameters and sympathetic activity vary between the follicular and luteal phase of the menstrual cycle before using sympathetic activity in pre-pregnancy risk assessment for preeclampsia. METHODS: We studied 39 healthy women at days 5 to 10 and days 18 to 25 of the menstrual cycle. Blood pressure, heart rate, cardiac output, and total peripheral resistance were measured continuously using noninvasive finger arterial pressure waveform registration (Portapres Model 2, BMI, The Netherlands). Baroreflex sensitivity (BRS) and sympathetic activity by phase angle difference were studied using spectral analysis and xBRS. RESULTS: There were no differences in hemodynamic parameters, BRS, and phase angle difference. CONCLUSION: There is no difference in blood pressure, BRS, and sympathetic activity between the first and second half of the menstrual period. We recommend using the first half of the cycle to be certain that no pregnancy exists, as the influence of very early pregnancy is unknown.