RESUMEN
Background: Exposure in utero to certain medications can disrupt processes of fetal development, including brain development, leading to a continuum of neurodevelopmental difficulties. Recognizing the deficiency of neurodevelopmental investigations within pregnancy pharmacovigilance, an international Neurodevelopmental Expert Working Group was convened to achieve consensus regarding the core neurodevelopmental outcomes, optimization of methodological approaches and barriers to conducting pregnancy pharmacovigilance studies with neurodevelopmental outcomes. Methods: A modified Delphi study was undertaken based on stakeholder and expert input. Stakeholders (patient, pharmaceutical, academic and regulatory) were invited to define topics, pertaining to neurodevelopmental investigations in medication-exposed pregnancies. Experts were identified for their experience regarding neurodevelopmental outcomes following medicinal, substances of misuse or environmental exposures in utero. Two questionnaire rounds and a virtual discussion meeting were used to explore expert opinion on the topics identified by the stakeholders. Results: Twenty-five experts, from 13 countries and professionally diverse backgrounds took part in the development of 11 recommendations. The recommendations focus on the importance of neurodevelopment as a core feature of pregnancy pharmacovigilance, the timing of study initiation and a core set of distinct but interrelated neurodevelopmental skills or diagnoses which require investigation. Studies should start in infancy with an extended period of investigation into adolescence, with more frequent sampling during rapid periods of development. Additionally, recommendations are made regarding optimal approach to neurodevelopmental outcome measurement, comparator groups, exposure factors, a core set of confounding and mediating variables, attrition, reporting of results and the required improvements in funding for potential later emerging effects. Different study designs will be required depending on the specific neurodevelopmental outcome type under investigation and whether the medicine in question is newly approved or already in widespread use. Conclusion: An improved focus on neurodevelopmental outcomes is required within pregnancy pharmacovigilance. These expert recommendations should be met across a complementary set of studies which converge to form a comprehensive set of evidence regarding neurodevelopmental outcomes in pregnancy pharmacovigilance.
RESUMEN
Losing a loved one is among the most common and stressful traumatic events that a child or and adolescent can experience and can be associated with mental health and somatic disorders, as well as a range of life issues and potentially negative outcomes that may impact longitudinal development. Complicated grief, a disorder that has been studied primarily among adults, has received increasing recognition among children and adolescents in recent years. The demonstration of the distinctive character of grief reactions in relation to major depressive disorder and posttraumatic stress disorder has resulted in the inclusion of "persistent complex bereavement disorder" in an annex section of DSM-5 and of "prolonged grief disorder" in ICD-11. The grieving process in children and adolescents is not linear and is often characterised by periods of regression. Developmental phases should be taken into account to understand and clinically describe grief reactions occurring during childhood and adolescence. There are currently numerous interventions for bereaved children and adolescents, but little evidence to support them. More research focusing on the understanding of the underlying mechanisms and the risk factors for complicated grief among children and adolescents, as well as the implementation of evidence-based interventions, is definitely warranted.
