The relationship between nociceptive brain activity, spinal reflex withdrawal and behaviour in newborn infants

Hartley, Caroline; Goksan, Sezgi; Poorun, Ravi; Brotherhood, Kelly; Mellado, Gabriela Schmidt; Moultrie, Fiona; Rogers, Richard; Adams, Eleri; Slater, Rebeccah

doi:10.1038/srep12519

Cited by 66 publications

(114 citation statements)

References 44 publications

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“…Infants subjected to repetitive heel lances, the most common skin-breaking procedure in neonates, have increased pain responses to subsequent skin cleansing and venipuncture (117). Heel lances in newborns elicit nociceptive-specific EEG brain activity associated with reflex withdrawal dependent on the stimulus intensity in the absence of clinical pain, which is difficult to measure (118). Brain imaging of newborn infants demonstrates increased sensitivity to nociceptive stimuli with greater amplitude and duration of reflex withdrawal compared to adults (119).…”

Section: Introductionmentioning

confidence: 99%

A “Wear and Tear” Hypothesis to Explain Sudden Infant Death Syndrome

Elhaik

2016

Front. Neurol.

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Sudden infant death syndrome (SIDS) is the leading cause of death among USA infants under 1 year of age accounting for ~2,700 deaths per year. Although formally SIDS dates back at least 2,000 years and was even mentioned in the Hebrew Bible (Kings 3:19), its etiology remains unexplained prompting the CDC to initiate a sudden unexpected infant death case registry in 2010. Due to their total dependence, the ability of the infant to allostatically regulate stressors and stress responses shaped by genetic and environmental factors is severely constrained. We propose that SIDS is the result of cumulative painful, stressful, or traumatic exposures that begin in utero and tax neonatal regulatory systems incompatible with allostasis. We also identify several putative biochemical mechanisms involved in SIDS. We argue that the important characteristics of SIDS, namely male predominance (60:40), the significantly different SIDS rate among USA Hispanics (80% lower) compared to whites, 50% of cases occurring between 7.6 and 17.6 weeks after birth with only 10% after 24.7 weeks, and seasonal variation with most cases occurring during winter, are all associated with common environmental stressors, such as neonatal circumcision and seasonal illnesses. We predict that neonatal circumcision is associated with hypersensitivity to pain and decreased heart rate variability, which increase the risk for SIDS. We also predict that neonatal male circumcision will account for the SIDS gender bias and that groups that practice high male circumcision rates, such as USA whites, will have higher SIDS rates compared to groups with lower circumcision rates. SIDS rates will also be higher in USA states where Medicaid covers circumcision and lower among people that do not practice neonatal circumcision and/or cannot afford to pay for circumcision. We last predict that winter-born premature infants who are circumcised will be at higher risk of SIDS compared to infants who experienced fewer nociceptive exposures. All these predictions are testable experimentally using animal models or cohort studies in humans. Our hypothesis provides new insights into novel risk factors for SIDS that can reduce its risk by modifying current infant care practices to reduce nociceptive exposures.

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Section: Introductionmentioning

confidence: 99%

A “Wear and Tear” Hypothesis to Explain Sudden Infant Death Syndrome

Elhaik

2016

Front. Neurol.

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“…Continued emphasis should be placed on the creation of novel animal models simulating the neonatal context. Additionally, the utilisation of a nontissue damaging acute experimental stimuli such as the PinPrick MRC system described by Hartley and colleagues holds excellent promise to help us better understand these questions.…”

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confidence: 99%

‘First, do no harm’ – the use of analgesia or placebo as control for babies in painful clinical trials

Campbell-Yeo

2016

Acta Paediatrica

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“…Although the ipsilateral and contralateral RMS were well correlated, the ipsilateral duration and amplitude of the reflexes were less well correlated with the contralateral EMG measures (Figure B). Both ipsilateral and contralateral responses were included in the full multimodal model, as they are likely to provide added discriminative value …”

Section: Resultsmentioning

confidence: 99%

Multimodal pain assessment improves discrimination between noxious and non‐noxious stimuli in infants

Vaart

Duff

Raafat

et al. 2019

Paediatric and Neonatal Pain

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Infants in neonatal intensive care units frequently experience clinically necessary painful procedures, which elicit a range of behavioral, physiological, and neurophysiological responses. However, the measurement of pain in this population is a challenge and no gold standard exists. The aim of this study was to investigate how noxious‐evoked changes in facial expression, reflex withdrawal, brain activity, heart rate, and oxygen saturation are related and to examine their accuracy in discriminating between noxious and non‐noxious stimuli. In 109 infants who received a clinically required heel lance and a control non‐noxious stimulus, we investigated whether combining responses across each modality, or including multiple measures from within each modality improves our ability to discriminate the noxious and non‐noxious stimuli. A random forest algorithm was used to build data‐driven models to discriminate between the noxious and non‐noxious stimuli in a training set which were then validated in a test set of independent infants. Measures within each modality were highly correlated, while different modalities showed less association. The model combining information across all modalities had good discriminative ability (accuracy of 0.81 in identifying noxious and non‐noxious stimuli), which was higher than the discriminative power of the models built from individual modalities. This demonstrates the importance of including multiple modalities in the assessment of infant pain.

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The relationship between nociceptive brain activity, spinal reflex withdrawal and behaviour in newborn infants

Cited by 66 publications

References 44 publications

A “Wear and Tear” Hypothesis to Explain Sudden Infant Death Syndrome

A “Wear and Tear” Hypothesis to Explain Sudden Infant Death Syndrome

‘First, do no harm’ – the use of analgesia or placebo as control for babies in painful clinical trials

Multimodal pain assessment improves discrimination between noxious and non‐noxious stimuli in infants

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