kangaroo care: cardio-respiratory relationships between the infant and caregiver
TRANSCRIPT
Early Human Development 90 (2014) 843–850
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Early Human Development
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Kangaroo care: cardio-respiratory relationships between the infantand caregiver
Elisabeth Bloch-Salisbury a,b,⁎, Ian Zuzarte a, Premananda Indic a, Francis Bednarek b,1, David Paydarfar a,c
a Department of Neurology University of Massachusetts Medical School, Worcester, MA 01655, USAb Department of Pediatrics, University of Massachusetts Medical School, Worcester, MA 01655, USAc Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA
⁎ Corresponding author at: Department of NeurologyNorth S5-718, Worcester, MA 01655. Tel.: +1 508 856 62
E-mail address: [email protected] (E1 Deceased July 15, 2013.
http://dx.doi.org/10.1016/j.earlhumdev.2014.08.0150378-3782/© 2014 Elsevier Ltd. All rights reserved.
a b s t r a c t
a r t i c l e i n f oArticle history:
Received 23 April 2014Received in revised form 15 August 2014Accepted 25 August 2014Available online xxxxKeywords:Preterm infantsSkin-to-skin cohabitationCardiorespiratory couplingApneaRespiratory stability
Background: Kangaroo care, i.e., skin-to-skin cohabitation (SSC) between an infant and caregiver, is often used inneonatal intensive care units to promote bonding, breastfeeding and infant growth. The direct salutary effects ofSSC on cardio-respiratory control in preterm infants remain equivocal; some reports suggest improved breathingstability, others indicate worsening of apnea, bradycardia and hypoxemia.Aim: The purpose of this study was to investigate physiological relationships between the infant and caregiverduring SSC. We hypothesized that respiratory stability of the premature infant is influenced by the caregiver'sheartbeat.Design: A prospective study was performed in eleven preterm infants (6 female; mean PCA 32 wks). SSC wascompared to a preceding incubator-control period (CTL)matched for time from feed and condition duration. Ab-dominal respiratory movement, electrocardiogram, skin temperature and blood-oxygen levels were recordedfrom the infant and the caregiver.
Results: During CTL, infant interbreath interval variance (IBIv; respiratory instability) was directly relatedto its own heart rate variance (HRv; rho = 0.770, p = 0.009). During SSC, infant IBIv and apnea incidencewere each related to caregiver HRv (rho 0.764, p = 0.006; rho 0.677, p = 0.022, respectively). Infant cardio-respiratory coupling was also enhanced during SSC compared to CTL in the eupneic frequency range (0.7–1.5 Hz, p = 0.018) and reduced for slower frequencies (0.15–0.45 Hz; p = 0.036).Conclusion: These findings suggest that during SSC, respiratory control of the premature infant is influenced bythe caregiver's cardiac rhythm.We propose that the caregiver's heartbeat causes sensory perturbations of the in-fant via somatic or other afferents, revealing a novel cohabitation-induced feed-back mechanism of respiratorycontrol in the neonate.© 2014 Elsevier Ltd. All rights reserved.
1. Introduction
“Kangaroo care” (KC) is a natural, cost-effective intervention used toreduce mortality and morbidity of premature and low birth-weight in-fants throughout the world [1–9]. In its simplest form the infant isclad only in a diaper and placed upright and prone on its caregiver'schest, skin-to-skin [2,3,6]. Research suggests that KC improves physio-logical function, promotes breastfeeding andmother-infant attachment,and reduces developmental risks of the infant [1,4,7–17]. However, thedirect salutary effects of KC on infant cardio-respiratory control remainequivocal. Some reports suggest thermal regulation and cardio-respiratory stability are achieved during KC; i.e., a reduction in the fre-quency of pathophysiological pause in breathing (apnea) and decreased
and Pediatrics, 55 Lake Avenue32.. Bloch-Salisbury).
heart rate (bradycardia) and improved oxygenation [4,12,16,18–22],whereas other studies report an increase in infant body temperature as-sociated with an increase in the number of apnea, bradycardia and/orblood-oxygen desaturation events [23–25]. The purpose of this studywas to investigate physiological relationships between the caregiverand the infant during KC to determine if cardio-respiratory stability ofthe premature infant was associated with that of its caregiver.
Despite a wide range of outcomemeasures that have been reported,including those affecting the infant's cardio-respiratory responses, tem-perature, pain response and sleep [12,13,15–30], there has beenno inte-grative study to determine the essential physiological interactionsbetween the infant and caregiver during KC necessary for improved in-fant response. The mechanisms for the therapeutic efficacy of KC thatstabilize respiration and improve heart rate remain elusive.We proposethat during KC, wherein the infant's head and chest wall overlay thechest wall of the caregiver, mechanical perturbations of the caregiver'sheartbeat affect underlying receptors of the cohabitating infant. Thesereceptors might include cutaneous, musculoskeletal, visceral and
844 E. Bloch-Salisbury et al. / Early Human Development 90 (2014) 843–850
vestibular-cochlear receptors that project to brain centers that are in-volved in respiratory control [31–35]. This study tested the hypothesisthat respiratory stability of the premature infant is influenced by senso-ry perturbations of the caregiver's heart beat during KC.
Though respiration and heart rate are under the control of two inde-pendent systems, coordination between the two has been shown to re-flect health and maturation [31,32]. Cardio-respiratory couplingquantifies the interaction between respiratory and heart rhythms. Theinterdependence is related to reflex activity between pulmonary affer-ents and vagal outflow [33,34]. In infants, cardio-respiratory interactionis vital for providing optimal balance between gas exchange and meta-bolic demands [32,34]. A second purpose of this studywas to determinewhether cardio-respiratory coupling of the infant would be enhancedduring SSC.
2. Methods
2.1. Human subjects
A prospective study was performed on 11 preterm infants (GA b35wks) at the University of Massachusetts Memorial Healthcare NeonatalIntensive Care Unit (NICU). Exclusion criteria were congenital malfor-mation, chromosomal disorders, congenital or perinatal infection ofthe central nervous system, intraventricular hemorrhage Ngrade II andhypoxic-ischemic encephalopathy. Infants treated with methylxan-thines were included if on maintenance dosing and the drug hadreached steady-state. One additional subjectwhodeveloped necrotizingenterocolitis was excluded. Hospital records and chart review wereused to obtain demographic and medical information. All mothersdenied smoking, illicit drug and alcohol use throughout pregnancy. In-formed consent was obtained from the mother of each infant enrolled;one father also provided informed consent to participate in the study.The study was approved by the University of Massachusetts's MedicalSchool Institutional Review Board for Human Subjects.
2.2. Measures and procedures
To test the hypothesis that respiratory stability of the premature in-fant is influenced by sensory perturbations of the caregiver's heart beatduring Kangaroo Care infants participated in two conditions: 1) Skin-to-skin cohabitation (SSC). Infantswere clad only in a diaper and placed in aprone position on its parent-caregiver to provide skin-to-skin contact inaccordance with Kangaroo-Care guidelines [3,6]. Blankets and a knittedcap (positioned above the infant's ear surfaced to the caregiver's body)were used to maintain warmth. Caregivers remained semi-supine(~15–30°) in a stationary, cushioned recliner chair. 2) Control Period(CTL). To provide a thermo-regulated environment, infants were stud-ied in their assigned incubator; one infant with mature thermoregula-tion was studied in his open crib using routine coverings. All infantswere placed prone with the mattress tilted head up at ~15–30° to bestmimic the positioning during SSC stimulation.
2.2.1. Physiological measurementsFor each infant and caregiver, respiratory inductance plethysmogra-
phy (RespIPleth)was used to record thoracic and abdominal respiratorymovements (Somnostar PT; Viasys Healthcare, Yorbalinda, CA; Embla).Electrodes placed over the skin surface of the chest (Hewlett Packard),3-lead configuration, were used to record electrocardiographic activity(ECG). Transcutaneous arterial-blood oxygen saturation (SaO2) wasmeasured using a separate pulse oximeter attached to the infant's footor wrist, and to the parent's index finger (Nellcor, Hayward, CA). Skintemperature was recorded continuously using disposable adhesivetemperature probes attached to the infant's and parent's axilla via sep-arate electronic monitoring thermometers (Physitemp TH-5, Clifton,NJ). Cardio-respiratory signals, SaO2, and skin temperature were
recorded continuously throughout both conditions for each infant andthroughout SSC for the caregiver.
2.2.2. Environmental and behavioral measurementsFor each condition a sound meter (ExTech Instr) placed near the
infant's head was used to measure changes in sound intensity (dBA).A light meter (AEMC, Industrial Process Measurements) placed by theinfant's head was used to measure changes in light levels (lux). Overtbehavioral data were recorded using a camera with a wide-angledlens (MicroCamera, Panasonic) within the infant's incubator or crib, orset to capture infant and parent during SSC stimulation, synchronizedwith the physiological, audiometry and light signals.
2.2.3. Data acquisitionInfant and adult ECG signals were sampled at 2000 Hz, RespIPleth at
50 Hz, SaO2 at 10 Hz, transcutaneous pulse-oximeter plethysmographicactivity at 100 Hz, and temperature, environmental light and soundsignals at 20 Hz. The data were displayed during the experimental pe-riods and stored on hard disk for offline analysis (Embla N7000, Broom-field, CO). Observations by the investigators were recorded as time-stamped text comments along with the signals. Fig. 1 illustrates anexample of recorded signals during SSC in one infant-caregiver dyad(Subject 9).
2.2.4. General proceduresStudies were conducted during daytime hours; CTL periods were
conducted between 7 a.m. and 1:00 p.m., SSC periods were conductedbetween 11:00 a.m. and 5:00 p.m. For each infant the CTL condition pre-ceded the SSC condition to control for potential carryover effects of theSSC experimental condition. After initial set up of equipment and at-tachment of all sensors, infants were given their routine feed (gavageor bottle); feeds were conducted either in the isolette, infant crib or inthe caregiver's arms. For the CTL condition, following feed the infantwas placed in their isolette/crib for the inter-feed interval (3–4 h, de-pending on the infant's routine feeding schedule). For SSC, infantswere held for the maximum holding period that the caregiver couldmanage not to exceed the inter-feed interval. Caregivers were askedto use the bathroom prior to holding their infant, and mothers whowere pumping breast milk were asked to pump prior to SSC. Allcaregivers were instructed to hold the infant in accordance withKangaroo-Care guidelines [3,6], for as long as they could sit in thesemi-reclined position. We did not control for conversation at the bed-side, but sought to allow conversation that parents typically provideduring holding in order to study response in real, NICU-bedside setting.For each condition, following the feed there was an observation periodof 30-min to assure integrity of the recordings, reduce potential con-founds of digestion and to allow the infant to resume sleep. Analysis pe-riods for each infant were determined by the maximum duration of theSSC condition (following the 30-min feed adjustment period) so thatCTL and SSC periods were matched for time from feed and duration.
2.3. Data processing and analyses
All data analyses involving manual measurements of physiologicalsignals were completed offline. Investigators were masked to conditionfor analyses of infant data; caregivers were only studied during SSC.
2.3.1. Movement periods and condition timeFor each condition, movement periods were defined by movement
that generated distortion in the transcutaneous pulse-oximeter plethys-mographic signal that exceeded 5 s. Movement artifact was defined bygross bodymovements that obscured the cardio and/or respiratory sig-nals. Video recordings and text comments written at the time of thestudywere used to further confirmperiods ofmovement and to identifynursing interventions and/or technical contamination, including infantRespIPleth contaminated by caregiver respiratory signal (indexed by
Inf SpO2
CG SpO2
Inf Rib
Inf Abd
CG Abd
Inf ECG
CG ECG
Inf Pleth
CG Pleth
Inf Temp
CG Temp
Sound
Light
10 sec100
%95100
%95
8.5mV
-2.60.93
mV-0.32
38 ºC
3638
ºC3670
dB40127
lux124
Fig. 1. Example of recorded signals during skin-to-skin cohabitation for one infant-caregiver dyad. INF= infant; CG= caregiver; SpO2 = blood-oxygen saturation; Rib= respiratory in-ductance plethysmography of chest wall; Abd= respiratory inductance plethysmography of abdominal muscle; ECG= electrocardiogram; temp= skin temperature; Pleth= plethys-mographic signal of transcutaneous pulse-oximeter used to indicate movement periods; sound = ambient sound levels; light = ambient light levels. Arrows demarcate peak ofinspiratory signal (Inf Abd) and R-R waves (ECG).
845E. Bloch-Salisbury et al. / Early Human Development 90 (2014) 843–850
caregiver RespIPleth bleed on the infant signal) [36]. Periodswith signalartifact were excluded from analyses. Valid condition time was definedas the period within each condition that was not distorted by move-ment artifact, infant hiccups that contaminated the respiratory signal,nursing interventions and technical contamination. Signals were ana-lyzed with respect to valid recording time. Contiguous physiologicalmeasurements recorded throughout each condition were calculatedfor the non-contaminated portion of each signal (detailed below) foreach subject.
2.3.2. Interbreath intervals (IBIs)For each infant, inductance plethysmography of abdominal move-
ments was used to generate a time series of IBIs, determined from thepeak of the inspiratory signal using automated peak-detection software(LabChart 7, ADI Instruments, Colorado Springs, CO). IBI peak detectionsare demarcated in Fig. 1. Statistical properties of the IBI histogram in-cluded the mean and variance of the IBI distribution (s), variancebeing ameasure of breathing stability. Incidents of IBIs N10 s, calculatedper unit of valid recording time, were defined as a pause in breathingrhythmicity. These pauses were always associated with a lack ofeffort in both the abdominal and rib plethysmographic activity.Therefore, pauses defined in this study were central (non-obstructive)apneas [37].
2.3.3. Cardiac intervalsIntervals between cardiac R waves were calculated using an auto-
mated peak detection program (MATLAB, MathWorks, Natick, MA).Mean and variance of heart rate (beats/min) were calculated for eachinfant during CTL and SSC, and for the caregiver during SSC. Fig. 1 illus-trates peak detection of R waves for infant and adult ECG.
2.3.4. Oxygen desaturationFor each infant SaO2 was calculated for CTL and SSC conditions. Ox-
ygen desaturation time was calculated as the percentage of time inwhich O2 saturation fell below 85%.
2.3.5. Skin temperature, ambient sound and light levelsMean and variance of infant skin temperature, and ambient sound
(dBA) and light (lux) levels were calculated during both conditions;caregiver skin temperature was also calculated during SSC.
2.3.6. Cardio-respiratory couplingTo determine coupling between heartbeat and respiration, cardio-
respiratory interaction was calculated in infants during CTL and SSCusing spectral methods. The similarity between the infant respirationsignal and the infant RR-interval (s) in the frequency domain was esti-mated by the magnitude square coherence function defined as
Cxy fð Þ ¼Pxy fð Þ���
���2
Pxx fð Þ Pyy fð Þ
where Pxx and Pyy are the power spectral densities of the infant respira-tion signal and infant RR-interval signal, respectively, and Pxy is the crossspectral density between the two signals. The cross-power spectrumwas defined as the Fourier transform of the cross correlation functionof the two signals. Both signals were resampled to 4 Hz to align themin time. MATLAB (MathWorks, Natick, MA) function ‘mscohere’ wasused to estimate themagnitude squared coherence, usingWelch's aver-aged periodogrammethod to find the power spectral densities [38]. Themagnitude squared coherence between the resampled signals wereestimated by segmenting each time series in overlapping windows(N = 1024 points; 50% overlap) and using a Hanning window lengthof 128 within each segment; each segment was approximate4.26 min. The peak coherence value within each of the four frequencybands [FB; 0.01–0.15 Hz (LF); 0.15–0.45 Hz (HF1); 0.45–0.7 Hz (HF2);and 0.7–1.5 Hz (HF3, eupnea)] [39] were calculated for every segmentand then averaged within each subject for both the CTL and SSC condi-tions. This provided a mean coherence value for each subject withineach frequency band for each condition.
846 E. Bloch-Salisbury et al. / Early Human Development 90 (2014) 843–850
2.3.7. Statistical analysisStatistical calculationswere performed using commercially available
software (SPSS, version 11.5, Chicago, IL). Pairwise t-tests were used todetermine whether differences in physiological signals, and ambientsound and light levels existed between CTL and SSC conditions duringvalid recording times. Separate repeated-measures ANOVAs were usedfor multi-factorial analyses. Greenhouse-Geisser correction was usedin instances where Mauchly's test indicated spherecity was violated; εwith unadjusted degrees of freedom is reported. Bonferroni adjustmentwas used for post hoc tests for factors with more than two levels. Non-parametric correlations (Spearman's rho)were used to establish associ-ation among infant and parent physiological signals and ambient soundand light for CTL and SSC conditions. All values are expressed as meansand SD. P values less than 0.05 were considered statistically significant.
3. Results
3.1. Clinical characteristics
Eleven premature infants (6 female) participated in the study atmean post-conceptional age (PCA) 31.9 wks (SD = 2.7 weeks; seeTable 1 for demographics). Mean age of the caregiver providing SSCwas 33.6 y (SD 6.8 y). All infants were studied in their incubator duringCTL period except Subject 11 who was studied in his crib. All infantswere held by their mother for SSC except Subject 8 who was held byher father. Six singletons, one twin pair (Subjects 5 and 6) and three un-paired twins (Subjects 2, 9 and 11) participated. Nine infants were ongavage feed, Subject 6 was on gavage and bottle feed, Subject 9 wason bottle feed.
3.2. Condition comparisons
3.2.1. Condition times and movement periodsThe total time caregivers held their infant skin-to-skin ranged be-
tween approximately 30 and 160 min (Table 1); the longer durationsreflect those infants who were held for feeds during SSC (gavage orbreastfed) vs infants whowere fed in their isolette. The equivalent por-tion of each condition period for CTL and SSC (i.e., matched from end offeed plus 30 min post-feed) was included for analyses (Table 1). Themean condition time for CTL and SSC was 41.3 min (SD 21.2, Table 1).Signal artifact due to infant movement (mean 10.9% SD 6.2), hiccups,nursing interventions and technical contamination were similar be-tween conditions; mean valid condition time used for CTL analyseswas 35.9 min (SD 21.8) and for SSC analyses was 35.4 min (SD 19.2;paired t test, p= 0.74). Therewas a trend for less infantmovement dur-ing SSC (mean 8.9% normalized/h; SD 4.8) than for CTL (mean 13.3%normalized/h, SD 7.4; p = 0.09).
Table 1Subject characteristics.
Subject Symbol GA(wks)
PCA (wks) Birthweight (g)
Studyweight (g)
Gender R
1 ○ 29.57 30.86 1180 1185 Male2 □ 32.86 33.71 1870 1635 Female3 w 25.86 27.43 430 500 Female Af4 ◆ 29.29 30.14 1598 1390 Male5 ▲ 29.43 32.71 1010 1260 Female6 Q 29.43 33.57 1390 1770 Female7 ▼ 32.43 33.43 1625 1545 Male8 △ 27.43 28.43 1410 1240 Female9 ▽ 34.86 35.71 2210 2120 Female10 ■ 26.57 30.29 795 1090 Male11 ● 30.86 34.86 1010 1590 Male
Mean (SD) 29.87 (2.74) 31.92 (2.67) 1321(506)
1393(127)
Note: symbol = subject identification for Fig. 2; GA = gestation Age; PCA = post conceptionamatched = equivalent SSC and CTL analysis periods; TCT = total time infants were held SSC.
3.2.2. Cardio-respiratory and temperature assessmentsTable 2 provides a summary of infant and adult physiological signals.
Neither the infant IBI mean (index of respiratory rate) or IBI variance(index of breathing stability) were different between CTL and SSC con-ditions, nor were there any differences in the incidents of apneic pausesN10 s between these conditions. Due to technical problems, ECG wasnot recorded in Subject 2 during CTL. For the 10 infants, mean heartrate trended slightly higher during SSC (150.8 bpm, SD 14.5) than CTL(148.1 bpm, SD 14.4; p = 0.07); variance of the infant heart rate wasnot different between conditions. Among all infants, mean oxygenationwas similar between conditions (mean 97.3%, SD 3.2). Time inwhich in-fant O2 saturation fell below 85% was also not different between condi-tions; only four infants presented with episodes of clinical desaturation,two in whom duration increased and two in whom duration decreasedwith SSC. Due to technical problems, infant skin temperature was notrecorded in Subject 7 during SSC. Among the remaining 10 infants,mean skin temperature was similar between conditions (36.3 ° C, SD0.5); skin temperature variance trended higher during SSC (0.008)than during CTL (0.003; p = 0.07).
Caregiversmean heart rate during SSCwas 72.0 bpm (SD 8.1); meanheart rate variance was 18.7 (SD 12.9). Caregivers mean temperatureduring SSC was 35.9 ° C (SD 0.6); temperature variance was 0.017 (SD0.034).
3.2.3. Ambient sound and light levelsDue to technical problems, ambient sound was not measured for
Subjects 2, 4 and 5, and light was not measured for Subjects 2 and 4.Among the remaining subjects, ambient sound was significantly louderduring SSC (mean51.3 dBA, SD 2.6) than during CTL (mean 48.9 dBA, SD1.3; p= 0.02). Sound variancewas also significantly greater during SSC(mean 18.0, SD 7.9) than during CTL (mean 10.2, SD 8.4; p = 0.03).There was no difference in light levels between CTL (mean 72.9 lux,SD 59.6) and SSC (mean 85.8 lux, SD 72.0; p = 0.35); light variancewas also not significantly different between conditions (p = 0.34).
3.3. Relationships among infants and caregivers
3.3.1. Cardio-respiratory associationsAmong infants, increased respiratory instability was directly related
to increased cessations in breathing, reflected by a direct relationshipbetween infant IBI variance and infant apneas N10 s for both CTL(rho = 0.853, p = 0.001) and SSC (rho = 0.830, p = 0.002). Cardio-respiratory relationships within infant and between infant and caregiv-er for each condition are illustrated in Fig. 2. During CTL, infant respira-tory instability (IBI variance) was directly related to infant heart ratevariance (rho = 0.770, p b 0.01). In contrast, during SSC, increased in-fant IBI variance was not significantly associated with increased infant
ace/ethnicity SSC caregiverage (yrs)
Conditiontime: matchedvs [TCT] (min)
Caffeinetreatment
at time of study
Respiratorysupport at
time of study
Hispanic 23 31.01 [33] Yes NoneCaucasian 25 21.13 [51] No None
rican American 28 39.57 [113] Yes Nasal Canula O2
Caucasian 31 28.55 [122] Yes NoneCaucasian 34 48.72 [83] No NoneCaucasian 34 69.81 [70] No NoneHispanic 40 43.93 [90] No NoneCaucasian 45 11.31 [66] Yes Vapotherm® O2
Caucasian 32 86.01 [89] No NoneCaucasian 37 38.51 [90] Yes Vapotherm® O2
Caucasian 41 36.00 [158] No None33.64(6.82)
41.32(21.18)
[88](35)
l Age at time of study; SSC caregiver Age = age of caregiver for skin-to-skin cohabitation;
Table 2Infant and caregiver physiological responses during control (CTL) and skin-to-skin cohab-itation (SSC).
CTLMean (SD)
SSCMean (SD)
P value
InfantRespiratory rate (per min) 55.14 (17.5) 50.30 (13.6) 0.106Interbreath interval (s) 1.21 (0.45) 1.28 (0.36) 0.410Interbreath interval variance 0.94 (0.86) 0.89 (0.79) 0.857Apnea N5 s (incidents/h) 39.37 (36.59) 33.79 (28.58) 0.551Apnea N10 s (incidents/h) 4.09 (5.57) 3.81 (5.72) 0.890Heart rate (per min) 148.14 (14.36) 150.78 (14.50) 0.072Heart rate variance 47.29 (25.07) 48.71 (34.73) 0.906Skin temperature (°C) 36.34 (0.46) 36.35 (0.49) 0.933Skin temperature variance 0.0028 (0.002) 0.0079 (0.008) 0.067SaO2 (%) 97.28 (2.32) 97.30 (4.13) 0.986SaO2 variance 6.32 (10.25) 3.75 (4.48) 0.454
CaregiverHeart rate (per min) n/a 72.01 (8.05)Heart rate variance n/a 18.71 (12.91)Skin temperature (°C) n/a 35.88 (0.57)Skin temperature variance n/a 0.027 (0.07)
847E. Bloch-Salisbury et al. / Early Human Development 90 (2014) 843–850
heart rate variance (rho= 0.545, p= 0.08; note, this trend toward sig-nificance is due to an outlier, Subject 8, which when excluded resultedin rho= 0.394, p = 0.26; Fig. 2, panel C). Rather, during SSC, increasedinfant IBI variance was associated with increased caregiver heart ratevariance (rho 0.764, p = 0.006). During SSC infant apnea incidence(N10 s) was also directly related to caregiver heart rate variance (rho
0 20 40 60 80 100 120 1400.0
0.5
1.0
1.5
2.0
2.5
3.0
0 20 40 60 80 100 120 1400.0
0.5
1.0
1.5
2.0
2.5
3.0
A) CTL within infant(rho 0.770, p=0.009)
C) SSC within infant (ns)
Infa
nt In
terb
reat
h Va
rianc
eIn
fant
Inte
rbre
ath
Varia
nce
Infant Heart Rate Variance
Infant Heart Rate Variance
Fig. 2. Cardio-respiratory associations within infant and between infant and caregiver dyad
0.677, p = 0.022), whereas during CTL infant apnea incidence was notrelated to caregiver heart rate (p= 0.221) nor to its own heart rate var-iance (p = 0.231). Although there was an increase in sound varianceduring SSC, infant IBI variance was not associated with sound variancefor either condition. Increased infant IBI variance was associated withmean infant temperature during CTL (rho = 0.636, p = 0.048), butnot during SSC (rho= 0.515, p= 0.128); infant IBI variancewas not as-sociated with infant temperature variance for either condition (p N 0.1).
3.3.2. Cardio-respiratory couplingCardiorespiratory coupling was measured in 10 infants (Subject 2
was excluded due to technical problemswith ECG recording). Repeatedmeasures ANOVA was performed to test the effects of Condition (CTLand SSC) and Frequency Band [0.01–0.15 Hz (LF); 0.15–0.45 Hz (HF1);0.45–0.7 Hz (HF2); and 0.7–1.5 Hz (HF3, eupnea)] on cardiorespiratorycoupling within infants. There was no main effect of Condition (p =0.345). There was a significant main effect of Frequency Band[F(1.458, 13.118) = 9.108, p = 0.006, Greenhouse-Geisser correction,ε = .486] due to greater coupling in HF3 (eupneic frequency range;mean 0.575, SD 0.076) compared to LF (apneic frequencies; mean0.448, SD 0.064, p = 0.003). An interaction was also observed betweenCondition and Frequency Band [F(3, 27) = 3.895, p = 0.020]. Post hoccomparisons revealed that coherence between infant heart rate (RRinterval) and infant respiration in the eupneic frequency range (HF3,0.7–1.5 Hz) increased significantly during SSC (mean 0.59, SD 0.07)compared to CTL (mean 0.56, SD 0.08, p = 0.018) and that forslower frequencies coupling was reduced significantly for HF1 (0.15–0.45 Hz) during SSC (mean 0.45, SD 0.08) compared to CTL (mean
0 10 20 30 40 500.0
0.5
1.0
1.5
2.0
2.5
3.0
0 10 20 30 40 500.0
0.5
1.0
1.5
2.0
2.5
3.0
B) CTL infant and caregiver (ns)
D) SSC infant and caregiver(rho 0.764, p=0.006)
Caregiver Heart Rate Variance
Caregiver Heart Rate Variance
during SSC and CTL. Symbols reflect individual subjects (see Table 1 for symbol key).
848 E. Bloch-Salisbury et al. / Early Human Development 90 (2014) 843–850
0.51, SD 0.10; p = 0.036) and approached significance for LF (0.01–0.15, p = 0.087; Fig. 3).
To determine whether cardio-respiratory coupling in the eupneicrange (HF3) changes over time, separate one-way ANOVAs were usedto test the effects of coherence segment order for SSC and CTL (seeSection 2.3.6). Due to variable durations in condition time among sub-jects (e.g., range approx. 11–70 min), we separately tested order effectsfor thefirst 9 coherence segments (9 subjects) and for the first 14 coher-ence segments (8 subjects), as well as for the 4.26 min alternating seg-ments to provide a non-overlap profile. For each of these analyses, therewas no effect of order, suggesting cardio-respiratory coupling did notadapt over the course of each condition.
4. Discussion
The present integrative study is the first to explore the physiologicalinteractions between the infant and caregiver during KC that may belinked to infant cardio-respiratory response. The findings support ourhypothesis that respiratory stability of the premature infant is influ-enced by sensory perturbations of the caregiver's heart beat duringSSC. We found that during SSC, infant respiration (IBI variance) andapnea episodes (N10 s) were each directly related to the variability ofthe caregiver's heart rate (RR variance). In contrast, during CTL infantrespiratory instability (IBI variance) was directly related to its ownheart rate instability. In addition, we demonstrated that within infantcardio-respiratory couplingwas enhanced in the eupneic breathing fre-quencies (0.7–1.5 Hz) and reduced in the slower frequencies (0.15–0.45 Hz) during SSC compared to CTL. These data suggest there are im-portant physiological interactions between the caregiver and infant thatmay optimize efficacy of cardio-respiratory control. A caveat to thestudy was the small sample size. Nonetheless we observed strong
(eupnea)
LF 0.01-0.15HzHF1 0.15-0.45HzHF2 0.45-0.70HzHF3 0.70-1.50Hz
Fig. 3. Infant cardio-respiratory coupling. Coherence was significantly greater during SSCthan CTL for the eupneic frequency range (0.7–1.5 Hz), and significantly reduced forslower frequencies (0.15–0.45 Hz).
associations. The ability to detect a significant effect in the small samplesuggests this is a robust phenomenon in the general population.
The importance of vestibular stimulation on early human develop-ment has been well established [35,40–43]. In particular vestibularstimulation has vital influences on the respiratory oscillator that includereducing apneic events and enhancing eupneic breathing in prematureinfants [35,43,44]. It is unclear whether it is the rocking movement perse that exerts phasic input on the respiratory pattern generator, or me-chanical perturbations that impinge upon underlying receptors of thevestibular system that help modulate respiratory control [35,43,44].For example, stochastic vibrotactile stimulation without rocking the in-fant has also been shown to improve respiratory stability and blood-oxygenation in preterm infants, supporting the use of stochastic pertur-bation for therapeutic management of respiratory dysrythmias inneonates [45]. Stimulation by rocking [35,43], by whole body motionsat frequencies close to breathing via an oscillating mattress [46–48], aswell stochastic stimulation among a range of frequencies [45] likelystimulate both vestibular and somatic afferents, which may entrain orenhance respiratory rhythms by resetting and pacing the system's oscil-lation via phasic input to its respiratory pattern [35,43–45]. The presentfinding that infant respiratory stability was associated with caregiver'sheart beat during SSC supports the notion that external, perturbationsimpinge upon the respiratory control centers to modulate breathing.Furthermore, that cardio-respiratory coupling in the frequency rangeof normal breathing was also improved suggests SSC may optimizecardio-respiratory synergies that promote healthyphysiology in prema-ture infants [32]. The exact phasic relationships and entrainment of in-fant breathing to external perturbations warrant further study.
There may be optimal perturbations for enhancing respiratory sta-bility and rhythms that provoke instability. For example, during SSC,there may be some threshold at which caregiver's heart beat improvesor worsens infant respiratory stability, which may explain in partwhy some infants show improved cardio-respiratory response withSSC [4,12,16,18–22], whereas others do not [23–25]. In the presentstudy we found that when caregiver's heart rate variance was N30there was an increase in infant IBI variance (e.g., Fig. 2D) and apneic in-cidence, but it remains unclear whether caregiver heart beat drives in-fant breathing or vice versa.
A constraint of the study was that unlike controlled stochastic oscil-lations of an experimental mattress that wax and wane within a well-defined range of frequencies [45], the perturbations of the caregiver'sheartbeat is not well defined, varies among caregivers, andmay includeunpredictable bursts of bradycardia and tachycardia. Due to such vari-able rhythms of the caregiver's heart beat and to inherent irregularityof breathing and frequent episodes of signal artifact due to frequentmovement in the premature infants, we were unable to determine thepoints in time when infant respiration shifted to stable or unstablerhythms in response to caregiver heartbeat, or when caregiver heart-beat may have in fact responded to changes in infant respiration(e.g., following an apneic pause). Accordingly, it is unclear during SSCwhether infant breathing rhythms followor precede certain frequenciesof caregiver's heart rate, or if caregiver's heart rate is responding tochange in the infant's breathing pattern, or both. We speculate thereare times during SSCwhen the infant respiration follows the caregiver'sheart rate, particularly during stable periods, as well as when thecaregiver's heart ratemay reflect periods of infant breathing, particular-ly during periods of apnea and instability when clinical monitors alarmand cause stress to the caregiver. Time-series algorithms that assess in-stantaneous changes, account for interruption of signal (e.g., due tomovement artifact; nursing intervention), and examine bi-directionalinfluence and not necessarily symmetric interrelationships may helpdiscern these unique relationships [49].
It is not surprising that infant temperature and ambient noisewere more variable during SSC than CTL. All but one infant requiredan incubator due to immature thermoregulation, so it was expectedthat infant temperature would be less variable in the thermo-
849E. Bloch-Salisbury et al. / Early Human Development 90 (2014) 843–850
regulated environment of an incubator. Analogously, noise level wasdampened in the incubator compared to the open-NICU environment.Notably, neither variance of infant temperature nor variance of ambientnoise was associated with infant IBI variance. Rather, during SSC infantrespiratory instability was associated with the caregiver's heart beatand not with the variability of temperature or ambient noise, furthersupporting the role of perturbation of the caregiver's heart beat ratherthan other external influences.
This study supports the hypothesis that respiratory stability of thepremature infant is influenced by the caregiver's cardiac rhythm duringSSC. We speculate that during SSC, perturbations of the caregiver'sheartbeat affect underlying receptors of the cohabitating infant. Howev-er, it is unclear whether the infant is responding to heart beatsomesthetic perturbations of the caregiver per se, or to auditory(e.g., cardio-respiratory sounds) and/or olfactory cues (e.g., secretionsfrom areola glands [50]) as the infant's head overlays the chest wall ofthe caregiver. Future studies designed to separate these cues may helpdiscern those sensory perturbations that optimize infant cardio-respiratory responses during skin-to-skin cohabitation.
5. Conclusion
The present study used a highly controlled experimental design thatmatched analysis periods between CTL and SSC for duration and timefrom feed. All infants were studied prone, with head of mattress slightlyelevated to help mimic the KC position. Respiratory muscle movementof the caregiver was recorded to ensure periods of cross-signal contam-ination were excluded from analysis of the infant's respiratory signal.CTL periods always preceded SSC to control for potential carryovereffects of SSC on cardio-respiratory control. We did not find differencesin group mean incidence of apnea, duration of blood-oxygendesaturation or levels of skin temperature between CTL and SSC condi-tions, suggesting the importance of examining individual variabilityrather than groupmean values per se for understanding interactions be-tween the infant and caregiver that may influence respiratory stabilityof the infant. The major findings that infant IBI variance and apneic ep-isodes were directly related to caregiver heart rate variance during SSCsupports our hypothesis that respiratory stability of the premature in-fant is influenced by sensory perturbations of the caregiver's heartbeat when the infant is held prone on its caregiver's chest skin-to-skin. Furthermore, that infant cardio-respiratory coupling was en-hanced during SSC compared to CTL in the eupneic frequency rangesuggest there are important physiological interactions between thecaregiver and infant during SSC that may optimize cardio-respiratorysynergies that promote healthy physiology in premature infants.
Funding support
This study was supported by a Grant in Aid and a Scientist Develop-ment Grant from the American Heart Association (EBS) and the WyssInstitute for Biologically Inspired Engineering, Harvard University(DP). The study sponsors had no involvement in study design, collec-tion, analysis and interpretation of data, manuscript writing, or decisionto submit the manuscript for publication.
Conflict of interest statement
The authors declare no conflicts of interest.
Acknowledgments
The authors gratefully acknowledge the infants and parents for par-ticipating in this study and appreciate the cooperation of theUMassMe-morial NICU medical team.
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