1. Oral Somatosensory Stimulation
in Newborns with CCHD
Dongli Song MD, PhD
Associate Chief, Division of Neonatology
Director, Newborn Clinical Research
Director, Newborn Neuroprotection Program
Santa Clara Valley Medical Center
Stanford University School of Medicine (Affiliated)
Department of Pediatrics, Division of Neonatal and Developmental Medicine
Stanford University School of Medicine
Thank you for the kind introduction, and I would like to thank the meeting organizer for giving me the opportunity to present the results from our recent multicenter RCT.

2. Disclosure: No personal financial disclosure
Study PI - multicenter RCT of Patterned Oral Somatosensory Stimulation in Preterm Infants
Funded by Innara Health, Inc.
I am not a cardiologist/cardiac surgeon
I am a neonatologist
I have no personal financial disclosure , I will talk about an innovative approach to address neonatal feeding difficulties

3. Feeding Difficulties in Children with Congenital Heart Disease
Malnutrition and failure to thrive are common in children with CHD post surgical repair
Poor oral feeding is a major cause of imbalanced nutritional intake
Nutritional/feeding issues in these infants often persist throughout the first years of life
Increased rate of oral motor and speech abnormalities and poor neurodevelopmental outcomes

4. Oral Feeding Difficulties in Neonates with CHD
The mode of feeding at time of discharge from hospital after the first stage of palliation in infants with hypoplastic left heart syndrome
Less than 50% infants went home on independent oral feeding.
Barbara Medoff-Cooper, Sharon Y. Irving
Cardiology in the Young (2009)

5. Normal Feeding Development
Reviewed by Bingham 2008, Costa 2008, Barlow 2009, Lau 2015 & 2016 36 30 34 32 28
PMA (weeks) 38
Breathe
Swallow
Suck
~18-20
weeks
Increase frequency, amplitude, suck bursts,
consistent rhythmic pattern
~11
30-32weeks
Coordinated
Suck-Swallow
26-29 weeks
1:1 Suck:Swallow
34-36 weeks
Suck-Swallow-Breathing 44
The coordination of the three rhythmic movements (suck, swallow, and breathe) is essential for safe and effective independent oral feeding.
These movements appear in early gestation, but become mature during late third trimester and early postnatal period.
Adverse experiences during the critical period of oral feeding development lead to delayed/abnormal oral feeding abilities

6. Feeding Difficulties in Infants with Congenital Heart Disease
Prolonged NPO and intubation -deprivation of normal oral experience
Multiple invasive procedures and surgeries- obnoxious stimulation and injuries in the peripheral (laryngeal nerve injury) and CNS
Cardiopulmonary instability and postoperative gastrointestinal dysfunction-poor endurance and feeding intolerance
pinterest.com
The normal oral feeding developmental process is interrupted in infants with CHD. They are often kept for prolonged NPO and intubation which deprive them from normal oral stimulation .
Multiple invasive procedures and surgeries, which are are necessary to saving the lives, cause obnoxious stimulation and injuries in peripheral and CNS

7. Feeding Difficulties in Neonates with Congenital Heart Disease
Infants with CHD are usually born at full term but their
feeding difficulties are very similar to that of preterm infants (Pereira et al., 2015, Medoff-Cooper and Irving, 2009)
Disorganized and weak suck
Delayed triggering of swallowing
Poor coordination in suck-swallow-breathe

8. Oral Somatosensory Input
The Cortical Homunculus
The strategy of preventing neonatal feeding difficulties is to minimize adverse stimuli and provide more positive physiological inputs to enhance normal oral feeding development
The lips, tongue, and palate have very high-density sensory receptors and provide dynamic inputs to the brain
During a critical developmental period the brain is highly sensitive and depends on proper external stimulation
Providing a pacifier in preterm infant’s mouth during gavage feeding is a safe NNS stimulation. It has been shown to improve premature infants’ oral feeding performance and decrease their length of NICU stay. However, this type of stimulation is passive an the beneficial effects are variable among different publications.
nobaproject.com
The representation of somatosensory in the brain is related to the number of sensory neuronal connections, not the physical size of the body parts

9. Oral Somatosensory Input Non-nutritive Sucking (NNS)
Suck on pacifier or recreational breastfeeding (No liquid ingestion)
A safe oral somatosensory stimulation to the developing brain
Improve infants’ oral feeding performance and decrease their length of NICU stay
Regular pacifier stimulation: passive NNS and the beneficial effects are variable in different studies
Providing a pacifier in preterm infant’s mouth is a safe NNS stimulation. It has been shown to improve premature infants’ oral feeding performance and decrease their length of NICU stay. However, this type of stimulation is passive an the beneficial effects are variable among different publications.

10. Patterned Oral Somatosensory Stimulation -NTrainer® Therapy
Barlow SM, 2008, 2009
A repeating pattern of 6 pulses (1.8 Hertz) with 2 seconds pause
The stimuli resemble the spatiotemporal features of normal infants’ NNS burst
Entrains rhythmic, natural NNS
Dr. Barlow has developed a bedside device to provide consistent and patterned oral somatosensory stimulation through a pulsatile pacifier.
Exaggerated
For viewing
275 um nipple
Distortion

11. Patterned Oral Somatosensory Stimulation -NTrainer® Therapy
Programmed, patterned, and consistent
oral somatosensory stimulation improves NNS and nutritive feeding skills in preterm infants
Dr. Barlow’s research team has conducted a series of studies and shown that the patterned oral stimulation is more effective than a regular pacifier.

12. Improvement in NNS after NTrainer Therapy
Presentation Version June 2012
Improvement in NNS after NTrainer Therapy
Increasing
Sucks per burst
Bursts per minute
Suck pressure
Reproducibility
Here is an example of an infant's NNS during a 12 day treatment course
KCBioMedix

13. B Govindaswami, MBBS, MPH
Standardized Patterned Somatosensory Oral Stimulation in Very Preterm Infants: A Multicenter Randomized Controlled Trial
D Song, MD, PhD, P Jegatheesan, MD, S Nafday MD, K Ahmad MD, J Nedrelow MD, M Wearden MD,
S Nemerofsky MD, S Pooley, MD, D Thompson PhD, Z Cohen RN, T Cornejo RN, C Garrett RN,
B Govindaswami, MBBS, MPH
Santa Clara Valley Medical Center, San Jose, CA
Children's Hospital at Montefiore-Weiler and Wakefield divisions, and Albert Einstein College of Medicine, Bronx, NY
Pediatrix Medical Group, North Central Baptist Hospital
Cook Children’s Medical Center, Fort Worth, TX
Sponsored by: Innara Health, Inc.
We have conducted a multicenter RCT to evaluate the clinical impact of this patterned oral simulation therapy in very premature infants.

14. Study Design Subjects: 210 preterm infants
GA 260/ /7 weeks (Median GA 28.8 weeks, and BW 1.16 kg)
Experimental group: - Pulsatile pacifier stimulation
x 3-4/d (during tube feeding) x 10 days
Initiation at 30 0/ /7weeks PMA
Control group : - Sham – Non-pulsatile pacifier
Primary outcome: Days from initiation to full oral feeding (FOF)
Secondary outcomes: Length of hospital stay (LOS)
Growth – weight gain and HC
Neonatal mortality and morbidity
(Breastfeeding is always given first priority!)
The study enrolled 210 preterm infants born at weeks gestation.
The experimental group received NTrainer therapy 3 to 4 times a day during tube feeding for ten days. The control group received the identical study protocol with a non-pulsatile pacifier.

15. Study Outcomes
Experimental
Sham
Difference
P value
(Mean + SD)
n=109
N=101
Completed training sessions (%) 97
0.124
Days to FOF
22.94 ± 10.54
26.96 ± 14.84 -4
0.029
LOS
59.75 ± 20.21
65.78 ± 19.80
-6.03
0.034
PMA at FOF (weeks)
35.83 ± 1.70
36.42 ± 2.28
-0.58
0.042
PMA at discharge (weeks)
37.29 ± 2.09
37.92 ± 2.35
-0.63
0.046
Wt gain during intervention
18.23 ± 5.43
17.95 ± 5.07
+ 28
0.708
Wt gain during NICU stay
12.63 ± 2.28
12.95 ± 2.24
+0.32
0.25
This slide summarizes the main findings of our study.
The interventions are well tolerated and 97% training sessions were completed.
Compared to the control group, the experimental group showed a 4 day reduction in transition to FOF and 6 day reduction in LOS.
There is no difference between the two groups in mortality and morbidities, including IVH, NEC, late on set infection, CLD and ROP.

16. Why Oral Sensory Entrainment Reduces LOS ?
A larger reduction in LOS compared to time to FOF
Ntrainer entrainment promotes integration of multiple systems involved in feeding and facilitates interactions between the infant and environment – enhance overall developmental maturation required for discharge

17. Oral Somatosensory Input Modulates aEEG
NTrainer System®
BRAINZ® + =
The synchronous sensory input relay in the brainstem and project to the thalamus, and subsequently relayed to orofacial regions of the sensorimotor cortex.

18. Summary:
Patterned oral somatosensory stimulation (NTrainer®) is a effective therapy in improving oral feeding development in preterm infants
Patterned oral somatosensory stimulation presents a new and exciting neurotherapeutic strategy to prevent and treat feeding disorders associated with CHD
It is non-invasive and well tolerated by infants on respiratory support and thus can be used before and after surgery
Feeding is important not only for nutrition, but may also have a significant impact on an infant’s speech development and long-term neurodevelopmental outcome

19. Improving Clinical Practice
Thank you !
Feeding guidelines
Evidence based practice
Innovative therapies
Change our practice model:
More attention and resources to infant feeding
Education: Feeding is important not only for nutrition, but also has a significant impact on an infant’s maturation and long-term neurodevelopmental outcome
Babies and their families
SCVMC NICU staff
Collaborators:
Children's Hospital at Montefiore-Weiler and Wakefield divisions, Albert Einstein
CollegePediatrix Medical Group, North Central
Baptist Hospital, Cook Children’s Medical Center.
Funding: Santa Clara First Five; Innara Health, Inc.

20. The unique orosensory experience offered by the ‘motorized pacifier nipple’ is physiologically salient and
The spectrally patterned stimuli resemble the spatiotemporal features of normal infants’ NNS burst.
This form of stimulation serves to entrain the activity patterns of sensory receptors located in the lips, tongue, and jaw.
The synchronous sensory input relay in the brainstem and project to the thalamus, and subsequently relayed to orofacial regions of the sensorimotor cortex. Descending neuromodulatory inputs are presumed to influence the firing patterns of facial, trigeminal, and hypoglossal motoneurons. The richness of the somatic sensory experience offered by an entraining pacifier nipple presents new and exciting neurotherapeutic applications

21. Improving Clinical Practice
Changing our feeding practice model:
Education: feeding is important not only for nutrition, but also has a significant impact on an infant’s maturation and long-term neurodevelopmental outcome
Put more attention and resources to infant feeding
Standardized feeding guidelines
Implement evidence based practice
Develop more innovative therapies

22. GA Subgroup Analysis
(Mean + SD)
Experimental
Sham
Difference
P value
Group A (GA weeks)
n-=55
n=57
Days to FOF
26.04=11.32
27.93=14.77
-1.89
0.471
LOS
73.33=15.92
72.04=14.59
+1.29
0.663
Group B (GA weeks)
n=52
n=39
19.84=9.04
25.00=15.05
-5.16
0.048
44.71=11.43
56.08=21.55
-11.37
0.002
There is no difference between the two groups in weight gain, mortality and morbidities, including IVH, NEC, late on set infection, CLD and ROP.

23. Timing of Intervention
Post hoc analysis
Timing of Intervention
Intervention was initiated between weeks PMA
Post hoc analysis to determine if the timing of intervention affects outcomes:
Early group (<31 weeks PMA)
Late group (>31 weeks PMA)

24. Subgroup Analysis

25. Oral Somatosensory Stimulation
Critical Period for
Oral Somatosensory Stimulation
Timing of
Intervention
Early
Late
PMA (weeks)
Critical
Period
The timing effect of the therapy may reflect the neurophysiological maturity of the infant at the time of intervention
We need to design a training regimen that targets the infant’s critical period of feeding development

26. Establishing Oral Feeding A Complex Developmental Process
Maturation and integration of multiple systems
Craniofacial
- somatosensory and motor
Specialized sensory systems
- olfactory, gustatory, hearing and vision
GI and Cardiorespiratory systems
Neuromuscular system - maintain tone and position
CNS – state and satiety and hunger regulation
Suck-Swallow-Breathing coordination
all cranial nerves
Hypothalamic feedback loops of