Paediatric and obstetrical pharmacology – Pushing the frontier forward

A little over a century ago, at the start of the twentieth century, a child in the United Kingdom faced grim odds over the first 5 years of their life; 20% of children – one in five – died before their fifth birthday, primarily of infection. Currently the odds are much more in the child's favour – in fact they are <0.4% (4 in 1000), with issues related to birth and congenital anomalies being the primary cause of death. This miraculous improvement –unprecedented in medical history – occurred because of three things: public sanitation, vaccination and effective drug therapy. Women – especially over the course of pregnancy – faced similar challenges, which also were markedly changed by the development of specific drug therapy. Although great progress has been made in the care of women and children, many obstacles remain. In the case of women, historical bias against including women in drug studies and in the process of drug development has led to significant under-representation in clinical research; this inequity has been associated with significant negative impacts on health outcomes for women, particularly due to the lack of actual data to guide pharmacotherapy. In the case of children, while the Elixir of Sulfanilamide tragedy led to the creation of the basis of the drug approval process used currently, the Thalidomide disaster resulted in the passage of legislation in the United States in 1962 – the Kefauver-Harris Amendment to the Food, Drug and Cosmetic Act – which, while intended to improve drug safety and enhance drug therapy for children, had the directly opposite effect. This resulted in the unfortunate circumstance of children being “therapeutic orphans”. However, recent regulatory and policy changes mandating drug studies in children for drugs likely to be used in children have driven drug research in children, answering key questions and also opening new frontiers. In this issue of BJCP, we have included several manuscripts focusing on important issues related to paediatric and obstetric pharmacology. Important developments over the past three decades that have transformed the regulatory and research environment for drug research in children, notably in the United States and Europe, are documented by Moore-Hepburn and Rieder in a perspectives piece in this issue. Regulatory and policy changes mandating drug studies in children for drugs likely to be used in children have in turn driven drug research in children, answering key questions and also opening new frontiers. Paediatrics and obstetrics pharmacological research has been greatly facilitated by the development of national and international research networks to address the problem of identifying adequate numbers of children or pregnant women for clinical trials, as described by Turner and colleagues in a European context. These research networks have made impacts not only in clinical outcomes but also in understanding the basic biology of drug disposition and response in children, key findings outlined by the elegant work described by Chapron, van Groen and colleagues on the ontogeny of drug disposition and transporter expression and activity in children. This work has in turn informed and enabled the translation of these new insights into better approaches for therapy including the use of pharmacogenomic data to inform effective and safe drug therapy, and a better appreciation of drug transfer into breast milk as described by Barker, Verstegen and colleagues. Patient empowerment is increasingly recognized as a key component of successful health care. Medications only work if patients take them. At the pragmatic edge of therapeutics, the importance of empowerment through health literacy around issues in pharmacotherapy for children and parents is emphasized in the work of Vaillancourt and Cameron. Taking medications implies that they are in a formulation that can in fact be taken. Emphasizing that children are not small adults, the need for child-friendly formulations and the processes by which they may be developed are described in paired work by Juárez-Hernández, Litalien and colleagues. This themed issue covers a number of key issues in pharmacology and therapeutics for children that demonstrate that there has been tremendous progress over the past two decades in understanding the biology of drug disposition and effects in children, that this progress has been driven by legislative and regulatory changes supported by research funding, and that this understanding has in turn provided clinicians with better approaches and more tools for safe and effective drug therapy. While much has been done, much remains to be done (e.g., available funding for research in drugs for children or pregnant women is but a fraction of that dedicated to researching drugs for non-pregnant adults), notably as biologic and genetic therapies enter the clinical realm. The next two decades promise to be more exciting still.