Background Perinatal hypoxic brain injury, commonly referred to as hypoxic-ischemic encephalopathy (HIE), is a birth complication with high rates of morbidity and mortality. Despite ongoing research, there is still significant variation in methods of describing and diagnosing affected infants, which has also contributed to variation in treatment. In this systematic review, we aimed to describe the variability in terminology and subsequent impact on diagnosis, description, and treatment of perinatal hypoxic brain injury as demonstrated by relevant studies published between 2000 and 2024.

Methods Initial searches of EMBASE and MEDLINE databases returned 1073 results. Studies were excluded if they were not in English, were secondary analyses, included data from an already-included research collaboration, used animal models, focused on non-infant populations, or lacked clearly defined inclusion/exclusion criteria. Ultimately, 245 studies published between 2000 and 2024 were reviewed for study design, country of origin, terminology used, and inclusion/exclusion criteria.

Results This systematic review included 245 studies from 6 continents and 49 countries. Of these, 138 (56.3%) studies were single center prospective, and 89 (36.3%) studies were multi-center prospective with the remaining 11 (6.5%) studies being retrospective. The total number of injured infants included per study ranged from 4 to 3095 (mean 105). There was considerable variation in the primary term used to describe the hypoxic injury (59.2% HIE, 30.6% asphyxia, 8.6% neonatal encephalopathy, 0.8% asphyxia encephalopathy) with 66.5% of studies including a secondary term. Inclusion criteria varied notably. Though the actual values used for cutoffs varied, commonly used criteria were minimum gestational age (89.4% of studies), need for resuscitation (57.6%), cord pH (56.3%), and modified Sarnat scoring (55.9%). There were varying categories of exclusion criteria including congenital anomalies (73.5%), postnatal age >6 hours at enrollment (26.5%), chromosomal abnormalities (25.7%), metabolic abnormalities (17.1%), congenital infection (16.3%), and imminent death (12.7%).

Conclusion The goal of this systematic review was to demonstrate the significant variation in description, definition, and management of perinatal hypoxic brain injury. Primary terminology and inclusion criteria notably varied across studies. Our findings highlight a critical gap in consensus as far as primary terminology and inclusion criteria, leading to confusion and ambiguity in both clinical and research settings. Future efforts should focus on standardizing definitions along with inclusion and exclusion criteria in order to allow for greater generalizability, targeted research, and enhanced clinical care of patients with this diagnosis.