Received: 12 February 2020

| Revised: 13 July 2020

| Accepted: 28 August 2020

DOI: 10.1002/ejp.1656

ORIGINAL ARTICLE

The impact of parental contact upon cortical noxious-related

activity in human neonates

Laura Jones1 | Maria Pureza Laudiano-Dray1 | Kimberley Whitehead1 | Judith Meek2 |

Maria Fitzgerald1 | Lorenzo Fabrizi1 | Rebecca Pillai Riddell3

1
Department of Neuroscience, Physiology
& Pharmacology, University College
Abstract
London, London, UK Background: Neonates display strong behavioural, physiological and cortical re-
2
Elizabeth Garrett Anderson Obstetric sponses to tissue-damaging procedures. Parental contact can successfully regulate
Wing, University College London
general behavioural and physiological reactivity of the infant, but it is not known
Hospitals, London, UK
3 whether it can influence noxious-related activity in the brain. Brain activity is highly
Department of Psychology, York
University, Toronto, ON, Canada dependent upon maternal presence in animal models, and therefore this could be an
important contextual factor in human infant pain-related brain activity.
Correspondence
Lorenzo Fabrizi, Department of
Methods: Global topographic analysis was used to identify the presence and inter-
Neuroscience, Physiology and group differences in noxious-related activity in three separate parental contexts. EEG
Pharmacology, University College London, was recorded during a clinically required heel lance in three age and sex-matched
Gower Street, London, WC1E 6BT, UK.
Email: [email protected] groups of neonates (a) while held by a parent in skin-to-skin (n = 9), (b) while held
by a parent with clothing (n = 9) or (c) not held at all, but in individualized care
Funding information
(n = 9).
This work was funded by the Medical
Research Council UK (MR/M006468/1, Results: The lance elicited a sequence of 4–5 event-related potentials (ERPs), in-
MR/L019248/1, and MR/S003207/1) and cluding the noxious ERP (nERP), which was smallest for infants held skin-to-skin
an International Association for the Study
and largest for infants held with clothing (p=0.016). The nERP was then followed
of Pain Collaborative Research Grant.
by additional and divergent long-latency ERPs (> 750 ms post-lance), not previously
described, in each of the groups, suggesting the engagement of different higher level
cortical processes depending on parental contact.
Conclusions: These results show the importance of considering contextual factors in
determining infant brain activity and reveal the powerful influence of parental con-
tact upon noxious-related activity across the developing human brain.
Significance: This observational study found that the way in which the neonatal
brain processes a noxious stimulus is altered by the type of contact the infant has
with their mother. Specifically, being held in skin-to-skin reduces the magnitude
of noxious-related cortical activity. This work has also shown that different neural
mechanisms are engaged depending on the mother/infant context, suggesting mater-
nal contact can change how a baby's brain processes a noxious stimulus.

Lorenzo Fabrizi and Rebecca Pillai Riddell, these authors should be considered joint senior author.

This is an open access article under the terms of the Creat​ive Commo​ns Attri​bution License, which permits use, distribution and reproduction in any medium, provided the original
work is properly cited.
© 2020 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC®

Eur J Pain. 2021;25:149–159. wileyonlinelibrary.com/journal/ejp | 149

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|    JONES et al.

1 | IN TRO D U C T ION of the cortex and neuronal threat system of the offspring,
and will therefore likely modulate infant cortical processing
Neonates have strong behavioural, physiological and cor- during a noxious stimulus.
tical responses to tissue breaking stimuli (Jansen, Beijers, Here we compare the electroencephalographic (EEG) re-
Riksen-Walraven, & de Weerth, 2010; Johnston et al., 2003; sponse to a clinically required heel lance across three groups
Jones et al., 2017; Slater, Worley, et al., 2010; Stevens, of age and sex-matched neonates who were (a) held by a par-
Yamada, Ohlsson, Haliburton, & Shorkey, 2016; Waxman, ent skin-to-skin (n = 9), (b) held by a parent with clothing
Pillai Riddell, Tablon, Schmidt, & Pinhasov, 2016). These (n = 9) or (c) not held at all, but in individualized care (n = 9)
measures are mediated by different parts of the nervous at the time of the lance. The analysis was conducted using a
system (i.e. subcortical somatic, autonomic and cortical global topography approach (Habermann, Weusmann, Stein,
centers respectively) and are therefore likely to reflect & Koenig, 2018), which is reference independent and accounts
different and partially independent aspects of the sensory for the distribution of the voltage field across the whole scalp.
response (Evans, 2001; Morison, Grunau, Oberlander, This allowed us to quantify the contextual influence of mater-
& Whitfield, 2001; Ranger, Johnston, & Anand, 2007; nal contact upon noxious-related activity in the human infant
Rinn, 1984; Slater, Cantarella, Franck, Meek, & brain.
Fitzgerald, 2008; Slater, Cornelissen, et al., 2010; Waxman
et al., 2020). Indeed, these measures are not always di-
rectly correlated (Jones et al., 2017), and can be differ- 2 | M ETHODS
entially modulated by contextual factors such as baseline
stress levels and sucrose administration following the same 2.1 | Participants
noxious stimulus (Jones et al., 2017; Slater, Cornelissen,
et al., 2010). Twenty-seven infants (23–41 gestational weeks at birth,
The presence and type of parental contact is effective 0–96 days old, 12 female; Table 1) were recruited from the
in regulating an infant's behaviour and physiology in re- postnatal, special care and high dependency wards within the
sponse to a noxious stimulus (Johnston et al., 2017; Pillai neonatal unit at University College London Hospital between
Riddell et al., 2015). However, it is not clear whether this June 2015 and May 2018. No infant had any clinical sign of
is also true for noxious stimulus processing in the brain. hypoxic ischaemic encephalopathy (HIE). Infants were ex-
Understanding the effect of parental contact upon brain cluded if they had > grade 2 intraventricular haemorrhage
activity is not only relevant to infant perception at the (IVH), or periventricular leukomalacia (PVL). Infants were
time of the procedure, but could also provide insight into split into three groups (n = 9 each) based on maternal contact
stimulus-dependent plasticity in the cortex, pain learn- (held in skin-to-skin, held with clothing, and individualized
ing and the negative impact of repeated pain exposure care in the cot). Sex proportion, gestational age at birth (GA)
(Brummelte et al., 2012; Schneider et al., 2017; Schwaller and postnatal age did not differ significantly between groups
& Fitzgerald, 2014). (sex: χ2(2) = 0.00, p = 1; GA: F(2,24)=0.27, p = 0.768; PNA:
In adults, contextual factors can transform pain expe- F(2,24) = 0.34, p = 0.714). Ethical approval for this study was
rience (Leknes et al., 2013; López-Solà, Geuter, Koban, given by the NHS Health Research Authority (London – Surrey
Coan, & Wager, 2019; Mancini, Longo, Canzoneri, Vallar, Borders) and conformed to the standards set by the Declaration
& Haggard, 2013) particularly if pain is associated with of Helsinki. Informed written parental consent was obtained
positive outcomes (Leknes et al., 2013; López-Solà, Koban, before each study.
& Wager, 2018). In rodents, maternal presence can impact
how pups learn what is threatening and what is safe, by al-
tering the activity of the relevant neural circuits during an 2.1.1 | Skin-to-Skin (S-S)
adverse event (Debiec & Sullivan, 2017). Maternal absence
from the nest and maternal stimulation alter cortical syn- Infants were held during the heel lance wearing only a dia-
chronization (Sarro, Wilson, & Sullivan, 2014) and increase per, against the bare chest of the mother who was sitting in
anterior cingulate cortex low-frequency activity in the a reclined chair or bed wearing an open hospital robe. Once
pups (Courtiol, Wilson, Shah, Sullivan, & Teixeira, 2018). in position, the infant was covered with a blanket. Infants
In humans, positive mother–infant interactions improve were free to feed during skin-to-skin care. Two infants
the development of cerebral white-matter microstructure were breastfeeding during the procedure and one infant was
(Milgrom et al., 2010) and accelerate maturation of corti- breastfed 5 min prior. On average, the infants were held for
cal functional coherence across frontal regions in the in- 30.2 min prior to the heel lance. Six infants were in active
fants (Myers et al., 2015). Maternal presence has therefore a sleep and three infants were quietly awake immediately pre-
powerful influence upon brain activity and the development ceding the lance.
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TABLE 1 Infant demographics

Group

Held with Cot,

Skin-to-skin clothing Individualized- care
GA (weeks) 33 (23–40) 35 (25–40) 34 (26–41)
PNA (days) 20 (1–63) 24 (2–96) 14 (0–41)
No. female 4 (44%) 4 (44%) 4 (44%)
Birth weight (g) 2,083 (480–3,520) 2,328 (775–3,580) 2,342 (625–4,592)
No. caesarean 4 (44%) 3 (33%) 3 (33%)
deliveries
Apgar score @ 5 mina 9 (5–10) 9 (4–10) 9 (6–10)
Note: GA is the number of weeks from the first day of the mothers last menstrual cycle to the birth, and PNA
refers to the number of days since birth. Values represent the median and range. GA in weeks represents a
completed week, that is, 29 = 29+0–29 + 6 (weeks + days). Term ≥37 weeks.
a
A simple and quick assessment, scored out of 10, to determine if a newborn requires any medical intervention
immediately after birth.

2.1.2 | Held with clothing (H) skin-to-skin care, or have their baby in their cot or incuba-
tor for the study, resulting in a naturalistic sample indicative
Infants were held by the mother during the study with cloth- of a realistic hospital population and protocol. For further
ing between them. Mothers were seated in a chair or bed description of the study see Jones et al. (Jones et al., 2018).
similar to the skin-to-skin group. Either mother or infant
was dressed preventing significant skin contact in the pe-
riod preceding and following the lance. Minimal skin con- 2.3 | Noxious stimulation
tact occurred in three cases (i.e. infant cheek and/or hand
on mother neck or chest). Infants were held on average All heel lances were performed by the same trained nurse
27.6 min prior to heel lance. Six infants were in active (MPL-D) using a disposable lancet, and standard hospital
sleep, two infants were in quiet sleep and one infant was practice was followed at all times. The heel was cleaned
quietly awake. with sterile water using sterile gauze and the lancet placed
against the heel for at least 30s prior to the release of the
blade. This was to obtain a baseline period free from other
2.1.3 | Cot, individualized care (C-IC) stimulation. The heel was then squeezed 30s after the release
of the blade, again to ensure a post-stimulus period free from
Infants were lying in their cot or incubator during the other stimuli.
study. These infants received developmentally sensitive
care during the procedure, which was individualized de-
pending on their needs (Als, 2009). Seven infants were 2.4 | Electroencephalography
swaddled, and two were nested while prone. No infant was
held or touched by a caregiver (aside from the research 2.4.1 | Recording
nurse administering the heel lance) immediately prior to or
during the lance. Four infants were in active sleep, four in EEG (time-locked to the lance) was recorded from up to 18
quiet sleep and one was quietly awake immediately prior electrodes (disposable Ag/AgCl cup electrodes) in addition
to the lance. to the ground and reference electrodes. Recording electrodes
were positioned individually by a clinical neurophysiologist
(KW) according to the international 10/20 electrode place-
2.2 | Experimental design ment system (F7, F8, F3, F4, Cz, C3, C4, T7, T8, P7, P8, O1,
O2), with additional central-parietal and temporal coverage
Brain activity (electroencephalography, EEG), facial re- (CPz, CP3, CP4, TP9, TP10). Reference and ground elec-
sponse (nasolabial furrow, eye-squeeze, and brow bulge) trodes were respectively placed at Fz and FC1/2. EEG activ-
and heart rate (electrocardiography, ECG) to a single clini- ity, from DC to ≥500 Hz, was recorded using the Neuroscan
cally -required noxious heel lance were recorded. Mothers SynAmps2 EEG/EP recording system. Signals were digitized
were informed that they could hold their baby dressed, in with a sampling rate of 2 kHz and a resolution of 24 bit.
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2.4.2 | Pre-processing 2.5 | Behavioural and

physiological responses
Pre-processing was conducted using MATLAB and EEGLAB.
Raw data were filtered with a second-order bidirectional Infant behavioural responses to the lance were scored sec-
Butterworth bandpass (1–25 Hz) and a notch (48–52 Hz) fil- ond-by-second according to the premature infant pain pro-
ter, and epoched between 0.5 s prior to and 1 s following the file (PIPP) (Stevens, Johnston, Petryshen, & Taddio, 1996).
stimulus. Baseline correction was carried out using the pre- Facial expressions were recorded on video and synchronized
stimulus interval. Epochs contaminated with movement arti- with the EEG recording with an LED placed within the frame
fact (signal exceeding ± 150 µV) were removed. Spherical that was activated by the blade release of the lance. Three
interpolation was used for electrodes that were not recorded facial features were assessed as present or not during a 15s
or contaminated with noise (maximum of four channels were pre-stimulus baseline period and 30s post-lance (nasolabial
interpolated per trial). Two trials exhibited heart rate artefact furrow, eye squeeze and brow bulge) by the same research
which was removed using independent component analysis. nurse. View of the infant face was obstructed in the video of
Data were re-referenced to the common average and trials three test occasions. Heart rate was monitored using the same
were Woody filtered to correct for inter-subject latency jitter system as the EEG, with a lead I electrocardiogram (ECG)
(during 350–700 ms based on electrode Cz, maximum jitter recorded from electrodes on both shoulders. Behavioural
±50 ms Bromm & Scharein, 1982; Woody, 1967)). score and heart rate were compared second-by-second across
groups using between-groups ANOVA. Statistical analysis
was conducted in SPSS. Significance was set at p<0.05.
2.4.3 | Scalp field analysis

The following analysis was conducted using Ragu 2.6 | Data and code sharing
(Habermann et al., 2018), which identifies the presence and
inter-group differences of event-related potentials (ERPs) Data used in this project can be accessed from the UK Data
across the scalp using non-parametric permutation statistics Service repository. Please see the related Data Descriptor for
timepoint-by-timepoint (n = 1,000 randomization runs, alpha more details (Jones et al., 2018).
level 0.05).
We first assessed timepoint-by-timepoint topographic
consistency within each group to identify the presence of
ERPs following the lance. This test assumes that within an
experimental group at a given latency, if the subjects recruit
the same cortical sources in response to the same stimulus,
this would appear as a consistent spatial distribution of the
voltage field across the scalp.
We then compared the topography and magnitude of
the peak ERPs at comparable latencies across groups. The
peak of the ERP was defined by the maximum global field
power (GFP) within each topographically consistent time
window, and the latencies of those ERPs were considered
comparable across the groups if the maximum GFP fell
within the same topographically consistent time window
of the grand average (Figure 2b). Differences in latency
across the groups were not assessed due to the use of
Woody filtering. Topographical differences were quanti-
fied using the topographic dissimilarity index (DISS) and
then compared across groups using topographic analysis
of variance (TANOVA; (Tzovara, Murray, Michel, & De
Lucia, 2012)). Significantly different topographies in-
dicate different cortical source configurations (location
and/or orientation). Finally, we compared the magnitude F I G U R E 1 Summary of ERP comparison across groups.
of the GFP of those ERPs which had similar latency and Summary of comparison steps (rectangles) across ERPs identified in
topography across groups to assess differences in activity the different groups and interpretation of the results (ovals). skin-to-
strength. For a summary of the analysis steps see Figure 1. skin (S-S), cot-individualized care (C-IC), and held with clothing (H)
JONES et al.    
| 153

3 | R E S U LTS and 155 BPM) than in infants in cot, individualized care

(1.3 and 150 BPM) or in infants in skin-to-skin (1.1 and
3.1 | Parental contact modulates the noxious 149 BPM) (Figure 4).
ERP

The EEG response for all groups comprised a sequence of 4 | DISCUSSION

three event-related potentials (ERPs) from 89 to 755 ms at
comparable latencies (Figure 2) with a concentric distribu- These data demonstrate the importance of context in de-
tion and a negative or positive peak at the vertex (Cz and/ termining how the human infant brain processes a noxious
or CPz), two of which did not significantly differ across stimulus. Parental contact strongly influences the pattern of
groups (Figure 3). The last of these events (497–755 ms) brain activity evoked by a clinically required heel lance sug-
is the previously described noxious ERP (nERP) (Fabrizi gesting a contextual effect on the way the incoming stimulus
et al., 2011; Jones et al., 2018; Verriotis, Chang, Fitzgerald, is processed.
& Fabrizi, 2016), and was modulated by parental contact,
with skin-to-skin having the lowest global field power (GFP)
(5.89 µV at 601 ms), followed by cot, individualized-care 4.1 | Skin-to-skin care dampens noxious-
(8.24 µV at 684 ms) then held with clothing (12.46 µV at related cortical activity
563 ms). Skin-to-skin had a significantly dampened nERP
compared to being held with clothes (p = 0.016), however, The brain response to a clinically required heel lance com-
the difference between skin-to-skin and cot, individualized- prised a sequence of three event-related potentials (ERPs)
care did not reach significance (p > 0.050). independently of presence and style of parental contact.
Based on their concentric distribution, polarity and latency, it
is clear that these events are the somatosensory and noxious
3.2 | Parental contact affects the cortical events observed in previous work at electrode Cz/CPz (N2,
processes engaged following the lance N3, P3 Fabrizi et al., 2011; Jones et al., 2018; Slater, Worley,
et al., 2010; Verriotis et al., 2016). The last of these cortical
Infants who were held with clothing had an early ERP peak- events is considered noxious-related (nERP) as it is evoked
ing at 45 ms, which was not present at comparable latencies only when the lancet blade cuts the skin, but not following a
in the other groups (Figure 2). This response was negative sham control procedure (Fabrizi et al., 2011). Here we show
over the frontal areas and bilaterally positive at the posterior- that this nERP is modulated by maternal contact in a natu-
temporal electrodes (Figure 3). After 755 ms, the activity ralistic hospital population. Infants held in skin-to-skin had
diverged as the three groups presented distinct ERPs with the smallest GFP, while those held with clothing the larg-
different latency (758, 821 and 920 ms; Figure 2) and topog- est, suggesting a reduction in cortical activation related to the
raphy (skin-to-skin vs. held with clothing: p = 0.008; skin- processing of the lance during skin-to-skin care. Although
to-skin versus. cot, individualized care: p=.015; held with non-significant, the same trend was observed in the behav-
clothing vs. cot, individualized care: p = 0.043; Figure 3). ioural and physiological measures.
Infants in skin-to-skin had a distribution positive at contralat- The immature and rapidly developing mammalian brain
eral central and negative at ipsilateral temporal electrodes; is highly plastic and its activity is substantially modulated
infants held with clothing had a distribution negative at the by environmental factors (Chaudhury, Sharma, Kumar, Nag,
vertex and contralateral frontal regions and bilaterally posi- & Wadhwa, 2016), which, in early life, are mainly depen-
tive at the posterior quadrants; infants in the cot had a posi- dent on mother/infant interactions. Moreover, threat learning
tive distribution over the bilateral centro-parietal strip and requires newborns to be sensitive to maternal cues in order
ipsilateral central electrode and negativity at the contralateral to regulate in the present and learn for the future (Debiec &
fronto-temporal regions. Sullivan, 2017). This manifests as altered activity of the rel-
evant neural circuits during an adverse event which is depen-
dent upon the nature of the parental interaction (Debiec &
3.3 | Facial expression and heart rate Sullivan, 2017). For example, maternal presence or absence
differentially alters the long-term development of cortical
There was no significant difference in behavioural score threat systems in humans (Gee et al., 2013, 2014). During
and heart rate between the three groups at any point dur- odour-shock conditioning in neonatal rat pups, maternal
ing baseline or after stimulation (ANOVA, p > 0.05), presence can prevent fear conditioning by attenuating amyg-
however, there was a trend for peak behavioural score and dala activity and the release of stress hormones (Debiec &
heart rate to be higher in infants held with clothing (1.7 Sullivan, 2017; Moriceau, Roth, & Sullivan, 2010; Moriceau
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|    JONES et al.

F I G U R E 2 Event-related potentials and Global Field Power across groups in response to a clinically required heel lance. ERPs and GFPs
following a heel lance (vertical dashed lines) for infant in skin-to-skin (S-S, red), cot-individualized care (C-IC, blue) and held with clothing (H,
yellow). Average EEG recording at each electrode in the three groups (a); average GFPs for the three groups (b). Coloured and grey blocks at
the bottom of panel (b) respectively indicate periods of topographic consistency within each group and for the grand average. Vertical solid lines
indicate the peak group GFP within each period. Peak group GFPs within the same grand average consistency period were considered as having a
comparable latency

& Sullivan, 2006). Therefore, maternal presence during a impact upon the noxious-related activity in the cortex, and
noxious procedure may result in a reduction in infant threat may reflect their ability to attenuate the activation of the
learning during a critical period when fear learning becomes systems that contribute to threat learning. Indeed, maternal
more hard-wired (Debiec & Sullivan, 2017). Here we have presence has also been shown to regulate physiological stress
shown that different naturalistic mother/infant contexts during acute noxious procedures in human neonates (Cong,
JONES et al.    
| 155

F I G U R E 3 Topographic and magnitude differences of the cortical response to the heel lance according to parental contact. Topographic maps
at the latency of peak ERP for each group (Figure 2b). Time windows are based on the topographically consistent events from the grand average
and the peak latency for each group fell within this time window. Brackets mark significant differences in topography (DISS) or magnitude (GFP).
Skin-to-skin (S-S, red), cot-individualized care (C-IC, blue), held with clothing (H, yellow)

Ludington-Hoe, McCain, & Fu, 2009), and our earlier work

has demonstrated a link between physiological stress and the
amplitude of the nERP (Jones et al., 2017). Three of the in-
fants in the skin-to-skin care group were also breastfeeding
during (or prior to) the lance. While breastfeeding is effec-
tive in reducing noxious-related behavioural and physiolog-
ical responses (Shah, Herbozo, Aliwalas, & Shah, 2012),
breastfeeding with skin-to-skin contact does not increase the
efficacy of skin-to-skin contact alone (Okan, Ozdil, Bulbul,
Yapici, & Nuhoglu, 2010). Considering that cortical, physi-
ological and behavioural noxious-related responses can vary
independently from one another, the effect of breastfeeding
on noxious-related cortical activity is not known.
Surprisingly, skin-to-skin care did not result in a signifi-
cantly smaller cortical response compared to neonates in
the cot/incubator. This is likely a reflection of the success
of the individualized and developmentally sensitive care
provided, rather than a failure of skin-to-skin care in damp-
ening noxious-related activity because: (1) containment
F I G U R E 4 Behavioural and heart rate scores. Average facial and swaddling are also effective in reducing noxious-re-
behaviour (a) and heart rate (b) for the three groups, Skin-to-skin (S-S, lated behaviours (Pillai Riddell et al., 2015) and (2) neo-
red), held with clothing (H, yellow), and cot-individualized care (C-IC, nates in the cot/incubator have a cortical response about
blue). Dashed lines indicate the time of the lance 51% smaller compared to those held while clothed (even if
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|    JONES et al.

not statistically significant). It may also be surprising that common ERPs across our groups may reflect the initial ar-
the held while clothed group had the largest nERP mag- rival of the signal to the somatosensory cortex and the basic
nitude, however, even gentle handling of the preterm ne- processing of stimulus features, which remain consistent re-
onate to move them out of the cot, before the heel lance, gardless of the degree of parental contact, but may be altered
may be physiologically dysregulating (Newnham, Inder, & in terms of magnitude.
Milgrom, 2009; Sweeney & Blackburn, 2013). This dys- In terms of this hierarchy, the longest latency response
regulation may be counteracted by the powerful multi-sen- should reflect the most complex processing, which is dif-
sory effects of skin-to-skin contact with mother (olfactory, ferent for neonates depending on the presence and type
tactile [heat and texture]), which may be reduced if the of parental contact during the procedure. Different forms
mother was clothed while holding an infant. of maternal contact in rodents (contact, latching and
It should also be noted that the magnitude of EEG activity feeding), can alter cortical resting state activity (Sarro
may not directly relate to the pain experienced. Amplitude et al., 2014), which may prime a different response to stim-
of laser-evoked potentials correlates with the self-reporting ulation. Indeed, physiological arousal prior to a painful
of pain in adults (Iannetti, Hughes, Lee, & Mouraux, 2008), procedure can influence the behavioural and cortical nox-
and pinprick evoked ERP magnitude reflects levels of cen- ious responses in human neonates (Ahola Kohut & Pillai
tral sensitization in pain pathways (Iannetti, Baumgärtner, Riddell, 2009; Jones et al., 2017), and baseline EEG activ-
Tracey, Treede, & Magerl, 2013; Liang, Lee, O’Neill, ity prior to a painful stimulus is correlated with subsequent
Dickenson, & Iannetti, 2016). However, these ERPs are not activity and pain perception in adults (Babiloni et al., 2006;
entirely modality specific and their magnitude may be mod- Tu et al., 2016).
ulated by the saliency of the stimulus (Iannetti et al., 2008;
Mouraux & Iannetti, 2009; Ronga, Valentini, Mouraux,
& Iannetti, 2012). Nevertheless, repeated or enhanced 4.3 | Parental contact does not significantly
noxious-related activity during a critical period of corti- change noxious-related behaviour or heart rate
cal development may contribute to negative long-term ef-
fects (Verriotis et al., 2016). Infant pain-related behaviour, There were no differences in heart rate or behavioural score
stress reactivity and brain maturation are affected by the between the groups, consistent with the lack of change in
number of painful procedures experienced (Anand, 2000; the composite behaviour and physiology score reported
Brummelte et al., 2012; Schneider et al., 2017; Schwaller elsewhere (Olsson, Ahlsén, & Eriksson, 2016). This is not
& Fitzgerald, 2014; Walker, 2017) and the absence of so- surprising as physiological, behavioural and cortical nox-
cial caregiver contact during early life can negatively im- ious-related responses can vary independently from one
pact cortical white matter and cognitive development (Bick another as they are mediated by different parts of the nerv-
et al., 2015; Nelson et al., 2007). Maternal contact in rat ous system (i.e. subcortical autonomic, somatic and corti-
pups can ameliorate the negative effect of early pain expe- cal centres respectively) (Evans, 2001; Jones et al., 2017;
rience (Walker, Xu, Rochford, & Celeste Johnston, 2008), Morison et al., 2001; Ranger et al., 2007; Rinn, 1984; Slater
and social behaviours such as huddling, contribute to nor- et al., 2008; Slater, Cornelissen, et al., 2010; Waxman
mal brain development (Naskar et al., 2019). The absence et al., 2020). Studies that have reported a significant decrease
of these physical interactions results in the disruption of in infant pain-related behavioural responses during skin-to-
functional synaptic connections within the somatosensory skin care were carried out over a longer time period and in-
cortex (Naskar et al., 2019). cluded the additional stimulus of squeezing the heel (Cong,
Ludington-Hoe, & Walsh, 2011; Johnston et al., 2003, 2008;
Pillai Riddell et al., 2015). However, we noted that the be-
4.2 | The longest latency activity is havioural and physiological data followed the same trend as
dependent on the degree of parental contact the cortical data, with the skin-to-skin group having the low-
est facial expression score and heart rate immediately follow-
The longest latency ERP observed following the lance does ing the lance, followed by the group in cot/incubator, then
not have a common cortical source across groups, which may those held while clothed.
reflect the impact of mother/infant context on higher order
and complex processing of the stimulus. ERPs at different
latencies correspond to the ascending stages in the hierarchi- 5 | CONCLUSIONS
cal processing of a sensory stimulus (Allison, McCarthy, &
Wood, 1992; Frot & Mauguière, 1999; Kitazawa, 2002; Libet, The mother/infant context can modulate the magnitude of the
Alberts, Wright, & Feinstein, 1967; Whitehead, Papadelis, noxious-related brain activity following a clinically required heel
Laudiano-Dray, Meek, & Fabrizi, 2019), therefore, the lance procedure. This highlights the importance of environmental
JONES et al.    
| 157

factors in altering neonatal noxious stimulus processing. Indeed, electrical stimulation in man. Electroencephalography and Clinical
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