Suchergebnisse

Abstract
Spontaneous preterm births (< 37 weeks gestation) are frequently associated with infection. Current treatment options are limited but new therapeutic interventions are being developed in animal models. In this PROSPERO-registered preclinical systematic review, we aimed to summarise promising interventions for infection/inflammation-induced preterm birth. Following PRISMA guidance, we searched PubMed, EMBASE, and Web of Science using the themes: "animal models", "preterm birth", "inflammation", and "therapeutics". We included original quantitative, peer-reviewed, and controlled studies applying prenatal interventions to prevent infection/inflammation-induced preterm birth in animal models. We employed two risk of bias tools. Of 4020 identified studies, 23 studies (24 interventions) met our inclusion criteria. All studies used mouse models. Preterm birth was most commonly induced by lipopolysaccharide (18 studies) or Escherichia coli (4 studies). Models varied according to infectious agent serotype, dose, and route of delivery. Gestational length was significantly prolonged in 20/24 interventions (83%) and markers of maternal inflammation were reduced in 20/23 interventions (87%). Interventions targeting interleukin-1, interleukin-6, and toll-like receptors show particular therapeutic potential. However, due to the heterogeneity of the methodology of the included studies, meta-analysis was impossible. All studies were assigned an unclear risk of bias using the SYRCLE risk of bias tool. Interventions targeting inflammation demonstrate therapeutic potential for the prevention of preterm birth. However, better standardisation of preterm birth models, including the dose, serotype, timing of administration and pathogenicity of infectious agent, and outcome reporting is urgently required to improve the reproducibility of preclinical studies, allow meaningful comparison of intervention efficacy, and aid clinical translation.

The specialty of fetal surgery or fetal intervention is one of the most exciting emerging fields of modern medicine. It is made possible by decades of major developments in antenatal imaging, obstetric anaesthesia, fetal medicine, paediatric surgery, and of course by the bold and novel practitioners willing to take new steps to advance the field. Beginning in the 1970s, it has now reached a stage of maturity where there are several established in utero procedures and countless clinical trials and studies to develop more. But what is the legal situation that fetal surgeons find themselves in? What are the rights and legal protections for the fetus and the mother, both of which are arguably the patient? This article will address this question, discussing and summarising the current legal frameworks governing fetal surgery in the jurisdictions of the United Kingdom, European Court of Human Rights, and the United States of America as well as discuss what the future may hold and how researchers and physicians in the specialty can best navigate the legal environment.

Acknowledgments Supported by the Wellcome Trust project grant 088208 (DJC), Wellbeing of Women research training fellowship 318 (DJC), Scottish Government Work package 4.2 (JMW, JSM and RPA), National Institute for Health Research University College London Hospitals Biomedical Research Centre (ALD) and Hatch ProjectND01748 (DAR). ; Peer reviewed ; Publisher PDF

Supported by Wellcome Trust project grant 088208 to A.L.D., J.M.W., D.M.P., I.C.Z., and J.F.M. Wellbeing of Women research training fellowship 318 to D.J.C., Scottish Government work package 4.2 to J.M.W., J.S.M., and R.P.A., as well as funding from the National Institute for Health Research University College London Hospitals Biomedical Research Centre A.L.D. and D.M.P., the British Heart Foundation to I.C.Z., and Ark Therapeutics Oy, Kuopio, Finland, which supplied adenovirus vectors free of charge. ; Peer reviewed ; Publisher PDF