Methodological Issues in the Study of the Development of Pain Responsivity in Preterm Neonates: A Systematic Review

The study of the development of neonatal pain responses is of key importance, both for research and for clinical reasons, with particular regard to the population of preterm neonates, given the amount of painful procedures they are exposed to on a daily basis. The aim of this work was to systematize our knowledge about the development of pain responses in prematurely born neonates by focusing on some key methodological issues. Studies on the impact of age variables, namely gestational age (GA), postmenstrual age (PMA) and chronological age (CH), on pain responsivity in premature neonates were identified using Medline and Scopus. Studies (N = 42) were categorized based on terminological and methodological approaches towards age variables, and according to output variables considered (facial, nonfacial behavioral, physiological). Distinct multidimensional developmental patterns were found for each age-sampling strategy. Overall, each of the three age variables seems to affect pain responsivity, possibly differently across age windows. Targeted as well as integrated approaches, together with a renewed attention for methodological consistency, are needed to further our knowledge on this topic.