Search

Necrotizing enterocolitis (NEC) is a relatively rare but very severe gastrointestinal disease primarily affecting very preterm infants. NEC is characterized by excessive inflammation and ischemia in the intestines, and is associated with prolonged, severe visceral pain. Despite its recognition as a highly painful disease, current pain management for NEC is often inadequate, and research on optimal analgesic therapy for these patients is lacking. Insight into the mechanisms underlying intestinal pain in infants with NEC-visceral pain-could help identify the most effective analgesics for these vulnerable patients. Therefore, this comprehensive review aims to provide an overview of visceral nociception, including transduction, transmission, modulation, and experience, and discuss the implications for analgesic therapy in preterm infants with NEC. The transmission of visceral pain differs from that of somatic pain, contributing to the diffuse nature of visceral pain. Studies evaluating the effectiveness of analgesics for treating visceral pain in infants are scarce. However, research in visceral pain models highlights agents that may be particularly effective for treating visceral pain based on their mechanisms of action. Further research is necessary to determine whether agents that have shown promise for treating visceral pain in preclinical studies and adults are effective in infants with NEC as well., Competing Interests: Declarations. Funding: No specific financial support was received for this study. Competing Interests: J.t.B. is funded by the Friends of Sophia Foundation (in Dutch: Vrienden van het Sophia; grant number WEL21-07). R.S. is funded via a Senior Wellcome Fellowship awarded to grant number 207457/Z/17/Z. N.v.d.H. is funded by an Alberta Innovates Postdoctoral Fellowship. None of the authors have any conflicts of interest to disclose. Ethics Approval: Not applicable. Consent: Not applicable. Data Availability Statement: Data sharing is not applicable to this article, as no datasets were generated or analyzed during the current study. Code Availability: Not applicable. Author Contributions: J.t.B. drafted the manuscript. G.v.d.B., R.S., N.v.d.H., I.R., and S.S. revisited the manuscript critically for important intellectual content. All authors have approved the final version of the manuscript., (© 2025. The Author(s).)

This study aims to quantify stress exposure related to clinical stressors in preterm infants during NICU admission and identify risk factors for high stress exposure. In this national cohort study, preterm infants (gestational age < 29 weeks) were prospectively followed during the first 28 days of their admission to one of the 10 NICUs in the Netherlands. The NeO-stress score, consisting of 38 clinical stressors graded with a severity index, was applied to describe stress exposure. We assessed the impact of infant characteristics at birth and postnatal age on NeO-stress scores using linear mixed modelling. In total, 446 infants were included with a median gestational age of 27 +2  weeks (IQR 26 +2 -28 +2 ). The median NeO-stress score per day was 61 (IQR 39-87) and highest (74, IQR 52-101) on the day of admission. Nasal/oral (37%) and endotracheal (14%) suctioning were key contributors to the cumulative NeO-stress scores. Linear mixed modelling showed that lower gestational age (B = -0.69, 95% CI - 0.94-0.44, p < 0.001), no antenatal administration of corticosteroids (B = 13.2, 95% CI 3.2-23.1, p = 0.010) and lower 5-min Apgar score (B = - 1.6, 95% CI - 3.0-0.25, p = 0.02) were significantly related with higher daily NeO-stress scores. Our model predicts that the NeO-stress score increases over time for the youngest infants., Conclusion: Stress exposure in preterm infants during NICU admission varies over time with infants with the lowest gestational age at risk for experiencing the highest levels of stress throughout NICU admission. This highlights the importance stress reduction and provides opportunities for future interventions aimed at reducing stress exposure., What Is Known: • Preterm birth and admission to a Neonatal Intensive Care Unit is very stressful. • High stress exposure in neonatal life is associated with adverse long term outcome., What Is New: • Stress exposure is highest in infants with the youngest gestational ages where it remains high or even increases during the first month of life. • Lower gestational age, no antenatal administration of corticosteroids and lower 5-min Apgar score were significantly related with higher daily NeO-stress scores., Competing Interests: Declarations. Ethics approval: The medical ethical committee of the Erasmus MC waived the need for approval within the Dutch Law on research with humans (MEC-2019–0574) because the study was judged to be a non-interventional study without exposing infants to procedures or additional rules of behavior. The medical ethical committees of the other participating NICUs subsequently adhered to this decision. Consent to participate: Written permission was obtained from the parents. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Introduction: Preterm infants born before 32 weeks of gestation are generally admitted to a neonatal intensive care unit (NICU) to receive life-saving treatment, resulting in early exposure to stressful events. Yet, NICU admission is not only stressful for the infant but can also have a long-lasting negative impact on parental mental health, who may worry about their child. Parental mental health problems might affect child development through parental behaviour and the parent-infant relationship. Simultaneously, adverse child development after preterm birth can (further) elevate parental stress and mental health problems, straining parental behaviour, the parent-infant relationship and child development. This systematic review and meta-analysis aims to examine the association between preterm-born children's development (<32 weeks' gestation) and parental mental health after preterm birth-related stress following NICU admission at any point in time., Methods and Analysis: A systematic review will be performed and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A concept-based search on preterm birth, child development and parental mental health is performed using MEDLINE, Embase, PsycINFO and Cochrane Library on 22 March 2024. Eligible are studies with original results on the association between child development after preterm birth (<32 weeks' gestation) and parental mental health. Independent reviewers will screen the articles, assess study quality using a Newcastle-Ottawa or Cochrane tool and determine the quality of evidence using Grading of Recommendations, Assessment, Development and Evaluation. Meta-analyses are planned on the association between child development and parental mental health after preterm birth., Ethics and Dissemination: No ethical approval is required. The results will enhance knowledge of the association between child development and parental mental health after preterm birth-related stress following NICU admission. This might lead to adjustments in follow-up care, optimising outcomes for infants and parents. Findings will be published in an international, peer-reviewed ad open-access journal., Prospero Registration Number: CRD42024518307., Competing Interests: Competing interests: The first author’s appointment is partly funded by the Cornelia Stichting. All other authors have no competing interest to declare., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Abstract: Studies on pain in preterm infants have usually been confined to observations of painful procedures, and information from extremely preterm infants is limited. Using registry data from a Swedish nationwide cohort, this study explored the epidemiology of pain in very preterm infants, its causes, assessments, and treatment strategies. We included liveborn infants <32 weeks' gestational age (GA) discharged between January 2020 and June 2024. Proportions of infants exposed to potentially painful procedures, experiencing pain, assessed with pain scales, and receiving pharmacological treatment were calculated by each postnatal day. Among 3686 infants (mean birthweight 1176 g, GA 28.2 weeks), 11.6% had a painful condition and 84.1% were exposed to at least 1 potentially painful procedure. In total, 74.6% experienced pain, corresponding to 28,137/185,008 (15.2%) days of neonatal care. For every 2-week increase in GA, significantly lower proportions of infants experienced pain. In infants <28 weeks of GA, proportions with reported pain were approximately half the rate of painful procedures, while in infants born at 28 to 31 weeks, reported pain closely matched exposure to painful procedures. Pain scales were used in 75.0% of the infants. Pharmacological pain treatment was administered to 81.7% of infants, primarily topically or orally. Among infants with pain, proportions treated intravenously were larger at higher GAs. Despite effective analgesia/anesthesia, many very preterm infants experience pain. Visualizing pain epidemiology, procedures, conditions, and treatment by postnatal and gestational age may guide clinical management and generate research hypotheses to reduce short- and long-term adverse effects., (Copyright © 2025 International Association for the Study of Pain.)

Sensory processing sensitivity (SPS) describes a common trait characterized by lower sensory threshold, depth of processing, and ease of overstimulation. Low sensory threshold is also potentially important in the context of pain. To date, the relationship between SPS and pain perception has not been investigated, particularly in adolescents. This randomized experimental study aimed to explore whether SPS was associated with pain threshold and tolerance in healthy adolescents. Further, we examined differences in pain perception following positive, negative, or neutral mood induction. Methods: A total of 100 healthy adolescents aged 16 to 19 years were recruited through schools and online advertisement. Participants completed psychosocial questionnaires and underwent a randomized mood induction (positive, negative, or neutral). Pain levels (in °C) and self-reported pain tolerance and threshold were assessed by an experimental heat pain paradigm. Regression models were applied to determine effects of mood induction on pain perception, while multiple analyses of variance (ANOVAs) were computed to compare sensitivity across groups. Results: The mood induction significantly influenced self-reported pain ratings, demonstrating a positive interaction coefficient for the positive mood condition (b = 1.140, p < 0.01). ANOVAs revealed significant differences between sensitivity groups for baseline scores of pain threshold (F(2,97) = 5.009, p < 0.01) and tolerance (F(2,97) = 7.431, p < 0.001). Conclusion: Our findings reveal that highly sensitive adolescents had the lowest ratings of measured pain tolerance and threshold measures at baseline, suggesting heightened sensitivity to pain. This highlights the importance of considering sensory processing sensitivity in pain research, particularly in adolescent populations. [ABSTRACT FROM AUTHOR]

Research on the cerebellum and its functional organization has significantly expanded over the last decades, expanding our comprehension of its role far beyond motor control, including critical contributions to cognition and affective processing. Notably, the cerebellar lateralization mirrors contralateral brain lateralization, a complex phenomenon that remains unexplored, especially across different stages of life. The present work aims to bridge this gap by providing a comprehensive scoping review of the lateralization of motor, cognitive, and affective functioning within the cerebellum across the lifespan. A methodical search in electronic databases (i.e., PubMed, Embase, and PsycINFO) was conducted up to October 2024, focusing on neuroimaging studies with healthy participants of all ages performing motor, cognitive, or affective tasks. Our selection process, which involved multiple independent reviewers, identified 128 studies reporting cerebellar asymmetries in individuals from early childhood to older age, with a significant portion of studies regarding young-middle adults (19-45 years old). The majority of the findings confirmed established lateralization patterns in motor and language processing, such as ipsilateral motor control and right-lateralized language functions. However, less attention has been paid to other cognitive functions and affective processing where more heterogeneous and less consistent asymmetries have been observed. To the best of our knowledge, this scoping review is the first to comprehensively investigate the motor, cognitive, and affective functional lateralization of the cerebellum across lifespan, highlighting previously overlooked dimensions of cerebellar contributions., Competing Interests: Declarations. Conflict of interests: The authors do not have any conflict of interest to declare., (© 2025. Springer-Verlag GmbH Germany, part of Springer Nature.)