Sex-related differences in response to noxious stimulation at the beginning of life explored through a secondary...

This study explored sex-related differences in neonatal nociception, an area that remains relatively understudied despite well-documented disparities in adult pain experience. The research aimed to highlight sex-related patterns in neonatal responses to noxious stimulation using both behavioural and neurophysiological data, obtained through the Neonatal Infant Pain Scale and cerebral near-infrared spectroscopy. Specifically, a secondary analysis was conducted on previously published data from our research group, collected from 100 healthy full-term newborns (48 males, 52 females) undergoing a routine heel-prick for metabolic screening. Participants in the original studies were randomly allocated to one of the following non-pharmacological analgesic methods: oral glucose solution, expressed breast milk, maternal holding with glucose administration, breastfeeding or maternal holding alone. Results showed that female newborns exhibit a significantly more pronounced behavioural response to noxious stimulation compared to male newborns (P = 0.031), with this difference being particularly evident during breastfeeding as an analgesic intervention (P = 0.010). Female newborns also showed an increased activation of the left somatosensory cortex in response to contralateral heel-prick (P = 0.005). During breastfeeding analgesia, this difference involved the right somatosensory cortex too (P = 0.010). These findings underscore the importance of incorporating sex-specific considerations in neonatal pain assessment and management protocols. The study suggests that developing tailored, sex-specific approaches may be crucial for ensuring optimal pain care in newborns, potentially leading to more effective and personalised neonatal care strategies. Ultimately, this research contributes to the growing body of evidence supporting the need for sex-specific considerations in pain management from early-life. PERSPECTIVE: This secondary analysis further demonstrates that female newborns show a significantly more pronounced behavioural response and a more intense cortical response to noxious stimulation than male newborns. Therefore, developing tailored, sex-specific approaches to pain management may lead to more effective and personalised neonatal care strategies.