ArticleFrontiers in behavioral neuroscience2014
Neonatal pain and COMT Val158Met genotype in relation to serotonin transporter (SLC6A4) promoter methylation in very preterm children at school age.
Article in Frontiers in behavioral neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 2 of them syntheses that pooled it.
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Who cites it
35 citing papers in PubMed, 2 syntheses or guidelines pooled it, 91 citations in OpenAlex.
- Transient Receptor Potential Ankyrin 1 (TRPA1) Methylation and Chronic Pain: A Systematic Review.Genes · 2023Pooled it
- Pooled it
- Longitudinal DNA methylation in parent-infant pairs impacted by intergenerational social adversity: An RCT of the Michigan Model of Infant Mental Health Home Visiting.Brain and behavior · 2024Trial
- Epigenome-wide Analysis Identifies Genes and Pathways Linked to Neurobehavioral Variation in Preterm Infants.Scientific reports · 2019Trial
- SLC6A4 Gene Methylation in Premature Infants Undergoing Kangaroo Mother Care: A Prospective Longitudinal Study.Biomedicines · 2026Article
- DNA Methylation ofBiological research for nursing · 2026Article
- Epigenetic age and neurodevelopmental outcomes in children born preterm.Genetics in medicine open · 2026Article
- Prematurity and Epigenetic Regulation ofBiomedicines · 2025Article
- Managing pain in newborns: A multidimensional approach.Paediatrics & child health · 2025Review
- Repetitive neonatal pain increases spinal cord DNA methylation of the µ-opioid receptor.Pediatric research · 2025Article
- Article
- Face Processing in Prematurely Born Individuals-A Systematic Review.Brain sciences · 2024Review
- DNA Methylation, Inflammation, and Neurobehavior in Preterm Infants.Biological research for nursing · 2024Article
- Contributions of prenatal risk factors and neonatal epigenetics to cognitive outcome in children born very preterm.Developmental psychology · 2024Article
- An industrialized diet as a determinant of methylation in the 1F region of theFrontiers in nutrition · 2024Article
- Current Evidence for Biological Biomarkers and Mechanisms Underlying Acute to Chronic Pain Transition across the Pediatric Age Spectrum.Journal of clinical medicine · 2023Article
- Association of Pediatric Buccal Epigenetic Age Acceleration With Adverse Neonatal Brain Growth and Neurodevelopmental Outcomes Among Children Born Very Preterm With a Neonatal Infection.JAMA network open · 2022Article
- Assessment and Management of Pain in Preterm Infants: A Practice Update.Children (Basel, Switzerland) · 2022Review
- The Behavioral Problems in 2.5-5 Years Old Children Linked with Former Neonatal/Infantile Surgical Parameters.Children (Basel, Switzerland) · 2021Article
- Serious neonatal morbidities are associated with differences in DNA methylation among very preterm infants.Clinical epigenetics · 2020Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Children born very preterm are exposed to repeated neonatal procedures that induce pain and stress during hospitalization in the neonatal intensive care unit (NICU). The COMT Val158Met genotype is involved with pain sensitivity, and early life stress is implicated in altered expression of methylation of the serotonin transporter. We examined: (1) whether methylation of the serotonin transporter gene (SLC6A4) promoter differs between very preterm children and full-term controls at school age, (2) relationships with child behavior problems, and (3) whether the extent of neonatal pain exposure interacts with the COMT Val158Met genotype to predict SLC6A4 methylation at 7 years in the very preterm children. We examined the associations between the COMT genotypes, neonatal pain exposure (adjusted for neonatal clinical confounders), SLC6A4 methylation and behavior problems. Very preterm children had significantly higher methylation at 7/10 CpG sites in the SLC6A4 promoter compared to full-term controls at 7 years. Neonatal pain (adjusted for clinical confounders) was significantly associated with total child behavior problems on the Child Behavior Checklist (CBCL) questionnaire (adjusted for concurrent stressors and 5HTTLPR genotype) (p = 0.035). CBCL Total Problems was significantly associated with greater SLC6A4 methylation in very preterm children (p = 0.01). Neonatal pain (adjusted for clinical confounders) and COMT Met/Met genotype were associated with SLC6A4 promoter methylation in very preterm children at 7 years (p = 0.001). These findings provide evidence that both genetic predisposition and early environment need to be considered in understanding susceptibility for developing behavioral problems in this vulnerable population.
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