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Children born preterm display altered sensory processing, which may manifest as hyper‐ and/or hypo‐sensitivity to sensory information. In this vulnerable population, exposure to neonatal pain‐related stress is associated with altered stress regulation, as indexed by alterations in cortisol levels. It is unknown whether sensory processing behaviors are also affected by early life adversity, and whether dysregulated cortisol is related to sensory processing problems in preterm children. We examined relationships between neonatal pain‐related stress, sensory processing profiles and cortisol levels at age 4 years, and whether pathways were sex‐specific. In a longitudinal prospective cohort study, N = 146 infants born 24–32 weeks gestational age were recruited from BC Women's Hospital, Vancouver, BC, Canada; neonatal factors were collected from daily chart review. At age 4 years, saliva to assay cortisol was collected three times across cognitive assessment (pre‐test, during, end) and parents completed the Short Sensory Profile questionnaire. Using generalized linear modeling, independent of other neonatal factors, higher number of invasive procedures (pain/stress) was associated with more sensory processing problems (total, hypo‐ and hyper‐sensitivity) for girls only. After accounting for neonatal factors, greater cortisol output across the assessment was associated with more total sensory processing problems in girls only, and hypersensitivity to sensory input in both boys and girls. Findings suggest that in children born very preterm, how a child responds to sensory input and cortisol reactivity to stress are related but may have different precursors. Girls may be somewhat more susceptible to neonatal pain‐related stress exposure in relation to sensory processing at preschool age.

ImportanceInternalizing (anxiety and/or depressive) behaviors are prevalent in children born very preterm (24-32 weeks’ gestation). Procedural pain-related stress in the neonatal intensive care unit (NICU) is associated with long-term internalizing problems in this population; however, whether positive parenting during toddlerhood attenuates development of internalizing behaviors across childhood is unknown.ObjectiveTo investigate whether neonatal pain-related stress is associated with trajectories of internalizing behaviors across 1.5, 3.0, 4.5, and 8.0 years, and whether supportive parenting behaviors and lower parenting stress at 1.5 and 3.0 years attenuate this association.Design, Setting, and ParticipantsIn this prospective longitudinal cohort study, preterm neonates (born at 24-32 weeks’ gestation) were recruited from August 16, 2006, to September 9, 2013, with follow-up visits at ages 1.5, 3.0, 4.5, and 8.0 years. The study was conducted at BC Women’s Hospital, Vancouver, Canada, with recruitment from a level III neonatal intensive care unit and sequential developmental assessments performed in a Neonatal Follow-up Program. Data analysis was performed from August to December 2021.Main Outcomes and MeasuresParental report of child internalizing behaviors on the Child Behavior Checklist at 1.5, 3.0, 4.5, and 8.0 years.ResultsA total of 234 neonates were recruited, and 186 children (101 boys [54%]) were included in the current study across ages 1.5 (159 children), 3.0 (169 children), 4.5 (162 children), and 8.0 (153 children) years. After accounting for clinical factors associated with prematurity, greater neonatal pain-related stress was associated with more internalizing behaviors across ages (B = 4.95; 95% CI, 0.76 to 9.14). Higher parenting stress at age 1.5 years (B = 0.17; 95% CI, 0.11 to 0.23) and a less supportive parent environment (less sensitivity, structure, nonintrusiveness, nonhostility, and higher parenting stress; B = −5.47; 95% CI, −9.44 to −1.51) at 3.0 years were associated with greater internalizing problems across development to age 8.0 years.Conclusions and RelevanceIn this cohort study of children born very preterm, exposure to repetitive neonatal pain-related stress was associated with persistent internalizing behavior problems across toddlerhood to age 8.0 years. Supportive parenting behaviors during early childhood were associated with better long-term behavioral outcomes, whereas elevated parenting stress was associated with more child anxiety and/or depressive behaviors in this population. These findings reinforce the need to prevent pain in preterm neonates and inform future development of targeted parent-led behavioral interventions.

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