Recorded sessions on demand will be available 24 hours after the session ends

Abstract Body

Translating a scientific discovery from the laboratory to human application involves a series of challenges. Each requirement must be satisfactorily answered before moving to the next phase. Initially, there are several issues associated with the reproducibility of the original discovery. Subsequently, additional preclinical aspects of safety, formulation, dose, administration route, timing of delivery, and pharmacokinetics must be completed before entering human trials. In this talk we will review examples of neonatal trials that had similair or different outcomes that were tested in the animal lab.

Abstract Body

Background Developmental pharmacology covers the research area between drug discovery and paediatric clinical trials. This research elucidates the impact of growth and development of the drug’s disposition, efficacy and safety, to be implemented in clinical trials. This paper aims to describe the current European landscape in developmental pharmacology and to explain the needed infrastructure for innovative paediatric drug development.

Methods In the framework of European Paediatric Translational Research Infrastructure (ID-EPTRI), an online survey was launched across Europe to identify and map expert research centres in developmental pharmacology and to collect information to clarify the scientific and technological context for paediatric research.

Results 38 potential service providers of a total of 329 distributed surveys across Europe responded to the survey. The analysis allowed to define a map of services to be provided within the developmental pharmacology platform. These services include: preclinical in vitro/ex vivo/juvenile in vivo research as well as modelling and simulation studies. They are provided by labs focusing on ADME research, microdosing studies, pharmacometrics, placental platforms and sensitive analytical assays.

Conclusion The current developmental pharmacology landscape is a multidisciplinary field with scientists from different background. This capacity presents outstanding opportunities for future academic and public-private partnerships collaboration. ID-EPTRI could play an important role in facilitating visibility of available services, as well as foster new collaborations, to stimulate developmental pharmacology research in Europe.

Acknowledgements

The research leading to these results has received funding from the European Union’s Horizon 2020 programme under Grant Agreement No. 777554

Abstract Body

Bronchopulmonary dysplasia (BPD) is a chronic lung disease of prematurity, characterized by an arrest in alveolarization. Treatments are not available and BPD patients experience lifelong disabilities. The hyperoxia-exposed preterm rabbit has recently been characterized as an advantageous model to study BPD due to its lab-fit size and similar lung development with humans. However, reliable in vitro models to study alveolarization, to perform drug screening and dose-finding experiments are lacking. Precision cut lung slices (PCLS) have been described as a reliable tool to study different lung pathological conditions. The goal of this study was to develop for the first time preterm rabbit PCLS as an in vitro tool for drug testing.

Lungs were harvested from rabbits delivered preterm in the saccular stage of lung development. PCLS were incubated in pseudo normoxia (to mimic the hypoxia condition in utero during physiological lung development) or in hyperoxia (to mimic the condition of preterm babies exposed to oxygen therapy). Viability assays, histological characterization and supernatant analysis were performed every 24h.

PCLS remained viable for 7 days in culture. Alveolarization continued during the first 48 hours. Starting from day 3, hyperoxia-exposed PCLS showed less alveoli and septal thickening. Cell death increased past day 5, indicating that 4-5 days is the maximum time which preserved both optimal viability and lung architecture in the specific conditions.

This new tool could be further characterized and then employed to perform drug screening to identify promising targets to preserve normal lung development during injury.

Abstract Body

Background and aims: Newborns are the most vulnerable patients after cardiac surgery. Although mortality risk scores before surgery may predict the risk of poor outcome or mortality, biomarkers could add objective individualized data. The aim was to assess the ability of MR-proadrenomedullin(proADM) to predict risk of poor outcome and mortality after cardiac surgery in newborn.

Methods: Prospective observational study of patients admitted to the neonatal intensive care unit after cardiac surgery from April-2018 to December-2019. ProADM were determined at admission.

Results: Thirty-six patients were included. Twenty-two (61.1%) had a STAT-Mortality category≥4. Four patients (11.1%) presented a poor outcome and three died (8.3%). ProADM was higher in patients with poor outcome (2.37nmol/L vs. 1.17nmol/L,p=0.007) and death (2.8nmol/L vs. 1.17nmol/L,p=0.009). STAT≥4 was less frequent in those who had a poor outcome (4.5% vs. 21.4%,p=0.277) or died (0% vs. 21.4%,p=0.051). Logistic regression model showed the independent association of proADM with poor outcome, OR 7.6(95%CI 1.4-41.6). The AUC of proADM was the best AUC for predicting poor outcome (0.895). ProADM was also associated to mortality risk (OR 11.7(95%IC 1.3-105)). Its AUC for predicting mortality was 0.929. The combination of STAT≥4 and proADM did not add power of prediction for poor outcome or mortality.

Conclusions: In this sample, STAT-Mortality score did not predict poor outcome or mortality effectively. In contrast, ProADM seems to be a good biomarker for predicting poor outcome and mortality after cardiac surgery in those vulnerable patients, thus checking this biomarker should be considered in the post-operative care.

Abstract Body

Background: Recent data suggest that fetuses conceived by assisted reproductive technologies (ART) undergo cardiovascular remodelling resulting in altered myocardial performance.

Objective: Our aim was to assess left (LV) and right (RV) ventricular function in infants conceived by ART during the early neonatal period and compare the findings with a control group conceived spontaneously.

Design/Methods: This was a prospective cohort study which included 25 term infants conceived by ART and 25 infants term infants conceived spontaneously. Echocardiography was performed on days 1, 2, and 3 following birth.

Results: ART infants were of a lower gestation (38.8 ± 1.0 vs. 39.8 ± 1.0 weeks, p<0.01) but similar birthweight (3.6 ± 0.6 vs. 3.7 ± 0.4 Kg, p=0.35). ART infants demonstrated lower RV and LV function over the study period (Figure). On Day 1, ART infants demonstrated a higher LV Eccentricity Index (1.8 ± 0.2 vs. 1.5 ± 0.2, p<0.01) and a lower PAAT (61 ± 14 vs. 70 ± 10, p=0.02) indicating more septal flattening and increased pulmonary vascular resistance. The relationship between ART and lower LV and RV function remained significant on linear regression when controlling for gestation, maternal age, gender and mode of delivery (all p<0.05, model R² between 0.29 – 0.42, standardised β coefficient between 0.63 – 0.74).

Conclusion: Infants conceived by ART present with evidence right and left ventricular dysfunction during the early neonatal period. Those findings further reinforce the concept of myocardial remodelling in infants conceived by ART.