Further studies have demonstrated that cumulative neonatal pain-related stress in very preterm neonates was associated with alteration in thalamic development, decreased frontal and parietal brain width, altered diffusion measures and functional connectivity in the temporal lobes, abnormalities in motor behaviour, and reduction in cerebellar size. Moreover, reduction of brain growth in relation to pain exposure in infants 24–32 weeks gestational age (GA) during NICU admission, while controlling for other important factors such as GA at birth and severity of illness, has been shown. A blunting of behavioural responses, increases in physiological responses, changes to pain thresholds, and alterations in hypothalamic-pituitary-adrenal axis development have been reported in relation to untreated pain exposure. For infants delivered very preterm, controlling for gestational age, severity of illness and morbidity exposure to early pain-related distress is associated with both immediate physiologic instability and pain sensitivity as well as long-lasting deleterious impacts on cognition and behavior and poor executive function and visual abilities. Poorly treated and/or prolonged pain exposure in preterm neonates has been linked to lasting consequences during a critical time in brain development. Predictors of the use of pharmacologic interventions (e.g., opiates) during tissue breaking procedures included being less ill at birth and receiving high frequency ventilator support, whereas parental presence significantly predicted the use of sweet taste or non-pharmacologic interventions (i.e., non-nutritive sucking, swaddling, rocking, positioning, skin-to-skin contact (SSC), breastfeeding). These findings are consistent with a prospective observational study over one week in 14 Canadian NICUs.
Studies in this review reported that infants went without any form of analgesia during painful procedures ranging from 42–100% of the time, with the majority of studies reporting no pain treatment. Additional routinely performed painful procedures include intubation, chest tube placement, lumbar puncture, insertion of arterial and venous umbilical catheters and peripheral arterial catheters, intramuscular and subcutaneous injections, tape removal, and retinopathy of prematurity eye examinations. A review including 18 studies examining pain exposure and analgesic practices across numerous countries conducted by Cruz and colleagues (2016) found that hospitalized neonates were undergoing 7–17 painful procedures per day, with the most common procedures being heel lancing, naso- and endo-tracheal suctioning, venipuncture, and insertion of peripheral venous catheters. Data from Canadian and European studies demonstrate that infants can undergo anywhere from one to 14 procedures per day when hospitalized in the neonatal intensive care unit (NICU). For infants delivered preterm, the majority requiring neonatal intensive care, pain exposure is even higher.
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