Somatosensory function and pain in extremely preterm young adults from the UK EPICure cohort: sex-dependent differences and impact of neonatal surgery

Abstract

BackgroundSurgery or multiple procedural interventions in extremely preterm neonates influence neurodevelopmental outcome and may be associated with long-term changes in somatosensory function or pain response.MethodsThis observational study recruited extremely preterm (EP, <26 weeks' gestation; n=102, 60% female) and term-born controls (TC; n=48) aged 18–20 yr from the UK EPICure cohort. Thirty EP but no TC participants had neonatal surgery. Evaluation included: quantitative sensory testing (thenar eminence, chest wall); clinical pain history; questionnaires (intelligence quotient; pain catastrophising; anxiety); and structural brain imaging.ResultsReduced thermal threshold sensitivity in EP vs TC participants persisted at age 18–20 yr. Sex-dependent effects varied with stimulus intensity and were enhanced by neonatal surgery, with reduced threshold sensitivity in EP surgery males but increased sensitivity to prolonged noxious cold in EP surgery females (P<0.01). Sex-dependent differences in thermal sensitivity correlated with smaller amygdala volume (P<0.05) but not current intelligence quotient. While generalised decreased sensitivity encompassed mechanical and thermal modalities in EP surgery males, a mixed pattern of sensory loss and sensory gain persisted adjacent to neonatal scars in males and females. More EP participants reported moderate–severe recurrent pain (22/101 vs 4/48; χ2=0.04) and increased pain intensity correlated with higher anxiety and pain catastrophising.ConclusionsAfter preterm birth and neonatal surgery, different patterns of generalised and local scar-related alterations in somatosensory function persist into early adulthood. Sex-dependent changes in generalised sensitivity may reflect central modulation by affective circuits. Early life experience and sex/gender should be considered when evaluating somatosensory function, pain experience, or future chronic pain risk.

Current Evidence on Cell Death in Preterm Brain Injury in Human and Preclinical Models

“…These biomarkers were found to be predictive for brain injury post-operatively. Walker et al (2018) in a cohort of United Kingdom Epicure in ELBW infants found an association of neonatal surgery in the volume of the amygdala and the somatosensory response and pain response in young adults ex-preterm. Filan et al (2012) analyzed post hoc 30 babies exposed to surgery who had more evidence of WMI and smaller brain volumes, particularly in the deep GM.…”

“…When looking at clinical risk factors for neurodevelopmental outcome, surgery is a major and constant contributor for impaired neurological outcome, and these concerns are true for neonates at term and premature infants (Sun, 2010;Morriss et al, 2014;Sinner et al, 2014;Stolwijk et al, 2016;Walker et al, 2018). Premature infants may undergo several surgical procedures such as ductus ligation, laparotomies, and thoracotomies defined as major surgeries and herniotomies or endoscopic laryngoscopies defined as minor surgeries.…”

“…Premature infants may undergo several surgical procedures such as ductus ligation, laparotomies, and thoracotomies defined as major surgeries and herniotomies or endoscopic laryngoscopies defined as minor surgeries. It is still unclear whether the surgical stress, the pain perception, or the administrated drugs for anesthesia are neurotoxic (Broad et al, 2017;Walker et al, 2018), but the combination of both seems to play a major role. This also explains the development of several preclinical models in rodent and primate animals in order to answer the unsolved questions (Baud and Saint-Faust, 2019).…”

Pediatric Erythromelalgia and SCN9A Mutations: Systematic Review and Single-Center Case Series

“…Following parental consent and child assent, we measured static thresholds for thermal (cool, warm, cold, heat) and mechanical (detection, pricking, pressure) stimuli, and dynamic allodynia for brush and thermal stimuli using a standardized QST protocol. [23][24][25]…”

“…Correlation between age of symptom onset and Na v 1.7 hyper-polarizing shift was assessed (2tailed Pearson's correlation coefficient)(SPSS® Version 23 IBM, Portsmouth, UK). QST results were calculated as Z-score comparisons with healthy control data (z=[(X patient -Mean controls )/SD controls ]) collected by the same investigator, 23,24 and sensory profiles were plotted with increased sensitivity as positive values and decreased sensitivity as negative values. 26…”