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Progesterone as a neuroprotective agent in neonatal hypoxic-ischaemic encephalopathy-a systematic review

Lee, Ming-Te; McNicholas, Roisin; Miall, Lawrence; Simpson, Nigel; Goss, Kevin CW; Robertson, Nicola JJ; Chumas, Paul; (2023) Progesterone as a neuroprotective agent in neonatal hypoxic-ischaemic encephalopathy-a systematic review. Developmental Neuroscience , 45 (2) 10.1159/000521540. Green open access

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Abstract

Hypoxic-ischaemic encephalopathy (HIE) in the newborn baby is a major contributor to neonatal mortality and morbidity across the world. Therapeutic hypothermia (TH) is the current standard treatment for moderate to severe HIE, but not all babies benefit. Potential neuroprotective actions of progesterone (PROG) include anti-apoptotic, anti-inflammatory, and anti-oxidative effects and reduction of energy depletion, tissue/cellular oedema, and excitotoxicity. In pre-clinical studies of neonatal HIE, PROG has neuroprotective properties but has not been the subject of systematic review. Here, our objective was to evaluate the evidence base for PROG as a potential therapeutic agent in HIE. The PICO framework was used to define the following inclusion criteria. Population: human neonates with HIE/animal models of HIE; intervention: PROG +/- other agents; comparison: V.S. control; outcome: pathological, neurobehavioural, and mechanistic outcome measures. Medline, EMBASE, and CINHAL were then searched between August to October 2018 using pre-defined medical subject heading and keywords. Study inclusion, data extraction, and risk of bias (ROB) analysis using the SYRCLE ROB tool were carried out by two authors. 14 studies were included in the review. They typically displayed a high ROB. This systematic review suggests that PROG reduced neuropathology and reduced neurobehavioural deficits post-hypoxic-ischaemic (HI) insult in 8 and 3 studies, respectively. However, there was sex dimorphism in the effects of PROG. In addition, there are limitations and biases in these studies, and there remains a need for well-designed large pre-clinical studies with greater methodological quality to further inform the efficacy, safety, dose, timing, and frequency of PROG administration. With such data, large animal studies could be planned combining PROG administration with and without TH.

Type: Article
Title: Progesterone as a neuroprotective agent in neonatal hypoxic-ischaemic encephalopathy-a systematic review
Location: Switzerland
Open access status: An open access version is available from UCL Discovery
DOI: 10.1159/000521540
Publisher version: https://doi.org/10.1159/000521540
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License.
Keywords: Progesterone, Neuroprotection, Hypoxia-ischemia, Hypoxic-ischemic encephalopathy, Neonatal brain injury, Perinatal brain injury, Brain injury
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health > Neonatology
URI: https://discovery.ucl.ac.uk/id/eprint/10172021
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