Stress-reducing interventions in pregnancy for the prevention of preterm birth: a systematic review and meta-analysis.

Preterm birth (PTB) is the leading cause of neonatal morbidity and mortality. Maternal stress during pregnancy is an established risk factor for PTB. We aimed to review the effects of stress-reducing interventions during pregnancy on PTB. Studies reporting on stress-reducing interventions during pregnancy and PTB rates in general low-risk obstetric populations were included. PTB rates, low birth weight (LBW) rates, mean gestational age and birth weight, maternal anxiety and stress, and adverse perinatal outcomes were investigated. Data were extracted using a standardized extraction form, pooled effect sizes were calculated with the random effects model. Ten studies with a total of 4.816 women were included. The interventions included Pilates, yoga, a multidisciplinary stress reduction program, combination therapy (combining mindfulness, yoga, music, baby bonding, and education), and hypnosis. The incidence of PTB was significantly lower in the intervention group (RR 0.50, 95% CI 0.35 - 0.71). The overall quality of the included studies was low, and the risk of bias was high. In conclusion, this study provides evidence supporting the potential efficacy of stress-reducing interventions in reducing the incidence of PTB in low-risk women. We propose a RCT of high quality to determine the effectiveness of stress-reducing interventions in reducing PTB risk.

Working conditions in women with multiple pregnancy-the impact on preterm birth and adherence to guidelines: a prospective cohort study.

BACKGROUND: Women with multiple pregnancies are at risk for maternal complications such as preterm birth. Hazardous working conditions, such as physically demanding work and long and irregular working hours, might increase the risk of preterm birth. OBJECTIVE: This study primarily aimed to determine whether certain working conditions up to 20 weeks of pregnancy increase the risk of preterm birth in multiple pregnancies. The secondary objective was to evaluate whether the working conditions of Dutch women with multiple pregnancy have been adjusted to the guidelines of the Netherlands Society of Occupational Medicine. STUDY DESIGN: We performed a prospective cohort study alongside the ProTWIN trial, a multicenter randomized controlled trial that assessed whether cervical pessaries could effectively prevent preterm birth. Women with paid work of >8 hours per week completed questionnaires concerning general health and working conditions between 16 and 20 weeks of pregnancy. Univariable and multivariable logistic regression analyses were performed to identify work-related factors associated with preterm birth (32-36 weeks' gestation) and very preterm birth (<32 weeks' gestation). We analyzed a subgroup of participants who worked for more than half of the week (>28 hours). We calculated the proportion of women who reported work-related factors not in accordance with guidelines. RESULTS: We studied 383 women, of whom 168 (44%) had been randomized to pessary, 142 (37%) to care as usual, and 73 (19%) did not participate in the randomized part of the study. After adjusting for confounding variables, working >28 hours was associated with very preterm birth (n=33; 78%) (adjusted odds ratio, 3.0; 95% confidence interval, 1.1-8.1), and irregular working times were associated with preterm birth (n=26, 17%) (adjusted odds ratio, 2.0; 95% confidence interval, 1.0-4.1) and very preterm birth (n=10; 24%) (adjusted odds ratio, 2.7; 95% confidence interval, 1.0-7.3). Within a subgroup of 213 participants working >28 hours per week, multivariable analysis showed that irregular working times (n=16; 20%) (adjusted odds ratio, 3.5; 95% confidence interval, 1.2-10.1) and no/little freedom in performance of tasks (n=23; 28%) (adjusted odds ratio, 3.0; 95% confidence interval, 1.3-7.3) were associated with preterm birth. Irregular working times (n=9; 27%) (adjusted odds ratio, 3.4; 95% confidence interval, 1.0-11.1), requiring physical strength (n=9; 27%) (adjusted odds ratio, 5.3; 95% confidence interval, 1.6-17.8), high physical workload (n=7; 21%) (adjusted odds ratio, 3.9; 95% confidence interval, 1.1-13.9), and no/little freedom in performing tasks (n=10; 30%) (adjusted odds ratio, 3.2; 95% confidence interval, 1.1-9.6) were associated with very preterm birth. Before 20 weeks of pregnancy, 224 (58.5%) women with multiple pregnancy continued to work under circumstances that were not in accordance with the guidelines. CONCLUSION: In our cohort study, nearly 60% of women with multiple pregnancy continued to work under circumstances not in accordance with the guidelines to avoid physical and job strain and long and irregular working hours. Irregular hours were associated with preterm and very preterm birth, and long hours were associated with preterm birth.

Working conditions in low risk nulliparous women in The Netherlands: are legislation and guidelines a guarantee for a healthy working environment? A cohort study.

OBJECTIVE: Hazardous working conditions increase the risk of adverse pregnancy outcomes. In this study, we examine adherence to legislation and guidelines aimed at improving working conditions in pregnancy. METHODS: Between 2014 and 2016, we recruited a prospective cohort of low-risk nulliparous pregnant women in paid employment or self-employed in 16 community midwifery practices in The Netherlands. Participants completed two questionnaires concerning demographics, education, general health and working conditions between 10-16 and 20-24 weeks of pregnancy. We calculated the proportion of participants with work-related risk factors not in accordance with legislation and/or guidelines. RESULTS: Of 269 participants included, 214 (80%) completed both questionnaires. At 10-16 weeks 110 (41%) participants and at 20-24 weeks 129 (63%) participants continued to work under circumstances that did not meet recommendations. Employers provided mandated information on work adjustment to 37 (15%) participants and 96 (38%) participants received no information about the potential hazards while working with biological and chemical hazards. Participants with lower educational attainment (aOR 2.2 95%CI 1.3-3.9), or employment in healthcare (aOR 4.5, 95%CI 2.2-9.0), education/childcare and social service (aOR 2.6, 95%CI 1.1-6.0 2),, catering (aOR 3.6, 95%CI 1.1-12) and industry, construction and cleaning (aOR 3.3, 95%CI 1.1-10.3) more often continued work which did not meet recommendations. CONCLUSION: There is poor adherence to national legislation and guidelines for safe working in pregnancy in The Netherlands: 50% of the pregnant women worked under hazardous conditions. Given the impact on adverse pregnancy outcomes as well as on the public purse, action to improve compliance must be taken by all stakeholders.

More home births during the COVID-19 pandemic in the Netherlands.

BACKGROUND: The aim of this observational study was to examine whether the course of pregnancy and birth and accompanying outcomes among low-risk pregnant women changed in the COVID-19 pandemic compared to the prepandemic period. METHODS: We analyzed data from the Dutch Midwifery Case Registration System (VeCaS). Differences in the course of pregnancy and birth, and accompanying maternal and neonatal outcomes, were calculated between women pregnant during the initial months of the COVID-19 pandemic (March 1 to August 3, 2020) and the prepandemic period (March 1-August 3, 2019). We also conducted a stratified analysis by parity. RESULTS: We included 5913 low-risk pregnant women of whom 2963 (50.1%) were pregnant during the first surge of the COVID-19 pandemic, and 2950 (49.9%) in the prepandemic period. During the COVID-19 pandemic, more women desired and had a home birth. More women used pain medication and fewer had an episiotomy in the COVID-19 period than prior. Multiparous women had a higher suspected rate of fetal growth restriction during COVID; however, the actual rate of small for gestational age infants was not significantly increased. We observed no differences for onset and augmentation of labor or for mode of birth, though the rate of vaginal births increased. CONCLUSIONS: During the COVID-19 pandemic, there was a higher rate of planned and actual home birth, and suspected growth restriction and a lower rate of episiotomy among low-risk pregnant women in the Netherlands.

Risk factors for spontaneous preterm birth among healthy nulliparous pregnant women in the Netherlands, a prospective cohort study.

Introduction: Spontaneous preterm birth (sPTB) is a major contributor to neonatal morbidity and mortality worldwide. The pathophysiology of sPTB is poorly understood, in particular among nulliparous women without apparent medical or obstetric risk factors. Therefore, we aimed to identify risk factors for sPTB in healthy nulliparous women. Material and Methods: We performed a prospective cohort study. Recruitment took place from February 2014 to December 2016 in 16 community midwifery centers in the Netherlands. Eligibility criteria were: ≥18 years, no previous pregnancy >16 weeks of gestation, healthy singleton pregnancy, and antenatal booking <24 weeks of gestation. At study inclusion, participants completed a questionnaire, including details on lifestyle, work, and medical history. Cervical length was measured by vaginal ultrasound at the second-trimester anomaly scan. Detailed information concerning pregnancy and birth was collected via antenatal charts. We calculated the adjusted odds ratio (aOR) and 95% confidence intervals (CI) for various risk factors with correction for socioeconomic status (SES) using logistic regression and Firth's correction. Results: We included 363 women of whom pregnancy outcomes were available in 349 (96.1%) participants. The cervical length measurement was available for 225 (62.0%) participants. sPTB occurred in 26 women (7.5%). SES was associated with sPTB (OR: 3.7, 95%  CI: 1.6-8.5) in univariate analysis. First or second trimester vaginal bleeding (aOR: 3.6, 95% CI: 1.4-9.0) and urinary tract infection during pregnancy (aOR: 4.9, 95% CI: 1.7-13.9) were associated with sPTB in multivariate analysis. Conclusions: This prospective cohort confirms established risk factors for sPTB in nulliparous women deemed at low risk of sPTB.

Evaluation of a blended care programme for caregivers and working pregnant women to prevent adverse pregnancy outcomes: an intervention study.

OBJECTIVE: Work-related activities can be a risk factor for pregnancy complications such as preterm birth. This study evaluates the effectiveness of a blended care programme, Pregnancy and Work, that provides pregnant workers and their obstetrical caregivers with advice on work adjustment. METHODS: Women less than 20 weeks of gestation, in paid employment or self-employed, in the care of four participating hospitals and their referring midwifery practices in the Netherlands received either the blended care programme (n=119), consisting of a training for professionals and a mobile health application, or care as usual (n=122) in a controlled intervention study with a follow-up in intervention and control populations. All participants completed three questionnaires concerning health and working conditions at 16, 24 and 32 weeks of pregnancy. Primary outcome was the percentage of women who received advice from their obstetrical caregiver about work adjustment. Secondary outcomes were work status, realised work adjustment and working conditions. Groups were compared using univariate and multivariate regression analyses. RESULTS: A total of 188 (78%) completed all three questionnaires. In the blended care group, women received more advice from obstetrical caregivers to adjust their work than in the control group, 41 (39%) vs 21 (18%) (adjusted relative risk (aRR) 2.2, 95% CI 1.4 to 3.4), but less from their employer 8 (8%) vs 31 (28%) (aRR 0.29, 95% CI 0.14 to 0.61). There were no significant differences in realised work adjustments. At 24 weeks, 30% of the pregnant women in both groups continued to work in hazardous workplaces. CONCLUSION: Among working pregnant women, the blended care intervention increases advice on work adjustment given by midwives and obstetricians, but does not lead to more work adjustments.

Ethnic differences in the impact of male fetal gender on the risk of spontaneous preterm birth.

OBJECTIVE: To study the impact of fetal gender on the risk of spontaneous preterm birth in various ethnicities. STUDY DESIGN: National cohort study in which all singleton live births from 25+0 weeks onwards without congenital anomalies were included of African, Asian, and Mediterranean women (1999-2010). Our primary outcome measure was preterm birth before 37 weeks. Per ethnic group, male and female neonates were compared. RESULT: In each ethnic group, male fetuses were at increased risk of preterm birth (adjusted odds ratio (aOR) 1.63 for African, aOR 1.71 for Asian, and aOR 1.84 for Mediterranean males). The population-attributable risk of male gender on spontaneous preterm birth is lower in African women (3.9%) than in Asian (10.3%) and Mediterranean women (9.0%). CONCLUSION: Male fetal gender is associated with spontaneous preterm birth in African, Asian, and Mediterranean women, but the total impact of ethnicity on spontaneous preterm birth rate is different.

The impact of mode of delivery on the outcome in very preterm twins.

Objective: Studies on the optimal mode of delivery in women with a twin pregnancy <32 weeks are scarce. We studied the effects of the mode of delivery on perinatal and maternal outcomes in very preterm twin pregnancy.Study Design: Population-based cohort study including all women with twin pregnancy who delivered very preterm (26-32 weeks of gestation) in the Netherlands between January 2000 and December 2010. We compared perinatal mortality and neonatal and maternal morbidity according to the intended mode of delivery as well as to the actual mode of delivery. Perinatal outcomes were paired taking into account the dependency between the children of the same twin pregnancy and were also analysed for each child separately. We used logistic regression to correct for possible confounding factors.Results: We studied 1,655 women with a very preterm delivery of a twin pregnancy. A planned caesarean section (n = 212) was associated with a significantly higher perinatal mortality compared to a planned vaginal delivery (n = 1.443) (10% compared to 6.5%; adjusted odds ratio (OR) 2.5, 95% confidence interval (CI) 1.5-4.2). The same applied for perinatal morbidity (66% compared to 63%; adjusted OR 1.5, 95% CI 1.1-2.0), maternal morbidity (17% compared to 4.9%; adjusted OR 4.0, 95% CI 2.6-6.3) and for perinatal mortality for the second twin (7.1% compared to 3.5% adjusted OR 2.9, 95% CI 1.7-5.2).Conclusion: In very preterm delivery of twins a vaginal delivery is the preferred mode of delivery.

Study protocol for a randomised trial for atosiban versus placebo in threatened preterm birth: the APOSTEL 8 study.

INTRODUCTION: Preterm birth complicates >15 million pregnancies annually worldwide. In many countries, women who present with signs of preterm labour are treated with tocolytics for 48 hours. Although this delays birth, it has never been shown to improve neonatal outcome. In 2015, the WHO stated that the use of tocolytics should be reconsidered and that large placebo-controlled studies to evaluate the effectiveness of tocolytics are urgently needed. METHODS AND ANALYSIS: We designed an international, multicentre, randomised, double-blinded, placebo-controlled clinical trial. Women with threatened preterm birth (gestational age 30-34 weeks), defined as uterine contractions with (1) a cervical length of < 15 mm or (2) a cervical length of 15-30 mm and a positive fibronectin test or (3) in centres where cervical length measurement is not part of the local protocol: a positive fibronectin test or insulin-like growth factor binding protein-1 (Actim-Partus test) or (4) ruptured membranes, will be randomly allocated to treatment with atosiban or placebo for 48 hours. The primary outcome is a composite of perinatal mortality and severe neonatal morbidity. Analysis will be by intention to treat. A sample size of 1514 participants (757 per group) will detect a reduction in adverse neonatal outcome from 10% to 6% (alpha 0.05, beta 0.2). A cost-effectiveness analysis will be performed from a societal perspective. ETHICS AND DISSEMINATION: This study has been approved by the Research Ethics Committee (REC) of the Amsterdam University Medical Centres, location AMC, as well as the REC's in Dublin and the UK. The results will be presented at conferences and published in a peer-reviewed journal. Participants will be informed about the results. TRIAL REGISTRATION NUMBER: Nederlands Trial Register (Trial NL6469).

Usability and Usefulness of a Mobile Health App for Pregnancy-Related Work Advice: Mixed-Methods Approach.

BACKGROUND: Pregnant women are often unaware of the potential risks that working conditions can cause to them and their unborn child. A mobile health (mHealth) app, the Pregnancy and Work (P and W) app, developed by a multidisciplinary team and based on an evidence-based guideline for occupational physicians, aims to provide advice on work adjustment during pregnancy. OBJECTIVE: This study evaluates the usability of the mHealth P and W app and the perceived usefulness of the work advice, the main goal of the app, by potential end users. METHODS: A total of 12 working pregnant women participated in think aloud usability sessions and performed 9 tasks. All think aloud sessions were recorded, transcribed, and coanalyzed. The usability problems were rated for their severity in accordance with Nielsen severity scale. The completion rates and time taken for completion of tasks were registered. In addition, participants were questioned on demographics and user characteristics and were asked to evaluate the value of the app by filling in the Intrinsic Motivation Inventory (IMI) score and the System Usability Scale (SUS) questionnaire. RESULTS: In total, 82 usability problems with a severity ≥1 were identified, of which 40 had severity ≥3. The main usability problems concerned the interpretation of terminology used in the app's questionnaires and difficulties in finding and understanding the work advice. Furthermore, 10 out of 12 participants were able to open the work advice page in the app. Only 7 out of these 10 participants understood and intended to follow the work advice. The overall mean IMI score was relatively high (5 out of 7), indicating that the participants did indeed value the use of the app. This IMI score corresponded to the overall mean SUS score (68 out of 100) and the mean grade given to the P and W app (7 out of 10). CONCLUSIONS: This think aloud usability study showed that the information provided in the P and W app was considered valuable by the end users, working pregnant women, and it meets their needs; however, usability issues severely impacted the perceived usefulness of the work advice given in the app.

Perinatal outcomes according to the mode of delivery in women with a triplet pregnancy in The Netherlands.

Objective: In women with a triplet pregnancy, there is debate on the preferred mode of delivery. We performed a nationwide cohort study to assess the impact of mode of delivery on perinatal outcome in women with a triplet pregnancy. Methods: Nationwide cohort study on women with a triplet pregnancy who delivered between 26 + 0 and 40 + 0 weeks of gestation in the years 1999-2008. We compared perinatal outcomes according to the intended mode of delivery and the actual mode of delivery. Outcome measures were perinatal mortality and neonatal morbidity. Perinatal outcomes were analyzed taking into account the dependency between the children of the same triplet pregnancy ("any mortality" and "any morbidity") and were also analyzed separately per child. Results: We identified 386 women with a triplet pregnancy in the study period. Mean gestational age at delivery was 33.1 weeks (SD 2.5 weeks; range 26.0-40.0 weeks). Perinatal mortality was 2.3% for women with a planned caesarean section and 2.4% in women with a planned vaginal delivery (aOR 0.37; 95% confidence interval (CI) 0.09-1.5) and neonatal morbidity was 26.0% versus 36.0%, (aOR 0.88; 95% CI 0.51-1.4) respectively. In the subgroup analyses according to gestational age and in the analysis of perinatal outcomes per child separately, there were also no large differences in perinatal outcomes. The same applied for perinatal outcomes according to the actual mode of delivery. Conclusion: In this large cohort study among women with a triplet pregnancy, caesarean delivery is not associated with reduced perinatal mortality and morbidity.

Cervical Pessary After Arrested Preterm Labor: A Randomized Controlled Trial.

OBJECTIVE: To assess the effectiveness of cervical pessary in reducing the rate of preterm birth in women at high risk for preterm birth who did not deliver after an episode of threatened preterm labor. METHODS: In a multicenter open-label randomized controlled trial, a cervical pessary was compared with no intervention (control group) (one-to-one ratio). Women between 24 and 34 weeks of gestation at high risk for preterm birth based on a short cervical length (less than 15 mm) or an intermediate cervical length (between 15 and 30 mm) with a positive fetal fibronectin test who did not deliver after an episode of threatened preterm labor were eligible. The primary outcome was birth before 37 weeks of gestation. Secondary outcomes were a composite adverse neonatal outcome, preterm birth before 34 and 32 weeks of gestation, and side effects. A total sample size of 200 women carrying singletons was planned so as to have adequate statistical power to detect a reduction in the rate of preterm birth from 40% to 20%. Women with twin gestations were also enrolled but were considered only in secondary analyses. After a planned interim analysis, the trial was stopped for futility. RESULTS: From November 2013 through September 2016, 130 women with a singleton pregnancy (65 pessary, 65 no treatment) were recruited. The groups had comparable baseline characteristics. In the cervical pessary group, 31 (48%) women delivered before 37 weeks of gestation compared with 25 (39%) in the no-treatment group (relative risk 1.2, 95% CI 0.83-1.8). Nine (15%) children in the cervical pessary group had the composite adverse perinatal outcome compared with eight (13%) in the control group (relative risk 1.2, 95% CI 0.49-2.9). CONCLUSION: In women at high risk for preterm birth who did not deliver after an episode of threatened preterm labor, treatment with a cervical pessary is not effective. CLINICAL TRIAL REGISTRATION: Netherlands Trial Register, NTR4210.

Development and internal validation of a clinical prediction model for external cephalic version.

OBJECTIVE: To develop a prediction model for the chance of successful external cephalic version (ECV). STUDY DESIGN: This is a secondary analysis of a multicenter, open-label randomized controlled trial that assessed the effectiveness of atosiban compared to fenoterol as uterine relaxant during ECV in women with a singleton fetus in breech presentation with a gestational age of 36 weeks or more. Potential predictors included maternal, pregnancy, fetal, and treatment characteristics and were recorded in all participants. Multivariable logistic regression analysis with a stepwise backward selection procedure was used to construct a prediction model for the occurrence of successful ECV. Model performance was assessed using calibration and discrimination. RESULTS: We included a total of 818 women with an overall ECV success rate of 37%. Ten predictive factors were identified with the stepwise selection procedure to be associated with a successful ECV: fenoterol as uterine relaxant, nulliparity, Caucasian ethnicity, gestational age at ECV, Amniotic Fluid Index, type of breech presentation, placental location, breech engagement, possibility to palpate the head and relaxation of the uterus. Our model showed good calibration and a good discriminative ability with a c-statistic of 0.78 (95% CI 0.75 to 0.81). CONCLUSION: Prediction of success of ECV seems feasible with a model showing good performance. This can be used in clinical practice after external validation.

The Usability and Effectiveness of Mobile Health Technology-Based Lifestyle and Medical Intervention Apps Supporting Health Care During Pregnancy: Systematic Review.

BACKGROUND: A growing number of mobile health (mHealth) technology-based apps are being developed for personal lifestyle and medical health care support, of which several apps are related to pregnancy. Evidence on usability and effectiveness is limited but crucial for successful implementation. OBJECTIVE: This study aimed to evaluate the usability, that is, feasibility and acceptability, as well as effectiveness of mHealth lifestyle and medical apps to support health care during pregnancy in high-income countries. Feasibility was defined as the actual use, interest, intention, and continued use; perceived suitability; and ability of users to carry out the activities of the app. Acceptability was assessed by user satisfaction, appreciation, and the recommendation of the app to others. METHODS: We performed a systematic review searching the following electronic databases for studies on mHealth technology-based apps in maternal health care in developed countries: EMBASE, MEDLINE Epub (Ovid), Cochrane Library, Web of Science, and Google Scholar. All included studies were scored on quality, using the ErasmusAGE Quality Score or the consolidated criteria for reporting qualitative research. Main outcome measures were usability and effectiveness of mHealth lifestyle and medical health care support apps related to pregnancy. All studies were screened by 2 reviewers individually, and the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement were followed. RESULTS: Our search identified 4204 titles and abstracts, of which 2487 original studies remained after removing duplicates. We performed full-text screening of 217 studies, of which 29 were included in our study. In total, 19 out of 29 studies reported on mHealth apps to adopt healthy lifestyles and 10 out of 29 studies to support medical care. The lifestyle apps evaluated in 19 studies reported on usability and effectiveness: 10 studies reported positive on acceptability, and 14 studies reported on feasibility with positive results except one study. In total, 4 out of 19 studies evaluating effectiveness showed significant results on weight gain restriction during pregnancy, intake of vegetables and fruits, and smoking cessation. The 10 studies on medical mHealth apps involved asthma care, diabetic treatment, and encouraging vaccination. Only one study on diabetic treatment reported on acceptability with a positive user satisfaction. In total, 9 out of 10 studies reported on effectiveness. Moreover, the power of most studies was inadequate to show significant effects. CONCLUSIONS: Most studies on mHealth apps to support lifestyle and medical care for high-income countries reveal the usability of these apps to reduce gestational weight gain, increase intakes of vegetables and fruit, to quit smoking cessation, and to support health care for prevention of asthma and infections during pregnancy. In general, the evidence on effectiveness of these apps is limited and needs further investigation before implementation in medical health care.

Continuous glucose monitoring during diabetic pregnancy (GlucoMOMS): A multicentre randomized controlled trial.

AIM: Diabetes is associated with a high risk of adverse pregnancy outcomes. Optimal glycaemic control is fundamental and is traditionally monitored with self-measured glucose profiles and periodic HbA1c measurements. We investigated the effectiveness of additional use of retrospective continuous glucose monitoring (CGM) in diabetic pregnancies. MATERIAL AND METHODS: We performed a nationwide multicentre, open label, randomized, controlled trial to study pregnant women with type 1 or type 2 diabetes who were undergoing insulin therapy at gestational age < 16 weeks, or women who were undergoing insulin treatment for gestational diabetes at gestational age < 30 weeks. Women were randomly allocated (1:1) to intermittent use of retrospective CGM or to standard treatment. Glycaemic control was assessed by CGM for 5-7 days every 6 weeks in the CGM group, while self-monitoring of blood glucose and HbA1c measurements were applied in both groups. Primary outcome was macrosomia, defined as birth weight above the 90th percentile. Secondary outcomes were glycaemic control and maternal and neonatal complications. RESULTS: Between July 2011 and September 2015, we randomized 300 pregnant women with type 1 (n = 109), type 2 (n = 82) or with gestational (n = 109) diabetes to either CGM (n = 147) or standard treatment (n = 153). The incidence of macrosomia was 31.0% in the CGM group and 28.4% in the standard treatment group (relative risk [RR], 1.06; 95% CI, 0.83-1.37). HbA1c levels were similar between treatment groups. CONCLUSIONS: In diabetic pregnancy, use of intermittent retrospective CGM did not reduce the risk of macrosomia. CGM provides detailed information concerning glycaemic fluctuations but, as a treatment strategy, does not translate into improved pregnancy outcome.

Barriers and Facilitators for the Use of a Medical Mobile App to Prevent Work-Related Risks in Pregnancy: A Qualitative Analysis.

BACKGROUND: The number of women participating in the labor market in Europe has increased over the last several decades. At the same time, there is growing evidence that certain conditions of employment during pregnancy may have a negative influence on pregnancy outcomes. In order to better inform pregnant women, we aim to develop an app to help assess the health risk as a result of personal and work-related factors and provide personal advice for these women and their health care providers. OBJECTIVE: The aim of this study was to compose a thematic overview of the perceived facilitators and barriers according to pregnant women, medical professionals, and employers for the use of a mobile app in obstetrical care to prevent occupational-related pregnancy complications. METHODS: Two multidisciplinary focus group meetings with in total 14 participants were conducted with pregnant women, occupational physicians, general practitioners, midwives, obstetricians, and representatives of trade unions and employer organizations. Transcripts were analyzed by qualitatively coding procedures and constant comparative methods. RESULTS: We identified 24 potential facilitators and 12 potential barriers for the use of the app in 4 categories: content of the app, the app as a mean to provide information, ease of use, and external factors. The 3 main facilitators identified were the need for a good interaction between the app and the user, apps were viewed as a more practical source of information, and the information should be understandable, according to the existing guidelines, and well-dosed. The 2 main barriers for use were extensive battery and memory use of the smartphone and sending frequent push notifications. CONCLUSIONS: The results of this study are important considerations in the developing process of a medical app implementing a guideline or evidence-based information in practice.

Low dose aspirin in the prevention of recurrent spontaneous preterm labour - the APRIL study: a multicenter randomized placebo controlled trial.

BACKGROUND: Preterm birth (birth before 37 weeks of gestation) is a major problem in obstetrics and affects an estimated 15 million pregnancies worldwide annually. A history of previous preterm birth is the strongest risk factor for preterm birth, and recurrent spontaneous preterm birth affects more than 2.5 million pregnancies each year. A recent meta-analysis showed possible benefits of the use of low dose aspirin in the prevention of recurrent spontaneous preterm birth. We will assess the (cost-)effectiveness of low dose aspirin in comparison with placebo in the prevention of recurrent spontaneous preterm birth in a randomized clinical trial. METHODS/DESIGN: Women with a singleton pregnancy and a history of spontaneous preterm birth in a singleton pregnancy (22-37 weeks of gestation) will be asked to participate in a multicenter, randomized, double blinded, placebo controlled trial. Women will be randomized to low dose aspirin (80 mg once daily) or placebo, initiated from 8 to 16 weeks up to maximal 36 weeks of gestation. The primary outcome measure will be preterm birth, defined as birth at a gestational age (GA) < 37 weeks. Secondary outcomes will be a composite of adverse neonatal outcome and maternal outcomes, including subgroups of prematurity, as well as intrauterine growth restriction (IUGR) and costs from a healthcare perspective. Preterm birth will be analyzed as a group, as well as separately for spontaneous or indicated onset. Analysis will be performed by intention to treat. In total, 406 pregnant women have to be randomized to show a reduction of 35% in preterm birth from 36 to 23%. If aspirin is effective in preventing preterm birth, we expect that there will be cost savings, because of the low costs of aspirin. To evaluate this, a cost-effectiveness analysis will be performed comparing preventive treatment with aspirin with placebo. DISCUSSION: This trial will provide evidence as to whether or not low dose aspirin is (cost-) effective in reducing recurrence of spontaneous preterm birth. TRIAL REGISTRATION: Clinical trial registration number of the Dutch Trial Register: NTR 5675 . EudraCT-registration number: 2015-003220-31.

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.

Which Factors Contribute to False-Positive, False-Negative, and Invalid Results in Fetal Fibronectin Testing in Women with Symptoms of Preterm Labor?

Objective We assessed the influence of external factors on false-positive, false-negative, and invalid fibronectin results in the prediction of spontaneous delivery within 7 days. Methods We studied symptomatic women between 24 and 34 weeks' gestational age. We performed uni- and multivariable logistic regression to estimate the effect of external factors (vaginal soap, digital examination, transvaginal sonography, sexual intercourse, vaginal bleeding) on the risk of false-positive, false-negative, and invalid results, using spontaneous delivery within 7 days as the outcome. Results Out of 708 women, 237 (33%) had a false-positive result; none of the factors showed a significant association. Vaginal bleeding increased the proportion of positive fetal fibronectin (fFN) results, but was significantly associated with a lower risk of false-positive test results (odds ratio [OR], 0.22; 95% confidence intervals [CI], 0.12-0.39). Ten women (1%) had a false-negative result. None of the investigated factors was significantly associated with a significantly higher risk of false-negative results. Twenty-one tests (3%) were invalid; only vaginal bleeding showed a significant association (OR, 4.5; 95% CI, 1.7-12). Conclusion The effect of external factors on the performance of qualitative fFN testing is limited, with vaginal bleeding as the only factor that reduces its validity.

Nifedipine versus placebo in the treatment of preterm prelabor rupture of membranes: a randomized controlled trial: Assessment of perinatal outcome by use of tocolysis in early labor-APOSTEL IV trial.

OBJECTIVE: Preterm birth is the most common cause of neonatal morbidity and mortality. Around one third of preterm deliveries starts with preterm prelabor rupture of membranes (PPROM). The aim of this trial was to study the effect of prolonged tocolysis with nifedipine versus placebo in women with PPROM on perinatal outcome and prolongation of pregnancy. STUDY DESIGN: The Apostel IV was a nationwide multicenter randomized placebo controlled trial. We included women with PPROM without contractions between 24(+0) and 33(+6) weeks of gestation. Participants were randomly allocated to daily 80mg nifedipine or placebo, until the start of labor, with a maximum of 18 days. The primary outcome measure was a composite of poor neonatal outcome, including perinatal death, bronchopulmonary dysplasia, periventricular leukomalacia>grade 1, intraventricular hemorrhage>grade 2, necrotizing enterocolitis>stage 1 and culture proven sepsis. Secondary outcomes were gestational age at delivery and prolongation of pregnancy. Analysis was by intention to treat. To detect a reduction of poor neonatal outcome from 30% to 10%, 120 women needed to be randomized. TRIAL REGISTRY: NTR 3363. RESULTS: Between October 2012 and December 2014 we randomized 25 women to nifedipine and 25 women to placebo. Due to slow recruitment the study was stopped prematurely. The median gestational age at randomization was 29.9 weeks (IQR 27.7-31.3) in the nifedipine group and 27.0 weeks (IQR 24.7-29.9) in the placebo group. Other baseline characteristics were comparable. The adverse perinatal outcome occurred in 9 neonates (33.3%) in the nifedipine group and 9 neonates (32.1%) in the placebo group (RR 1.04, 95% CI 0.49-2.2). Two perinatal deaths occurred, both in the nifedipine group. Bronchopulmonary dysplasia was seen less frequently in the nifedipine group (0% versus 17.9%; p=0.03). Prolongation of pregnancy did not differ between the nifedipine and placebo group (median 11 versus 8 days, HR 1.02; 95% CI 0.58-1.79). CONCLUSION: This randomized trial did not show a beneficial effect of prolonged tocolysis on neonatal outcomes or prolongation of pregnancy in women with PPROM without contractions. However, since results are based on a small sample size, a difference in effectiveness cannot be excluded.