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Title  by  Presenter  Name  

Sandra  Smith,  PhD,  APRN,  NNP-­‐BC   Autonomic Nervous System Function and the Effect of Massage Therapy on Enhancing Parasympathetic Activity in

Preterm Infants Sandra L. Smith, PhD, APRN, NNP-BC

Associate Professor University of Louisville, School of Nursing

slsmit51@louisville.edu

OVERVIEW OF AUTONOMIC

NERVOUS SYSTEM

DEVELOPMENT IN THE FETUS

AND INFANT

Three Subsystems (Circuits) of the Autonomic Nervous System (ANS)

1)  Social communication—highest levels of communication

1)  Partially available at term gestation

2)  Mobilization—tantrums, behavioral acting-out

3)  Immobilization--oldest circuit associated with survival—possum feigning death, physiologic shutdown

(Porges    &  Furman,  2011)  

ANS: Focus on the Vagus Nerve •  Mammalian ANS developed beyond the reptilian

survival function

– Rapidly adapted to accommodate fight-flight events and social interactions

•  High vagal tone via myelinated vagal pathways to the heart

– Acts as a brake, slowing the heart, calming the person

– Low vagal tone: no inhibition on the heart (Porges,  Doussard-­‐Roosevelt,  et  al.,  1996)  

Vagal Pathways in Infants

•  Partially myelinated at birth –  Myelination is necessary for effective nerve signal

transmission

•  Myelinated fibers increase from 24 weeks gestation through adolescence

•  Greatest increase occurs between 32 and 34 weeks gestation to ~ 6 months of age –  Vagal tone through myelinated fibers increases with

gestational age

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Vagal Pathways in Infants

•  Thus infants born prior to 30 weeks gestation lack the high vagal efferent and vagal brake activity on the heart

–  Myelination is not complete

–  Reactivity to stressors is exaggerated and recovery impaired

•  Long term effects are unknown but may affect social and behavioral development

Preterm Infant ANS Function •  Preterm infants demonstrate a prolonged

ANS dysfunction

– Yiallourou et al. (2013): preterm infants have a persistent depressed parasympathetic activity at 5-6 months of age

– Patural (2008): Preterm infants have depressed ANS activity at 1 year of age

Given  the  interrupMon  of  ANS  development  and  the  prolonged  ANS  dysfuncMon  experienced  by  

preterm  infants,  what  treatments  may  enhance  ANS  development  in  this  vulnerable  

group?    

Effect of Massage Therapy on Preterm Infants

•  Improved weight gain •  Increased IGF-1 expression (enhanced growth) •  Decreased length of hospital stay (~5 days) •  Increased gastric motility •  Improved bone mineral deposition •  Alterations in brain waves (sleep) •  No difference between massage and controls (Arora et al., 2005; Diego et al., 2003, 2007; Field et al., 2006, Guzzetta, 2011)

Methodological Concerns •  Massage treatment given 2 x/day for 5-10 days •  Variability in who delivered the massage

– Mothers – Others (OT, PT) – LMTs

•  Underpowered due to small sample sizes •  Lack of blinding by the researchers

Autonomic Nervous System Function and the Effect of Massage Therapy on Enhancing Parasympathetic Activity in

Preterm Infants

Longitudinal, randomized controlled trial of 44 medically stable preterm infants born

between 29 and 32 weeks gestation.

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Environmental Sources of Neonatal Stress

u  Painful procedures

u  Noise and lighting

u  Maternal separation

u  Temperature fluctuation

u  Hypoxia and hyperoxia

u  Glucocorticoids

u  Oxygen consumption

u  Energy expenditure

u  Temperature fluctuations

u  Hypoxemia

Consequences of Neonatal Stress

The stress response is meant to be limited and of short duration

Massage may improve vagal activity, sleep, and growth (Arora et al., 2005; Diego et al., 2003, 2007; Field et al., 2006)

NICU ENVIRONMENTAL STRESSORS

Hypothalamus  

Pituitary  

Adrenal  

Medulla  Cortex  

Catecholamine  GlucocorMcoids  

Sympathetic Nervous System ‘fight or flight’

response

Parasympathetic Nervous System

‘recovery & restoration’

Overriding  SNS  response  ++  Catecholamine  &  GlucocorMcoid  

           SNS/PNS  balance,  -­‐-­‐  Catecholamine  &  GlucocorMcoid  

PHYSIOLOGIC INSTABILITY ↑ HR, RR, BP, oxygen

saturation

PHYSIOLOGIC STABILITY Normal HR, RR, BP, increased

quiet sleep

HPA  AXIS  

↑  

MASSAGE THERAPY

Hypotheses •  In preterm infants, twice daily MT will

– promote ANS function as measured by heart rate variability (HRV) and urine catecholamine

– improve growth quality

– improve bone accretion

Intervention and Testing Schema

•  Medically  stable  29-­‐32  week  preterms  •  Randomized  to  group  (MT  or  CTL)  

•  Masked  to  HCP  and  Parents  •  LMTs  provided  intervenMon  

Intervention and Testing Schema Infant Characteristics (Enrollment 7/08-5/11)

MT Control

Gender 12F/10M   12F/10M  

Ethnicity 36%  Hispanic  64%  White  

32%  Hispanic  68%  White  

Birth PMA (wk) 31.4  ±  0.8   31.0  ±  0.9  

Entry PMA (wk) 32.5  ±  1.0   32.4  ±  0.9  

Birth Weight (g) 1573  ±  231   1618  ±  289  

Entry Weight (g) 1522  ±  238   1590  ±  272  

Smith  et  al.,  J.Perinatol.,  2012  

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HRV  

•  ANS  mediates  physiological  fluctuaMons  in  R-­‐R  interval    –  InteracMon  and  adaptability  of  SNS  and  PNS  

•  Data  were  acquired  conMnuously  prior  to,  during,  and  post  MT  or  CTL  –  Pre,  during,  and  post  session  epochs  were  extracted  for  analysis  

•  Fast  Fourier  Transform  (FFT)  analysis  –  EsMmates  cardiac  modulaMon  by  ANS  –  Regions  are  specific  to  the  SNS  and  PNS  

Burr, 1992; David et al., 2007; Malik & Camm, 1993; Longin et al., 2006; Ori et al., 1992; Patural et al., 2004; Sanhi et al., 2000  

Sympathetic nervous system (0.02-0.2 Hz)

Parasympathetic nervous system (>0.2 – 2.0 Hz)

LF/HF ratio Higher = Sympathetic Lower = Parasympathetic

0.2    .02     2.0    Hertz  

HRV  Regions  of  ANS  AcFvity  

0

2

4

6

8

10

12

14

16

18

wk 0 wk 1 wk 2 wk 3 wk 4

MT  Control  

LF:H

F R

atio

(SEM

)

0

2

4

6

8

10

12

14

16

18

wk 0 wk 1 wk 2 wk 3 wk 4

*  

‡  

*  

Males (n = 18) Females (n = 19)

*p  <  0.5  between  MT  &  CTL  at  wk  3  and  4  ‡p  <  0.05  MT  baseline  to  wk  4   J.Perinatol.    (2012)  

PRE  SESSION  

0  

5  

10  

15  

20  

25  

wk  0   wk  1   wk  2   wk  3   wk  4  

LF:H

F R

atio

(SEM

)

0  

5  

10  

15  

20  

25  

wk  0   wk  1   wk  2   wk  3   wk  4  

MT  Control  

Males (n = 18) Females (n = 19)

J.Perinatol.    (2012)  NS  between  groups  by  sex  

MT  or  CTL  SESSION  

0

2

4

6

8

10

12

14

16

18

wk 0 wk 1 wk 2 wk 3 wk 4 0

2

4

6

8

10

12

14

16

18

wk 0 wk 1 wk 2 wk 3 wk 4

LF:H

F R

atio

(SEM

) MT  Control  

Males  (n  =  18)   Females  (n  =  19)  

*

*p  <  0.5  between  MT  &  CTL  at  wk  3   J.Perinatol.    (2012)  

POST  SESSION   HRV 6 HOURS POST SESSION WEEK 2 Males (4 MT, 4 CONTROL)

LF:H

F R

atio

(SEM

)

Smith, et al. E. Hum Dev, 2013

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HRV 6 HOURS POST SESSION WEEK 2 Females (6 MT, 7 CONTROL)

Smith, et al. E. Hum Dev, 2013

LF:H

F R

atio

(SEM

)

Urine Catecholamine Levels were Decreased in MT infants

0

4

8

12

16

20

Day1 Day8 Day15 Day22 Day29

MT CTL *p=0.06

Mean (SEM): MT = 8, CTL = 11

pg/m

l

Moyer-­‐Mileur,  Smith,  Haley,  Unpublished  data  

Back (Trunk) Fat Increase was Highest in Control Male & MT Female Preterm Infants

0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

5

wk  0   wk  1   wk  2   wk  3   wk4  0

1

2

3

4

5

6

wk  0   wk  1   wk  2   wk  3   wk4  

•  Males •  Females

Moyer-­‐Mileur,  Smith,  &  Haley,  2012  J.  Peds.  

Subs

capu

lar

Skin

fold

(mm

)

* *

MT  

Blood Markers Indicate Higher Abdominal Fat in Control Male Preterm Infants

0

0.05

0.1

0.15

0.2

0.25

0.3

wk  0   wk  2   wk  4  0

0.05

0.1

0.15

0.2

0.25

0.3

wk  0   wk  2   Wk4  

•  Males •  Females

Moyer-Mileur, Smith, & Haley, 2012 J. Peds.

Adi

pone

ctin

:Lep

tin R

atio

*

MT  

MT Attenuates the Decrease in Tibial Speed of Sound seen in Preterm Infants

tSOS (m/sec) reflects cortical thickness and bone mineral density.

Faster tSOS = stronger bone

Haley, Moyer-Mileur, & Smith, Bone, 2012 *  p  <  0.05    

Hypotheses Revisited

•  In  preterm  infants  twice  daily  MT  promoted  improved  ANS  funcMon  as  measured  by  HRV  in  preterm  male  infants  

•  Infants  who  received  MT  had  lower  urinary  catecholamine,  an  indicator  of  decreased  stress  response,  although  not  staMsMcally  significant  

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Hypotheses Revisited

•  Although  males  had  increased  adiponecMn/lepMn  raMo  suggesMve  of  increased  abdominal  fat,  we  have  insufficient  data  to  support  improved  growth  quality  

•  Twice  daily  MT  improved  bone  strength  in  male  and  female  preterm  infants  

Future Research

•  Long  term  benefits  of  massage  on  ANS  funcMon  in  preterm  infants  –  Is  there  a  carry  over  effect  aier  discharge?  – What  are  the  effects  on  neurobehavioral  development?  

•  What  are  the  mechanisms  of  massage  in  promoMng  ANS  funcMon  in  preterm  infants  

•  Laurie  Moyer-­‐Mileur,  PhD  (PI)  •  Shannon  Haley,  PhD,  LMT  &  LMT  Team  •  Hillarie  Slater,  BS  •  Robert  Lux,  PhD  •  Nancy  Allen  •  Funding  

– NIH  NCCAM  R  21  – University  of  Utah  Interdisciplinary  Research,  College  of  Nursing,  and  Division  of  Neonatology  Grants  

Presenter  Name: