Enhancing Caregiver-Infant Communication to Prevent Obesity
Phase: NA
Conditions: Infant Obesity, Parenting, Feeding Behavior
Sponsor: University of North Carolina, Chapel Hill

 
LiTTLe Me: Learning Together to Love Mealtime 
 
 
 
NCT number NCT04502979    
Document Date 01/01/2017 
 

Complete Title: LiTTLe Me: Learning Together to Love Mealtime  
 
 
 
 
 
Short Title: LiTTLe Me 
Drug or Device Name(s): N/A 
FDA IND/IDE (if applicable): N/A 
Sponsor: The University of North Carolina at Chapel Hill 
Protocol Date: January 1, 2017 
Amendment 1 Date: 
Amendment 2 Date:  
Amendment 3 Date: 
Amendment 4 Date:  
 
Funding Source: 
NIH/NICHD 
1 Center Dr. 
Bethesda, MD 20892 
The United States of America 
Study Principal Investigator: Eric A. Hodges, PhD, FNP-BC, FAAN 
5016 Carrington Hall, CB 7460 
Chapel Hill, NC 27599-7460 
Phone: 919-966-0534 
email: eahodges@email.unc.edu 
 
PROTOCOL TITLE:  LiTTLe Me: Learning Together to Love Mealtime  
Short Title:  
LiTTLe Me  
Lead Investigator: 
Eric A. Hodges, PhD, FNP-BC, FAAN 
 
 
 University of North Carolina at Chapel Hill 
Protocol Version: 1.0  
Version Date: January 1, 2017 
 
I confirm that I have read this protocol and understand it.    
Principal Investigator Name:   
Eric A. Hodges, PhD, FNP-BC, FAAN 
Principal Investigator Signature:  
 
Date:   
 
 
 
January 1, 2017 
 
 
 
 
 

 
 
 
1
TABLE OF CONTENTS 
Table of Contents ................................................................................................................. 1 
Abbreviations and Definitions of Terms ................................................................................ 2 
Protocol Synopsis ................................................................................................................. 3 
1 
BACKGROUND  AND RATIONALE .......................................................................................................................... 6 
2 
STUDY OBJECTIVES .............................................................................................................................................. 12 
3 
INVESTIGATIONAL PLAN ..................................................................................................................................... 12 
4 
STUDY PROCEDURES ........................................................................................................................................... 13 
5 
STUDY EVALUATIONS AND MEASUREMENTS ................................................................................................... 14 
6 
STATISTICAL CONSIDERATIONS .......................................................................................................................... 15 
7 
STUDY INTERVENTION (DEVICE OR OTHER INTERVENTION) ............................................................................ 16 
8 
STUDY INTERVENTION ADMINISTRATION ......................................................................................................... 17 
9 
SAFETY MANAGEMENT ....................................................................................................................................... 17 
10  DATA COLLECTION AND MANAGEMENT ........................................................................................................ 17 
11 RECRUITMENT STRATEGY ................................................................................................................................... 19 
12 CONSENT PROCESS ............................................................................................................................................. 19 
13 PUBLICATION ....................................................................................................................................................... 20 
14 REFERENCES ........................................................................................................................................................ 20 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
2
ABBREVIATIONS AND DEFINITIONS OF TERMS 
 
Abbreviation 
Definition 
ASL 
American Sign Language 
RSA 
Respiratory Sinus Arrhythmia 
T1 
Time 1 
T2 
Time 2 
T3 
Time 3 
BMI 
Body Mass Index 
SES 
Socio-economic status 
RCFCS 
Responsiveness to Child Feeding Cues Scale 
NDS-R 
Nutrition Data System for Research 
CEBQ-T 
Child Eating Behavior Questionnaire-Toddler 
IFSQ 
Infant Feeding Styles Questionnaire 
IBQR 
Revised Infant Behavior Questionnaire 
NGSE 
New Generalized Self-Efficacy Scale 
IIQ 
Infant Intentionality Questionnaire 
PHQ-4 
Patient Health Questionnaire-4 
PI 
Principal Investigator 
Co-I 
Co-Investigator 
IRB 
Institutional Review Board 
ECG 
Electrocardiogram 
IBI 
Interbeat Interval 
REDCap 
Research Electronic Data Capture 
UNC 
The University of North Carolina at Chapel Hill 
CTSA 
Clinical and Translational Science Awards Program 
FTP 
File Transfer Protocol 
ITS 
Information Technology Services 
WIC 
The Special Supplemental Nutrition Program for Women, Infants, and Children 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
3
PROTOCOL SYNOPSIS 
 
Study Title 
Enhancing Caregiver-Infant Communication to Prevent Obesity 
Funder 
Eunice Kennedy Shriver National Institute of Child Health and 
Human Development  
Clinical Phase 
Stage 1 for Behavioral Intervention Development 
Study Rationale 
Once obese as an infant, the relative risk of remaining obese appears 
to rise with increasing age. Thus, the early years of life have been 
posited as an important target period for obesity prevention. Widely 
viewed as a response to genetic, interpersonal, and environmental 
factors, obesity fundamentally reflects an imbalance between energy 
intake and expenditure. Self-regulation of energy intake aligned 
with physiologic need is essential to this balance. The process(es) 
by which infants begin to disassociate eating behavior from 
physiologic need is unclear, thus it is crucial to better understand 
predictors of individual differences in self-regulation of energy 
intake.  
A chronic mismatch between a caregiver’s feeding behavior and the 
infant’s state (feeding in the absence of hunger and/or feeding 
beyond fullness), is thought to contribute to obesity by undermining 
the infant’s capacity to self-regulate intake; the current proposal will 
be the first to examine the effects on autonomic regulation. 
 
Study Objective(s) 
Primary Outcome 
To evaluate the initial impact of the intervention. We expect the 
following for the experimental group:  
Infants will have more optimal growth (weight-for-
length Z scores closer to 50th %) than the control group 
by T3. 
Secondary Outcome 
To evaluate the initial impact of the intervention. We expect the 
following for the experimental group: 
o Infants will have enhanced self-regulation of energy 
intake (closer to estimated energy requirements) than the 
control group by T3. 
Tertiary Outcomes 
To evaluate the initial impact of the intervention. We expect the 
following for the experimental group: 
o A) Dyads will demonstrate (1) improvement in observed 
feeding responsiveness and (2) higher observed feeding 
responsiveness than the control group by T3 (6-months 
post-baseline). 
o B) Mothers will (1) perceive higher infant satiety 
responsiveness and (2) report more responsiveness 

 
 
 
4
feeding behaviors and beliefs than the control group by 
T3. 
Evaluate the feasibility and acceptability (e.g., burden) of the 
intervention and study methods including recruitment, enrollment, 
and data collection (self-report, anthropometrics, video 
observations, and respiratory sinus arrhythmia [RSA]) for infants 
and their mothers. 
Exploratory Outcome 
• 
Explore preliminary data on concordance between dyadic 
feeding interactions and autonomic regulation in both mothers 
and infants (RSA). We expect higher observed dyadic feeding 
responsiveness to be associated with larger change scores in 
RSA (enhanced self-regulation) for both mother and infant.  
 
Test Article(s) 
(If Applicable) 
N /A 
Study Design 
 
Two-group randomized repeated measures design. 
Subject Population 
key criteria for 
Inclusion and Exclusion: 
Inclusion Criteria 
1. Subjects age 3 months to 50 years.  
2. Mothers must be able to read, understand, and speak English 
or Spanish and be willing to be randomized and participate 
in data collection. Those who are randomized into the 
experimental group must also be willing to learn ASL 
specific to communication of hunger, thirst, and fullness. 
Exclusion Criteria 
1. Dyads will be excluded if infants: 
a.  were born more than 6 weeks earlier than their 
estimated due date,  
b. have any developmental delays or disabilities that 
make it difficult for them to eat, drink, or 
communicate,  
c. attend regular daycare,  
d. or will be younger than 4 months or older than 9 
months at the time of the first ASL training. 
Number of Subjects  
 
160  
Study Duration 
Each subject’s participation will last between 6-6.5 months 
depending on how long it takes to schedule the last dietary recalls.  
The entire study is expected to last 2 years. 
Study Phases 
Screening 
Screening: screening for eligibility and obtaining consent  

 
 
 
5
Study Treatment 
Follow-Up   
Study Treatment: study intervention/experimental treatment from 
baseline visit (T1) monthly until 3-months post-baseline (T2) 
Follow-up: 6-months post-baseline (T3) 
Efficacy Evaluations 
Primary efficacy evaluation measures: 
1. Infants in the intervention group will have more optimal 
growth (weight-for-length Z scores closer to 50th %) than 
the control group by T3. 
Pharmacokinetic 
Evaluations 
N/A 
Safety Evaluations 
• Assessment of self-reported health of parent and infant prior 
to data collection 
• Monitoring of parent’s and infant’s responses during 
intervention and data collection 
• Reports of adverse events 
Statistical And Analytic 
Plan 
To evaluate the initial impact of the intervention longitudinally for 
each maternal and infant outcome listed in the primary, secondary, 
and first two tertiary outcomes above, we will fit separate linear 
mixed-effects random coefficients models. These will model the 
linear trajectories of the group-specific means across all available 
time points using the actually observed timing.  The initial impact of 
the intervention will be formally assessed through a statistical 
hypothesis test of model parameter representing the difference in 
these slopes. More specifically, these models will include terms for 
the intervention group (as an indicator variable), actual time of data 
collection (as continuous weeks from baseline), and their 
interaction.  Covariates identified above to correct for imbalance 
will be included, as well as the factors stratified in the 
randomization, and the models will account for the repeated 
measures correlation structure. Statistical contrasts will also be 
constructed to estimate and test the changes over time separate for 
each group.   
DATA AND SAFETY 
MONITORING PLAN 
Study personnel will be on-site in subjects' homes for the duration 
of data collection and will monitor the response of subjects during 
data collection. Should any concerns arise during data collection, 
they will be addressed immediately by study personnel and the PI 
and Co-I will be notified as soon as possible if they are not on site. 
Though unlikely, should any concerns arise after data collection, 
subjects will be given the PI's contact information to share their 
concerns and the PI will address concerns directly or through 
appropriate referrals. Any concerns that arise over the course of the 
study will be recorded and aggregated as part of the feasibility data 
and shared with the research team and the IRB as necessary. 
 
 
 

 
 
 
6
1 
BACKGROUND AND RATIONALE 
1.1 
Introduction 
Once obese as an infant, the relative risk of remaining obese appears to rise with increasing age.1,2 Thus, 
the early years of life have been posited as an important target period for obesity prevention.3 Widely 
viewed as a response to genetic, interpersonal, and environmental factors, obesity fundamentally reflects 
an imbalance between energy intake and expenditure.3 Self-regulation of energy intake aligned with 
physiologic need is essential to this balance.3,4 The process(es) by which infants begin to disassociate 
eating behavior from physiologic need is unclear, thus it is crucial to better understand predictors of 
individual differences in self-regulation of energy intake. It is well established that autonomic regulation 
may support infant behavioral regulation5, suggesting that autonomic function may be a critical area to 
consider here. Moreover, self-regulation is strongly influenced by dyadic interaction quality during 
infancy, and findings reveal that more responsive interactions are associated with more effective 
autonomic regulation.6 A chronic mismatch between a caregiver’s feeding behavior and the infant’s state 
(feeding in the absence of hunger and/or feeding beyond fullness), is thought to contribute to obesity by 
undermining the infant’s capacity to self-regulate intake7–9; the current proposal will be the first to 
examine the effects on autonomic regulation. 
     We propose an intervention to enrich the capacity of mother-infant dyads to perform their respective 
interactive tasks. We plan to teach mothers American Sign Language (ASL) signs indicative of hunger, 
thirst, and satiety, which they will in turn teach their preverbal infant. This training in ASL will be 
augmented with targeted information for mothers about infants’ capacities to self-regulate energy intake 
in response to hunger and satiety and communicate those states with intention.  Mothers also will be 
taught about expected development of infants’ eating behaviors and nutritional requirements to support 
healthy growth. 
     Using a two-group randomized repeated measures design, this study aims to 1) evaluate the 
feasibility and acceptability of the intervention and study methods, including recruitment, enrollment, 
and data collection (self-report, anthropometrics, video observations, and respiratory sinus arrhythmia 
[RSA]) for infants and their mothers; 2) evaluate the initial impact of the intervention on infant growth 
and nutritional intake, observed feeding interactions, and reported infant feeding behaviors and maternal 
feeding behaviors/beliefs; and, 3) explore preliminary data on concordance between dyadic feeding 
interactions and autonomic regulation in both mothers and infants (RSA). In addition to a variety of self-
report and anthropometric measures, this study will use integrated behavioral (video) and physiologic 
(RSA) measures to better understand feeding dynamics and their relationship with obesity risk. 
Understanding these processes is essential for developing appropriate preventions, or interventions, that 
will help reduce the prevalence of early childhood obesity and its extension into later childhood and 
beyond. 
The study’s interventions and data collection will take place in participants’ homes.  
 
1.2 
Name and Description of Investigational Product or Intervention  
We propose an intervention to enrich the capacity of mother-infant dyads to perform their respective 
interactive tasks. We plan to teach mothers American Sign Language (ASL) signs indicative of hunger, 
thirst, and satiety, which they will in turn teach their preverbal infant. This training in ASL will be 
augmented with targeted information for mothers about infants’ capacities to self-regulate energy intake 
in response to hunger and satiety and communicate those states with intention. Mothers also will be 
taught about expected development of infants’ eating behaviors and nutritional requirements to support 
healthy growth. 
 
1.3 
Non-Clinical and Clinical Study Findings 
Nearly 10% of U.S. infants were obese in 2009-2010. 10 Given increased relative risk of remaining obese 
later in life1,2 and poor health consequences of childhood obesity during childhood11 and adulthood,12 

 
 
 
7
obesity prevention during infancy has become a priority for research.13,14 Research in this area is 
relatively new and results have been mixed regarding measures of obesity.15–25 Obesity intervention 
components have included: teaching caregivers strategies for improving infant sleep 
quality/duration19,20, increasing infant physical activity21–23, providing nutritional education to support 
breastfeeding20–22,24, increasing food variety16–19,21–23, appropriate timing of complementary food 
introduction16–23, and increased responsiveness to infant hunger and satiety cues.16–20,23,25 These studies 
report improvements in several factors that have been associated with obesity risk, including: improved 
infant sleep,19,20 less TV exposure20,22,23, decreased sweet/juice intake18,23, delayed introduction of 
solids19–21, increased breastfeeding duration20 and/or rates24, and increased parental responsiveness (self-
reported) to infant hunger and satiety cues.16,17 Most studies have failed to impact significantly body 
mass index (BMI) or Weight/Length.17,18,20,23 Two have found a decrease in either weight for length %19 
or BMI22 while two other studies have noted an increase in weight and length25 or BMI.24 While impact 
on BMI or Weight/Length appears equivocal, it is quite possible that effects on obesity status and 
growth will become evident later in development; most of the studies reported outcomes < 6 months 
after delivery of the last intervention component.  Of importance regarding safety, none of the 
intervention studies demonstrated concerning weight loss or growth delay.  
While the etiology of obesity is considered multifactorial, it arises fundamentally through an imbalance 
in energy intake and output. The aforementioned studies used multi-focal intervention components, yet 
there was little focus on the assessment of support for energy intake self-regulation and no focus on 
evidence of self-regulation (eating behavior responsive to physiologic state [i.e., hungry or satiated]). 
Several studies included efforts to increase caregiver responsiveness to infant hunger and satiety cues14–
18,21,23, which is thought to support self-regulation7–9, yet only one investigative team has reported 
improvement in parental responsiveness (self-reported).16,17 In short-term protocols (meal to meal), 
infants have demonstrated the ability to self-regulate energy intake over days26 and weeks27, through 
compensation or adjustment for variations in the energy content of food. This self-regulatory capacity 
appears to increasingly diminish in the years following toddlerhood, at least in short-term protocols.28–31 
Thus, it has been suggested that the first 2 years of life may be a critical period for the development of 
self-regulation of intake.30  
     There is strong evidence in the extant literature that social, emotional, and cognitive self-regulation6 
can be nurtured or derailed within the caregiver-infant relationship; evidence among older children 
suggests that self-regulation of energy intake may be influenced by the 
caregiving environment, too.28,31–33 This is an integral component of our 
theoretical orientation, which is guided by a model linking feeding 
responsiveness to obesity (Figure 1). For our study, this model is situated 
within the larger relational developmental systems paradigm34, in which the 
biological, psychological, and sociocultural systems interpenetrate and 
mutually influence one another over the course of development. This 
paradigm requires us to acknowledge that energy intake self-regulation is 
modifiable by relational developmental processes. Thus, we examine this 
phenomenon across multiple levels in order to understand its development 
and consider how interventions may affect it. 
     Although self-regulation is most easily assessed by observable 
behavioral patterns, it is critical to understand the psychobiological 
processes that support these behaviors. One of the most studied correlates 
of behavioral self-regulation is within the autonomic nervous system, more specifically vagal tone, 
which is often assessed through respiratory sinus arrhythmia (RSA).35 Baseline cardiac patterns are 
considered to be a neurophysiological mechanism underlying autonomic and behavioral reactivity. 
Although RSA is relatively stable during a calm and restful state, it is sensitive to environmental 
demands and thus extant research also measures change in RSA from baseline to an external challenge.35 
Figure 1. Feeding Responsiveness & Obesity 

 
 
 
8
The ability to effectively reduce RSA during challenge, followed by a return to baseline levels, may be 
an adaptive process allowing participation in demanding tasks by shifting attention from internal 
homeostatic demands to external ones to support the use of coping strategies to control affective or 
behavioral arousal. Withdrawal of RSA (larger RSA change scores) during a challenging situation has 
been related to better emotion regulation in infants5,36,37 and caregivers.38  
     Thus far, most studies of infant and toddler self-regulation of eating have focused on the 
contributions of temperament (e g., attention spans, soothability, negative reaction to food). Findings 
have revealed an association between these characteristics at 1 year of age and larger weight increases 
over time and obesity at 6 years of age.39 To our knowledge, only one study has looked at the autonomic 
correlates of these behaviors, and found that older children (5.5 years old) who demonstrated lower 
levels of RSA withdrawal (a purported indicator of less regulation) during lab stressors were 
significantly more likely to be overweight five years later, but this was only true among African-
American children.40 This finding was unclear, but the authors suggested, “future research should 
examine whether individual differences in cardiac regulation relate to observable differences in 
children’s eating behavior”(p. 1824).  
     In adults, obesity has been related to low baseline RSA41–43 and smaller RSA change during a 
stressor.44 Increased vagal control in adult dieters could be a physiological endophenotype of successful 
eating self-regulation.45 Findings revealed that dieting success (i.e., self-control of food intake) was 
associated with increased parasympathetic control, even after controlling for BMI, smoking, alcohol, 
and exercise. We propose an innovative assessment of the development of parasympathetic function 
during feeding interactions earlier in life to better understand the direction of this effect.  We are 
particularly interested in exploring patterns of infant and maternal RSA change in relation to infant and 
maternal behaviors during feeding, as an index of engagement and early regulation of food intake. This 
is particularly relevant in light of global46 and particularly energy intake30 development of self-
regulation in infancy and toddlerhood.       
Our proposed linkage of dyadic feeding responsiveness and autonomic regulation (RSA) with indicators 
of enhanced energy intake self-regulation, optimal growth, and adiposity addresses the call for obesity 
prevention efforts focused on the bidirectional, mutually responsive orientation between parent and 
child.47 The study will be the first systematic assessment of a well-established communication system 
(ASL) to enhance dyadic communication between infants and their caregivers specific to feeding. The 
study acknowledges the caregiver and infant as each having a responsibility during feeding and moves 
beyond a focus on the caregiver to both partners, equipping them with new ways of communicating and 
perceiving one another during feeding. We propose to use ASL as it has been shown to facilitate 
communication, parental perception of infants’ capacity to communicate with intent, and caregiver 
responsiveness with hearing infants.48–51 Our focus on hunger, thirst, and satiety signs should not 
overwhelm the dyad. The public health impact could be profound if the intervention is found to be 
promising.       
     While this is an exploratory/developmental study, we do acknowledge the existing literature on 
additional characteristics that may affect mutual responsiveness between infant and caregiver. These 
include infant characteristics (temperament) and caregiver characteristics (education, socio-economic 
status (SES), prior parenting experience, depression and anxiety, perception of infant intention, and 
parenting self-efficacy).51–54 Therefore, we plan to assess the feasibility of measuring these 
characteristics as part of planning for our larger future study of biopsychosocial systems and their role in 
obesity risk in infancy and early childhood.   
 
 
1.4 
Relevant Literature and Data 
 
1.  
Baird J, Fisher D, Lucas P, Kleijnen J, Roberts H, Law C. Being big or growing fast: systematic review of 

 
 
 
9
size and growth in infancy and later obesity. BMJ. 2005;331(7522):929. 
doi:10.1136/bmj.38586.411273.E0 
2.  
Mei Z, Grummer-Strawn LM, Scanlon KS. Does overweight in infancy persist through the preschool 
years? An analysis of CDC Pediatric Nutrition Surveillance System data. Sozial-und 
Präventivmedizin/Social and Preventive Medicine. 2003;48(3):161-167. 
3.  
Birch LL, Parker L, Burns A, eds. Early Childhood Obesity Prevention Policies. Washington, D.C.: 
National Academies Press; 2011. doi:10.17226/13124 
4.  
Herman CP, Polivy J. The self-regulation of eating: Theoretical and practical problems. In: Vohs KD, F. 
BR, eds. 2nd ed. Handbook of self-regulation: Research, theory, and applications. New York: The 
Guilford Press; 2011:522-536. 
5.  
Calkins SD. Cardiac vagal tone indices of temperamental reactivity and behavioral regulation in young 
children. Developmental psychobiology. 1997;31(2):125-135. 
6.  
Propper CB, Holochwost SJ. The influence of proximal risk on the early development of the autonomic 
nervous system. Developmental Review. 2013;33(3):151-167. doi:10.1016/j.dr.2013.05.001 
7.  
Bruch H. Eating Disorders. Obesity, Anorexia Nervosa, and the Person Within. Routledge & Kegan Paul.; 
1974. 
8.  
Costanzo PR, Woody EZ. Domain-specific parenting styles and their impact on the child’s development 
of particular deviance: the example of obesity proneness. J Soc Clin Psychol. 1985;3(4):425-445. 
9.  
DiSantis KI, Hodges EA, Johnson SL, Fisher JO. The role of responsive feeding in overweight during 
infancy and toddlerhood: a systematic review. Int J Obes. 2011;35(4):480-492. doi:10.1038/ijo.2011.3 
10.  Ogden CCL. Prevalence of Obesity and Trends in Body Mass Index Among US Children and 
Adolescents, 1999-2010. JAMA : the journal of the American Medical Association. 2012;307(5):483. 
11.  Pulgarón ER. Childhood obesity: a review of increased risk for physical and psychological comorbidities. 
Clin Ther. 2013;35(1):A18-32. doi:10.1016/j.clinthera.2012.12.014 
12.  Reilly JJ, Kelly J. Long-term impact of overweight and obesity in childhood and adolescence on 
morbidity and premature mortality in adulthood: systematic review. Int J Obes. 2011;35(7):891-898. 
doi:10.1038/ijo.2010.222 
13.  Birch LL, Anzman-Frasca S, Paul IM. Starting Early: Obesity Prevention during Infancy. 2012. 
14.  Dattilo AM, Birch L, Krebs NF, Lake A, Taveras EM, Saavedra JM. Need for early interventions in the 
prevention of pediatric overweight: a review and upcoming directions. J Obes. 2012;2012:1-18. 
15.  Barlow J, Whitlock S, Hanson S, et al. Preventing obesity at weaning: parental views about the 
EMPOWER programme. Child Care Health Dev. 2010;36(6):843-849. doi:10.1111/j.1365-
2214.2010.01107.x 
16.  Daniels LA, Mallan KM, Battistutta D, Nicholson JM, Parey R, Magarey A. Evaluation of an intervention 
to promote protective infant feeding practices to prevent childhood obesity: outcomes of the NOURISH 
RCT at 14 months of age and 6 months post the first of two intervention modules. International journal of 
obesity (2005). 2012;36(10):1292-1298. 
17.  Daniels LA, Mallan KM, Nicholson JM, Battistutta D, Magarey A. Outcomes of an early feeding 
practices intervention to prevent childhood obesity. Pediatrics. 2013;132(1):e109-18. 
doi:10.1542/peds.2012-2882 
18.  French GM, Nicholson L, Skybo T, et al. An evaluation of mother-centered anticipatory guidance to 
reduce obesogenic infant feeding behaviors. Pediatrics. 2012;130(3):e507-17. doi:10.1542/peds.2011-
3027 
19.  Paul IM, Savage JS, Anzman SL, et al. Preventing obesity during infancy: a pilot study. Obesity (Silver 
Spring). 2011;19(2):353-361. doi:10.1038/oby.2010.182 
20.  Taveras EM, Blackburn K, Gillman MW, et al. First steps for mommy and me: a pilot intervention to 
improve nutrition and physical activity behaviors of postpartum mothers and their infants. Matern Child 
Health J. 2011;15(8):1217-1227. doi:10.1007/s10995-010-0696-2 
21.  Wen LM, Baur LA, Simpson JM, Rissel C, Flood VM. Effectiveness of an early intervention on infant 

 
 
 
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feeding practices and “tummy time”: a randomized controlled trial. Arch Pediatr Adolesc Med. 
2011;165(8):701-707. doi:10.1001/archpediatrics.2011.115 
22.  Wen LM, Baur LA, Simpson JM, Rissel C, Wardle K, Flood VM. Effectiveness of home based early 
intervention on children’s BMI at age 2: randomised controlled trial. BMJ: British Medical Journal. 
2012;344. 
23.  Campbell KJ, Lioret S, McNaughton SA, et al. A parent-focused intervention to reduce infant obesity risk 
behaviors: a randomized trial. Pediatrics. 2013;131(4):652-660. doi:10.1542/peds.2012-2576 
24.  Karanja N, Lutz T, Ritenbaugh C, et al. The TOTS community intervention to prevent overweight in 
American Indian toddlers beginning at birth: a feasibility and efficacy study. Journal of community health. 
2010;35(6):667-675. 
25.  Kavanagh KF, Cohen RJ, Heinig MJ, Dewey KG. Educational intervention to modify bottle-feeding 
behaviors among formula-feeding mothers in the WIC program: impact on infant formula intake and 
weight gain. J Nutr Educ Behav. 2008;40(4):244-250. doi:10.1016/j.jneb.2007.01.002 
26.  Pearcey SM, De Castro JM. Food intake and meal patterns of one year old infants. Appetite. 
1997;29(2):201-212. doi:10.1006/appe.1997.0099 
27.  Fomon SJ, Filmer IJ, Thomas LN, Anderson TA, Nelson SE. Influence of formula concentration on 
caloric intake and growth of normal infants. Acta Paediatr. 1975;64(2):172-181. doi:10.1111/j.1651-
2227.1975.tb03818.x 
28.  Cecil JE, Palmer CNA, Wrieden W, et al. Energy intakes of children after preloads: adjustment, not 
compensation. Am J Clin Nutr. 2005;82(2):302-308. doi:10.1093/ajcn.82.2.302 
29.  Fox MK, Devaney B, Reidy K, Razafindrakoto C, Ziegler P. Relationship between portion size and 
energy intake among infants and toddlers: evidence of self-regulation. J Am Diet Assoc. 2006;106(1 Suppl 
1):S77-83. doi:10.1016/j.jada.2005.09.039 
30.  Kral TVE, Stunkard AJ, Berkowitz RI, Stallings VA, Brown DD, Faith MS. Daily food intake in relation 
to dietary energy density in the free-living environment: a prospective analysis of children born at 
different risk of obesity. Am J Clin Nutr. 2007;86(1):41-47. doi:10.1093/ajcn/86.1.41 
31.  Johnson SL, Taylor-Holloway LA. Non-Hispanic white and Hispanic elementary school children’s self-
regulation of energy intake. Am J Clin Nutr. 2006;83(6):1276-1282. doi:10.1093/ajcn/83.6.1276 
32.  Birch LL, McPheee L, Shoba BC, Steinberg L, Krehbiel R. “Clean up your plate”: Effects of child feeding 
practices on the conditioning of meal size. Learn Motiv. 1987;18(3):301-317. doi:10.1016/0023-
9690(87)90017-8 
33.  Faith MS, Scanlon KS, Birch LL, Francis LA, Sherry B. Parent-child feeding strategies and their 
relationships to child eating and weight status. Obes Res. 2004;12(11):1711-1722. 
doi:10.1038/oby.2004.212 
34.  Overton WF. Relationism and relational developmental systems: a paradigm for developmental science in 
the post-Cartesian era. Advances in Child Development and Behavior. 2012;44:21-64. 
35.  Porges S. Vagal tone: An autonomic mediator of affect. In: Garber J, Dodge KA, eds. The Development of 
Emotion Regulation and Dysregulation. Cambridge: Cambridge University Press; 1991:111-128. 
doi:10.1017/CBO9780511663963.007 
36.  Porges SW, Doussard-Roosevelt JA, Portales AL, Greenspan SI. Infant regulation of the vagal “brake” 
predicts child behavior problems: a psychobiological model of social behavior. Dev Psychobiol. 
1996;29(8):697-712. doi:10.1002/(SICI)1098-2302(199612)29:8&lt;697::AID-DEV5&gt;3.0.CO;2-O 
37.  Santucci AK, Silk JS, Shaw DS, Gentzler A, Fox NA, Kovacs M. Vagal tone and temperament as 
predictors of emotion regulation strategies in young children. Developmental psychobiology. 
2008;50(3):205-216. 
38.  Moore GA, Hill‐Soderlund AL, Propper CB, Calkins SD, Mills‐Koonce WR, Cox MJ. Mother–Infant 
Vagal Regulation in the Face‐To‐Face Still‐Face Paradigm Is Moderated by Maternal Sensitivity. Child 
development. 2009;80(1):209-223. 
39.  Faith MS, Hittner JB. Infant temperament and eating style predict change in standardized weight status 

 
 
 
11 
and obesity risk at 6 years of age. Int J Obes. 2010;34(10):1515-1523. doi:10.1038/ijo.2010.156 
40.  Graziano PA, Calkins SD, Keane SP, O’Brien M. Cardiovascular regulation profile predicts 
developmental trajectory of BMI and pediatric obesity. Obesity (Silver Spring). 2011;19(9):1818-1825. 
doi:10.1038/oby.2011.98 
41.  Coles J, Vögele C, Hilbert A, Tuschen-Caffier B. Fasten und (Über)-essen. Zeitschrift für Klinische 
Psychologie und Psychotherapie. 2005;34(2):95-103. 
42.  Karason K, Mølgaard H, Wikstrand J, Sjöström L. Heart rate variability in obesity and the effect of 
weight loss. Am J Cardiol. 1999;83(8):1242-1247. doi:10.1016/s0002-9149(99)00066-1 
43.  Latchman PL, Mathur M, Bartels MN, Axtell RS, De Meersman RE. Impaired autonomic function in 
normotensive obese children. Clin Auton Res. 2011;21(5):319-323. doi:10.1007/s10286-011-0116-8 
44.  Friederich HC, Schild S, Schellberg D, et al. Cardiac parasympathetic regulation in obese women with 
binge eating disorder. Int J Obes. 2006;30(3):534-542. doi:10.1038/sj.ijo.0803181 
45.  Meule A, Lutz A, Vögele C, Kübler A. Food cravings discriminate differentially between successful and 
unsuccessful dieters and non-dieters. Validation of the Food Cravings Questionnaires in German. 
Appetite. 2012;58(1):88-97. doi:10.1016/j.appet.2011.09.010 
46.  Calkins SD. The emergence of self-regulation: Biological and behavioral control mechanisms supporting 
toddler competencies. 
47.  Skouteris H, McCabe M, Ricciardelli LA, et al. Parent-child interactions and obesity prevention: a 
systematic review of the literature. Early Child Dev Care. 2012;182(2):153-174. 
48.  Thompson RRH. Enhancing Early Communication through Infant Sign Training. J Appl Behav Anal. 
2007;40(1):15-23. 
49.  Vallotton CD. Infant signs as intervention? Promoting symbolic gestures for preverbal children in low-
income families supports responsive parent–child relationships. Early Child Res Q. 2012;27(3):401-415. 
doi:10.1016/j.ecresq.2012.01.003 
50.  Góngora X, Farkas C. Infant sign language program effects on synchronic mother-infant interactions. 
Infant Behav Dev. 2009;32(2):216-225. doi:10.1016/j.infbeh.2008.12.011 
51.  Kirk E, Howlett N, Pine KJ, Fletcher BC. To sign or not to sign? The impact of encouraging infants to 
gesture on infant language and maternal mind-mindedness. Child Dev. 2013;84(2):574-590. 
doi:10.1111/j.1467-8624.2012.01874.x 
52.  Kochanska G, Aksan N. Development of mutual responsiveness between parents and their young 
children. Child development. 2004;75(6):1657-1676. 
53.  Murray L, Fiori‐Cowley A, Hooper R, Cooper P. {The impact of postnatal depression and associated 
adversity on early mother‐infant interactions and later infant outcome}. Child development. 
1996;67(5):2512-2526. 
54.  Skuban EM, Shaw DS, Gardner F, Supplee LH, Nichols SR. The correlates of dyadic synchrony in high-
risk, low-income toddler boys. Infant Behavior and Development. 2006;29(3):423-434. 
55.  Birch LL, Fisher JO. Development of eating behaviors among children and adolescents. Pediatrics. 
1998;101(3 Pt 2):539-549. 
56.  Hodges EA, Johnson SL, Hughes SO, Hopkinson JM, Butte NF, Fisher JO. Development of the 
responsiveness to child feeding cues scale. Appetite. 2013;65:210-219. doi:10.1016/j.appet.2013.02.010 
57.  van Jaarsveld CHM, Llewellyn CH, Johnson L, Wardle J. Prospective associations between appetitive 
traits and weight gain in infancy. Am J Clin Nutr. 2011;94(6):1562-1567. doi:10.3945/ajcn.111.015818 
58.  Thompson AL, Mendez MA, Borja JB, Adair LS, Zimmer CR, Bentley ME. Development and validation 
of the Infant Feeding Style Questionnaire. Appetite. 2009;53(2):210-221. doi:10.1016/j.appet.2009.06.010 
59.  Gartstein MA, Rothbart MK. Studying infant temperament via the Revised Infant Behavior Questionnaire. 
Infant Behavior and Development. 2003;26(1):64-86. doi:10.1016/S0163-6383(02)00169-8 
60.  Chen G, Gully SM, Eden D. Validation of a New General Self-Efficacy Scale. Organizational Research 
Methods. 2001;4(1):62-83. doi:10.1177/109442810141004 
61.  Reznick JS, Feldman R. {Infant Intentionality Questionnaire—Version 4.2. Psychology Department, 

 
 
 
12 
University of North Carolina at Chapel Hill, CB{\#} 3270, Chapel Hill, NC 27599-3270}. 
62.  Löwe B, Wahl I, Rose M, et al. A 4-item measure of depression and anxiety: validation and 
standardization of the Patient Health Questionnaire-4 (PHQ-4) in the general population. J Affect Disord. 
2010;122(1-2):86-95. doi:10.1016/j.jad.2009.06.019 
63.  Butte NF. Energy requirements of infants. Public Health Nutr. 2005;8(7A):953-967. 
doi:10.1079/PHN2005790 
64.  Brage S, Brage N, Franks PW, Ekelund U, Wareham NJ. Reliability and validity of the combined heart 
rate and movement sensor Actiheart. European journal of clinical nutrition. 2005;59(4):561-570. 
65.  Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture 
(REDCap)--a metadata-driven methodology and workflow process for providing translational research 
informatics support. J Biomed Inform. 2009;42(2):377-381. doi:10.1016/j.jbi.2008.08.010 
66.  Willett W. Nutritional Epidemiology. 2nd ed. New York: Oxford University Press; 1998. 
 
2 
STUDY OBJECTIVE  
2.1 
Primary Objective 
To evaluate the initial impact of the intervention. We expect the following for the experimental group: 
• Infants will have more optimal growth (weight-for-length Z scores closer to 50th %) than the 
control group by T3. 
 
2.2 
Secondary Objective 
To evaluate the initial impact of the intervention. We expect the following for the experimental group: 
• Infants will have enhanced self-regulation of energy intake (closer to estimated energy 
requirements) than the control group by T3. 
 
3 
INVESTIGATIONAL PLAN  
3.1 
Study Design 
Two-group randomized repeated measures design with an intervention group and a control group of 
mother-infant dyads. For the intervention, we plan to teach mothers American Sign Language (ASL) 
signs indicative of hunger, thirst, and satiety, which they will in turn teach their preverbal infant. This 
training in ASL will be augmented with targeted information for mothers about infants’ capacities to 
self-regulate energy intake in response to hunger and satiety and communicate those states with 
intention. Mothers also will be taught about expected development of infants’ eating behaviors and 
nutritional requirements to support healthy growth. For the control group, dyads will participate in the 
same data collection as the intervention group and engage in their usual care provided by their health 
care provider, but they will not receive intervention content unless they elect to receive written lesson 
content once the study’s data collection has ended and they have been debriefed.  
 
Study Phases:  
Screening: screening for eligibility and obtaining consent  
Study Treatment: study intervention/experimental treatment from baseline visit (T1: age 4-9-months) 
monthly until 3-months post-baseline (T2: age 7-12-months) 
Follow-up: 6-months post-baseline (T3: age 10-15-months) 
 
3.2 
Allocation to Treatment Groups and Blinding  
Randomization will be stratified by age group (for developmental differences; 4-5-months-old, 6-7-
months-old, and 8-9-months old).  Computerized randomization lists will be generated by study 

 
 
 
13 
statistician and will be administered by the project manager. Study personnel who code videos of 
feeding interactions will be blind to group status.  
 
3.3 
Study Duration, Enrollment and Number of Subjects 
We plan for 80 parent-infant dyads (160 subjects) randomized to invention (40 dyads) or control (usual 
care; 40 dyads). Length of participation will be 6-6.5 months and planned study duration is 2 years.  
 
3.4 
Study Population 
Inclusion Criteria 
1. Subjects age 3 months to 50 years.  
2. Mothers must be able to read, understand, and speak English or Spanish and be willing to be randomized 
and participate in data collection. Those who are randomized into the experimental group must also be 
willing to learn ASL specific to communication of hunger, thirst, and fullness. 
Exclusion Criteria 
1. Dyads will be excluded if infants: 
a.  were born more than 6 weeks earlier than their estimated due date,  
b. have any developmental delays or disabilities that make it difficult for them to eat, drink, or 
communicate,  
c. attend regular daycare,  
d. or will be younger than 4 months or older than 9 months at the time of the first ASL training. 
 
4 
STUDY PROCEDURES  
4.1 
Screening/Baseline Visit procedures: Families will be recruited from a community sample through a 
variety of means, including email listservs, in-person interactions with study personnel, social media 
posting to local parenting groups, and publicly posted flyers. Those wishing to learn more about the 
study will contact our project manager, who will conduct screening and enrollment for those wishing to 
participate in the study. 
4.2 
Intervention/Treatment procedures (by visits): Intervention families will receive approximately 4 
hours of ASL and development specific content related to language and feeding during home visits and 
phone calls. The initial in-home session with families will focus on teaching ASL signs indicative of 
hunger, thirst, and satiety. A video and placemat of mealtime signs will be left with families at the 
completion of the first visit. The remaining sessions, in-home over the next 3 months and by phone 
monthly thereafter for 6 months total, will focus on reinforcing ASL signing in addition to focused 
education on particular aspects of language development (receptive language preceding expressive 
language and increasing intentional communication), feeding development (such as hunger and fullness 
cues, fear of new foods, the importance of repeated food exposures, variations in intake from meal-to-
meal, and the propensity to reject bitter tastes [many vegetables]55], and appropriate portion sizes and 
variety for healthy growth.  
 
In person visit lesson schedule (monthly from baseline at 4-9 months of age): 
Visit 1 (baseline: T1): Signing with infants 
Visit 2: Infant communication and responsive feeding  
Visit 3: Nutrition, portion sizes, and neophobia 
Visit 4 (T2): Infant intentionality 
 

 
 
 
14 
All families will be offered $25, $30, and $35 at T1, T2, and T3 data collections, respectively. At the 
end of the study, control families will have the opportunity at the end of the 6-month study period to 
learn about what educational content was offered to the Experimental Group and study personnel will 
provide a booklet of this content to them and an ASL Signs of Feeding placemat if they wish. 
If subjects withdraw or are withdrawn from the study prior to arrival of the study personnel at their 
home for data collection, then no monetary incentive will be offered. If participating parent or infant 
withdraws or is withdrawn from the study once data collection has been initiated in their home, they will 
be offered one half of the possible monetary incentive amount for that visit for their attempt to 
participate. All subjects will be thanked for their interest and participation regardless of whether they 
complete all data collections.  
 
See section 5 below for data collected at each visit.  
  
4.3 
Follow- up procedures (by visits): Within a week of T1, T2, and T3 (6-months post-baseline), two 24-
hour dietary recalls (to account for day-to-day variation) will be collected using NDS-R software by 
telephone five to 10 days apart. Intervention participants will also be contacted by the project manager 
with 48-hours of in-home study visits (1-4 above) to assess whether relevant intervention content was 
delivered.  
4.4 
Unscheduled visits: N/A 
4.5 
Concomitant Medication documentation: N/A 
4.6 
Rescue medication administration (if applicable): N/A 
4.7 
Subject Completion/ Withdrawal procedures: Subjects will complete the study at the completion of 
data collection associated with T3. At the end of the in-home data-collection visit at T3, all participants 
will be asked to provide feedback on their experiences with recruitment, interactions with study 
personnel, data collection, and anything else they would like to share about the study. If a participating 
dyad chooses to withdraw from the study or we are unable to reach them after three attempts for 
scheduling of visits or data collection, they will be withdrawn from the study, but their data will be kept 
for analysis. All subjects will be thanked for their interest and participation regardless of whether they 
complete all data collections.   
   
4.8 
Screen failure procedures: If the subject and/or child do not meet inclusion criteria, then inform them 
that they do not meet inclusion criteria for this particular study, ask if they would be interested in being 
contacted about future studies, and thank them for their time.  
 
5 
STUDY EVALUATIONS AND MEASUREMENTS  
Variables and Their 
Measurement 
Measure 
Data Source T1 T2 T3Alpha 
Aims 1: Feasibility & 
Acceptability 
Screening and Enrollment logs 
Project 
Manager 
X 
Field Notes 
RA’s 
X X X 
Exit Interview 
Mothers 
X 
Aims 2 & 3 
Dyadic Feeding Responsiveness 
Mutual Responsiveness 
during 
Responsiveness to Child Feeding Cues Scale 
(RCFCS) 56 
Infants & 
Mothers 
X X X 0.85-
0.94 

 
 
 
15 
 
5.1 
Efficacy Evaluation: N/A 
5.2 
Pharmacokinetic Evaluation (if applicable): N/A 
5.3 
Safety Evaluations: Study visit confirmation will occur prior to study visits and assessment of self-
reported health of parent and infant will be conducted prior to data collection. Study personnel will be 
on-site in subjects' homes for the duration of data collection and will monitor the response of subjects 
during data collection. Should any concerns arise during data collection, they will be addressed 
immediately by study personnel and the PI and Co-I will be notified as soon as possible if they are not 
on site. Though unlikely, should any concerns arise after data collection, subjects will be given the PI's 
contact information to share their concerns and the PI will address concerns directly or through 
appropriate referrals. Any concerns that arise over the course of the study will be recorded and 
aggregated as part of the feasibility data and shared with the research team and the IRB as necessary. 
 
6 
STATISTICAL CONSIDERATION    
6.1 
Primary Endpoint 
T3 (6-months post-baseline) will serve as the primary endpoint for the study.   
6.2 
Secondary Endpoint 
There are no plans for a secondary endpoint, though safety will be monitored as discussed above in 5.3.   
6.3 
Statistical Methods 
Descriptive statistics will be calculated for each measure (see Aims 2 & 3 in Table of Measures, Section 
5) at each time point by group. All analyses will be conducted using an intention-to-treat approach. 
Feeding 
Infant Eating Behavior 
 Dietary Intake 
Nutrition Data System for Research (NDS-
R) 
Mothers 
X X X 
 Eating Behavior 
Child Eating Behavior Questionnaire-
Toddler (CEBQ-T) 57  
Mothers 
X X X 0.65-
0.87 
Infant Anthropometry 
 Growth 
Weight-for-length% & Z score 
Infants 
X X X 
Maternal Feeding 
Behavior/Beliefs 
Infant Feeding Styles Questionnaire (IFSQ) 
58 
Mothers 
X X X 0.75-
0.94b 
Autonomic Regulation 
Respiratory Sinus Arrythmia (RSA) 
Infants & 
Mothers 
X X X 
Additional Characteristics 
Infant  
 Temperament 
Revised Infant Behavior Questionnaire 
(IBQR) 59 
Mothers 
X X X 0.91-
0.92 
 Sex, Birthweight, & 
Gestational Age 
Demographics 
Mothers 
X 
Maternal  
 Parental Self-Efficacy 
New Generalized Self-Efficacy Scale 
(NGSE) 60 
Mothers 
X X X 0.85-
0.88 
 Perception of Infant 
 Intentionality 
Infant Intentionality Questionnaire (IIQ) 61 
Mothers 
X X X 0.77-
0.87 
 Depression & Anxiety 
Patient Health Questionnaire-4 (PHQ-4) 62 
Mothers 
X X X 0.82 
 Demographic Characteristics Demographics & Pregnancy History 
Mothers 
X 

 
 
 
16 
Preliminary analyses will be conducted to determine whether, despite randomization, the intervention 
and control groups exhibit a random imbalance at baseline on any measured variable. If important 
imbalances are found, the corresponding variable will be considered as a covariate in subsequent models 
to statistically correct for the imbalance. To evaluate the initial impact of the intervention longitudinally 
for each maternal and infant outcome listed above as primary, secondary, and the first two tertiary 
outcomes (i.e., more optimal growth, indicators of enhanced self-regulation of energy intake [NDS-R 
data compared to age- and sex-specific estimated energy requirements63], reported infant feeding 
behavior and maternal feeding behaviors/beliefs , and observed dyadic feeding responsiveness), we will 
fit separate linear mixed-effects models. These could include a random coefficients model to examine 
the linear trajectories of the group-specific means across all available time points using the actually 
observed timing.  The initial impact of the intervention will be formally assessed through a statistical 
hypothesis test of model parameter representing the difference in these slopes. More specifically, these 
models will include terms for the intervention group (as an indicator variable), actual time of data 
collection (as continuous weeks from baseline), and their interaction.  An alternative modeling strategy 
would be to utilize mixed-effects model in a repeated measures context to examine the trajectories of the 
group-specific means across all available time points using the visit timepoint; these models will include 
terms for the intervention group (as an indicator variable), visit timepoint (as one or more indicators to 
reflect this categorical variable), and their interaction term(s).  In this scenario, the initial impact of the 
intervention will be formally assessed through a statistical hypothesis test of linear contrasts of model 
parameters representing the between-group difference at each timepoint. Covariates identified above to 
correct for imbalance will be considered for inclusion in these models, as well as the factors stratified in 
the randomization, and the models will account for the repeated measures correlation structure. 
Statistical contrasts will also be constructed to estimate and test the changes over time separately for 
each intervention group.  As useful information for planning subsequent studies, effect sizes for each 
measure will be calculated for each follow-up time point as the ratio of the mean difference between the 
intervention and the control groups to its standard deviation, as well as the producing the estimated 
correlation matrices across the repeated measures.  
  
6.4 
Sample Size and Power: Dyads will be randomized to either the intervention (n = 40) or the control (n = 
40) group. Conservatively, a 20% attrition rate will be assumed, though less attrition will result in 
greater statistical power. Hence, we assume two-group, longitudinal comparisons of complete data on 32 
dyads per group, as well as incomplete data (at some, but not all, time points), for analyses of each 
measure. Power calculations are performed with the POWERLIB20 SAS/IML module, which 
incorporates methods to calculate power for the general linear multivariate model, which is closely 
related to the general linear mixed model, assuming a first-order autoregressive correlation structure 
across the repeated measures with parameter p=0.9. We intend to estimate the power for the initial 
impact of the intervention through a test of mean linear change between the two groups across the three 
timepoints for each maternal and infant outcome in Aim 2 in separate multivariate models. The study 
will be well-powered to detect moderate changes in slope across the group trajectories over time. A 
linear difference of .4 SD by T3 with 32 dyads per group will provide statistical power exceeding .86 at 
the one-sided .05 significance level. 
 
6.5 
Interim Analysis: N/A 
 
7 
STUDY INTERVENTION  
 
Intervention families will receive approximately 4 hours of ASL and development specific content 
related to language and feeding during home visits and phone calls. The initial in-home session with 
families will focus on teaching ASL signs indicative of hunger, thirst, and satiety. A video and placemat 
of mealtime signs will be left with families at the completion of the first visit. The remaining sessions, in-

 
 
 
17 
home over the next 3 months and by phone monthly thereafter for 6 months total, will focus on 
reinforcing ASL signing in addition to focused education on particular aspects of language development 
(receptive language preceding expressive language and increasing intentional communication), feeding 
development (such as hunger and fullness cues, fear of new foods, the importance of repeated food 
exposures, variations in intake from meal-to-meal, and the propensity to reject bitter tastes [many 
vegetables]55], and appropriate portion sizes and variety for healthy growth.  
 
In person visit lesson schedule (monthly from baseline at 4-9 months of age): 
Visit 1 (baseline: T1): Signing with infants 
Visit 2: Infant communication and responsive feeding  
Visit 3: Nutrition, portion sizes, and neophobia 
Visit 4 (T2): Infant intentionality 
 
Intervention participants will be contacted by the project manager with 48-hours of in-home study visits 
(1-4 above) to assess and record whether relevant intervention content was delivered.  
 
8 
STUDY INTERVENTION ADMINISTRATION  
 
Randomization will be stratified by age group (for developmental differences; 4-5-months-old, 6-7-
months-old, and 8-9-months old).  Computerized randomization lists will be generated by study 
statistician and will be administered by the project manager. Study personnel who code videos of feeding 
interactions will be blind to group status. 
 
9 
SAFETY MANAGEMENT 
Study visit confirmation will occur prior to study visits and assessment of self-reported health of parent 
and infant will be conducted prior to data collection. Study personnel will be on-site in subjects' homes 
for the duration of data collection and will monitor the response of subjects during data collection. 
Should any concerns arise during data collection, they will be addressed immediately by study personnel 
and the PI and Co-I will be notified as soon as possible if they are not on site. Though unlikely, should 
any concerns arise after data collection, subjects will be given the PI's contact information to share their 
concerns and the PI will address concerns directly or through appropriate referrals. Any concerns that 
arise over the course of the study will be recorded and aggregated as part of the feasibility data and 
shared with the research team and the IRB as necessary. 
 
We do not anticipate that any questions, anthropometric measurements, observations, or collection of 
cardiac data will cause discomfort or embarrassment, but mothers may stop interviews at any time, tell us 
that they do not wish to answer a question, refuse to allow infant measurement, stop an observation, or 
refuse collection of cardiac data at any time. We will respect their wishes. We will also let 
parents/primary caregivers know the following: "In addition, there may be uncommon or previously 
unknown risks that might occur. You should report any problems to the researchers. We are mandated to 
report any instances of child abuse." 
 
Thus, individual subjects may electively withdraw from the study or the PI may withdraw an individual 
subject, or in this case mother-infant dyad, if they fail or are unable to comply with study procedures. 
 
10 
DATA COLLECTION AND MANAGMENT  
Home visits will be scheduled to start about 45 minutes before a normal feeding time. Mothers will 
provide all food and will be encouraged to feed their children a typical meal. Upon arrival, four tripod-
mounted digital video cameras will be set up; two in the typical place the baby is fed and two in the room 

 
 
 
18 
where the rest of data collection will take place to minimize participant reactivity. After ASL and 
knowledge content delivery by the parent educator (experimental group only), participants will then 
prepare for cardiac data monitoring and video-recording. The initial period of training by the parent 
educator should allow some time for mother and child to adjust to the presence of study staff in their 
home and recover from any physiological arousal or reactivity in response to them. Then, an ambulatory 
electrocardiogram (ECG) monitor will be placed on mother’s and infant’s chests in order to record RSA 
patterns throughout the observation. This single channel ECG waveform recorder (Actiwave Cardio; 
Camntech) will be connected to two disposable ECG electrodes (ConMed Neonatal/Pediatric Huggables) 
placed below the sternum and on the left side of the body (connected to each other by a short lead). The 
Actiwave Cardio monitors are flat, lightweight (<8 g), and comfortable with high levels of intra- and 
inter-instrument reliability as well as good validity of measures.64 Interbeat interval (IBI) data will be 
monitored and recorded for R-wave detection (providing an estimate of the degree of vagal influence on 
heart rate).  RA’s will instruct mothers on how to place 2 electrodes onto her chest and her infant’s chest. 
After a brief test of the signal strength, the infant’s length and weight (in clean dry diaper only) will be 
measured in triplicate, using a calibrated length board and digital scale. Given the much shorter duration 
of our proposed monitoring (~1 hour), we feel confident in our ability to capture RSA data in both 
mother and infant. Then, mothers and infants will be given a 5-minute break to relax in order to give 
them time for de-escalation after physical measurements. Next, infants will listen to soothing music while 
seated in a baby seat (or other arrangement recommended by mother; for example, if infant is more 
comfortable and less likely to become distressed on a blanket or in a crib, we will do this instead) and 
mothers will read a neutral magazine (gardening) for a 4-min baseline measurement. Monitors will be 
worn for the entirety of the visit and feeding events will be marked within the time-stamped data. Video-
recording will begin after intervention (or usual care) delivery, with mothers asked to wait at least 10 
minutes after the video-recording begins before feeding their child. They can then feed their child 
whenever they feel it is appropriate. One camera will focus on the mother’s facial expressions and 
movements and the second camera will focus on the infant’s facial expressions and movements. As long 
as the infant is stationary during feeding (in mother’s lap, a highchair, or booster seat), the infant’s 
videographer will focus the camera at the beginning of the recording and then step away from the camera 
to minimize intrusiveness. Both videographers will swivel the camera and use the digital zoom to follow 
mother or child throughout the observation. From this position, the videographers can use the digital 
viewfinder and be out of view from the feeding room if possible. Video-recording will last until 2 
minutes after the child’s last bite of food. We are currently testing and refining these data collection 
protocols. All other self-report data from questionnaires other than NDSR will be entered in the field 
using Research Electronic Data Capture (REDCap)65 through UNC-Chapel Hill CTSA. Within a week of 
T1, T2, and T3, two 24-hour recalls (to account for day-to-day variation) will be collected using NDS-R 
software by telephone five to 10 days apart. Twenty-four-hour recalls provide intake during a specified 
period, are open-ended, can accommodate various foods or food combinations, do not require literacy 
and have a relatively low respondent burden. 66 
 
In order to protect against breach of confidentiality, access to relevant data will be restricted to research 
team members for the proposed study. All data other than the videos will be accessible only through a 
password-protected database (REDCap). Video and cardiac data will be downloaded from their 
respective collection devices and transmitted via secure authentication through the UNC ITS Research 
Computing Secure FTP Server. Video and cardiac data will then be downloaded onto encrypted and 
password protected external hard drives that will be housed in one locked room within the Observational 
Suite of the Biobehavioral Laboratory in the UNC School of Nursing. Research assistants involved in 
data collection will notify the PI and Co-I when new data is available for review in the Biobehavioral 
Laboratory. Dr. Hodges will supervise access to the videos by the two research assistants involved in 
video coding. 

 
 
 
19 
 
  
11 
RECRUITMENT STRATEGY 
Families will be recruited from a community sample through a variety of means, including email 
listservs, in-person interactions with study personnel, social media posting to local parenting groups, 
publicly posted flyers, posting on Craigslist, and contact through local church leaders. Those wishing to 
learn more about the study will contact our project manager, who will conduct screening and initial 
enrollment for those wishing to participate in the study. In the case of social media (a local parenting 
group on Facebook in this case), our rationale is accessing a local community of parents as potential 
participants in the study. Dr. Hodges has permission from the moderator of this local parenting group to 
post information about the study to their group. The information would match what we have submitted to 
the IRB for consideration as the email to go out across the UNC listserv. We will designate that the 
posting is only to let families know about the study and that any questions should not be asked on the 
Facebook site, but instead directed to our project manager at her email or phone. No data will be 
collected through social media; it is purely informational to facilitate recruitment contact through email 
or phone directly to project manager. As Dr. Hodges will be the one posting the announcement about the 
study within the group, he can respond to anyone who does pose questions on Facebook and direct them 
to contact our project manager rather than use Facebook. If possible, Dr. Hodges will turn off the 
comment feature on the post to prevent disclosure of the identities of people interested in the study. 
In-person recruitment strategies include approaching caregivers with infants in waiting rooms of WIC 
clinics to ask if they are interested in learning about the study. Any conversation regarding the specifics 
of the study should be conducted in a private location. The onsite recruiter will notify subjects that their 
decision to participate in the study will not affect the care they receive at the clinic. To protect the privacy 
of potential subjects during recruitment, eligible and interested subjects will be screened in a private 
room. If a private room is unavailable, subjects will be screened and initially enrolled in the study via 
phone at a later date. Identification through local church leaders will be through church leaders' 
willingness to share information from our study flyer with their congregation. 
 
Those wishing to learn more about the study will contact our project manager, who will conduct 
screening and initial enrollment for those wishing to participate in the study. Screening and initial 
enrollment occurs by telephone. Any contact information for individuals who decline to participate or are 
not eligible is immediately deleted from the contact database. 
 
Potential subjects will be contacted through their preferred method, telephone or email. An initial email 
from the project manager, research assistant, or PI will include a question about whether our research 
team can leave a voicemail with a request for call back. If potential subjects choose to call rather than 
email and they are put through to voicemail, the voicemail will instruct them to answer the question 
about whether our research team can leave a voicemail with a request for call back. Contact information 
will be entered into a password protected contact database.  
 
 
12 
CONSENT PROCESS 
Subjects will be contacted by telephone prior to the home visit for data collection. During the telephone 
conversation, the study will be described and telephone consent to participate will be obtained. Once in 
the family home, the study will be described once more and written consent will be obtained. 
 
We have put together a combined Adult Consent and Parental Permission form. Parents will be given the 
form for review on-site and study staff will go through the permission form verbally with the parent(s) 

 
 
 
20 
and offer to answer any questions prior to parental signature. If mothers of infants are adolescents, we 
will obtain their permission for their infant to participate, their assent to participate, and their parent or 
legal guardian's permission for them (the adolescent parent) to participate. We will have Spanish 
language versions of the Combined Adult Consent and Parental Permission forms for review in Spanish-
speaking participants' homes. A bilingual research staff member on site will provide oral interpretation as 
needed. 
 
13 
PLANS FOR PUBLICATION 
We plan to disseminate findings from primary, secondary, and tertiary outcomes through top-tier 
pediatric and nutrition journals.  
 
14 
REFERENCES: See Bibliography below.   
 
 
Bibliography 
 
1.  
Baird J, Fisher D, Lucas P, Kleijnen J, Roberts H, Law C. Being big or growing fast: systematic review of 
size and growth in infancy and later obesity. BMJ. 2005;331(7522):929. 
doi:10.1136/bmj.38586.411273.E0 
2.  
Mei Z, Grummer-Strawn LM, Scanlon KS. Does overweight in infancy persist through the preschool 
years? An analysis of CDC Pediatric Nutrition Surveillance System data. Sozial-und 
Präventivmedizin/Social and Preventive Medicine. 2003;48(3):161-167. 
3.  
Birch LL, Parker L, Burns A, eds. Early Childhood Obesity Prevention Policies. Washington, D.C.: 
National Academies Press; 2011. doi:10.17226/13124 
4.  
Herman CP, Polivy J. The self-regulation of eating: Theoretical and practical problems. In: Vohs KD, F. 
BR, eds. 2nd ed. Handbook of self-regulation: Research, theory, and applications. New York: The 
Guilford Press; 2011:522-536. 
5.  
Calkins SD. Cardiac vagal tone indices of temperamental reactivity and behavioral regulation in young 
children. Developmental psychobiology. 1997;31(2):125-135. 
6.  
Propper CB, Holochwost SJ. The influence of proximal risk on the early development of the autonomic 
nervous system. Developmental Review. 2013;33(3):151-167. doi:10.1016/j.dr.2013.05.001 
7.  
Bruch H. Eating Disorders. Obesity, Anorexia Nervosa, and the Person Within. Routledge & Kegan Paul.; 
1974. 
8.  
Costanzo PR, Woody EZ. Domain-specific parenting styles and their impact on the child’s development 
of particular deviance: the example of obesity proneness. J Soc Clin Psychol. 1985;3(4):425-445. 
9.  
DiSantis KI, Hodges EA, Johnson SL, Fisher JO. The role of responsive feeding in overweight during 
infancy and toddlerhood: a systematic review. Int J Obes. 2011;35(4):480-492. doi:10.1038/ijo.2011.3 
10.  Ogden CCL. Prevalence of Obesity and Trends in Body Mass Index Among US Children and 
Adolescents, 1999-2010. JAMA : the journal of the American Medical Association. 2012;307(5):483. 
11.  Pulgarón ER. Childhood obesity: a review of increased risk for physical and psychological comorbidities. 
Clin Ther. 2013;35(1):A18-32. doi:10.1016/j.clinthera.2012.12.014 
12.  Reilly JJ, Kelly J. Long-term impact of overweight and obesity in childhood and adolescence on 
morbidity and premature mortality in adulthood: systematic review. Int J Obes. 2011;35(7):891-898. 
doi:10.1038/ijo.2010.222 
13.  Birch LL, Anzman-Frasca S, Paul IM. Starting Early: Obesity Prevention during Infancy. 2012. 
14.  Dattilo AM, Birch L, Krebs NF, Lake A, Taveras EM, Saavedra JM. Need for early interventions in the 
prevention of pediatric overweight: a review and upcoming directions. J Obes. 2012;2012:1-18. 
15.  Barlow J, Whitlock S, Hanson S, et al. Preventing obesity at weaning: parental views about the 

 
 
 
21 
EMPOWER programme. Child Care Health Dev. 2010;36(6):843-849. doi:10.1111/j.1365-
2214.2010.01107.x 
16.  Daniels LA, Mallan KM, Battistutta D, Nicholson JM, Parey R, Magarey A. Evaluation of an intervention 
to promote protective infant feeding practices to prevent childhood obesity: outcomes of the NOURISH 
RCT at 14 months of age and 6 months post the first of two intervention modules. International journal of 
obesity (2005). 2012;36(10):1292-1298. 
17.  Daniels LA, Mallan KM, Nicholson JM, Battistutta D, Magarey A. Outcomes of an early feeding 
practices intervention to prevent childhood obesity. Pediatrics. 2013;132(1):e109-18. 
doi:10.1542/peds.2012-2882 
18.  French GM, Nicholson L, Skybo T, et al. An evaluation of mother-centered anticipatory guidance to 
reduce obesogenic infant feeding behaviors. Pediatrics. 2012;130(3):e507-17. doi:10.1542/peds.2011-
3027 
19.  Paul IM, Savage JS, Anzman SL, et al. Preventing obesity during infancy: a pilot study. Obesity (Silver 
Spring). 2011;19(2):353-361. doi:10.1038/oby.2010.182 
20.  Taveras EM, Blackburn K, Gillman MW, et al. First steps for mommy and me: a pilot intervention to 
improve nutrition and physical activity behaviors of postpartum mothers and their infants. Matern Child 
Health J. 2011;15(8):1217-1227. doi:10.1007/s10995-010-0696-2 
21.  Wen LM, Baur LA, Simpson JM, Rissel C, Flood VM. Effectiveness of an early intervention on infant 
feeding practices and “tummy time”: a randomized controlled trial. Arch Pediatr Adolesc Med. 
2011;165(8):701-707. doi:10.1001/archpediatrics.2011.115 
22.  Wen LM, Baur LA, Simpson JM, Rissel C, Wardle K, Flood VM. Effectiveness of home based early 
intervention on children’s BMI at age 2: randomised controlled trial. BMJ: British Medical Journal. 
2012;344. 
23.  Campbell KJ, Lioret S, McNaughton SA, et al. A parent-focused intervention to reduce infant obesity risk 
behaviors: a randomized trial. Pediatrics. 2013;131(4):652-660. doi:10.1542/peds.2012-2576 
24.  Karanja N, Lutz T, Ritenbaugh C, et al. The TOTS community intervention to prevent overweight in 
American Indian toddlers beginning at birth: a feasibility and efficacy study. Journal of community health. 
2010;35(6):667-675. 
25.  Kavanagh KF, Cohen RJ, Heinig MJ, Dewey KG. Educational intervention to modify bottle-feeding 
behaviors among formula-feeding mothers in the WIC program: impact on infant formula intake and 
weight gain. J Nutr Educ Behav. 2008;40(4):244-250. doi:10.1016/j.jneb.2007.01.002 
26.  Pearcey SM, De Castro JM. Food intake and meal patterns of one year old infants. Appetite. 
1997;29(2):201-212. doi:10.1006/appe.1997.0099 
27.  Fomon SJ, Filmer IJ, Thomas LN, Anderson TA, Nelson SE. Influence of formula concentration on 
caloric intake and growth of normal infants. Acta Paediatr. 1975;64(2):172-181. doi:10.1111/j.1651-
2227.1975.tb03818.x 
28.  Cecil JE, Palmer CNA, Wrieden W, et al. Energy intakes of children after preloads: adjustment, not 
compensation. Am J Clin Nutr. 2005;82(2):302-308. doi:10.1093/ajcn.82.2.302 
29.  Fox MK, Devaney B, Reidy K, Razafindrakoto C, Ziegler P. Relationship between portion size and 
energy intake among infants and toddlers: evidence of self-regulation. J Am Diet Assoc. 2006;106(1 Suppl 
1):S77-83. doi:10.1016/j.jada.2005.09.039 
30.  Kral TVE, Stunkard AJ, Berkowitz RI, Stallings VA, Brown DD, Faith MS. Daily food intake in relation 
to dietary energy density in the free-living environment: a prospective analysis of children born at 
different risk of obesity. Am J Clin Nutr. 2007;86(1):41-47. doi:10.1093/ajcn/86.1.41 
31.  Johnson SL, Taylor-Holloway LA. Non-Hispanic white and Hispanic elementary school children’s self-
regulation of energy intake. Am J Clin Nutr. 2006;83(6):1276-1282. doi:10.1093/ajcn/83.6.1276 
32.  Birch LL, McPheee L, Shoba BC, Steinberg L, Krehbiel R. “Clean up your plate”: Effects of child feeding 
practices on the conditioning of meal size. Learn Motiv. 1987;18(3):301-317. doi:10.1016/0023-
9690(87)90017-8 

 
 
 
22 
33.  Faith MS, Scanlon KS, Birch LL, Francis LA, Sherry B. Parent-child feeding strategies and their 
relationships to child eating and weight status. Obes Res. 2004;12(11):1711-1722. 
doi:10.1038/oby.2004.212 
34.  Overton WF. Relationism and relational developmental systems: a paradigm for developmental science in 
the post-Cartesian era. Advances in Child Development and Behavior. 2012;44:21-64. 
35.  Porges S. Vagal tone: An autonomic mediator of affect. In: Garber J, Dodge KA, eds. The Development of 
Emotion Regulation and Dysregulation. Cambridge: Cambridge University Press; 1991:111-128. 
doi:10.1017/CBO9780511663963.007 
36.  Porges SW, Doussard-Roosevelt JA, Portales AL, Greenspan SI. Infant regulation of the vagal “brake” 
predicts child behavior problems: a psychobiological model of social behavior. Dev Psychobiol. 
1996;29(8):697-712. doi:10.1002/(SICI)1098-2302(199612)29:8&lt;697::AID-DEV5&gt;3.0.CO;2-O 
37.  Santucci AK, Silk JS, Shaw DS, Gentzler A, Fox NA, Kovacs M. Vagal tone and temperament as 
predictors of emotion regulation strategies in young children. Developmental psychobiology. 
2008;50(3):205-216. 
38.  Moore GA, Hill‐Soderlund AL, Propper CB, Calkins SD, Mills‐Koonce WR, Cox MJ. Mother–Infant 
Vagal Regulation in the Face‐To‐Face Still‐Face Paradigm Is Moderated by Maternal Sensitivity. Child 
development. 2009;80(1):209-223. 
39.  Faith MS, Hittner JB. Infant temperament and eating style predict change in standardized weight status 
and obesity risk at 6 years of age. Int J Obes. 2010;34(10):1515-1523. doi:10.1038/ijo.2010.156 
40.  Graziano PA, Calkins SD, Keane SP, O’Brien M. Cardiovascular regulation profile predicts 
developmental trajectory of BMI and pediatric obesity. Obesity (Silver Spring). 2011;19(9):1818-1825. 
doi:10.1038/oby.2011.98 
41.  Coles J, Vögele C, Hilbert A, Tuschen-Caffier B. Fasten und (Über)-essen. Zeitschrift für Klinische 
Psychologie und Psychotherapie. 2005;34(2):95-103. 
42.  Karason K, Mølgaard H, Wikstrand J, Sjöström L. Heart rate variability in obesity and the effect of 
weight loss. Am J Cardiol. 1999;83(8):1242-1247. doi:10.1016/s0002-9149(99)00066-1 
43.  Latchman PL, Mathur M, Bartels MN, Axtell RS, De Meersman RE. Impaired autonomic function in 
normotensive obese children. Clin Auton Res. 2011;21(5):319-323. doi:10.1007/s10286-011-0116-8 
44.  Friederich HC, Schild S, Schellberg D, et al. Cardiac parasympathetic regulation in obese women with 
binge eating disorder. Int J Obes. 2006;30(3):534-542. doi:10.1038/sj.ijo.0803181 
45.  Meule A, Lutz A, Vögele C, Kübler A. Food cravings discriminate differentially between successful and 
unsuccessful dieters and non-dieters. Validation of the Food Cravings Questionnaires in German. 
Appetite. 2012;58(1):88-97. doi:10.1016/j.appet.2011.09.010 
46.  Calkins SD. The emergence of self-regulation: Biological and behavioral control mechanisms supporting 
toddler competencies. 
47.  Skouteris H, McCabe M, Ricciardelli LA, et al. Parent-child interactions and obesity prevention: a 
systematic review of the literature. Early Child Dev Care. 2012;182(2):153-174. 
48.  Thompson RRH. Enhancing Early Communication through Infant Sign Training. J Appl Behav Anal. 
2007;40(1):15-23. 
49.  Vallotton CD. Infant signs as intervention? Promoting symbolic gestures for preverbal children in low-
income families supports responsive parent–child relationships. Early Child Res Q. 2012;27(3):401-415. 
doi:10.1016/j.ecresq.2012.01.003 
50.  Góngora X, Farkas C. Infant sign language program effects on synchronic mother-infant interactions. 
Infant Behav Dev. 2009;32(2):216-225. doi:10.1016/j.infbeh.2008.12.011 
51.  Kirk E, Howlett N, Pine KJ, Fletcher BC. To sign or not to sign? The impact of encouraging infants to 
gesture on infant language and maternal mind-mindedness. Child Dev. 2013;84(2):574-590. 
doi:10.1111/j.1467-8624.2012.01874.x 
52.  Kochanska G, Aksan N. Development of mutual responsiveness between parents and their young 
children. Child development. 2004;75(6):1657-1676. 

 
 
 
23 
53.  Murray L, Fiori‐Cowley A, Hooper R, Cooper P. {The impact of postnatal depression and associated 
adversity on early mother‐infant interactions and later infant outcome}. Child development. 
1996;67(5):2512-2526. 
54.  Skuban EM, Shaw DS, Gardner F, Supplee LH, Nichols SR. The correlates of dyadic synchrony in high-
risk, low-income toddler boys. Infant Behavior and Development. 2006;29(3):423-434. 
55.  Birch LL, Fisher JO. Development of eating behaviors among children and adolescents. Pediatrics. 
1998;101(3 Pt 2):539-549. 
56.  Hodges EA, Johnson SL, Hughes SO, Hopkinson JM, Butte NF, Fisher JO. Development of the 
responsiveness to child feeding cues scale. Appetite. 2013;65:210-219. doi:10.1016/j.appet.2013.02.010 
57.  van Jaarsveld CHM, Llewellyn CH, Johnson L, Wardle J. Prospective associations between appetitive 
traits and weight gain in infancy. Am J Clin Nutr. 2011;94(6):1562-1567. doi:10.3945/ajcn.111.015818 
58.  Thompson AL, Mendez MA, Borja JB, Adair LS, Zimmer CR, Bentley ME. Development and validation 
of the Infant Feeding Style Questionnaire. Appetite. 2009;53(2):210-221. doi:10.1016/j.appet.2009.06.010 
59.  Gartstein MA, Rothbart MK. Studying infant temperament via the Revised Infant Behavior Questionnaire. 
Infant Behavior and Development. 2003;26(1):64-86. doi:10.1016/S0163-6383(02)00169-8 
60.  Chen G, Gully SM, Eden D. Validation of a New General Self-Efficacy Scale. Organizational Research 
Methods. 2001;4(1):62-83. doi:10.1177/109442810141004 
61.  Reznick JS, Feldman R. {Infant Intentionality Questionnaire—Version 4.2. Psychology Department, 
University of North Carolina at Chapel Hill, CB{\#} 3270, Chapel Hill, NC 27599-3270}. 
62.  Löwe B, Wahl I, Rose M, et al. A 4-item measure of depression and anxiety: validation and 
standardization of the Patient Health Questionnaire-4 (PHQ-4) in the general population. J Affect Disord. 
2010;122(1-2):86-95. doi:10.1016/j.jad.2009.06.019 
63.  Butte NF. Energy requirements of infants. Public Health Nutr. 2005;8(7A):953-967. 
doi:10.1079/PHN2005790 
64.  Brage S, Brage N, Franks PW, Ekelund U, Wareham NJ. Reliability and validity of the combined heart 
rate and movement sensor Actiheart. European journal of clinical nutrition. 2005;59(4):561-570. 
65.  Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture 
(REDCap)--a metadata-driven methodology and workflow process for providing translational research 
informatics support. J Biomed Inform. 2009;42(2):377-381. doi:10.1016/j.jbi.2008.08.010 
66.  Willett W. Nutritional Epidemiology. 2nd ed. New York: Oxford University Press; 1998.