Recent advances in medicines for children and neonates

Abstract

The European Society for Developmental, Perinatal and Paediatric Pharmacology held its 13th Biennial Congress in Oslo, Norway. The congress was attended by over 100 health professionals from all around the world. The focus of the congress was recent advances in drug therapy in neonates and children. Alongside invited speakers, there were a host of presentations by young investigators which consisted of oral and poster presentations.

Keywords::

• children
• clinical trials
• drug toxicity
• medicines
• neonates
• pharmacovigilance
• rational use of medicines

The European Society for Developmental, Perinatal and Paediatric Pharmacology (ESDP) is composed of pediatric clinical pharmacologists, pediatricians and pediatric clinical pharmacists, alongside young researchers and trainees in this speciality. The majority of the members are from Europe but as the only regional society with an interest in this area, the meeting attracts investigators from all over the world. At this congress, there were individuals attending from Argentina, Canada, Cuba, China, Australia, Japan, Ghana, Israel, Mexico and the USA, as well as delegates from 15 European countries.

Drug therapy & heart failure

Stephanie Läer (University of Düsseldorf, Germany) gave a state-of-the-art lecture on the management of heart failure in pediatric patients. She critically reviewed the limited evidence related to medicines that are routinely used in pediatric patients with heart failure. She highlighted the need for more research in this area. Stephanie Läer was also elected as Secretary-General of the Society at the congress.

Pharmacovigilance & drug safety

Kristina Star from the Uppsala Monitoring Centre (Uppsala, Sweden) presented an update on the importance of pharmacovigilance. She highlighted the work of the Uppsala Monitoring Centre, which is a WHO collaborating center for international drug safety. The center receives individual case reports from over 100 national pharmacovigilance centers around the world. She highlighted the recognition by the center of the importance of pharmacovigilance in children and showed examples of recent collaborative work that highlighted safety issues. She highlighted the successes of different countries throughout the word in identifying adverse drug reactions and reporting them to the monitoring centres. New Zealand was the country with the highest reporting rate of suspected adverse drug reactions to the WHO (1200 reports per million inhabitants per year). The European countries with the highest reporting rates were Switzerland, Ireland, Denmark, Norway, The Netherlands and Sweden. Within Latin America, the country with the highest reporting rate was Cuba and this served as an excellent introduction for the next speaker, Zeina Bárzaga Arencibia.

Arencibia is a pediatric clinical pharmacist who works in the Provincial Pharmacovigilance Centre in Camagüey Province (Cuba), which has a particular interest in stimulating reports of suspected adverse drug reactions in children. She highlighted the success in Cuba, a low-to-middle income country, in establishing a national pharmacovigilance program. In addition, she described the focus on drug safety in children in Camagüey Province, which had received 634 reports of suspected adverse drug reactions per year per million children [1]. This was a significant improvement on the previous reporting rates of 226 reports per year per million children which had been identified in Sweden [2]. She pointed out, however, that the Cuban pharmacovigilance system still required significant improvement in that considerable numbers of adverse drug reactions were not reported. Finally, she described preliminary data showing how they had managed to improve their reporting rate by working in conjunction with the drug and therapeutics committee at the hospital.

The final speaker in this session was Bruce Carleton (University of British Columbia, Vancouver, Canada) who spoke about the Canadian Pharmacovigilance Program and its link to pharmacogenomics that aimed to help reduce drug toxicity in a selected group of patients. Pharmacogenomics is unlikely to play a role in reducing drug toxicity in acute admissions. However, it can be beneficial in children with chronic diseases, such as cancer, epilepsy and rheumatoid arthritis, who require long-term therapy.

Neonates

Steve Leeder (University of Missouri, MO, USA) gave an insight into the effect of pharmacogenetic polymorphisms and drug metabolism in infancy. Drug metabolism in the neonatal period is impaired and the neonate is at risk of greater toxicity. The importance of the influence of pharmacogenetics on drug metabolism was discussed. Astri Lang (University of Oslo, Norway) described the effects of multi-organ failure and its impact on drug metabolism in the neonate. There is increasing recognition that excipients can have a significant adverse effect on patients. This is potentially a greater problem in the neonatal period as the newborn infant receives a greater amount of excipient in relation to their bodyweight than older patients do. Karel Allegaert (University Hospitals Leuven, Belgium) described a prospective study of the effects of propylene glycol in neonates [3].

Clinical trials in children

The need to conduct clinical trials in children is now recognized. Owing to the fact that many conditions are uncommon, there is a requirement for networks. In many cases, these networks need to involve several different countries. The success of the Pediatric Rheumatology Network was highlighted by Alberto Martini (Professor of Pediatrics at the University of Genoa, Italy). He highlighted how the Pediatric Rheumatology Network, over the last 15 years, has helped to enrol over 10,000 children into studies that have evaluated the efficacy and safety of different medicines used in children with chronic rheumatic conditions alongside studies that have evaluated the quality of life of children receiving different treatments [4]. He highlighted the novel approaches to clinical trial design that had been used by the group, alongside the importance of ensuring that clinical trials performed in low-income countries involved an ethical approach that ensured the children benefited from the clinical trial. Kalle Hoppu (University of Helsinki, Finland) described pediatric legislation and its effect on clinical trials in pediatric patients. He described how the number of pediatric clinical trials in the USA had increased dramatically but the number of pediatric clinical trials within Europe had not significantly increased following the European legislation [5]. He also described some of the networks that have been established in different European countries to facilitate pediatric clinical trials.

Rational use of medicines

It has been recognized that clinical trials are important to establish an appropriate scientific base for the use of medicines in children. This led on to the focus of the session on the rational use of medicines. Antonio Clavenna (Mario Negri Institute for Pharmacological Research, Milan, Italy) highlighted the differences in the use of antibiotics in different European countries [6]. He also highlighted the differences in relation to treatment for children with asthma. His data demonstrated that drugs are more extensively prescribed in Italy than in other European countries. Kai Håkon Carlsen (University of Oslo, Norway) described some of the problems associated with the use of corticosteroids in asthma. The last speaker in this session was Helen Sammons (University of Nottingham, Derby, UK) who described the different assessment tools that had been used to study the rational use of medicines. Most of these studies were performed in low-income countries and very few studies involved children. It was clear that more work needed to be carried out on the problems associated with the irrational use of medicines in pediatric patients of all ages.

Treatment of acute lymphoblastic leukemia

Kjeld Schmiegelow (University of Copenhagen, Denmark) highlighted the recent advances made by the Scandinavian investigators in identifying children with acute lymphoblastic leukemia who are more likely to experience drug toxicity [7]. He explained that the cytotoxic drugs used to treat children with acute lymphoblastic leukemia by their very nature were associated with significant toxicity. This toxicity would often be associated with death. By identifying children who were likely to respond well to chemotherapy, the number of medicines and the doses could be kept to a minimum. This should hopefully significantly reduce the number of treatment-related deaths [7].

The congress was successful in that it involved a wide range of health professionals from across Europe, as well as around the world. It even involved undergraduate medical students from Germany who presented a poster describing a study of the acceptability of small-sized solid dosage forms in young children. These consist of minitablets that are 2 mm in diameter. The involvement of undergraduate medical students by more senior investigators is an excellent example of how we can all help to train the future researchers in this field.

Financial & competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.