Neonatal intensive care unit stress is associated with brain development in preterm infants

Smith, Gillian Crampton; Gutovich, Jordan; Smyser, Christopher D.; Pineda, Roberta; Newnham, Carol; Tjoeng, Tiong Han; Vavasseur, Claudine; Wallendorf, Michael; Neil, Jeffrey J.; Inder, Terrie E.

doi:10.1002/ana.22545

Cited by 442 publications

(327 citation statements)

References 27 publications

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“…Many previous studies have suggested that several risk factors within the NICU relate to adverse cognitive outcomes, including postnatal infection, 34,35 bronchopulmonary dysplasia, 36 suboptimal nutrition, 37 postnatal dexamethasone, 38 and stress. 39,40 However, few have defined the neuroanatomical pathway by which such exposures influence cognitive outcome. Our study contributes to this literature by confirming the importance of inotrope exposure, oxygen at 36 weeks, necrotizing enterocolitis, treated PDA, and prolonged parenteral nutrition as factors associated with the small BPW brain pattern at TEA, which, in turn, is associated with adverse cognitive development at age 2 years.…”

Section: Discussionmentioning

confidence: 99%

Brain Injury and Altered Brain Growth in Preterm Infants: Predictors and Prognosis

et al. 2014

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Brain Injury and Altered Brain Growth in Preterm Infants: Predictors and PrognosisWHAT'S KNOWN ON THIS SUBJECT: Term MRI can assist in identifying the nature and extent of brain injury in preterm infants. However, brain injury detected by MRI does not fully account for neurodevelopmental impairments, particularly cognitive and behavioral impairments, common in preterm survivors. WHAT THIS STUDY ADDS:In addition to brain injury, an assessment of brain growth by using one-dimensional measurements on MRI is helpful for predicting neurodevelopment. Two different patterns of impaired brain growth are observed that relate independently to early cognitive development in preterm infants. abstract BACKGROUND: To define the nature and frequency of brain injury and brain growth impairment in very preterm (VPT) infants by using MRI at term-equivalent age and to relate these findings to perinatal risk factors and 2-year neurodevelopmental outcomes.METHODS: MRI scans at term-equivalent age from 3 VPT cohorts (n = 325) were reviewed. The severity of brain injury, including periventricular leukomalacia and intraventricular and cerebellar hemorrhage, was graded. Brain growth was assessed by using measures of biparietal width (BPW) and interhemispheric distance. Neurodevelopmental outcome at age 2 years was assessed across all cohorts (n = 297) by using the Bayley Scales of Infant Development, Second Edition (BSID-II) or Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), and evaluation for cerebral palsy. RESULTS:Of 325 infants, 107 (33%) had some grade of brain injury and 33 (10%) had severe injury. Severe brain injury was more common in infants with lower Apgar scores, necrotizing enterocolitis, inotropic support, and patent ductus arteriosus. Severe brain injury was associated with delayed cognitive and motor development and cerebral palsy. Decreased BPW was related to lower gestational age, inotropic support, patent ductus arteriosus, necrotizing enterocolitis, prolonged parenteral nutrition, and oxygen at 36 weeks and was associated with delayed cognitive development. In contrast, increased interhemispheric distance was related to male gender, dexamethasone use, and severe brain injury. It was also associated with reduced cognitive development, independent of BPW.CONCLUSIONS: At term-equivalent age, VPT infants showed both brain injury and impaired brain growth on MRI. Severe brain injury and impaired brain growth patterns were independently associated with perinatal risk factors and delayed cognitive development. Pediatrics 2014;134:e444-e453 Dr Kidokoro contributed to the study concept and design, assessed the MRI findings, performed the statistical analyses, and wrote the first draft of the manuscript; Drs Anderson and Doyle contributed to the collection of the Australian data presented in this article and revised the manuscript for important intellectual content; Dr Woodward contributed to the collection of the New Zealand data presented in this article and revised the manuscript for important i...

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Section: Discussionmentioning

confidence: 99%

Brain Injury and Altered Brain Growth in Preterm Infants: Predictors and Prognosis

et al. 2014

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“…40,41 New and emerging technologies to measure pain responses, such as near-infrared spectroscopy, amplitude-integrated electroencephalography, functional MRI, skin conductance, and heart rate variability assessment, are being investigated. 53,54 These innovations hold promise in the development of neurophysiologically based methods for assessing noxious stimuli processing at the cortical level in neonates while they are awake, sedated, or anesthetized. If the neurophysiologic measures prove to be reliable and quantifiable, these measures could be used in the future to simultaneously correlate with the physiologic and behavioral pain assessment scales to determine the most clinically useful tool(s).…”

Section: Assessment Of Pain and Stress In The Neonatementioning

confidence: 99%

Prevention and Management of Procedural Pain in the Neonate: An Update

Keels¹,

Sethna²,

Watterberg³

et al. 2016

Pediatrics

301

156

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The prevention of pain in neonates should be the goal of all pediatricians and health care professionals who work with neonates, not only because it is ethical but also because repeated painful exposures have the potential for deleterious consequences. Neonates at greatest risk of neurodevelopmental impairment as a result of preterm birth (ie, the smallest and sickest) are also those most likely to be exposed to the greatest number of painful stimuli in the NICU. Although there are major gaps in knowledge regarding the most effective way to prevent and relieve pain in neonates, proven and safe therapies are currently underused for routine minor, yet painful procedures. Therefore, every health care facility caring for neonates should implement (1) a pain-prevention program that includes strategies for minimizing the number of painful procedures performed and (2) a pain assessment and management plan that includes routine assessment of pain, pharmacologic and nonpharmacologic therapies for the prevention of pain associated with routine minor procedures, and measures for minimizing pain associated with surgery and other major procedures.

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“…Previously, it has been demonstrated that a higher number of invasive and stressful procedures was associated with delayed WM maturation in infants born very preterm both during NICU care and at term-equivalent age. 7,8,25 Higher numbers of invasive procedures are associated with lower stress hormone cortisol responses at 32 weeks' postmenstrual age and higher levels at 8 and 18 months' corrected age. 26,27 Brain regions rich in glucocorticoid receptors (eg, prefrontal cortex) are particularly vulnerable to the effects of ongoing stress.…”

Section: Discussionmentioning

confidence: 99%

Invasive Procedures in Preterm Children: Brain and Cognitive Development at School Age

2014

PEDIATRICS

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WHAT'S KNOWN ON THIS SUBJECT: Greater numbers of invasive procedures from birth to term-equivalent age, adjusted for clinical confounders, are associated with altered brain microstructure during neonatal care and poorer cognitive outcome at 18 months' corrected age in children born very preterm.WHAT THIS STUDY ADDS: Altered myelination at school age is associated with greater numbers of invasive procedures during hospitalization in very preterm children without severe brain injury or neurosensory impairment. Greater numbers of invasive procedures and altered brain microstructure interact to predict lower IQ. abstract BACKGROUND: Very preterm infants (born 24-32 weeks' gestation) undergo numerous invasive procedures during neonatal care. Repeated skin-breaking procedures in rodents cause neuronal cell death, and in human preterm neonates higher numbers of invasive procedures from birth to term-equivalent age are associated with abnormal brain development, even after controlling for other clinical risk factors. It is unknown whether higher numbers of invasive procedures are associated with long-term alterations in brain microstructure and cognitive outcome at school age in children born very preterm. METHODS:Fifty children born very preterm underwent MRI and cognitive testing at median age 7.6 years (interquartile range, 7.5-7.7). T 1 -and T 2 -weighted images were assessed for the severity of brain injury. Magnetic resonance diffusion tensor sequences were used to measure fractional anisotropy (FA), an index of white matter (WM) maturation, from 7 anatomically defined WM regions. Child cognition was assessed using the Wechsler Intelligence Scale for Children-IV. Multivariate modeling was used to examine relationships between invasive procedures, brain microstructure, and cognition, adjusting for clinical confounders (eg, infection, ventilation, brain injury). RESULTS:Greater numbers of invasive procedures were associated with lower FA values of the WM at age 7 years (P = .01). The interaction between the number of procedures and FA was associated with IQ (P = .02), such that greater numbers of invasive procedures and lower FA of the superior WM were related to lower IQ. CONCLUSIONS:Invasive procedures during neonatal care contribute to long-term abnormalities in WM microstructure and lower IQ. Pediatrics 2014;133:412-421

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Neonatal intensive care unit stress is associated with brain development in preterm infants

Cited by 442 publications

References 27 publications

Brain Injury and Altered Brain Growth in Preterm Infants: Predictors and Prognosis

Brain Injury and Altered Brain Growth in Preterm Infants: Predictors and Prognosis

Prevention and Management of Procedural Pain in the Neonate: An Update

Invasive Procedures in Preterm Children: Brain and Cognitive Development at School Age

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