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

Abstract Body

Cystic fibrosis has been described more than 80 years ago and was long known as a very severe pediatric genetic disease. Due to aggressive symptomatic treatments and holistic care in dedicated centres, life expectancy has dramatically increased and half of the patients are now adults. Since the cloning of the CFTR gene in 1989, research aiming at understanding how CFTR mutations translate to abnormal synthesis or function of the CFTR protein has opened the way to genomically-guided therapy to improve CFTR function. A CFTR potentiator to enhance CFTR channel function has been approved in 2012 for specific and quite rare mutations, and it is now approved in Europe for patients from 6 months of age. Subsequently, combinations of a corrector to increase CFTR expression at the cell membrane, plus a potentiator, have been approved for patients homozygous for the most frequent p.Phe508del mutation. One combination is now approved for patients aged 2 years and above. To obtain more robust correction of the CFTR protein, new combinations of drugs are being studied. If data of clinical trials are confirmed, a triple combination associating two correctors and one potentiator could be a robust and well tolerated CFTR modulator for patients bearing at least one p.Phe508del mutation. This recent progress in clinically very effective CFTR modulator therapies is opening a new era full of promess of a healthier life for patients with cystic fibrosis who are eligible to these drugs and have access to them.

Abstract Body

Abstract Body

Background: Juvenile idiopathic arthritis (JIA) is a heterogeneous autoimmune pathology that is most common in children. Understanding of the complex of immunoregulatory mechanisms coupled with genetic analysis reveals a complex relationship between autoimmune responses and primary immunodeficiency (PID).

Ukraine, with its leading organisation Institute of Pediatrics, Obstetrics and Gynecology, is one of the founding member of EPTRI (European Paediatric Translational Research Infrastructure), a pan-European Research Infrastructure dedicated to paediatric research is being developed, with the aim to create the new paediatric Research Infrastructure to enhance technology-driven paediatric research in drug development process to be translated into clinical research.

Objective. To study the prognostic value of PID genes in JIA.

Methods. Sequencing of 207 PID genes was performed in 53 patients with JIA.

Results: Changes in the nucleotide sequence in the genes were detected: NOD2, CARD11, JAK3, IL21R, IL10RA, STAT3, NFKB2, IRAK4. Increased risk in NOD2 gene was identified in 20,0% patients. Pathogenic mutations in PID genes were detected in 16,6 % children (IL7R, MUTYH, WFS1, SP110,TREX1). Mutation in IL7R increased the severity of arthritis with early joint destruction. TREX1 mutations lead to accumulation of self-DNA in the cytosol of TREX1-deficient cells. Persistence of the ssDNA species substrate of TREX1 triggers systemic inflammation and uncontrolled autoimmunity by activation IFNs.

Conclusions: Identified mutation PID – genes JIA expand the understanding of the pathogenesis, spectrum of phenotypic manifestations of the disease, prognosis and choise of personalized therapy.

This Project has received funding from the European Union’s Horizon 2020 programme under Grant Agreement No.777554”

Abstract Body

Background/aims: Studies on the association between maternal education and cognitive development among children born very preterm (VPT) are sparse and contradictory. We investigated the association of maternal education level with cognitive outcomes in European cohorts of children born <32 weeks’ gestational age.

Methods: The study included 15 VPT cohorts from 13 countries constituted between 1984 and 2012 with information on maternal education and assessment of early general development at 2-3 years old and/or IQ between 4-15 years old. The International Standard Classification of Education was used to classify maternal education: (1) primary/lower secondary; (2) secondary/short tertiary; (3) bachelors or higher. We used a meta-analytical approach based on harmonised aggregate and summary data provided by each cohort. We estimated pooled standardized mean differences (SMD) using random effects models comparing low with high and medium with high education for children assessed at 2-3, 4-7 and 8-15 years of age.

Results: The study included 8201 children from 12 cohorts at 2-3 years, 8856 from 12 cohorts at 4-8 years and 1605 children from 6 cohorts at 8-15 years. Children whose mothers had low, compared with high, educational attainment scored lower on cognitive measures (SMD 2-3y=-0.37 (95%CI: -0.45;-0.28); SMD 4-7y= -0.59 (-0.77;-0.41); SMD 8-15y=-0.54 (-0.72;-0.37)). Significant, but lower magnitude effects were observed in children of mothers with medium, compared with high, education. Restricting analyses to extremely preterm (<27 weeks) births yielded similar results.

Conclusion: Across diverse settings and regardless of VPT severity, low maternal education was associated with lower cognition in children born VPT.

Abstract Body

Background

Preterm born children are at high risk for, among others, adverse motor neurodevelopment. The aim of this study was to establish the relationship between motor outcome and multimodal neuroimaging outcomes in a Dutch cohort of very preterm born children at 9-10 years of age.

Methods

In 64 very preterm born children, motor outcome was assessed by the Movement Assessment Battery for Children, second Dutch edition (M-ABC-II-NL). Magnetic resonance imaging (MRI), diffusion tensor imaging (DTI) and electroencephalography (EEG) were acquired and evaluable in 51, 54 and 54 children, respectively. We investigated the relationship between motor outcome and white matter, deep grey matter, cerebellum and ventricular volume, fractional anisotropy, mean diffusivity, axial diffusivity, radial diffusivity, upper alpha (A2) functional connectivity and relative A2 power. Per modality, the most significant measure was selected for a final Generalized Estimating Equation (GEE) model to investigate if measures were independent predictors of motor outcome.

Results

Ventricular volume, radial diffusivity, mean diffusivity, relative A2 power and A2 functional connectivity were significantly correlated to motor outcome. The GEE model, which included ventricular volume, radial diffusivity and relative A2 power, showed that the ventricular volume and relative A2 power were independent predictors of motor outcome (B = -9.42*10^-5, p = .027 and B = 28.9, p = .007, respectively).

Conclusion

The results of this study highlight the importance of multimodal neuroimaging in the preterm population; the combination of multiple modalities provides spatio-temporal complementarity and the revealed (in)dependencies provide novel insights into underlying mechanisms.

Abstract Body

Background and aims

The infant mortality rate (IMR) serves as a key indicator of population health, given its strong relationship with socio-economic development and quality of preventive and curative care. We explored recent trends in IMR in France, which continual decrease since World War II appears to be slowing.

Methods

We used data from the French National Institute of Statistics and Economic Studies on births and deaths during the first year of life from 2000 to 2018 to calculate monthly IMR (number of deaths of infants under 1 year old/1,000 live births).We conducted a time-series analysis using the autoregressive integrated moving average technique to explore the possibility of trends, seasonality, and outliers. We ran segmented linear regressions based on identified change-points to assess changes in linear trends over time.

Results

Over the 19-year study period, 59,056 infant deaths occurred, for an average IMR of 4.02/1,000 (4.2 in male, 3.4 in female); 46.8% and 67.5% of infant deaths occurred during the early neonatal (D0-D7) and neonatal (D0-D28) periods, respectively. Outlier detection routines identified two selected change-points in 2004 and 2011 (Figure). Initially, the IMR significantly decreased over time, sharply from 2000 to 2004 (slope: -0.012 deaths/1000 live births/month; 95%CI: -0.016 to -0.008) then slightly from 2004 to 2011 (slope: -0.003; 95%CI: -0.004 to -0.001). Then, from 2011 to 2018, a significant increase was observed (slope: 0.005; 95%CI: 0.003 to 0.007).

Conclusions

The significant increase in IMR since 2011 in France should prompt in-depth investigations to prepare corrective actions.