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Introduction Currently, the majority of women worldwide with threatened preterm birth are treated with tocolytics. Although tocolytics can effectively delay birth for 48 hours, no tocolytic drug has convincingly been shown to improve neonatal outcomes and effects on long-term child development are unknown. The aim of this follow-up study of a placebo controlled randomised trial is to investigate the long-term effects of atosiban administration in case of threatened preterm birth on child’s neurodevelopment and behaviour development, overall health and mortality.Methods and analysis This protocol concerns a follow-up study of the multicentre randomised double-blind placebo controlled APOSTEL 8 trial (NL61439.018.17, EudraCT-number 2017-001007-72). In this trial, women with threatened preterm birth (between 30 and 34 weeks of gestation) defined as uterine contractions with (1) a cervical length of

Abstract Background Given the polysemy of the concept resilience, is it possible to have a unified conceptualisation of food system resilience? This paper provides a multidisciplinary evaluation of the literature to identify common themes that prevail in food system resilience debates and the challenges to reach a unified conceptualisation. The aim is to provide insights into some of the main issues and tensions that we identified during our research which will then allow academics and policymakers to identify the most significant themes and topics for discussion in the debate. While we only focus on one application of resilience, namely, food system resilience during extreme events, we believe that our approach and findings could be integrated and applied to other areas of resilience, as well. Results Our ontological exploration shows that ‘resilience’ is a rich concept that has an important bearing on many themes and topics in the domain of food systems. This makes it highly relevant to develop and apply the concept of ‘food system resilience’. The application of the concept in research and practice, however, faces many challenges that are rooted in ontological and epistemological differences among different disciplines and practices. While posing serious challenges in interdisciplinary collaboration and communication, these challenges also foster new research opportunities as knowledge gaps are discovered. We propose that there is a need to critically investigate the social, environmental, and economic trade-offs implied in policy strategies towards resilience at various levels of food systems and among different actors or groups of actors. Conclusion Interdisciplinary communication between different fields can be difficult and divisive. The ambition to unify the theory may be counterproductive in addressing practical problems that often require multidisciplinary collaboration. The challenge is to identify context-specific challenges and policy options using the ‘resilience lens’ and translating the concept into measurable indicators. Our research identifies some of these challenges and aims to provide a way to improve dialogue between different actors, through discussions about tensions and issues within their research. The ontological differences and debates are unlikely to be resolved anytime soon, nor should it be a priority to resolve these differences. A pragmatic case-specific approach can be adopted to address the problem while considering ontological differences. Our research will provide food system resilience researchers with some guidance about challenges in their research, as well as those working on developing ontologies.

Abstract Background Perinatally chikungunya infected neonates have been reported to have high rates of post-infection neurologic sequelae, mainly cognitive problems. In older children and adults chikungunya does not appear to have sequelae, but data on postnatally infected infants are lacking. Methods We performed a prospective, non-controlled, observational study of infants infected before the age of 6 months with a severe chikungunya infection during the 2014–2015 epidemic in Curaçao, Dutch Antilles. Two years post-infection cognitive and motor - (BSID-III) and social emotional assessments (ITSEA) were performed. Results Of twenty-two infected infants, two died and two were lost to follow up. Eighteen children were seen at follow-up and included in the current study. Of these, 13 (72%) had abnormal scores on the BSID-III (cognitive/motor) or ITSEA. Conclusion In the first study aimed at postnatally infected infants, using an uncontrolled design, we observed a very high percentage of developmental problems. Further studies are needed to assess causality, however until these data are available preventive measure during outbreaks should also include young infants. Those that have been infected in early infancy should receive follow up.

Because of its hands-on and integrative approach to STEM, educational robotics has become increasingly popular in recent years. Yet, a gender gap still exists in attitudes towards STEM studies and careers, especially among middle and high school students, potentially resulting in a lack of women in the STEM workforce. This study explores the effect of a robotics curriculum on Dutch 7th- and 8th-grade students’ attitude towards STEM subjects and careers, as assessed by the S-STEM survey. The results revealed no difference between the pre-test and post-test in attitudes toward STEM for both boys and girls. However, boys scored significantly higher than girls on attitude towards technology, engineering and future STEM studies on the post-test. A post hoc analysis revealed a significant difference between boys and girls on their attitude towards engineering and technology during the pre-test. These results demonstrate the difference between boys and girls in their attitudes towards STEM subjects and careers within the context of robotics education. Considering the lack of research on educational robotics among young teenagers, this field needs to be further studied to assess its effect on gender differences within attitudes towards STEM.

Introduction Late preterm prelabour rupture of membranes (PROM between 34+0 and 36+6 weeks gestational age) is an important clinical dilemma. Previously, two large Dutch randomised controlled trials (RCTs) compared induction of labour (IoL) to expectant management (EM). Both trials showed that early delivery does not reduce the risk of neonatal sepsis as compared with EM, although prematurity-related risks might increase. An extensive, structured long-term follow-up of these children has never been performed.Methods and analysis The PPROMEXIL Follow-up trial (NL6623 (NTR6953)) aims to assess long-term childhood outcomes of the PPROMEXIL (ISRCTN29313500) and PPROMEXIL-2 trial (ISRCTN05689407), two multicentre RCTs using the same protocol, conducted between 2007 and 2010 evaluating IoL versus EM in women with late preterm PROM. The PPROMEXIL Follow-up will analyse children of mothers with a singleton pregnancy (PPROMEXIL trial n=520, PPROMEXIL-2 trial n=191, total IoL n=359; total EM n=352). At 10–12 years of age all surviving children will be invited for a neurodevelopmental assessment using the Wechsler Intelligence Scale for Children-V, Color-Word Interference Test and the Movement Assessment Battery for Children-2. Parents will be asked to fill out questionnaires assessing behaviour, motor function, sensory processing, respiratory problems, general health and need for healthcare services. Teachers will fill out the Teacher Report Form and answer questions regarding school attainment. For all tests means with SDs will be compared, as well as predefined cut-off scores for abnormal outcome. Sensitivity analyses consisting of different imputation techniques will be used to deal with lost to follow-up.Ethics and dissemination The study has been granted approval by the Medical Centre Amsterdam (MEC) of the AmsterdamUMC (MEC2016_217). Results will be disseminated through peer-reviewed journals and summaries shared with stakeholders. This protocol is published before analysis of the results.Trial registration number NL6623 (NTR6953).

Abstract Background The achievement of age-specific developmental milestones in youth is of great importance to the adjustment in adult life. Young adults who were born preterm, might go through a different developmental trajectory and transition into adulthood than their peers. This study aimed to compare the psychosocial developmental trajectory of young adults who were born preterm with peers from the general population. Young adults from the POPS (Project On Preterm and Small for gestational age infants) cohort study, born in 1983 in the Netherlands, completed online the Course of Life Questionnaire (CoLQ - achievement of psychosocial developmental milestones) at 28 years of age. Analysis of variance by group, age and gender was performed to test differences on the CoLQ scale scores between the POPS-group and 211 peers (25–30 years) from the general population (Ref-group). Differences on item level, representing the achievement of individual milestones, were analyzed with logistic regression analyses by group, age and gender. Results The POPS-group (n = 300, 32,3% biased response) scored significantly lower than the Ref-group on the scales Psychosexual Development (effect size − 0.26, p

Abstract Objective The objective of the Dutch Sildenafil therapy in dismal prognosis early onset fetal growth restriction (STRIDER) randomised clinical trial is to assess the beneficial and harmful effects of sildenafil versus placebo on fetal and neonatal mortality in pregnant women with severe early-onset fetal growth restriction. The objective of this detailed statistical analysis plan is to minimize the risks of selective reporting and data-driven analysis. Setting The setting is 10 tertiary care hospitals and one secondary care hospital in The Netherlands. Participants The participants will be 360 pregnant women with severe early-onset fetal growth restriction. Interventions The intervention is sildenafil 25 mg or placebo orally three times a day. Primary and secondary outcome measures The primary outcome is a composite of death or major neonatal morbidity assessed at hospital discharge. The secondary outcomes are neurodevelopmental impairment; mean scores of the Bayley III cognitive and motor assessment; the proportion of patients experiencing either preeclampsia or haemolysis, elevated liver enzymes, and low platelets syndrome; pulsatility index of uterine arteries, umbilical artery, and middle cerebral artery; birthweight; and gestational age at either delivery or intra-uterine death. Results A detailed statistical analysis is presented, including pre-defined exploratory outcomes and planned subgroup analyses. One interim analysis after 180 patients had completed the study was planned and a strategy to minimise the risks of type I errors due to repetitive testing is presented. During review of this manuscript the interim analysis was performed by the Data Safety Monitoring Board and early stopping of the trial was recommended. Final analyses will be conducted independently by two statistically qualified persons following the present plan. Conclusion This pre-specified statistical analysis plan was written and submitted without knowledge of the unblinded data and updated after stopping of the trial at interim analysis. Trial registration ClinicalTrials.gov, NCT02277132. Registered on 29 September 2014. Original protocol for the study: doi:https://doi.org/10.5281/zenodo.56148

With the many promises it holds in addressing problems concerning information exchange and digital transactions in multi-actor processes, blockchain technology (BCT) has gained considerable traction in the agrifood sector. Governments, international organisations, private companies, consortia of public and private actors are launching various blockchain projects for improving transparency, traceability, and many other key issues in the agrifood sector. This has resulted in a large number of use cases. It is often unclear, however, what and how technical, social and economic aspects were considered in different usecases. Due to the novelty and elusiveness of the technology, there is no ready-to-use analytical framework or guideline yet for assessing its applicability and choosing the right technical and organisational setup. As a result, many stakeholders have to grope in the dark when designing and implementing their “blockchain application.” Based on studies of use cases worldwide and experiences in organizing different blockchain pilots in the Netherlands, this paper seeks to address this problem by providing an overview of the choices to be made at three layers of a blockchain application: the ledger, the governance structure and the ecosystem. This can serve as a reference framework for understanding different blockchain applications and choosing key parameters for new use cases in the agrifood sector. It is expected that such demystification of the blockchain will contribute to more realistic and effective application of the technology to pressing problems in agriculture and food.

Abstract Background Severe, early-onset fetal growth restriction due to placental insufficiency is associated with a high risk of perinatal mortality and morbidity with long-lasting sequelae. Placental insufficiency is the result of abnormal formation and function of the placenta with inadequate remodelling of the maternal spiral arteries. There is currently no effective therapy available. Some evidence suggests sildenafil citrate may improve uteroplacental blood flow, fetal growth, and meaningful infant outcomes. The objective of the Sildenafil TheRapy In Dismal prognosis Early onset fetal growth Restriction (STRIDER) collaboration is to evaluate the effectiveness of sildenafil versus placebo in achieving healthy perinatal survival through the conduct of randomised clinical trials and systematic review including individual patient data meta-analysis. Methods Five national/bi-national multicentre randomised placebo-controlled trials have been launched. Women with a singleton pregnancy between 18 and 30 weeks with severe fetal growth restriction of likely placental origin, and where the likelihood of perinatal death/severe morbidity is estimated to be significant are included. Participants will receive either sildenafil 25 mg or matching placebo tablets orally three times daily from recruitment to 32 weeks gestation. Discussion The STRIDER trials were conceived and designed through international collaboration. Although the individual trials have different primary outcomes for reasons of sample size and feasibility, all trials will collect a standard set of outcomes including survival without severe neonatal morbidity at time of hospital discharge. This is a summary of all the STRIDER trial protocols and provides an example of a prospectively planned international clinical research collaboration. All five individual trials will contribute to a pre-planned systematic review of the topic including individual patient data meta-analysis. Trial registrations New Zealand and Australia: ACTRN12612000584831 . Registered 30/05/2012. Canada: NCT02442492 . Registered 05/05/2015. Ireland: CT 900/572/1 . Registered 15/07/2015. The Netherlands: NCT02277132 . Registered 29/09/2014. United Kingdom: ISRCTN39133303 . Registered 31/07/2014.

ObjectiveVery preterm children have poorer attentional, behavioral and emotional functioning than term-born children. Problems on these domains have been linked to poorer executive function (EF). This study examined effects of a game-formatted, comprehensive EF training on attentional, behavioral and emotional functioning and self-perceived competence in very preterm children.Study DesignEighty-five children participated in a multi-center, double-blind, placebo and waitlist-controlled randomized trial. Children were recruited from neonatal follow-up units of two academic medical centers in The Netherlands. Eligible for inclusion were 8–12 year old children born very preterm (

Objective: The aim of this study was to study growth patterns of children born after suspected fetal growth restriction (FGR) at term and to compare the effect of induction of labor (IoL) and expectant management (EM), also in relation to neurodevelopmental and behavioral outcome at age 2.Methods: We performed a 2 years' follow-up of growth of children included in the Disproportionate Intrauterine Growth Restriction Trial at Term (DIGITAT) study, a Randomized Controlled Trial (RCT) comparing IoL with EM in pregnancies with suspected FGR at term. We collected data on child growth until the age of 2 years. Standard deviation scores (SDSs) for height and weight were calculated at different ages. We assessed the effects of IoL compared with EM and the effects of a birth weight below or above the 3rd or 10th centile on catch-up growth. Target height SDSs were calculated using the height of both parents.Results: We found a significant increase in SDS in the first 2 years. Children born after EM showed more catch-up growth in the first month [height: mean difference −0.7 (95% CI: 0.2; 1.3)] and weight [mean difference −0.5 (95% CI: 0.3; 0.7)]. Children born with a birth weight below the 3rd and 10th centiles showed more catch-up growth after 1 year [mean difference −0.8 SDS (95% CI: −1.1; −0.5)] and after 2 years [mean difference −0.7 SDS (95% CI: −1.2; −0.2)] as compared to children with a birth weight above the 3rd and 10th centiles. SDS at birth had the strongest effect on adverse neurodevelopmental outcome at 2 years of age.Conclusion: After FGR at term, postnatal catch-up growth is generally present and associated with the degree of FGR. Obstetric management in FGR influences postnatal growth. Longer-term follow-up is therefore needed and should be directed at growth and physical health.Clinical Trial Registration:www.ClinicalTrials.gov, identifier SRCTN10363217.