Systematic review about hospital admission times for neonates with hypoxic-ischemic encephalopathy in low- and middle-income countries

Hypoxic-ischemic encephalopathy (HIE) remains a leading cause of neonatal mortality and morbidity in low- and middle-income countries (LMICs). Several factors contribute to this high incidence: limited (access to) prenatal care, inadequate equipment and the lack of trained healthcare personnel and neonatal intensive care units. While neuroprotective strategies like therapeutic hypothermia have demonstrated effectiveness in high-income countries, its use in LMICs remains contentious. Given the critical importance of timely intervention, the potential timing of hospital admission for neonates with HIE is crucial. Aim: To describe the hospital admission times of neonates with moderate to severe HIE in LMICs. Methods: A systematic review was conducted following PRISMA guidelines. Electronic databases (PubMed and Google scholar) were searched with no restrictions for time and language using the following terms: “perinatal asphyxia”, “neuroprotection”, “HIE” and “developing countries” or “LMIC”. Full- text papers in English or French language, that specified interval between birth and hospital admission or the initiation of neuroprotective therapy for HIE were included. Manuscripts that did not clearly state the cause of admission were excluded. Results: A total of 142 papers were identified, of which 10 fulfilled the inclusion criteria. The studied period ranged from 2008-2021 and included 1811 patients, eligible for neuroprotective intervention. Three studies were performed in Asia, one in the Middle-East and six in Sub Saharan Africa. All studies were performed in an urban region in tertiary centers; 43% of patients were inborn, and 65% were male. The weighted mean and pooled SD of the hospital admission time was 3.1±1.1h; 25% of patients were not able to reach the hospital within 6h after birth. Especially, in Sub Saharan countries the admission times were more variable (range 1-63h). Conclusion: In LMIC about three fourth of patients can timely reach the hospital to receive treatment within the first six hours of life, although admission times varied widely. The possible causes for this wide variation in admission time and the consequences for specific neuroprotective therapies are discussed.