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).

Accuracy of Pulse Oximetry Screening for Critical Congenital Heart Defects after Home Birth and Early Postnatal Discharge.

OBJECTIVE: To assess the accuracy of pulse oximetry screening for critical congenital heart defects (CCHDs) in a setting with home births and early discharge after hospital deliveries, by using an adapted protocol fitting the work patterns of community midwives. STUDY DESIGN: Pre- and postductal oxygen saturations (SpO2) were measured ≥1 hour after birth and on day 2 or 3. Screenings were positive if the SpO2 measurement was <90% or if 2 independent measures of pre- and postductal SpO2 were <95% and/or the pre-/postductal difference was >3%. Positive screenings were referred for pediatric assessment. Primary outcomes were sensitivity, specificity, and false-positive rate of pulse oximetry screening for CCHD. Secondary outcome was detection of noncardiac illnesses. RESULTS: The prenatal detection rate of CCHDs was 73%. After we excluded these cases and symptomatic CCHDs presenting immediately after birth, 23 959 newborns were screened. Pulse oximetry screening sensitivity in the remaining cohort was 50.0% (95% CI 23.7-76.3) and specificity was 99.1% (95% CI 99.0-99.2). Pulse oximetry screening was false positive for CCHDs in 221 infants, of whom 61% (134) had noncardiac illnesses, including infections (31) and respiratory pathology (88). Pulse oximetry screening did not detect left-heart obstructive CCHDs. Including cases with prenatally detected CCHDs increased the sensitivity to 70.2% (95% CI 56.0-81.4). CONCLUSION: Pulse oximetry screening adapted for perinatal care in home births and early postdelivery hospital discharge assisted the diagnosis of CCHDs before signs of cardiovascular collapse. High prenatal detection led to a moderate sensitivity of pulse oximetry screening. The screening also detected noncardiac illnesses in 0.6% of all infants, including infections and respiratory morbidity, which led to early recognition and referral for treatment.

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.

Macroscopic and microscopic morphology of first trimester miscarriage and subsequent pregnancy outcome - An exploratory study.

INTRODUCTION: Reduced chorionic villous vascularization is associated with first trimester miscarriage and second trimester fetal loss. Differences in villous vascularization have been observed in combination with complications in the third trimester of pregnancy. The aim of this study was to investigate whether abnormal morphology and reduced chorionic villous vascularization in first trimester miscarriages are associated with an increased risk on adverse outcome and/or pregnancy complications in subsequent pregnancy. Secondly, to assess the influence of these parameters on the length of the interpregnancy interval and infertility. METHODS: In a retrospective cohort study 134 consecutive women who underwent dilatation and curettage for a miscarriage were included. The degree of chorionic villous vascularization in miscarriage tissue was determined by a pathologist. Ultrasound details of these miscarriages and clinical data on the subsequent pregnancy of these women were obtained. RESULTS: Neither reduced vascularization nor early embryonic arrest in first trimester miscarriages are associated with an increased risk of a subsequent miscarriage or adverse obstetric and perinatal outcome of subsequent pregnancy. Abnormal morphology of the first trimester miscarriage did not influence the time to subsequent pregnancy. A shorter mean interpregnancy interval between miscarriages was observed after miscarriages with reduced chorionic villous vascularization (5.5 vs. 10.7 months; p = 0.051), showing a trend towards an association. DISCUSSION: Chorionic villous vascularization and morphology have no influence on subsequent pregnancy outcome. Therefore it remains unknown what aspects of miscarriage are causing the increased risk on subsequent miscarriage and complications in the third trimester of the subsequent pregnancy.

Women's Experiences with and Preference for Induction of Labor with Oral Misoprostol or Foley Catheter at Term.

Objective We assessed experience and preferences among term women undergoing induction of labor with oral misoprostol or Foley catheter. Study Design In 18 of the 29 participating hospitals in the PROBAAT-II trial, women were asked to complete a questionnaire within 24 hours after delivery. We adapted a validated questionnaire about expectancy and experience of labor and asked women whether they would prefer the same method again in a future pregnancy. Results The questionnaire was completed by 502 (72%) of 695 eligible women; 273 (54%) had been randomly allocated to oral misoprostol and 229 (46%) to Foley catheter. Experience of the duration of labor, pain during labor, general satisfaction with labor, and feelings of control and fear related to their expectation were comparable between both the groups. In the oral misoprostol group, 6% of the women would prefer the other method if induction is necessary in future pregnancy, versus 12% in the Foley catheter group (risk ratio: 0.70; 95% confidence interval: 0.55-0.90; p = 0.02). Conclusion Women's experiences of labor after induction with oral misoprostol or Foley catheter are comparable. However, women in the Foley catheter group prefer more often to choose a different method for future inductions.

Reference values for interleukin-6 and interleukin-8 in cord blood of healthy term neonates and their association with stress-related perinatal factors.

BACKGROUND: Automated interleukin assays are promising diagnostic aids for early-onset neonatal sepsis, however, reference values for healthy term neonates are incompletely known. The goal of this study is to determine reference values for interleukin-6 (IL-6) and interleukin-8 (IL-8) in cord blood of healthy term neonates. METHODS AND FINDINGS: Women were recruited from April 2012 to August 2012. IL-6 and IL-8 levels were measured using an automated immunometric assay (Immulite) in cord blood of 93 healthy term newborns, 60 of them were born via vaginal delivery and 33 by elective caesarean section (ECS). A mean value for IL-8 of 8.1 ± 3.0 pg/mL was found in cord blood of healthy term neonates, which apply to both vaginal delivery and ECS. Regarding IL-6, two values apply. For vaginal delivery, a median value of 3.3 pg/mL (range, <2 to 9.53 pg/mL) was found, while for ECS, a median value of <2 pg/mL (range, <2 to 48 pg/mL) applies. CONCLUSIONS: We propose a reference value of <14.1 pg/mL for IL-8 (mean + 2SD), applying to vaginally delivered and ECS-delivered healthy term newborns. From a clinical point of view, we also propose one reference value for IL-6 to be applied to vaginally delivered and ECS-delivered healthy term newborns, which is <10.2 pg/mL (97.5th percentile total group). These values have to be validated in larger cohorts of neonates, inclusive of those with and without early-onset neonatal sepsis.

Women's opinions on the offer and use of nuchal translucency screening for Down syndrome.

OBJECTIVE: To study the attitude of Dutch women to the offer and subsequent (non)use of nuchal translucency (NT) screening for Down syndrome in the first trimester of pregnancy, in a country where screening is not routinely offered under 36 years of age. METHODS: An experimental NT screening programme offered to pregnant women, together with a series of questionnaires to be completed before and after the offer and (non)use of screening, in 12 midwife practices in three different health districts. PARTICIPANTS: Cohort of pregnant women who had their first prenatal care visit in the participating midwife practices between 1 June 1999 and 1 January 2001. MAIN OUTCOME MEASURES: Women's knowledge and understanding of prenatal screening tests; attitude towards screening offer; perceived freedom of choice; satisfaction with information given; change in attitude over time. RESULTS: Eighty-six percent of women accepted the offer of NT screening. Seventy percent had previous knowledge of NT screening and 92% considered the information given before screening clear and sufficient. Thirty-nine percent of women felt worried to some extent after being given the information, but only 3% would have preferred not to have been informed at all. Ninety percent of women (including 68% of decliners) agree that information on Down syndrome screening should be extended to all pregnant women and feel competent in deciding on screening participation. CONCLUSION: When NT screening is offered as a new screening strategy its concept is understood and well accepted. The large majority of women, including the decliners, are in favour of its standard offer.

A comparison of the impact of screen-positive results obtained from ultrasound and biochemical screening for Down syndrome in the first trimester: a pilot study.

OBJECTIVE: To compare the experiences of women who received a screen-positive test result for Down syndrome after nuchal translucency screening or after biochemical screening in the first trimester of pregnancy in the Netherlands. METHOD: Semi-quantitative questionnaires were sent to 40 women with a screen-positive test result for Down syndrome in the first trimester of pregnancy: 20 had undergone nuchal translucency screening (NT group) and 20 had undergone serum screening (PAPP-A and free beta-hCG) (SS group). In all the cases, chorionic villus sampling (CVS) had not revealed any chromosomal abnormalities. RESULTS: The major reason for undergoing the screening test in both groups of women was to be more reassured about the health of the baby. In the NT group, 5 out of the 20 women stated that they had suddenly been confronted with the NT measurement during the ultrasound examination without even being asked, or had been caught by surprise about the possibility. Together with two other women, they felt that at that stage they had been insufficiently informed about what the test meant. In the SS group, two women also held this opinion. In 10 out of the 20 women in the SS group, the positive-screening result had caused (a great deal of) anxiety. In the NT group, this proportion was as high as 18 out of the 20. Six of the women in the NT group mentioned that 'seeing the baby' had been an important factor in their decision to undergo CVS. Even after a favourable result of CVS, a proportion of the pregnant women were still feeling anxious about the health of their baby (5 women in the SS group and 12 in the NT group). Nevertheless, a large proportion of the women in both groups was pleased that they had undergone the screening test. Only a few of them stated that they would not choose the same screening test again in a future pregnancy. CONCLUSIONS: An unfavourable screening result after NT screening appeared to have a greater impact than an unfavourable result after serum screening. This might partly be explained by the ultrasound examination visualising the increased risk during NT screening. An additional important role may have been played by the fact that an abnormal NT screening result implies an increased risk of other disorders besides Down syndrome, which the women should be informed about beforehand. Several factors place special demands on the counselling prior to NT screening.