10-year follow-up of the teratogenic effects and neurocognitive development after prenatal ACE-inhibitor exposure: a case report

Background/Aims: Angiotensin-converting enzyme inhibitors (ACE-inhibitors) are among the most frequently prescribed antihypertensive drugs. Ingestion during pregnancy has a known increased risk of fetopathy, with well-described congenital malformations. Until now, little is known about the long-term outcome and the impact on a child’s life. The objective of this case report is to analyze long term outcome following prenatal exposure to ACE-inhibitors and describe the subsequent impact. Case report: A 10-year-old child has been in follow-up for almost a decade. During his fetal period, his mother suffered malignant hypertension and had to continue her prescribed ACE-inhibitors despite known teratogenic effects.. The mother gave birth to a 33 weeks old infant through a semi-urgent caesarean section. During the neonatal phase, a severe kidney impairment due to bilateral hypodysplasia was observed. After initial need for dialysis, renal function recovered partially, but caused the need for dialysis and kidney transplantation at the age of 4-years. Aside from renal impairment, the child was born with hypocalvaria (i.e. incompletely formed skull bones) as well as severe abnormalities of the central nervous system, resulting in motor impairment (including a right-sided paresis) as well as cognitive retardation Conclusion: renal hypoplasia is well known in newborns prenatally exposed to ACE-inhibition, but there is a gap in knowledge on other organs and long-term prognosis. This case documents that other organs are equally involved, and that long-term neurocognitive development is compromised

Development and performance of the c4c national clinical trial networks for optimizing pediatric trial facilitation

Introduction:The high failure rate of industry-driven pediatric clinical trials leads to insufficient timely labeling of drugs in children and a lack of scientific evidence, resulting in the persistently high off-label drug use. National clinical trial networks can facilitate collaboration between sites, investigators, and experts, increasing the likelihood of successful trials. Within the conect4children (c4c) network, an Innovative Medicines Initiative 2-funded project, National Hubs hosted by National Clinical Trials Networks were set up across 21 European countries to facilitate the setup and execution of pediatric clinical trials. In this paper, we aim to present the performance metrics of the trial feasibility process as well as learnings and challenges encountered by the Belgian and Dutch Networks in working within the European c4c project.Method:The c4c National Hubs streamline pediatric clinical trials by initiating early country outreach, identifying overlapping studies, recommending quality trial sites, and supporting trial budgeting for both industry and academic settings. To show the impact of Pedmed-NL and Belgian Pediatric Clinical Research Network (BPCRN), internal metrics were collected from 2019 to 2022 on four industry-sponsored and three academic trials performed within the c4c network. Timelines and outcomes of the site identification were collected and analyzed for industry trials. A qualitative analysis was conducted through c4c platforms, sponsor interactions, and stakeholder engagement to evaluate the added value of a research network.Results:In industry-sponsored trials, full feasibility questionnaires were completed within 2 weeks (n = 48), and inclusion rates were up to 80% of clinical sites. Before committing to c4c, 14% of sites were contacted by industry, leading to communication burdens. Utilizing national infrastructure knowledge and therapeutic environment insights helped optimize trial timelines and address feasibility challenges. In addition, national adaptations, such as bilingual staff and site development, played a role in streamlining trial operations in both academic and industry settings. Performance and experiences were similar for both networks.Conclusion:The early-facilitation examples from the c4c trials demonstrated promising metrics for two National Hubs, including optimized start-up timelines and aiding site selection quality. The learnings and challenges of the Belgian and Dutch Networks provided insights for the development of clinical research networks

The European Paediatric Clinical Trials Network conect4children : activities of the Belgium National Network and its progression

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Development and performance of the c4c national clinical trial networks for optimizing pediatric trial facilitation

IntroductionThe high failure rate of industry-driven pediatric clinical trials leads to insufficient timely labeling of drugs in children and a lack of scientific evidence, resulting in the persistently high off-label drug use. National clinical trial networks can facilitate collaboration between sites, investigators, and experts, increasing the likelihood of successful trials. Within the conect4children (c4c) network, an Innovative Medicines Initiative 2-funded project, National Hubs hosted by National Clinical Trials Networks were set up across 21 European countries to facilitate the setup and execution of pediatric clinical trials. In this paper, we aim to present the performance metrics of the trial feasibility process as well as learnings and challenges encountered by the Belgian and Dutch Networks in working within the European c4c project.MethodThe c4c National Hubs streamline pediatric clinical trials by initiating early country outreach, identifying overlapping studies, recommending quality trial sites, and supporting trial budgeting for both industry and academic settings. To show the impact of Pedmed-NL and Belgian Pediatric Clinical Research Network (BPCRN), internal metrics were collected from 2019 to 2022 on four industry-sponsored and three academic trials performed within the c4c network. Timelines and outcomes of the site identification were collected and analyzed for industry trials. A qualitative analysis was conducted through c4c platforms, sponsor interactions, and stakeholder engagement to evaluate the added value of a research network.ResultsIn industry-sponsored trials, full feasibility questionnaires were completed within 2 weeks (n = 48), and inclusion rates were up to 80% of clinical sites. Before committing to c4c, 14% of sites were contacted by industry, leading to communication burdens. Utilizing national infrastructure knowledge and therapeutic environment insights helped optimize trial timelines and address feasibility challenges. In addition, national adaptations, such as bilingual staff and site development, played a role in streamlining trial operations in both academic and industry settings. Performance and experiences were similar for both networks.ConclusionThe early-facilitation examples from the c4c trials demonstrated promising metrics for two National Hubs, including optimized start-up timelines and aiding site selection quality. The learnings and challenges of the Belgian and Dutch Networks provided insights for the development of clinical research networks

C4C et structuration de la recherche clinique en néphrologie pédiatrique

Avant les années 1980, la recherche en médecine pédiatrique était largement négligéechangement de paradigme! À partir de 2007 : modification de la réglementation européenne et passage aux plans d'investigation pédiatrique (PIP), mais le nombre de PIP reste faible. Nécessité évidente d'un réseau paneuropéen pour faciliter la résolution des problèmes spécifiques à la pédiatrie par le biais du réseau conect4children (c4c)