Background: Post-term pregnancy, a pregnancy exceeding 294 days or 42 completed weeks, is associated with increased perinatal morbidity and mortality and is considered a high-risk condition which requires specialist surveillance and induction of labour. However, there is uncertainty on the policy concerning the timing of induction for post-term pregnancy or impending post-term pregnancy, leading to practice variation between caregivers. Previous studies on induction at or beyond 41 weeks versus expectant management showed different results on perinatal outcome though conclusions in meta-analyses show a preference for induction at 41 weeks. However, interpretation of the results is hampered by the limited sample size of most trials and the heterogeneity in design. Most control groups had a policy of awaiting spontaneous onset of labour that went far beyond 42 weeks, which does not reflect usual care in The Netherlands where induction of labour at 42 weeks is the regular policy. Thus leaving the question unanswered if induction at 41 weeks results in better perinatal outcomes than expectant management until 42 weeks. Methods/design: In this study we compare a policy of labour induction at 41 + 0/+1 weeks with a policy of expectant management until 42 weeks in obstetrical low risk women without contra-indications for expectant management until 42 weeks and a singleton pregnancy in cephalic position. We will perform a multicenter randomised controlled clinical trial. Our primary outcome will be a composite outcome of perinatal mortality and neonatal morbidity. Secondary outcomes will be maternal outcomes as mode of delivery (operative vaginal delivery and Caesarean section), need for analgesia and postpartum haemorrhage (≥1000 ml). Maternal preferences, satisfaction, wellbeing, pain and anxiety will be assessed alongside the trial. Discussion: his study will provide evidence for the management of pregnant women reaching a gestational age of 41 weeks.
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Background: Adverse outcome pathway (AOP) networks are versatile tools in toxicology and risk assessment that capture and visualize mechanisms driving toxicity originating from various data sources. They share a common structure consisting of a set of molecular initiating events and key events, connected by key event relationships, leading to the actual adverse outcome. AOP networks are to be considered living documents that should be frequently updated by feeding in new data. Such iterative optimization exercises are typically done manually, which not only is a time-consuming effort, but also bears the risk of overlooking critical data. The present study introduces a novel approach for AOP network optimization of a previously published AOP network on chemical-induced cholestasis using artificial intelligence to facilitate automated data collection followed by subsequent quantitative confidence assessment of molecular initiating events, key events, and key event relationships. Methods: Artificial intelligence-assisted data collection was performed by means of the free web platform Sysrev. Confidence levels of the tailored Bradford-Hill criteria were quantified for the purpose of weight-of-evidence assessment of the optimized AOP network. Scores were calculated for biological plausibility, empirical evidence, and essentiality, and were integrated into a total key event relationship confidence value. The optimized AOP network was visualized using Cytoscape with the node size representing the incidence of the key event and the edge size indicating the total confidence in the key event relationship. Results: This resulted in the identification of 38 and 135 unique key events and key event relationships, respectively. Transporter changes was the key event with the highest incidence, and formed the most confident key event relationship with the adverse outcome, cholestasis. Other important key events present in the AOP network include: nuclear receptor changes, intracellular bile acid accumulation, bile acid synthesis changes, oxidative stress, inflammation and apoptosis. Conclusions: This process led to the creation of an extensively informative AOP network focused on chemical-induced cholestasis. This optimized AOP network may serve as a mechanistic compass for the development of a battery of in vitro assays to reliably predict chemical-induced cholestatic injury.
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Background Psychological aspects of labor and birth have received little attention within maternity care service planning or clinical practice. The aim of this paper is to propose a model demonstrating how neurohormonal processes, in particular oxytocinergic mechanisms, not only control the physiological aspects of labor and birth, but also contribute to the subjective psychological experiences of birth. In addition, sensory information from the uterus as well as the external environment might influence these neurohormonal processes thereby influencing the progress of labor and the experience of birth. Methodology In this new model of childbirth, we integrated the findings from two previous systematic reviews, one on maternal plasma levels of oxytocin during physiological childbirth and one meta-synthesis of women´s subjective experiences of physiological childbirth. Findings The neurobiological processes induced by the release of endogenous oxytocin during birth influence maternal behaviour and feelings in connection with birth in order to facilitate birth. The psychological experiences during birth may promote an optimal transition to motherhood. The spontaneous altered state of consciousness, that some women experience, may well be a hallmark of physiological childbirth in humans. The data also highlights the crucial role of one-to-one support during labor and birth. The physiological importance of social support to reduce labor stress and pain necessitates a reconsideration of many aspects of modern maternity care. Conclusion By listening to women’s experiences and by observing women during childbirth, factors that contribute to an optimized process of labor, such as the mothers’ wellbeing and feelings of safety, may be identified. These observations support the integrative role of endogenous oxytocin in coordinating the neuroendocrine, psychological and physiological aspects of labor and birth, including oxytocin mediated. decrease of pain, fear and stress, support the need for midwifery one-to-one support in labour as well as the need for maternity care that optimizes the function of these neuroendocrine processes even when birth interventions are used. Women and their partners would benefit from understanding the crucial role that endogenous oxytocin plays in the psychological and neuroendocrinological process of labor.
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