Management of perinatal hypoxic-ischaemic encephalopathy in MSF settings: palliative care? or shall we seek potential pharmacological alternatives?
Laurent Hiffler1,&, Nadia Lafferty1
1Médecins Sans Frontieres, OCBA, Barcelona, Spain
Laurent Hiffler, Médecins Sans Frontieres, OCBA, Barcelona, Spain
hypoxic-ischaemic encephalopathy (HIE) accounts for a significant proportion of neonatal deaths in resource limited settings (12% MSF-OCBA 2016). Moderate hypothermia started within the first 6 hours after birth is known to improve survival and outcome at 18 months. To date however, this is not feasible in MSF settings, where HIE continues to carry a poor prognosis with very high mortality rates and associated morbidities. While prevention is the goal, cases of HIE will always exist and, alternative treatments that could significantly improve outcome are nevertheless urgently needed.
pubmed search using the following key words: birth asphyxia, perinatal hypoxic ischaemic encephalopathy, neuroprotection, oxygen free radical inhibitors and scavengers.
we identified medications with high safety profiles which could be of potential interest for HIE management in MSF contexts: melatonin and vitamin k (VK). Melatonin preserves the developing brain from injury. Its neuro-protective mechanisms include antioxidant, anti-apoptotic and anti-inflammatory processes via cell membrane and nuclear receptors. Additionally, melatonin reduces vascular permeability after acute hypoxia and detoxifies reactive oxygen species via non receptor-mediated actions. In 2 studies involving new borns with HIE, melatonin has shown positive results. It is safe and non-toxic. Beyond the haemostatic functions of VK, VK-dependent proteins contribute to brain function.
Animal models show that VK seems to be involved in sphingolipid metabolism, which is key in brain cell membrane and cell-signal functions. VK metabolites have anti-inflammatory activity and prevent oxidative cell death in vitro and in animal models. VK is routinely used in neonates but repeated doses may be beneficial.
the burden of perinatal HIE remains unacceptably high in MSF settings where standard management with moderate hypothermia is not feasible, therefore alternative treatments are needed. Amongst potential candidates, melatonin and VK, alone or in combination, represent promising neuroprotectors to reduce brain injury and long-term sequelae in infants. MSF should consider field studies to evaluate these potential treatments that could have a major public health impact, alongside reinforcement of prevention measures.
Dates: 15 Dec 17 - 16 Dec 17
Venue: Hotel Ngor Diarama
Contact person: Dr. Laurent Hiffler (email@example.com)