Latitudinal differences on the global epidemiology of infantile spasms: systematic review and meta-analysis.

Background: Infantile spasms represent the catastrophic, age-specific seizure type associated with acute and long-term neurological morbidity. However, due to rarity and heterogenous determination, there is persistent uncertainty of its pathophysiological and epidemiological characteristics. The purpose of the current study was to address a historically suspected latitudinal basis of infantile spasms incidence, and to interrogate a geographical basis of epidemiology, including the roles of latitude and other environmental factors, using meta-analytic and -regression methods.

Methods: A systematic search was performed in Ovid MEDLINE and Embase for primary reports on infantile spasms incidence and prevalence epidemiology.

Results: One thousand fifteen studies were screened to yield 54 eligible publications, from which 39 incidence figures and 18 prevalence figures were extracted. The pooled incidence was 0.249 cases/1000 live births. The pooled prevalence was 0.015 cases/1000 population. Univariate meta-regression determined a continental effect, with Europe demonstrating the highest onset compared from Asia (OR = 0.51, p = 0.004) and from North America (OR = 0.50, p = 0.004). Latitude was also positively correlated with incidence globally (OR = 1.02, p < 0.001). Sub-analyses determined a particularly elevated Scandinavian incidence compared to the rest of world (OR = 1.88, p < 0.001), and lack of latitudinal effect with Scandinavian exclusion (p = 0.10). Metrics of healthcare quality did not predict incidence. Multiple meta-regression determined that latitude was the key predictor of incidence (OR = 1.02, p = 0.001).

Conclusions: This is the first systematic epidemiological study of infantile spasms. Limitations included lack of Southern hemispheric representation, insufficient study selection and size to support some sub-continental analyses, and lack of accessible ethnic and healthcare quality data. Meta-analyses determined a novel, true geographical difference in incidence which is consistent with a latitudinal and/or ethnic contribution to epileptogenesis. These findings justify the establishment of a global registry of infantile spasms epidemiology to promote future systematic studies, clarify risk factors, and expand understanding of the pathophysiology.