Early-Stage Translational Research in Perinatal Medicine

Abstract

Background: Pre-clinical research, which encompasses studies in animals and in the laboratory, has made significant contributions to the improvement of neonatal outcomes. Methods: Here, we describe examples of how pre-clinical research can be the starting point on the journey to the development of new interventions to improve neonatal care and outcomes and discuss recent progress in ensuring methodological and ethical rigour in pre-clinical research involving animal models. Results: Studies in pregnant sheep led to the serendipitous discovery that preterm lambs born after exogenous corticosteroid exposure were able to aerate their lungs. Subsequent clinical trials confirmed that antenatal corticosteroids given to women at risk of preterm delivery substantially reduce mortality and morbidity in babies born preterm. Animal research also contributed to discoveries in the mechanism of brain injury after hypoxic ischaemic encephalopathy, leading to the use of therapeutic hypothermia as an effective treatment. However, animals are sentient creatures and there are significant ethical concerns with their use in studies to benefit human health. Mandated institutional animal research ethics committees ensure adherence to ethical requirements. To provide high-quality data which can be translated into clinical research, pre-clinical research needs to follow rigorous standards of study design and reporting. The ARRIVE guidelines provide guidance for pre-clinical research similar to that provided in the CONSORT guidelines for clinical trials and are gaining acceptance among researchers and journal editors. Conclusion: Improved scientific rigour in the use of animal research will increase the likelihood that pre-clinical research will continue to translate into improved neonatal outcomes.

Validity and Utility of Experimental Animal Models in Perinatal Research

“…Research studies using experimental animal models have underpinned the development of strategies that have improved care and outcomes of preterm of sick newborn infants [1]. These include transformative interventions such as antenatal corticosteroids to promote endogenous surfactant production in very preterm infants, exogenous surfactant replacement for infants with or at risk of respiratory distress syndrome, therapeutic hypothermia for term and near-term neonates with moderate or severe encephalopathy, and nitric oxide treatment for infants with respiratory failure associated with pulmonary hypertension [2][3][4][5].…”