The WHO 2013 oral glucose tolerance test: The utility of isolated glucose measurements - A retrospective cohort study.

OBJECTIVE: The WHO 2013 guidelines recommend screening for gestational diabetes mellitus (GDM) by 3-point oral glucose tolerance test (OGTT). The objective of this retrospective cohort study was to evaluate GDM diagnosed by an isolated high glucose. STUDY DESIGN: We included pregnant women deemed at risk for GDM were offered GDM screening. We examined the records of 1939 consecutively screened pregnancies at two teaching hospitals in Amsterdam during 2016-2020. Using the WHO 2013 diagnostic criteria, we calculated the proportion of GDM cases diagnosed by isolated abnormal glucose values. RESULTS: Among those screened in our high risk cohort, GDM incidence was 31.5%. Of the GDM diagnoses, 57.0% were based on an isolated fasting glucose value, 30.9% based on multiple raised glucose measurements, 7.4% on an isolated raised 2-hour glucose and 4.7% on an isolated raised 1-hour glucose. For 1-hour glucose, the number needed to screen was 67 persons for one additional GDM case. CONCLUSION: The 1-hour glucose in the 3 point OGTT, as suggested by the WHO 2013 guidelines for GDM, contributes only small numbers of GDM cases and a high number needed to screen (67 for 1 additional case in a selective high risk GDM screening strategy), and is likely even less effective in universally screened populations.

Fetal and post-natal outcomes in offspring after intrauterine metformin exposure: A systematic review and meta-analysis of animal experiments.

AIMS: The impact of maternal metformin use during pregnancy on fetal, infant, childhood and adolescent growth, development, and health remains unclear. Our objective was to systematically review the available evidence from animal experiments on the effects of intrauterine metformin exposure on offspring's anthropometric, cardiovascular and metabolic outcomes. METHODS: A systematic search was conducted in PUBMED and EMBASE from inception (searched on 12th April 2023). We extracted original, controlled animal studies that investigated the effects of maternal metformin use during pregnancy on offspring anthropometric, cardiovascular and metabolic measurements. Subsequently, risk of bias was assessed and meta-analyses using the standardized mean difference and a random effects model were conducted for all outcomes containing data from 3 or more studies. Subgroup analyses were planned for species, strain, sex and type of model in the case of 10 comparisons or more per subgroup. RESULTS: We included 37 articles (n = 3133 offspring from n = 716 litters, containing n = 51 comparisons) in this review, mostly (95%) on rodent models and 5% pig models. Follow-up of offspring ranged from birth to 2 years of age. Thirty four of the included articles could be included in the meta-analysis. No significant effects in the overall meta-analysis of metformin on any of the anthropometric, cardiovascular and metabolic offspring outcome measures were identified. Between-studies heterogeneity was high, and risk of bias was unclear in most studies as a consequence of poor reporting of essential methodological details. CONCLUSION: This systematic review was unable to establish effects of metformin treatment during pregnancy on anthropometric, cardiovascular and metabolic outcomes in non-human offspring. Heterogeneity between studies was high and reporting of methodological details often limited. This highlights a need for additional high-quality research both in humans and model systems to allow firm conclusions to be established. Future research should include focus on the effects of metformin in older offspring age groups, and on outcomes which have gone uninvestigated to date.

Community midwives' perspectives on perinatal care for asylum seekers and refugees in the Netherlands: A survey study.

BACKGROUND: The rise of forced migration worldwide compels birth care systems and professionals to respond to the needs of women giving birth in these vulnerable situations. However, little is known about the perspective of midwifery professionals on providing perinatal care for forcibly displaced women. This study aimed to identify challenges and target areas for improvement of community midwifery care for asylum seekers (AS) and refugees with a residence permit (RRP) in the Netherlands. METHODS: For this cross-sectional study, data were collected through a survey aimed at community care midwives who currently work or who have worked with AS and RRP. We evaluated challenges identified through an inductive thematic analysis of respondents' responses to open-ended questions. Quantitative data from close-ended questions were analyzed descriptively and included aspects related to the quality and organization of perinatal care for these groups. RESULTS: Respondents generally considered care for AS and RRP to be of lower quality, or at best, equal quality compared to care for the Dutch population, while the workload for midwives caring for these groups was considered higher. The challenges identified were categorized into five main themes, including: 1) interdisciplinary collaboration; 2) communication with clients; 3) continuity of care; 4) psychosocial care; and 5) vulnerabilities among AS and RRP. CONCLUSIONS: Findings suggest that there is considerable opportunity for improvement in perinatal care for AS and RRP, while also providing direction for future research and interventions. Several concerns raised, especially the availability of professional interpreters and relocations of AS during pregnancy, require urgent consideration at legislative, policy, and practice levels.

Predictive value of fetal growth trajectory from 20 weeks of gestation onwards for severe adverse perinatal outcome in low-risk population: secondary analysis of IRIS study.

OBJECTIVES: The placental dysfunction underlying fetal growth restriction (FGR) may result in severe adverse perinatal outcome (SAPO) related to fetal hypoxia. Traditionally, the diagnostic criteria for FGR have been based on fetal size, an approach that is inherently flawed because it often results in either over- or underdiagnosis. The anomaly ultrasound scan at 20 weeks' gestation may be an appropriate time at which to set a benchmark for growth potential of the individual fetus. We hypothesized that the fetal growth trajectory from that point onwards may be informative regarding third-trimester placental dysfunction. The aim of this study was to investigate the predictive value for SAPO of a slow fetal growth trajectory between 18 + 0 to 23 + 6 weeks and 32 + 0 to 36 + 6 weeks' gestation in a large, low-risk population. METHODS: This was a post-hoc data analysis of the IUGR Risk Selection (IRIS) study, a Dutch nationwide cluster-randomized trial assessing the (cost-)effectiveness of routine third-trimester sonography in reducing SAPO. In the current analysis, for the first ultrasound examination we used ultrasound data from the routine anomaly scan at 18 + 0 to 23 + 6 weeks' gestation, and for the second we used data from an ultrasound examination performed between 32 + 0 and 36 + 6 weeks' gestation. Using multilevel logistic regression, we analyzed whether SAPO was predicted by a slow fetal growth trajectory, which was defined as a decline in abdominal circumference (AC) and/or estimated fetal weight (EFW) of more than 20 percentiles or more than 50 percentiles or as an AC growth velocity (ACGV) < 10th percentile (p10). In addition, we analyzed the combination of these indicators of slow fetal growth with small-for-gestational age (SGA) (AC or EFW < p10) and severe SGA (AC/EFW < 3rd percentile) at 32 + 0 to 36 + 6 weeks' gestation. RESULTS: Our sample included the data of 6296 low-risk singleton pregnancies, among which 82 (1.3%) newborns experienced at least one SAPO. Standalone declines in AC or EFW of > 20 or > 50 percentiles or ACGV < p10 were not associated with increased odds of SAPO. EFW < p10 between 32 + 0 and 36 + 6 weeks' gestation combined with a decline in EFW of > 20 percentiles was associated with an increased rate of SAPO. The combination of AC or EFW < p10 between 32 + 0 and 36 + 6 weeks' gestation with ACGV < p10 was also associated with increased odds of SAPO. The odds ratios of these associations were higher if the neonate was SGA at birth. CONCLUSIONS: In a low-risk population, a slow fetal growth trajectory as a standalone criterion does not distinguish adequately between fetuses with FGR and those that are constitutionally small. This absence of association may be a result of diagnostic inaccuracies and/or post-diagnostic (e.g. intervention and selection) biases. We conclude that new approaches to detect placental insufficiency should integrate information from diagnostic tools such as maternal serum biomarkers and Doppler ultrasound measurements. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Virtual Reality Experience during Labour (VIREL); a qualitative study.

BACKGROUND: There is increasing evidence that virtual reality (VR) is effective in the reduction of labour pain. The implementation of alternative methods like VR to reduce labour pain can contribute to reduce patient request for pharmacological pain management methods and associated side effects. The aim of this study is to examine women's experiences, preferences and satisfaction in regard to the use of VR during labour. METHODS: A qualitative interview study was conducted in a non-university teaching hospital in The Netherlands. Two VR applications, respectively a guided meditation and an interactive game were tested in eligible women with a singleton pregnancy, scheduled for induction of labour. For the primary outcome, patients' VR experience and application preference (meditation vs. game) were examined using a post-intervention questionnaire and a semi-structured interview. Three categories (with sub-categories) were used to guide interviews: "The VR experience", "Pain reduction", and "Usability of the VR application". Labour pain before and directly after VR was evaluated using the NRS score. RESULTS: Twenty-four women, of whom 14 were nulliparous and ten multiparous, were included and 12 of these women participated in semi-structured interviews. Using within-subject paired t-test comparisons, compared to pain pre-VR, patients reported a highly significant 26% decrease in mean NRS scores during VR meditation (pain pre-VR = 6.71 + - 1.65 vs. pain after VR = 4.96 + - 2.01) [p < 0.001]. Compared to pain before VR game, patients also reported a highly significant 19% decrease in mean NRS scores during VR game (pain before VR game = 6.89 + - 1.88 vs. pain after VR game = 5.61 + - 2.23) [p = 0.001]. CONCLUSION: All women were highly satisfied with VR use during labour. Patients reported a highly significant reduction in pain during the interactive VR game and during meditation, patients preferred guided meditation. These results can contribute to the development of a potential promising new non-pharmacological tool to reduce labour pain. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04858984, date of registration: 26/04/2021 (retrospectively registered).

Implication of third-trimester screening accuracy for small-for-gestational age and additive value of third-trimester growth-trajectory indicators in predicting severe adverse perinatal outcome in low-risk population: pragmatic secondary analysis of IRIS study.

OBJECTIVES: To examine the implications of third-trimester small-for-gestational-age (SGA) screening accuracy on severe adverse perinatal outcome (SAPO) and obstetric intervention in a low-risk population. Furthermore, we aimed to explore the additive value of third-trimester sonographic growth-trajectory measurements in predicting SAPO and obstetric intervention. METHODS: This was a secondary analysis of a Dutch national multicenter stepped-wedge-cluster randomized trial among 11 820 low-risk pregnant women. Using multilevel multivariable logistic regression analysis, we compared SAPO and obstetric interventions in SGA neonates with and without SGA suspected prenatally (true positives and false negatives) and non-SGA neonates with and without SGA suspected prenatally (false positives and true negatives). In a subsample (n = 7989), we analyzed the associations of abdominal circumference (AC) and estimated fetal weight (EFW) < 10th centile (p10) and third-trimester growth-trajectory indicators AC and EFW crossing > 20 and AC crossing > 50 centiles and the lowest decile of AC growth-velocity Z-scores (ACGV < 10%) with SAPO and obstetric interventions. RESULTS: SGA infants, i.e. the true-positive and false-negative cases, had an increased risk of SAPO (adjusted odds ratio (aOR), 4.46 (95% CI, 2.28-8.75) and aOR 2.61 (95% CI, 1.74-3.89), respectively), and obstetric intervention (aOR for: induction of labor, 2.99 (95% CI, 2.15-4.17) and 1.38 (95% CI, 1.14-1.66); Cesarean section, 1.82 (95% CI, 1.25-2.66) and 1.27 (95% CI, 1.05-1.54); medically indicated preterm delivery, 2.67 (95% CI, 1.97-3.62) and 1.20 (95% CI, 1.03-1.40)). The false-positive cases did not differ from the true negatives for all outcomes, including obstetric intervention. Of the third-trimester growth-trajectory indicators, only ACGV < 10% was associated moderately with SAPO (aOR, 2.15 (95% CI, 1.17-3.97)), while AC and EFW crossing > 20 and AC crossing > 50 centiles were not. Both EFW < p10 alone (aOR, 1.95 (95% CI, 1.13-3.38)) and EFW < p10 combined with ACGV < 10% (aOR, 4.69 (95% CI, 1.99-11.07)) were associated with SAPO, and they performed equally well in predicting SAPO (area under the receiver-operating-characteristics curve, 0.71 (95% CI, 0.65-0.76) vs 0.72 (95% CI, 0.67-0.77), P = 0.51). CONCLUSION: Neonates who had been suspected falsely of being SGA during pregnancy had no higher rates of obstetric intervention than did those without suspicion of SGA prenatally. Our results do not support that third-trimester low fetal growth velocity (ACGV < 10%) may be of additive value for the identification of fetuses at risk of SAPO in populations remaining at low risk throughout pregnancy. AC and EFW crossing > 20 and AC crossing > 50 centiles performed poorly in identifying abnormal fetal growth. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

The effect of a locally tailored intervention on the uptake of preconception care in the Netherlands: a stepped-wedge cluster randomized trial (APROPOS-II study).

BACKGROUND: The preconception period provides a window of opportunity for interventions aiming to reduce unhealthy lifestyle behaviours and their negative effect on pregnancy outcomes. This study aimed to assess the effectiveness of a locally tailored preconception care (PCC) intervention in a hybrid-II effectiveness implementation design. METHODS: A stepped-wedge cluster randomized controlled trial was performed in four Dutch municipalities. The intervention contained a social marketing strategy aiming to improve the uptake (prospective parents) and the provision (healthcare providers) of PCC. Prospective parents participated by administering a questionnaire in early pregnancy recalling their preconceptional behaviours. Experiences of healthcare providers were also evaluated through questionnaires. The composite primary outcome was adherence to at least three out of four preconceptional lifestyle recommendations (early initiation of folic acid supplements, healthy nutrition, no smoking or alcohol use). Secondary outcomes were preconceptional lifestyle behaviour change, (online) reach of the intervention and improved knowledge among healthcare providers. RESULTS: A total of 850 women and 154 men participated in the control phase and 213 women and 39 men in the intervention phase. The composite primary outcome significantly improved among women participating in the municipality where the reach of the intervention was highest (Relative Risk (RR) 1.57 (95% Confidence Interval (CI) 1.11-2.22). Among women, vegetable intake had significantly improved in the intervention phase (RR 1.82 (95%CI 1.14-2.91)). The aimed online reach- and engagement rate of the intervention was achieved most of the time. Also, after the intervention, more healthcare providers were aware of PCC-risk factors (54.5% vs. 47.7%; p = 0.040) and more healthcare providers considered it easier to start a conversation about PCC (75.0% vs. 47.9%; p = 0.030). CONCLUSION: The intervention showed some tentative positive effects on lifestyle behaviours among prospective parents. Primarily on vegetable intake and the knowledge and competence of healthcare providers. The results of this study contribute to the evidence regarding successfully implementing PCC-interventions to optimize the health of prospective parents and future generations. TRIAL REGISTRATION: Dutch Trial Register: NL7784 (Registered 06/06/2019).

Differential effects of renin-angiotensine-aldosteron system inhibition, sympathoinhibition and low sodium diet on blood pressure in women with a history of preeclampsia: A double-blind, placebo-controlled cross-over trial (the PALM study).

Current guidelines lack sufficient evidence to recommend a specific blood pressure lowering strategy to prevent cardiovascular disease after preeclampsia. We conducted a double-blind cross-over trial to identify the most potent antihypertensive strategy: renin-angiotensin-aldosterone system (RAAS) inhibition (losartan), sympathoinhibition (moxonidine), low sodium diet and placebo (n = 10). Due to low inclusion rate our study stopped prematurely. Initiatory analyses showed no significant effect of antihypertensive strategy on office blood pressure and 24-hour blood pressure. However, nocturnal dipping was significantly higher on RAAS inhibition and low sodium diet compared to placebo and sympathoinhibition. Optimal cardiovascular prevention after preeclampsia should be further explored.

Lessons learned during implementation of MR-guided High-Intensity Focused Ultrasound treatment of uterine fibroids.

BACKGROUND: Although promising results have been reported for Magnetic Resonance image-guided High-Intensity Focused Ultrasound (MR-HIFU) treatment of uterine fibroids, this treatment is not yet widely implemented in clinical practice. During the implementation of a new technology, lessons are learned and an institutional learning-curve often has to be completed. The primary aim of our prospective cohort study was to characterize our learning-curve based on our clinical outcomes. Secondary aims included identifying our lessons learned during implementation of MR-HIFU on a technical, patient selection, patient counseling, medical specialists and organizational level. RESULTS: Our first seventy patients showed significant symptom reduction and improvement of quality of life at 3, 6 and 12 months after MR-HIFU treatment compared to baseline. After the first 25 cases, a clear plateau phase was reached in terms of failed treatments. The median non-perfused volume percentage of these first 25 treatments was 44.6% (range: 0-99.7), compared to a median of 74.7% (range: 0-120.6) for the subsequent treatments. CONCLUSIONS: Our findings describe the learning-curve during the implementation of MR-HIFU and include straightforward suggestions to shorten learning-curves for future users. Moreover, the lessons we learned on technique, patient selection, patient counseling, medical specialists and organization, together with the provided supplements, may be of benefit to other institutions aiming to implement MR-HIFU treatment of uterine fibroids. Trial registration ISRCTN14634593. Registered January 12, 2021-Retrospectively registered, https://www.isrctn.com/ISRCTN14634593 .

Prognostic models versus single risk factor approach in first-trimester selective screening for gestational diabetes mellitus: a prospective population-based multicentre cohort study.

OBJECTIVES: To evaluate whether (1) first-trimester prognostic models for gestational diabetes mellitus (GDM) outperform the currently used single risk factor approach, and (2) a first-trimester random venous glucose measurement improves model performance. DESIGN: Prospective population-based multicentre cohort. SETTING: Thirty-one independent midwifery practices and six hospitals in the Netherlands. POPULATION: Women recruited before 14 weeks of gestation without pre-existing diabetes. METHODS: The single risk factor approach (presence of at least one risk factor: BMI ≥30 kg/m2 , previous macrosomia, history of GDM, positive first-degree family history of diabetes, non-western ethnicity) was compared with the four best performing models in our previously published external validation study (Gabbay-Benziv 2014, Nanda 2011, Teede 2011, van Leeuwen 2010) with and without the addition of glucose. MAIN OUTCOME MEASURES: Discrimination was assessed by c-statistics, calibration by calibration plots, added value of glucose by the likelihood ratio chi-square test, net benefit by decision curve analysis and reclassification by reclassification plots. RESULTS: Of the 3723 women included, a total of 181 (4.9%) developed GDM. The c-statistics of the prognostic models were higher, ranging from 0.74 to 0.78 without glucose and from 0.78 to 0.80 with glucose, compared with the single risk factor approach (0.72). Models showed adequate calibration, and yielded a higher net benefit than the single risk factor approach for most threshold probabilities. Teede 2011 performed best in the reclassification analysis. CONCLUSIONS: First-trimester prognostic models seem to outperform the currently used single risk factor approach in screening for GDM, particularly when glucose was added as a predictor. TWEETABLE ABSTRACT: Prognostic models seem to outperform the currently used single risk factor approach in screening for gestational diabetes.

Impact of preventive screening and lifestyle interventions in women with a history of preeclampsia: A micro-simulation study.

BACKGROUND: Preeclampsia is a female-specific risk factor for the development of future cardiovascular disease. Whether early preventive cardiovascular disease risk screenings combined with risk-based lifestyle interventions in women with previous preeclampsia are beneficial and cost-effective is unknown. METHODS: A micro-simulation model was developed to assess the life-long impact of preventive cardiovascular screening strategies initiated after women experienced preeclampsia during pregnancy. Screening was started at the age of 30 or 40 years and repeated every five years. Data (initial and follow-up) from women with a history of preeclampsia was used to calculate 10-year cardiovascular disease risk estimates according to Framingham Risk Score. An absolute risk threshold of 2% was evaluated for treatment selection, i.e. lifestyle interventions (e.g. increasing physical activity). Screening benefits were assessed in terms of costs and quality-adjusted-life-years, and incremental cost-effectiveness ratios compared with no screening. RESULTS: Expected health outcomes for no screening are 27.35 quality-adjusted-life-years and increase to 27.43 quality-adjusted-life-years (screening at 30 years with 2% threshold). The expected costs for no screening are €9426 and around €13,881 for screening at 30 years (for a 2% threshold). Preventive screening at 40 years with a 2% threshold has the most favourable incremental cost-effectiveness ratio, i.e. €34,996/quality-adjusted-life-year, compared with other screening scenarios and no screening. CONCLUSIONS: Early cardiovascular disease risk screening followed by risk-based lifestyle interventions may lead to small long-term health benefits in women with a history of preeclampsia. However, the cost-effectiveness of a lifelong cardiovascular prevention programme starting early after preeclampsia with risk-based lifestyle advice alone is relatively unfavourable. A combination of risk-based lifestyle advice plus medical therapy may be more beneficial.

Home-based telemonitoring versus hospital admission in high risk pregnancies: a qualitative study on women's experiences.

BACKGROUND: Hospital admission during pregnancy complications is considered to be an event of significant impact. Besides conventional in-clinic maternal and fetal monitoring, recent technologies enable home-based telemonitoring with self-measurements in high risk pregnancy. This study is part of a feasibility pilot to explore the usability and acceptability of telemonitoring and aims to gain insight in the experiences and preferences of high risk pregnant women concerning the novel strategy of telemonitoring, opposed to women who were hospitalized in pregnancy. METHODS: Using secured Facebook Groups, we conducted four online focus groups: two focus groups with women who were admitted during pregnancy (n = 11) and two with women who received home telemonitoring in the pilot phase (n = 11). The qualitative data were analyzed thematically. RESULTS: Four major themes emerged from both participant groups: [1] care experience, [2] emotions regarding pregnancy, [3] privacy and [4] impact on daily life. Different views were reported on all four themes, resulting in a direct comparison of experiences during hospitalization and telemonitoring. Most admitted patients reported a growing sense of boredom and anxiety during their clinical admission. Lack of privacy on ward was a great concern, as it affected their contact with hospital staff and family. This issue was not reported amongst telemonitored women. These participants still felt like a patient at times but responded that the comfort of their own home and bed was pleasant. Only a minority of telemonitored participants reported being anxious at times at home, while not having a physician or nurse nearby. Being at home resulted in less travel time for partners or family for hospital visits, which had its positive effects on family life. CONCLUSIONS: Telemonitoring of a high-risk pregnancy provides an innovative manner to monitor fetal and maternal condition from home. Compared to the experiences of hospital admission in high risk pregnancy, it allows women to be in a comforting and private environment during an anxious time in their lives. As future studies should further investigate the safety and cost effectiveness of this novel strategy, women's views on the preference of telemonitoring need to be taken into consideration.

Automatic extraction of the intracranial volume in fetal and neonatal MR scans using convolutional neural networks.

MR images of infants and fetuses allow non-invasive analysis of the brain. Quantitative analysis of brain development requires automatic brain tissue segmentation that is typically preceded by segmentation of the intracranial volume (ICV). Fast changes in the size and morphology of the developing brain, motion artifacts, and large variation in the field of view make ICV segmentation a challenging task. We propose an automatic method for segmentation of the ICV in fetal and neonatal MRI scans. The method was developed and tested with a diverse set of scans regarding image acquisition parameters (i.e. field strength, image acquisition plane, image resolution), infant age (23-45 weeks post menstrual age), and pathology (posthaemorrhagic ventricular dilatation, stroke, asphyxia, and Down syndrome). The results demonstrate that the method achieves accurate segmentation with a Dice coefficient (DC) ranging from 0.98 to 0.99 in neonatal and fetal scans regardless of image acquisition parameters or patient characteristics. Hence, the algorithm provides a generic tool for segmentation of the ICV that may be used as a preprocessing step for brain tissue segmentation in fetal and neonatal brain MR scans.

Views and preferences of medical professionals and pregnant women about a novel primary prevention intervention for hypertensive disorders of pregnancy: a qualitative study.

BACKGROUND: Calcium and low-dose aspirin are two potential approaches for primary prevention of hypertensive disorders of pregnancy (HDP). This study aimed to explore the acceptability, views and preferences of pregnant women and primary healthcare providers for a fixed-dose combined preparation of aspirin and calcium (a polypill) as primary prevention of HDP in an unselected pregnant population. METHODS: In this qualitative study eight in-depth semi-structured interviews were conducted with Dutch primary care midwives and general practitioners. Seven focus group discussions were organised with women with low-risk pregnancies. Topics discussed were: perceptions of preeclampsia; information provision about preeclampsia and a polypill; views on the polypill concept; preferences and needs regarding implementation of a polypill. Thematic analysis of the data transcripts was carried out to identify emerging themes. RESULTS: Two major themes shaped medical professionals' and women's views on the polypill concept: 'Informed Choice' and 'Medicalisation'. Both could be divided into subthemes related to information provision, personal choice and discussions with regard to the balance between 'unnecessary medicalisation' and 'scientific progress'. CONCLUSIONS: In general, women and healthcare practitioners expressed a positive attitude towards a polypill intervention as primary prevention strategy with aspirin and calcium, providing some conditions are met. The most important conditions for implementation of such a strategy were safety, effectiveness and the possibility to make a well-informed autonomous decision.

Feasibility and effectiveness of a lifestyle intervention after complicated pregnancies to improve risk factors for future cardiometabolic disease.

OBJECTIVES: To evaluate the feasibility and effectiveness of a postpartum lifestyle intervention after pregnancies complicated by preeclampsia, fetal growth restriction (FGR) and/or gestational diabetes mellitus (GDM) to improve maternal risk factors for future cardiometabolic disease. METHODS: Women following a complicated pregnancy were included six months postpartum in this specific pre-post controlled designed study. It has been conducted in one tertiary and three secondary care hospitals (intervention group) and one secondary care hospital (control group). The program consisted of a computer-tailored health education program combined with three individual counselling sessions during seven months. Primary outcome measures were the proportion of eligible women and weight change during the intervention. RESULTS: Two hundred and six women were willing to participate. The proportion of eligible women who complied with the intervention was 23%. Major barrier was lack of time. Adjusted weight change attributed to lifestyle intervention was -1.9 kg (95%-CI -4.3 to -0.3). Further changes were BMI (-0.9 kg/m2 (95%-CI -1.4 to -0.3)), waist-to-hip ratio (-0.04 cm/cm (95%-CI -0.06 to -0.03)), blood pressure medication use (19% (95%-CI 9% to 28%)), HOMA2-score (59 %S (95%-CI 18 to 99)) and total fat intake (-2.9 gr (95%-CI -4.6 to -1.2)). CONCLUSIONS: The results support feasibility and effectiveness of a lifestyle intervention after complicated pregnancies to improve maternal cardiometabolic risk factors. Further randomized controlled studies are needed with longer follow-up to evaluate durability. In the meantime, we suggest health care professionals to offer lifestyle interventions to women after complicated pregnancies.

Cost effectiveness of nifedipine compared with atosiban in the treatment of threatened preterm birth (APOSTEL III trial).

OBJECTIVE: To assess the cost-effectiveness of treatment with nifedipine compared with atosiban in women with threatened preterm birth. DESIGN: An economic analysis alongside a randomised clinical trial (the APOSTEL III study). SETTING: Obstetric departments of 12 tertiary hospitals and seven secondary hospitals in the Netherlands and Belgium. POPULATION: Women with threatened preterm birth between 25 and 34 weeks of gestation, randomised for tocolysis with either nifedipine or atosiban. METHODS: We performed an economic analysis from a societal perspective. We estimated costs from randomisation until discharge. Analyses for singleton and multiple pregnancies were performed separately. The robustness of our findings was evaluated in sensitivity analyses. MAIN OUTCOME MEASURES: Mean costs and differences were calculated per woman treated with nifedipine or atosiban. Health outcomes were expressed as the prevalence of a composite of adverse perinatal outcomes. RESULTS: Mean costs per patients were significantly lower in the nifedipine group [singleton pregnancies: €34,897 versus €43,376, mean difference (MD) -€8479 [95% confidence interval (CI) -€14,327 to -€2016)]; multiple pregnancies: €90,248 versus €102,292, MD -€12,044 (95% CI -€21,607 to € -1671). There was a non-significantly higher death rate in the nifedipine group. The difference in costs was mainly driven by a lower neonatal intensive care unit admission (NICU) rate in the nifedipine group. CONCLUSION: Treatment with nifedipine in women with threatened preterm birth results in lower costs when compared with treatment with atosiban. However, the safety of nifedipine warrants further investigation. TWEETABLE ABSTRACT: In women with threatened preterm birth, tocolysis using nifedipine results in lower costs when compared with atosiban.

MRI-derived aortic characteristics after pregnancy: The AMBITYON study.

OBJECTIVES: Pregnancy and pregnancy complications have been associated with increased arterial stiffness even at young age. In this study we assessed the impact of parity on CMR-derived aortic characteristics as early markers of atherosclerosis and arterial stiffness in healthy women between 25 and 35 years. STUDY DESIGN: We studied 68 women who participated in the AMBITYON study, a prospective population-based cohort study for assessment of atherosclerotic burden by MRI and traditional CVD risk factors in healthy, young adults. Of these women, 40 (58.8%) were nulliparous, 13 (19.1%) were primiparous and 15 (22.1%) were multiparous. MAIN OUTCOME MEASURES: Descending thoracic aortic wall thickness (AWT) and pulse wave velocity (PWV) were measured using 3.0T CMR. RESULTS: AWT measurements were similar between nulliparous women and primi- or multiparous women (1.6 mm ±â€¯0.2 mm vs. 1.6 mm ±â€¯0.2 mm; p = 0.79). Correction for age and systolic blood pressure did not change these results. Applying percentile based cut-off values showed a non-significant increase in AWT in parous women. PWV measurements did not differ between nulliparous women and parous women (4.5 m/s ±â€¯0.7 m/s vs. 4.5 m/s ±â€¯0.8 m/s; p = 0.78). Correction for age and systolic blood pressure did not influence these results. Using percentile based cut-off values, showed an increasing likelihood of higher PWV-values in parous women, although not statistically significant. CONCLUSIONS: Direct measurement of aortic AWT and PWV by CMR showed no difference between nulliparous and parous women, probably indicating limited effect of pregnancy on arterial stiffness and early markers of atherosclerosis. TRIAL REGISTRATION: Netherlands Trial Register (NTR) number: 4742.

H3K27 acetylation and gene expression analysis reveals differences in placental chromatin activity in fetal growth restriction.

Background: Posttranslational modification of histone tails such as histone 3 lysine 27 acetylation (H3K27ac) is tightly coupled to epigenetic regulation of gene expression. To explore whether this is involved in placenta pathology, we probed genome-wide H3K27ac occupancy by chromatin immunoprecipitation sequencing (ChIP-seq) in healthy placentas and placentas from pathological pregnancies with fetal growth restriction (FGR). Furthermore, we related specific acetylation profiles of FGR placentas to gene expression changes. Results: Analysis of H3K27ac occupancy in FGR compared to healthy placentas showed 970 differentially acetylated regions distributed throughout the genome. Principal component analysis and hierarchical clustering revealed complete segregation of the FGR and control group. Next, we identified 569 upregulated genes and 521 downregulated genes in FGR placentas by RNA sequencing. Differential gene transcription largely corresponded to expected direction based on H3K27ac status. Pathway analysis on upregulated transcripts originating from hyperacetylated sites revealed genes related to the HIF-1-alpha transcription factor network and several other genes with known involvement in placental pathology (LEP, FLT1, HK2, ENG, FOS). Downregulated transcripts in the vicinity of hypoacetylated sites were related to the immune system and growth hormone receptor signaling. Additionally, we found enrichment of 141 transcription factor binding motifs within differentially acetylated regions. Of the corresponding transcription factors, four were upregulated, SP1, ARNT2, HEY2, and VDR, and two downregulated, FOSL and NR4A1. Conclusion: We demonstrate a key role for genome-wide alterations in H3K27ac in FGR placentas corresponding with changes in transcription profiles of regions relevant to placental function. Future studies on the role of H3K27ac in FGR and placental-fetal development may help to identify novel targets for therapy of this currently incurable disease.

Recurrence of pre-eclampsia and the risk of future hypertension and cardiovascular disease: a systematic review and meta-analysis.

BACKGROUND: Women with a history of hypertensive disorders, including pre-eclampsia, during pregnancy have a two- to-five-fold increased risk of cardiovascular disease (CVD). In 15% of women, pre-eclampsia recurs in the following pregnancy. OBJECTIVES: To evaluate all evidence on the future risk of developing hypertension and CVD after multiple pregnancies complicated by pre-eclampsia compared with pre-eclampsia in a single pregnancy followed by normal subsequent pregnancy. SEARCH STRATEGY: Embase and Medline were searched until June 2017. SELECTION CRITERIA: All relevant studies on the risk of developing hypertension, atherosclerosis, ischaemic heart disease, cerebrovascular accident (CVA), thromboembolism, heart failure or overall hospitalisation and mortality due to CVD after having had recurrent pre-eclampsia. DATA COLLECTION AND ANALYSIS: Twenty-two studies were included in the review. When possible, we calculated pooled risk ratios (RR) with 95% CI through random-effect analysis. MAIN RESULTS: Recurrent pre-eclampsia was consistently associated with an increased pooled risk ratio of hypertension (RR 2.3; 95% CI 1.9-2.9), ischaemic heart disease (RR 2.4; 95% CI 2.2-2.7), heart failure (RR 2.9; 95% CI 2.3-3.7), CVA (RR 1.7; 95% CI 1.2-2.6) and hospitalisation due to CVD (RR 1.6; 95% CI 1.3-1.9) when compared with women with subsequent uncomplicated pregnancies. Other studies on thromboembolism, atherosclerosis and cardiovascular mortality found a positive effect, but data could not be pooled. CONCLUSIONS: This systematic review and meta-analysis support consistent higher risk for future development of hypertension and CVD in women with recurring pre-eclampsia as opposed to women with a single episode of pre-eclampsia. TWEETABLE ABSTRACT: The risk of future cardiovascular disease increases when women have recurrence of pre-eclampsia compared with a single episode.

Effect of nifedipine and atosiban on perinatal brain injury: secondary analysis of the APOSTEL-III trial.

OBJECTIVE: Brain injury in neonates born prematurely is associated strongly with poor neurodevelopmental outcome. The aim of this study was to evaluate whether tocolysis with nifedipine or atosiban in women with threatened preterm birth can reduce the incidence of overall brain injury in neonates born prematurely. METHODS: This was a secondary analysis of the APOSTEL-III trial (Dutch Clinical Trial Registry, no. NTR2947), a randomized clinical trial in which women with threatened preterm labor between 25 and 34 weeks of gestation were allocated to treatment with nifedipine or atosiban. In this secondary analysis, women delivered at ≤ 32 weeks of gestational age in the two main contributing centers were included. Primary outcome was the presence of neonatal brain injury, which was defined as presence of abnormalities on ultrasound investigation and classified into mild and severe. To evaluate type and severity of brain injury, all neonatal ultrasounds performed during neonatal intensive and medium care admission were analyzed. To test the robustness of our results, a sensitivity analysis was performed assessing differences in baseline or known risk factors for brain injury. RESULTS: A total of 117 neonates (from 102 women) were studied, of which 51 had been exposed to nifedipine and 66 to atosiban. Brain injury was observed in 22 (43.1%) neonates in the nifedipine group compared with 37 (56.1%) in the atosiban group (OR, 0.60; 95% CI, 0.29-1.24). Presence of mild brain injury was comparable between the nifedipine (33.3%) and atosiban (48.5%) groups (OR, 0.53; 95% CI, 0.25-1.13). Severe brain injury was also comparable between the groups, observed in 9.8% of neonates in the nifedipine vs 7.6% of those in the atosiban group (OR, 1.33; 95% CI, 0.36-4.85). Intraventricular hemorrhage (≥ Grade I) was the most frequently seen ultrasound abnormality, observed in 18 (35.3%) neonates in the nifedipine group vs 25 (37.9%) in the atosiban group (OR, 0.90; 95% CI, 0.42-1.91). The sensitivity analysis, with adjustment for maternal age and gestational age at randomization, showed no statistical difference between the groups for presence of brain injury (OR, 0.58; 95% CI, 0.27-1.27). CONCLUSION: In children born before 32 weeks of gestation after the use of tocolytics, the prevalence of brain injury was high. No significant differences were found with respect to overall brain injury between neonates exposed to nifedipine and those exposed to atosiban. However, as this study was a secondary analysis of the APOSTEL III trial, it was underpowered for brain injury. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.