ArticlePloS one2013
Neonatal pain-related stress and NFKBIA genotype are associated with altered cortisol levels in preterm boys at school age.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 2 of them syntheses that pooled it.
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Who cites it
40 citing papers in PubMed, 2 syntheses or guidelines pooled it, 102 citations in OpenAlex.
- Identifying the risk factors of autism spectrum disorders in infants born preterm: a systematic review and meta-analysis.European child & adolescent psychiatry · 2026Pooled it
- Cross-sectional relation of long-term glucocorticoids in hair with anthropometric measurements and their possible determinants: A systematic review and meta-analysis.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2022Pooled it
- Effects of Kangaroo care during retinopathy screening examination: a randomised clinical trial.BMJ paediatrics open · 2026Trial
- Cortisol awakening response and developmental outcomes at 6-7 years in children born extremely preterm.Pediatric research · 2023Trial
- The contribution of childhood adversity to cortisol measures of early life stress amongst infants in rural India: Findings from the early life stress sub-study of the SPRING cluster randomised controlled trial (SPRING-ELS).Psychoneuroendocrinology · 2019Trial
- Hair Cortisol Concentrations in Children: A Longitudinal Analysis Across Childhood.Developmental psychobiology · 2026Article
- A Cross-Lagged Panel Analysis of Cortisol Levels and Internalizing Behaviors in Children Born Very Preterm Across Early Childhood: Associations Differ for Boys and Girls at Age 1.5 Years.Developmental psychobiology · 2025Article
- DNA Methylation, Inflammation, and Neurobehavior in Preterm Infants.Biological research for nursing · 2024Article
- Current Evidence for Biological Biomarkers and Mechanisms Underlying Acute to Chronic Pain Transition across the Pediatric Age Spectrum.Journal of clinical medicine · 2023Article
- Infant regulatory problems and the quality of dyadic emotional connection-a proof-of-concept study in a multilingual sample.Frontiers in child and adolescent psychiatry · 2023Article
- Trends of fecal calprotectin levels and associations with early life experience in preterm infants.Interdisciplinary nursing research · 2022Article
- Association of Neonatal Pain-Related Stress and Parent Interaction With Internalizing Behaviors Across 1.5, 3.0, 4.5, and 8.0 Years in Children Born Very Preterm.JAMA network open · 2022Article
- Saliva cortisol diurnal variation and stress responses in term and preterm infants.Archives of disease in childhood. Fetal and neonatal edition · 2022Article
- Benefits of Kangaroo Mother Care on the Physiological Stress Parameters of Preterm Infants and Mothers in Neonatal Intensive Care.International journal of environmental research and public health · 2022Article
- Sexual Dimorphism in the Effect of Neonatal Inflammatory Pain on Stress Reactivity of Hormonal Response and Cognitive Functions in Adult Rats.Journal of evolutionary biochemistry and physiology · 2022Article
- Lifetime stressors, hair cortisol, and executive function: Age-related associations in childhood.Developmental psychobiology · 2021Article
- The social ecology of childhood and early life adversity.Pediatric research · 2021Review
- Local injury and systemic infection in infants alter later nociception and pain affect during early life and adulthood.Brain, behavior, & immunity - health · 2020Article
- Personal perspectives: Infant pain-A multidisciplinary journey.Paediatric & neonatal pain · 2020Review
- Self-reported mental health and cortisol activity at 27-28 years of age in individuals born with very low birthweight.Acta paediatrica (Oslo, Norway : 1992) · 2020Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Neonatal pain-related stress is associated with elevated salivary cortisol levels to age 18 months in children born very preterm, compared to full-term, suggesting early programming effects. Importantly, interactions between immune/inflammatory and neuroendocrine systems may underlie programming effects. We examined whether cortisol changes persist to school age, and if common genetic variants in the promoter region of the NFKBIA gene involved in regulation of immune and inflammatory responses, modify the association between early experience and later life stress as indexed by hair cortisol levels, which provide an integrated index of endogenous HPA axis activity. Cortisol was assayed in hair samples from 128 children (83 born preterm ≤ 32 weeks gestation and 45 born full-term) without major sensory, motor or cognitive impairments at age 7 years. We found that hair cortisol levels were lower in preterm compared to term-born children. Downregulation of the HPA axis in preterm children without major impairment, seen years after neonatal stress terminated, suggests persistent alteration of stress system programming. Importantly, the etiology was gender-specific such that in preterm boys but not girls, specifically those with the minor allele for NFKBIA rs2233409, lower hair cortisol was associated with greater neonatal pain (number of skin-breaking procedures from birth to term), independent of medical confounders. Moreover, the minor allele (CT or TT) of NFKBIA rs2233409 was associated with higher secretion of inflammatory cytokines, supporting the hypothesis that neonatal pain-related stress may act as a proinflammatory stimulus that induces long-term immune cell activation. These findings are the first evidence that a long-term association between early pain-related stress and cortisol may be mediated by a genetic variants that regulate the activity of NF-κB, suggesting possible involvement of stress/inflammatory mechanisms in HPA programming in boys born very preterm.
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Registered trials
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