Effect of Repeated Painful Stimuli on Pain Response in Term and Late Preterm Neonates: An Obstetric - Neonatal Continuum - Based Prospective Cohort Study

Background: It is documented that neonatal pain perception is well structured, but the and capacity of repeated painful procedures carried out at early neonatal life stages in changing consecutive pain responses is disputed. Obstetric factors that affect fetal stress, maturity, and admission of newborns to the neonatal intensive care unit (NICU) can be critical in the modulation of neonatal pain processing; yet, they are frequently not adequately represented in studies of neonatal pain. The objective is to assess how repeated painful stimuli affect behavioural pain response in neonates 34 weeks old or older, after conception, and combine/ ingest any prenatal and birth-related obstetric factors that could moderate neonatal pain adjustment. Material and Methods: It was a prospective cohort study conducted at a tertiary-care teaching hospital from October 2021 to September 2022. A total of 100 neonates (34 weeks post-conceptional age) were recruited and divided into cases (undergoing more than 10 painful procedures in the NICU) and controls (undergoing fewer than three painful procedures). The matching of the groups was based on post-conceptional age, postnatal age (within a range of 7 days), and sex. A uniform, painful stimulus was used: intramuscular injections of Hepatitis B vaccine at the time of discharge. Duration of cry (Primary outcome), latency to cry, and Modified Facial Coding Score (MFCS) were used to evaluate the behavioural pain reactions. Obstetric variables, including details of antenatal, intrapartum, and delivery-room care, were prospectively documented and studied as possible factors in modifying the response to pain. Results: The median length of cry was not significantly different between cases [26 seconds (IQR 20 48 seconds)] and controls [30.5 seconds (IQR 20 78 seconds)] (p > 0.05). There was equal latency to cry. Immediately after the injection, the MFCS scores in NICU-exposed neonates were much higher, but the disparities resolved by 1 and 3 minutes. Antenatal complications, mode of delivery, and delivery-room interventions remained unaffected in the independent effects of obstetric risk factors on pain response when gestational maturity was factored in. Conclusion: Repeated exposure to painful procedures in infants with a neonatal age of at least 34 weeks after conception gained no significant changes in general behavioural pain response. Neonatal pain processing seems to be moderated by gestational maturity factor and obstetric antecedents rather than being influenced by cumulative procedural exposure per se. These results highlight the role of combined obstetric-neonatal interventions, focused on reducing stress in the first days and improving neurodevelopmental outcomes. Keywords: Neonatal pain; Repeated painful procedures; Gestational maturity; Late Preterm neonates; Neonatal intensive care unit; Behavioural pain response