Califormula Study: Calibrated Formula Feeding to Optimize Infant Growth
Phase: NA
Conditions: Overweight and Obesity
Sponsor: Milton S. Hershey Medical Center

Page 1 of 32 (IRB USE ONLY: V. 03/01/2021)  
                                                                                        
 
HRP-591 - Protocol for  
Human Subject Research 
 
Protocol Title: 
Provide the full title of the study as listed in item 1 on the “Basic Information” page in CATS IRB (http://irb.psu.edu).  
Califormula Study: Calibrated Formula Feeding to Optimize Infant Growth 
 
Principal Investigator: 
Name: Ian M. Paul, MD, MSc 
Department: Pediatrics 
Telephone: (717) 531-8006 
E-mail Address: ipaul@psu.edu 
 
Version Date: 
Provide a version date for this document. This date must be updated each time this document is submitted to the IRB 
office with revisions.  DO NOT revise the version date in the footer of this document.  
September 29, 2021 
 
Clinicaltrials.gov Registration #: 
Provide the registration number for this study, if applicable. See “HRP-103- Investigator Manual”, under 
“ClinicalTrials.gov” for more information.  
NCT05104073 
 
Important Instructions for Using This Protocol Template: 
This template is provided to help investigators prepare a protocol that includes the necessary information needed by the 
IRB to determine whether a study meets all applicable criteria for approval. 
 
1. 
GENERAL INSTRUCTIONS:   
• 
Prior to completing this protocol, ensure that you are using the most recent version by verifying the protocol 
template version date in the footer of this document with the current version provided in the CATS IRB 
Library. 
• 
Do not change the protocol template version date located in the footer of this document. 
• 
Some of the items may not be applicable to all types of research.  If an item is not applicable, please indicate 
as such or skip question(s) if indicated in any of the instructional text.  
• 
GRAY INSTRUCTIONAL BOXES: Type your protocol responses below the gray instructional boxes of guidance 
language.  If the section or item is not applicable, indicate not applicable. 
o Do NOT delete the instructional boxes from the final version of the protocol. 
• 
Add the completed protocol template to your study in CATS IRB (http://irb.psu.edu) on the “Basic 
Information” page.   
 
2. 
CATS IRB LIBRARY:  
• 
Documents referenced in this protocol template (e.g. SOP’s, Worksheets, Checklists, and Templates) can be 
accessed by clicking the Library link in CATS IRB (http://irb.psu.edu). 
 
3. 
PROTOCOL REVISIONS:  
• 
When making revisions to this protocol as requested by the IRB, please follow the instructions outlined in 
the guides available in the Help Center in CATS IRB (http://irb.psu.edu) for using track changes.  

Page 2 of 32 (IRB USE ONLY: V. 03/01/2021)  
• 
Update the Version Date on page 1 each time this document is submitted to the IRB office with revisions. 
 
If you need help… 
 
All locations:  
Human Research Protection Program 
Office for Research Protections 
The 330 Building, Suite 205 
University Park, PA 16802-7014 
Phone: 814-865-1775 
Fax: 814-863-8699 
Email: irb-orp@psu.edu 
https://www.research.psu.edu/irb 
 
 

Page 3 of 32 (IRB USE ONLY: V. 03/01/2021)  
Table of Contents 
1.0 
Objectives 
2.0 
Background 
3.0 
Inclusion and Exclusion Criteria 
4.0 
Recruitment Methods 
5.0 
Consent Process and Documentation 
6.0 
HIPAA Research Authorization and/or Waiver or Alteration of Authorization 
7.0 
Study Design and Procedures 
8.0 
Number of Subjects and Statistical Plan 
9.0 
Data and Safety Monitoring Plan 
10.0 
Risks 
11.0 
Potential Benefits to Subjects and Others 
12.0 
Sharing Results with Subjects 
13.0 
Subject Payment and/or Travel Reimbursements 
14.0 
Economic Burden to Subjects 
15.0 
Resources Available 
16.0 
Other Approvals 
17.0 
Multi-Site Study 
18.0 
Adverse Event Reporting 
19.0 
Study Monitoring, Auditing and Inspecting 
20.0 
Future Undetermined Research: Data and Specimen Banking 
21.0 
References 
22.0 
Confidentiality, Privacy and Data Management 
 
 
 

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1.0 
Objectives 
 
1.1 
Study Objectives 
Describe the purpose, specific aims or objectives.  State the hypotheses to be tested. 
 
This pilot study seeks to determine if formula feeding recommendations that are calibrated using age 
and weight specific caloric intake recommendations can prevent excessive infant weight gain and reduce 
overweight in the first 6 months after birth among infants born to mothers with overweight prior to 
pregnancy electing to exclusively formula feed their infants. Calibrated formula feeding refers to 
adjusting the recommended daily caloric formula intake to account for weight status. A cohort of 60 
infants will be recruited and randomized 2-3 weeks after birth to an intervention arm characterized by 
calibrated formula feeding recommendations or a control group with ad lib feeds as per usual care. 
Intervention group parents will also be given written instructions on infant hunger and satiety cues as 
well as copies of videos with guidance on bottle feeding and how to soothe fussy infants without 
feeding. We hypothesize that the calibrated formula intake intervention will reduce rapid infant gain 
and overweight during infancy resulting in lower weight-for-length at age 6 months.  
 
1.2 
Primary Study Endpoints 
State the primary endpoints to be measured in the study.   
 
Clinical trials typically have a primary objective or endpoint. Additional objectives and endpoints are 
secondary.  The endpoints (or outcomes), determined for each study subject, are the quantitative 
measurements required by the objectives.  Measuring the selected endpoints is the goal of a trial 
(examples: response rate and survival). 
 
- 
Conditional Weight Gain between Birth and Age 6 months 
 
1.3 
Secondary Study Endpoints 
State the secondary endpoints to be measured in the study. 
 
- 
Conditional Weight Gain during the intervention period spanning Ages 1-6 Months 
- 
Mean Weight-for-Length Z-score (WLZ) at Age 6 Months 
- 
Growth Trajectory during the intervention period spanning Ages 1-6 Months (repeated measures of 
weight-for-length) 
- 
Proportion of Infants with Overweight (Weight-for-Length ≥95th Percentile on WHO Growth Charts) 
at Age 6 months 
- 
Feasibility: a) recruitment, b) ability to give tailored formula volume recommendations, c) visit 
completion, d) retention through 6 months 
- 
Acceptability: parent adherence to formula volume recommendations as measured by 3 day feeding 
diaries at 2, 3, 4, 5, and 6 months for the intervention group 
2.0 
Background  
 
2.1 
Scientific Background and Gaps 
Describe the scientific background and gaps in current knowledge.  
 
For clinical research studies being conducted at Penn State Health/Penn State College of Medicine, and 
for other non-PSH locations as applicable, describe the treatment/procedure that is considered standard 
of care (i.e., indicate how patients would be treated in non-investigational setting); and if applicable, 
indicate if the study procedure is available to patient without taking part in the study. 

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Infant obesity predicts childhood and adult obesity,1-6 as the highest quintile of weight gain between 
birth and 5 months of age doubles the odds of overweight at 4.5 years.1 Although familial lifestyle and 
environmental factors may contribute to the epidemic,7-9 we propose that developmental programming 
effects of the maternal environment during in utero and newborn periods result in early onset and 
persistent overweight/obesity (OW/OB). 
 
What are the mechanisms that account for this generational cycle of OB and critical fetal/newborn 
periods? Increased energy intake, not reduced energy expenditure, largely explains population weight 
gain in children and adults.10-13 Even a small mismatch (<0.5%) in intake/expenditure will lead to weight 
gain over time.14  Thus, the combination of appetite/satiety and the energy content of foods represent a 
critical regulator of energy intake and OB in both adults and infants. As described below, we propose 
that programmed offspring hyperphagia combined with feeding of high caloric value breast milk or 
infant formula potentiates early life accelerated weight gain and the cycle of OW/OB.  
 
Programmed Offspring Hyperphagia: During pregnancy maternal OW/OB impacts fetal brain 
development leading to a diversity of offspring neurodevelopmental disorders (e.g., cognitive, 
neurodegenerative)15-17 among which hyperphagia-induced OB may be the most recognizable. Maternal 
body mass index (BMI) is correlated with fetal and infant weight gain. Mothers with OW/OB have an 
increased risk of large for gestational age (LGA) newborns,18 which have a >2-fold risk of preschool OB19 
and adult metabolic syndrome.20-28 The importance of the pregnancy environment is evidenced by the 
finding that children of mothers with OB who have undergone bariatric surgery are three-times less 
likely to be severely obese when compared to siblings born prior to surgery.29 Furthermore, the critical 
role of maternal OW/OB is evidenced by the finding that paternal OB is associated with a four-fold 
increased risk of OB in daughters at age 18 years, while maternal OB results in an eight-fold increased 
risk.9  
 
Animal studies have replicated evidence of human programmed obesity. In mice, offspring of OB, 
high fat diet rodents are predisposed to newborn OW and adult OB,30,31 and a spectrum of neurologic 
disorders.32-35 Within the hypothalamus, the maternal OW/OB nutritional environment alters neural 
cellular and epigenetic signaling that result in increased appetite and reduced satiety gene expression 
and neurons. Laboratory studies have demonstrated that maternal OB (and high fat diet) increases 
offspring hypothalamic neuronal peptides and orexigenic neurons,36-39 and programs offspring 
hyperphagia.30,36,40-43 Maternal OB reduces offspring pro-opiomelanocortin (POMC) expression with an 
increase in arcuate neuropeptide Y (NPY) signaling,44 while offspring born to dams fed a high-
carbohydrate diet demonstrate increased NPY release.45 In rodents, offspring of obese dams exhibit 
decreased hypothalamic tissue expression of select neurogenic signal factors (Ngn3 and Mash1) which 
regulate neural progenitor cell differentiation to appetite vs satiety neurons, consistent with increased 
arcuate agouti-related peptide (AgRP) and reduced POMC expression.36,46  Maternal OB reduces 
offspring Mash1 mRNA expression and increases NPY neurons.38 With evidence of programmed 
neurogenesis and hyperphagia, OW/OB LGA human and mouse offspring gain weight more rapidly than 
appropriate for gestational age (AGA) offspring. 
 
What can be done: Despite these findings, effective interventions short of bariatric surgery to break the 
generational cycle of OB are limited to those promoting responsive parenting behavioral 
interventions.47,48 Although maternal lifestyle interventions and exclusive breastfeeding are optimal for 
many reasons, reports suggest limited efficacy at preventing obesity among offspring. Randomized 
studies have attempted pre-pregnancy weight loss or controlled gestational weight gain, also with 
limited effects on neonatal body composition.49-52 Although neonatal care has incorporated nutrient 
fortification to preterm, low birth weight newborns to augment weight gain,53 there have been no 
studies calibrating intake to prevent excess weight gain among term newborns at risk of OW/OB. 
 
We propose several discrete benefits of calibrated formula feeding recommendations that are age 
and weight-status specific to promote healthy newborn growth. The prevention of OW infants at 6 
months of age would be predicted to reduce the rate of childhood and even adult OB. This may occur, in 
part, by preventing OB-associated leptin resistance. Thus, preventing the onset of infant OB, 

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hyperleptinemia and leptin resistance54-57 may normalize appetite throughout childhood. Further, 
consistent with evidence in animal models, calibrated intake and newborn growth may potentially 
reprogram the newborn hypothalamic arcuate nucleus, correcting the appetite/satiety neuronal ratio.58-
61 In this project, we will examine the potential efficacy of a novel preventive strategy to normalize 
infant weight gain to prevent the development of infant OW and interrupt the cycle of OB.  
 
2.2 
Previous Data 
Describe any relevant preliminary data. 
 
N/A 
 
2.3 
Study Rationale 
Provide the scientific rationale for the research. 
 
 
Infancy is a critical period of developmental plasticity with lasting metabolic and behavioral 
consequences.62 Obesity is an outcome that is affected by this plasticity during infancy. The obesity 
epidemic is a public health crisis that will severely impact US children across their lifecourse and place a 
substantial burden on our healthcare system. Nearly 1 in 5 US children aged 2-19 are obese, and ~1 in 3 
are overweight (BMIs ≥95th and 85th percentiles, respectively).63,64 For many children, this problem 
begins early as 23% of 2-5 years olds are already overweight64 and 9-14% are already obese.63,65 Primary 
prevention is likely the best solution, as recent simulation data in the New England Journal of Medicine 
suggest that “a 2 year old who is obese is more likely to be obese at 35 years of age than an overweight 
19 year old.”66  
 
Though somewhat controversial, there is evidence that formula feeding is associated with a 
modestly increased risk obesity67-71 and rapid infant weight gain,72 with further evidence that the volume 
of formula consumed, overfeeding, an important contributor to excess weight gain73,74 as might be 
expected. Similar findings have been reported for bottle feeding.75 Adjusting or calibrating the 
recommended amount of formula across the first 6 months after birth shows promise as a strategy to 
reduce rapid infant weight gain and early life overweight.74 
3.0 
Inclusion and Exclusion Criteria 
Create a numbered list below in sections 3.1 and 3.2 of criteria subjects must meet to be eligible for study 
enrollment (e.g., age, gender, diagnosis, etc.).  
 
Vulnerable Populations: 
 
Indicate specifically whether you will include any of the following vulnerable populations in this research. You 
MAY NOT include members of these populations as subjects in your research unless you indicate this in your 
inclusion criteria because specific regulations apply to studies that involve vulnerable populations.   
 
The checklists referenced below outline the determinations to be made by the IRB when reviewing research 
involving these populations. Review the checklists as these will help to inform your responses throughout the 
remainder of the protocol. 
 
• 
Children –Review “HRP-416- Checklist - Children” 
• 
Pregnant Women – Review “HRP-412- Checklist - Pregnant Women” 
• 
Cognitively Impaired Adults- Review “HRP-417- Checklist - Cognitively Impaired Adults”  
• 
Prisoners- Review “HRP-415- Checklist - Prisoners” 
• 
Neonates of uncertain viability or non-viable neonates- Review “HRP-413- Checklist - Non-Viable 
Neonates” or “HRP-414- Checklist - Neonates of Uncertain Viability” 
[Do not type here] 

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3.1 
Inclusion Criteria 
Create a numbered list of the inclusion criteria that define who will be included in your final study 
sample (e.g., age, gender, condition, etc.)  
 
1. Term or Early Term (≥37 weeks), singleton infants 
2. Infant birthweight ≥50th percentile based on the 2013 Fenton Growth Charts (which account for sex 
of child and gestational age at birth) 
3. Infant without substantial neonatal morbidity that would affect feeding or weight gain (e.g. known 
chromosomal abnormality, metabolic disorder, cleft lip/palate, etc.) 
4. Infant age ≤1 month 
5. Mothers with pre-pregnancy body mass index ≥25 kg/m2 
6. Mothers ≥18 years old 
7. Parental plan to exclusively feed infant 19-20 kcal/ounce formula upon delivery or by the start of the 
intervention period ~1 month after delivery 
8. Parental intention to have infant well child visits through age 6 months at a Division of Academic 
General Pediatrics practice site (Hope Drive, Elizabethtown, Nyes Road) 
9. English speaking parent 
3.2 
Exclusion Criteria 
Create a numbered list of the exclusion criteria that define who will be excluded in your study. 
 
1. Infants who weigh less than their birthweight 21 days after delivery 
3.3 
Early Withdrawal of Subjects 
3.3.1 
Criteria for removal from study 
Insert subject withdrawal criteria (e.g., safety reasons, failure of subject to adhere to protocol 
requirements, subject consent withdrawal, disease progression, etc.). 
 
1. Infants exhibiting failure-to-thrive defined as: 
a. Weight-for-length <5th percentile for sex and age on the WHO growth chart 
b. Downward crossing of >2 major centile lines on the WHO growth chart (relevant 
major lines include 95th, 90th, 75th, 50th, 25th, 10th, 5th) after enrollment 
2. Non-adherence to the study visit schedule characterized by failing to complete two 
scheduled study intervention visits within 2 weeks of turning 1, 2, 3, 4, and 5 months old 
(does not include enrollment and final visit) 
3.3.2 
Follow-up for withdrawn subjects 
Describe when and how to withdraw subjects from the study; the type and timing of the data to 
be collected for withdrawal of subjects; whether and how subjects are to be replaced; the 
follow-up for subjects withdrawn from investigational treatment. 
 
 
Study personnel will contact consenting parents by phone notifying them of their removal 
from the study and the reason for withdrawal. If the reason is due to failure-to-thrive, the 
infant’s pediatrician will also be notified. If study personnel are unable to reach the consenting 
parent, a letter will be sent via US mail. 
 
No further data will be collected on participants that are withdrawn, and these participants 
will not be replaced. 

Page 8 of 32 (IRB USE ONLY: V. 03/01/2021)  
4.0 
Recruitment Methods 
 Upload recruitment materials for your study in CATS IRB (http://irb.psu.edu).  DO NOT include the actual 
recruitment wording in this protocol.   
 StudyFinder:  If StudyFinder (http://studyfinder.psu.edu) is to be used for recruitment purposes, separate 
recruitment documents do not need to be uploaded in CATS IRB. The necessary information will be captured 
from the StudyFinder page in your CATS IRB study.   
 Any eligibility screening questions (verbal/phone scripts, email, etc.) used when contacting potential 
participants must be uploaded to your study in CATS IRB (http://irb.psu.edu). 
[Do not type here] 
 
4.1 
Identification of subjects 
Describe the source of subjects and the methods that will be used to identify potential subjects (e.g., 
organizational listservs, established recruitment databases, subject pools, medical or school records, 
interactions during a clinic visit, etc.).   If not recruiting subjects directly (e.g., database query for eligible 
records or samples) state what will be queried, how and by whom. 
 
StudyFinder:   
o If you intend to use StudyFinder (http://studyfinder.psu.edu) for recruitment purposes, include this 
method in this section.  
o Information provided in this protocol needs to be consistent with information provided on the 
StudyFinder page in your CATS IRB study. 
 
For Penn State Health submissions using Enterprise Information Management (EIM) for recruitment, and 
for non-Hershey locations as applicable, attach your EIM Design Specification form on in CATS IRB 
(http://irb.psu.edu). See “HRP-103- Investigator Manual, What is appropriate for study recruitment?” 
for additional information. DO NOT include the actual recruitment material or wording in this protocol. 
 
 
Participants will be identified during the birth hospitalization at Penn State Hershey Children’s 
Hospital and through newborn visits at a practice site within the Division of Academic General Pediatrics 
(offices at Hope Drive, Elizabethtown, Nyes Road) via review of birth hospitalization and neonatal 
electronic medical records. 
 
4.2 
Recruitment process 
Describe how potential subjects first learn about this research opportunity or indicate as not applicable 
if subjects will not be prospectively recruited to participant in the research.  Subject recruitment can 
involve various methods (e.g., approaching potential subjects in person, contacting potential subjects via 
email, letters, telephone, ResearchMatch, or advertising to a general public via flyers, websites, 
StudyFinder, newspaper, television, and radio etc.). DO NOT include the actual recruitment material or 
wording in this protocol. 
[Do not type here] 
4.2.1 
How potential subjects will be recruited. 
 
Parents of eligible neonates will be given information regarding the opportunity to participate by 
research staff during the birth hospitalization or at a pediatric clinic during the first weeks after birth. 
4.2.2 
Where potential subjects will be recruited. 
1. Penn State Hershey Children’s Hospital 
2. Penn State Hershey Division of Academic General Pediatrics practice sites (Hope Drive, 
Elizabethtown, Nyes Road) 

Page 9 of 32 (IRB USE ONLY: V. 03/01/2021)  
4.2.3 
When potential subjects will be recruited. 
 
Participants will be recruited and consented during the birth hospitalization or during routine 
outpatient visits within the first month after birth 
 
4.2.4 
Describe the eligibility screening process and indicate whether the screening process will 
occur before or after obtaining informed consent. Screening begins when the investigator 
obtains information about or from a prospective participant in order to determine their 
eligibility.  In some studies, these procedures may not take place unless HIPAA Authorization 
is obtained OR a waiver of HIPAA Authorization when applicable for the screening procedures 
is approved by the IRB.  [For FDA regulated studies, consent for any screening activities would 
need to be obtained prior to screening unless specifically waived by the IRB.] 
 
 
Participants will first be screened through review of their electronic medical record to 
determine potential eligibility. 
5.0 
Consent Process and Documentation  
Refer to the following materials: 
• 
The “HRP-090- SOP - Informed Consent Process for Research” outlines the process for obtaining informed 
consent.   
• 
The “HRP-091– SOP - Written Documentation of Consent” describes how the consent process will be 
documented. 
• 
The “HRP-314- Worksheet - Criteria for Approval” section 7 lists the required elements of consent. 
• 
The “HRP-312- Worksheet - Exemption Determination” includes information on requirements for the 
consent process for exempt research.  In addition, the CATS IRB Library contains consent guidance and 
templates for exempt research. 
• 
The CATS IRB library contains various consent templates for expedited or full review research that are 
designed to include the required information. 
• 
Add the consent document(s) to your study in CATS IRB (http://irb.psu.edu). Links to Penn State’s consent 
templates are available in the same location where they are uploaded. DO NOT include the actual consent 
wording in this protocol. 
[Do not type here] 
 
5.1 
Consent Process: 
Check all applicable boxes below: 
 
 Informed consent will be sought and documented with a written consent form [Complete Sections 
5.2 and 5.6]  
 
 Implied or verbal consent will be obtained – subjects will not sign a consent form (waiver of 
written documentation of consent) [Complete Sections 5.2, 5.3 and 5.6]  
 
  Informed consent will be sought but some of the elements of informed consent will be omitted or 
altered (e.g., deception). [Complete section 5.2, 5.4 and 5.6]  
 
 Informed consent will not be obtained – request to completely waive the informed consent 
requirement. [Complete Section 5.5] 
 
 
The following checkbox is for all locations EXCEPT Penn State Health and College of Medicine:  
 

Page 10 of 32 (IRB USE ONLY: V. 03/01/2021)  
 
 Exempt Research at all Locations Except Penn State Health and the College of Medicine: If you 
believe that the research activities outlined meet one or more of the criteria outlined in “HRP-312- 
Worksheet- Exemption Determination.” Please verify by checking this box that if conducting an 
exempt research study, the consent process will disclose the following (all of which are included in 
“HRP-590- Consent Guidance for Exempt Research”): 
 
Penn State affiliation; name and contact information for the researcher and advisor (if the 
researcher is a student); the activities involve research; the procedures to be performed; 
participation is voluntary; that there are adequate provisions to maintain the privacy interests of 
subjects and the confidentiality of the data; and subjects may choose not to answer specific 
questions.   
 
 
If the research includes the use of student educational records include the following language in 
this section (otherwise delete): The parent or eligible student will provide a signed and dated 
written consent that discloses: the records that may be disclosed; the purpose of the disclosure; the 
party or class of parties to whom the disclosure may be made; if a parent or adult student requests, 
the school will provide him or her with a copy of the records disclosed; if the parent of a student 
who is not an adult so requests, the school will provide the student with a copy of the records 
disclosed. 
 
 
Note: If this box has been checked, skip the remainder of section 5 and proceed to section 6 of this 
protocol. If the investigator’s assessment is inaccurate, an IRB Analyst will request revision to the 
protocol and that an informed consent form be submitted for review and approval. Except for 
exemptions where Limited IRB Review (see “HRP-312- Worksheet- Exemption Determination”) is 
required or where otherwise requested by the IRB, informed consent forms for research activities 
determined to be exempt without Limited IRB Review are generally not required to be submitted 
for review and approval by the University Park IRB.  
 
 
5.2 
Obtaining Informed Consent  
5.2.1 
Timing and Location of Consent  
Describe where and when the consent process will take place. 
 
Consent will be obtained from eligible parents within the first month of childbirth. It can occur 
on the maternity floors of Penn State Health Children’s Hospital or at outpatient clinics where 
Division members from Academic General Pediatrics practice (Hope Drive, Elizabethtown, Nyes 
Road). 
5.2.2 
Coercion or Undue Influence during Consent  
Describe the steps that will be taken to minimize the possibility of coercion or undue influence 
in the consent process. 
 
Parents will be reassured that participation in the study is completely optional and will not 
affect the care that their child receives regardless of the decision to participate or not. 
 
5.3 
Waiver of Written Documentation of Consent  
Review “HRP – 411 – Checklist – Waiver of Written Documentation of Consent.”  
5.3.1 
Indicate which of the following conditions applies to this research: 
  The research presents no more that minimal risk of harm to subjects and involves no 
procedures for which written consent is normally required outside of the research context. 
OR 

Page 11 of 32 (IRB USE ONLY: V. 03/01/2021)  
  The only record linking the subject and the research would be the consent document and the 
principal risk would be potential harm resulting from a breach of confidentiality. Each subject 
will be asked whether the subject wants documentation linking the subject with the research, 
and the subject’s wishes will govern. (Note: This condition is not applicable for FDA-regulated 
research. If this category is chosen, include copies of a consent form and /or parental 
permission form for participants who want written documentation linking them to the 
research.) 
OR 
  If the subjects or legally authorized representatives are members of a distinct cultural group 
or community in which signing forms is not the norm, that the research presents no more 
than minimal risk of harm to subjects and provided there is an appropriate alternative 
mechanism for documenting that informed consent was obtained.  (Note: This condition is not 
applicable for FDA-regulated research.)  
 
Describe the alternative mechanism for documenting that informed consent was obtained: 
 
N/A 
5.3.2 
Indicate what materials, if any, will be used to inform potential subjects about the research 
(e.g., a letter accompanying a questionnaire, verbal script, implied consent form, or summary 
explanation of the research) 
 
 N/A 
5.4 
Informed consent will be sought but some of the elements of informed consent will be omitted or altered 
(e.g., deception). 
Review “HRP-410-Checklist -Waiver or Alteration of Consent Process” to ensure that you have provided 
sufficient information.   
5.4.1 
Indicate the elements of informed consent to be omitted or altered 
 
N/A 
5.4.2 
Indicate why the research could not practicably be carried out without the omission or 
alteration of consent elements 
 
N/A 
5.4.3 
Describe why the research involves no more than minimal risk to subjects. 
 
N/A 
5.4.4 
Describe why the alteration/omission will not adversely affect the rights and welfare of 
subjects. 
 
N/A 
5.4.5 
If the research involves using identifiable private information or identifiable biospecimens, 
describe why the research could not be practicably be carried out without using such 
information or biospecimens in an identifiable format. 
 

Page 12 of 32 (IRB USE ONLY: V. 03/01/2021)  
N/A 
5.4.6 
Debriefing  
Explain whether and how subjects will be debriefed after participation in the study. If subjects 
will not be debriefed, provide a justification for not doing so.  Add any debriefing materials to 
the study in CATS IRB. 
 
Participants will not be debriefed at the end of the study as parents will already receive 
information on their child’s growth from the infant’s pediatrician. 
5.5 
Informed consent will not be obtained – request to completely waive the informed consent requirement 
Review “HRP-410-Checklist -Waiver or Alteration of Consent Process” to ensure that you have provided 
sufficient information. 
5.5.1 
Indicate why the research could not practicably be carried out without the waiver of consent 
 
N/A 
5.5.2 
Describe why the research involves no more than minimal risk to subjects. 
 
N/A 
5.5.3 
Describe why the alteration/omission will not adversely affect the rights and welfare of 
subjects. 
 
N/A 
5.5.4 
If the research involves using identifiable private information or identifiable biospecimens, 
describe why the research could not be practicably be carried out without using such 
information or biospecimens in an identifiable format. 
 
N/A 
5.5.5 
Additional pertinent information after participation 
Explain if subjects will be provided with additional pertinent information after participation. If 
not applicable, indicate “not applicable.”    
 
N/A 
 
5.6 
Consent – Other Considerations  
 
5.6.1 
Non-English-Speaking Subjects 
Indicate what language(s) other than English are understood by prospective subjects or 
representatives. 
 
If subjects who do not speak English will be enrolled, describe the process to ensure that the 
oral and written information provided to those subjects will be in that language. Indicate the 
language that will be used by those obtaining consent. 
 
Indicate whether the consent process will be documented in writing with the long form of the 
consent documentation or with the short form of the consent documentation.  Review “HRP-

Page 13 of 32 (IRB USE ONLY: V. 03/01/2021)  
091 –SOP- Written Documentation of Consent” and “HRP-103 -Investigator Manual” to ensure 
that you have provided sufficient information.  
 
N/A 
 
5.6.2 
Cognitively Impaired Adults 
Refer “HRP-417 -CHECKLIST- Cognitively Impaired Adults” for information about research 
involving cognitively impaired adults as subjects.  
 
5.6.2.1 Capability of Providing Consent 
Describe the process to determine whether an individual is capable of consent. 
 
N/A 
 
5.6.2.2 Adults Unable to Consent 
Describe whether and how informed consent will be obtained from the legally 
authorized representative.  Describe who will be allowed to provide informed 
consent. Describe the process used to determine these individual’s authority to 
consent to research. 
 
For research conducted in the state of Pennsylvania, review “HRP-013 -SOP- Legally 
Authorized Representatives, Children and Guardians” to be aware of which 
individuals in the state of Pennsylvania meet the definition of “legally authorized 
representative.” 
 
For research conducted outside of the state of Pennsylvania, provide information 
that describes which individuals are authorized under applicable law to consent on 
behalf of a prospective subject to their participation in the procedure(s) involved in 
this research.  One method of obtaining this information is to have a legal counsel or 
authority review your protocol along with the definition of “children” in “HRP-013 -
SOP- Legally Authorized Representatives, Children, and Guardians.” 
 
N/A 
 
5.6.2.3 Assent of Adults Unable to Consent 
Describe the process for assent of the subjects.  Indicate whether assent will be 
required of all, some or none of the subjects.  If some, indicate which subjects will 
be required to assent and which will not.  
 
If assent will not be obtained from some or all subjects, provide an explanation of 
why not. 
 
Describe whether assent of the subjects will be documented and the process to 
document assent.  The IRB allows the person obtaining assent to document assent 
on the consent document and does not routinely require assent documents and 
does not routinely require subjects to sign assent documents. 
 
N/A 

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5.6.3 
Subjects who are not yet adults (infants, children, teenagers)  
 
5.6.3.1 Parental Permission 
Describe whether and how parental permission will be obtained. If permission will 
be obtained from individuals other than parents, describe who will be allowed to 
provide permission.  Describe the process used to determine these individual’s 
authority to consent to each child’s general medical care. 
 
For research conducted in the state of Pennsylvania, review “HRP-013-SOP- Legally 
Authorized Representatives, Children and Guardians” to be aware of which 
individuals in the state of Pennsylvania meet the definition of “children.”  
 
For research conducted outside of the state of Pennsylvania, provide information 
that describes which persons have not attained the legal age for consent to 
treatments or procedures involved in the research, under the applicable law of the 
jurisdiction in which research will be conducted.  One method of obtaining this 
information is to have a legal counsel or authority review your protocol along with 
the definition of “children” in “HRP-013-SOP- Legally Authorized Representatives, 
Children, and Guardians.” 
 
Parental permission will be obtained through the written consent. Parents will 
provide consent for study participation. 
 
5.6.3.2 Assent of subjects who are not yet adults 
Indicate whether assent will be obtained from all, some, or none of the children. If 
assent will be obtained from some children, indicate which children will be required 
to assent. When assent of children is obtained describe whether and how it will be 
documented. 
 
The children involved are infants and will not be old enough to assent during the 
course of the study.  
6.0 
HIPAA Research Authorization and/or Waiver or Alteration of Authorization 
This section is about the access, use or disclosure of Protected Health Information (PHI). PHI is individually 
identifiable health information (i.e., health information containing one or more 18 identifiers) that is transmitted 
or maintained in any form or medium by a Covered Entity or its Business Associate. A Covered Entity is a health 
plan, a health care clearinghouse or health care provider who transmits health information in electronic form.  
See “HRP-103 -Investigator Manual” for a list of the 18 identifiers.   
 
If requesting a waiver/alteration of HIPAA authorization, complete sections 6.2 and 6.3 in addition to section 
6.1. The Privacy Rule permits waivers (or alterations) of authorization if the research meets certain conditions. 
Include only information that will be accessed with the waiver/alteration.  
[Do not type here] 
 
6.1 
Authorization and/or Waiver or Alteration of Authorization for the Uses and Disclosures of PHI 
 
Check all that apply: 
  
Not applicable, no identifiable protected health information (PHI) is accessed, used or 
disclosed in this study. [Mark all parts of sections 6.2 and 6.3 as not applicable] 
 

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Authorization will be obtained and documented as part of the consent process. [If this is the 
only box checked, mark sections 6.2 and 6.3 as not applicable] 
 
 
Partial waiver is requested for recruitment purposes only (Check this box if patients’ medical 
records will be accessed to determine eligibility before consent/authorization has been 
obtained). [Complete all parts of sections 6.2 and 6.3] 
 
 
Full waiver is requested for entire research study (e.g., medical record review studies). 
[Complete all parts of sections 6.2 and 6.3] 
 
 
Alteration is requested to waive requirement for written documentation of authorization 
(verbal authorization will be obtained). [Complete all parts of sections 6.2 and 6.3] 
 
6.2 
Waiver or Alteration of Authorization for the Uses and Disclosures of PHI 
 
6.2.1 
Access, use or disclosure of PHI representing no more than a minimal risk to the privacy of the 
individual 
6.2.1.1 
Plan to protect PHI from improper use or disclosure 
Include the following statement as written – DO NOT ALTER OR DELETE 
unless this section is not applicable because the research does not involve a 
waiver of authorization. If the section is not applicable, remove the 
statement and indicate as not applicable.  
 
Information is included in the “Confidentiality, Privacy and Data 
Management” section of this protocol. 
 
6.2.1.2 
Plan to destroy identifiers or a justification for retaining identifiers  
Describe the plan to destroy the identifiers at the earliest opportunity 
consistent with the conduct of the research. Include when and how 
identifiers will be destroyed. If identifiers will be retained, provide the legal, 
health or research justification for retaining the identifiers. 
 
All identifiable data will be destroyed after all publications have been 
published and the study is closed. 
 
6.2.2 
Explanation for why the research could not practicably be conducted without access to and 
use of PHI 
Provide an explanation for why the research could not practicably be conducted without access 
to and use of PHI. 
 
 
A partial waiver for uses and disclosures of PHI is required for the practical conduction of 
this research. The waiver will allow team members involved in recruitment to access electronic 
medical records of patients who meet basic inclusion criteria. This will save time and protect 
privacy for non-eligible families. 
 
6.2.3 
Explanation for why the research could not practicably be conducted without the waiver or 
alteration of authorization 
Provide an explanation for why the research could not practicably be conducted without the 
waiver or alternation of authorization. 
 

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Without review of potential participants’ medical records prior to study explanation would 
result in non-eligible families being approached for the research. This would cause an 
unnecessary invasion of privacy for families that would not be able to participate. 
6.3 
Waiver or alteration of authorization statements of agreement 
 
By submitting this study for review with a waiver of authorization, you agree to the following statement – 
DO NOT ALTER OR DELETE unless this section is not applicable because the research does not involve a 
waiver or alteration of authorization. If the section is not applicable, remove the statement and indicate 
as not applicable. 
 
Protected health information obtained as part of this research will not be reused or disclosed to any other 
person or entity, except as required by law, for authorized oversight of the research study, or for other 
permitted uses and disclosures according to federal regulations.  
 
The research team will collect only information essential to the study and in accord with the ‘Minimum 
Necessary’ standard (information reasonably necessary to accomplish the objectives of the research) per 
federal regulations.  
 
Access to the information will be limited, to the greatest extent possible, within the research team. All 
disclosures or releases of identifiable information granted under this waiver will be accounted for and 
documented. 
7.0 
Study Design and Procedures 
Data collection materials that will be seen or used by subjects in your study must be uploaded to CATS IRB 
(http://irb.psu.edu).   DO NOT include any actual data collection materials in this protocol (e.g., actual survey or 
interview questions) 
 
[Do not type here] 
 
7.1 
Study Design 
Describe and explain the study design. 
 
 
This study is a randomized, clinical trial involving 60 exclusively formula fed infants born at ≥37 
weeks gestational age who are at-risk for overweight based upon maternal pre-pregnancy overweight or 
obesity (or alternatively at first prenatal visit if pre-pregnancy weight/height not known) and infant 
birthweight ≥50th percentile. Infants will be enrolled at Penn State Health Children’s Hospital or at 
affiliated clinics within the Division of Academic General Pediatrics between birth and age 1 month, 
where they will be randomized to a calibrated formula intake intervention or control. Participating 
infants in the intervention group will be seen monthly until age 6 months where they will be weighed 
and measured, and parents will complete surveys related to volume of formula consumed, infant 
appetite, parent feeding style, and infant temperament. Control infants will follow the same procedures, 
but will not have scheduled visits at ages 3 and 5 months. Instead their visits will correspond to usual 
care well child visits at ages 1, 2, 4, and 6 months. 
 
7.2 
Study Procedures 
Provide a step by step description of all research procedures being conducted (broken down by visit, if 
applicable) including such information as below (where and when applicable); describe the following: 
• 
HOW: (e.g., data collection via interviews, focus groups, forms such as surveys and questionnaires, 
medical/school records, audio/video/digital recordings, photographs, EKG procedures, MRI, mobile 
devices such as electronic tablets/cell phones, observations, collection of specimens, experimental 
drug/device testing, manipulation of behavior/use of deception, computer games, etc.) 

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• 
WHERE: (e.g., classrooms, labs, internet/online, places of business, medical settings, public spaces, 
etc.) 
 
Prior to enrollment, infants will be screened by study coordinators to ensure eligibility consistent with 
study inclusion/exclusion criteria. 
 
7.2.1 
Visit 1  
Provide a description of what procedures will be performed on visit 1 or day 1 or pre-test in 
order of how these will be done.  If your study only involves one session or visit, use this section 
only and indicate 7.2.2 as not applicable.  
 
Birth – infant age 1 month: Parents will then review and complete the informed consent 
document during the birth hospitalization or at a clinic visit allowing for continued participation. 
Demographic data will be collected from parent-completed surveys on Redcap. Study 
coordinators will review the electronic medical record to obtain data related to pregnancy and 
birth history (e.g. birthweight, gestational age, maternal pre-pregnancy BMI, etc.). Additionally, 
parent contact information will be obtained. 
 
Anthropometrics – if enrollment occurs during the birth hospitalization, birth weight and birth 
length will be recorded from the electronic medical record. If enrollment occurs at an outpatient 
clinic visit, the following procedures will be used (and for all subsequent weights and lengths): 
 
Weight – will be measured to the nearest 0.001 kg using a calibrated, digital 
electronic scale 
 
Recumbent Length – will be measured to the nearest 0.1 cm using a portable 
stadiometer (Shorr) 
 
Diary card - Parents will be given a diary card to record volume of infant formula consumed for 
the 3 days prior to the 1 month well child visit (Visit 2) and all subsequent visits. Instructions for 
the diary card will ask parents: 
a) Volume consumed in each feeding for the day (volume is the amount that passes the 
infant’s lips – if formula is spit-up, it still counts as having been consumed) 
b) Type of infant formula 
c) Size of bottle used 
d) Other sources of nutrition (e.g. juice, water, foods) 
 
Randomization – following the visit, infants will be randomized to intervention or control using 
a computer-generated randomization program generated by a statistician not affiliated with the 
trial. Randomization will include stratification for sex of the infant (male/female) and maternal 
pre-pregnancy BMI category (25-29.9 kg/m2 vs. ≥30 kg/m2). 
 
7.2.2 
Visit 2  
Provide a description of what procedures will be performed on visit 2 or day 2 or post-test in 
order of how these will be done.  If your study involves more than two sessions or visits 
replicate this section for each additional session or visit (e.g., 7.2.3, 7.2.4, etc.).  
 
Age 1 Month Visit (ages 24 – 41 days) 
 
Both study groups:  
1. Anthropometrics of infant (weight, recumbent length) 
2. Parent-completed Surveys 
a. Baby Eating Behavior Questionnaire76 
b. Babies Basic Needs Questionnaire 

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c. Single item adapted from the Infant Feeding Practices Study II77:“I encourage my 
infant to finish his or her bottle of formula”78; responses include: 
Never ....... … Rarely........ … Sometimes ....... … Most of the time ...... … Always....... … 
3. Diary cards to be completed for the 3 days following the visit 
4. Diary cards to be completed x 3 days prior to next study visit 
 
Intervention group only: 
1. Parents will be provided with handouts on hunger/satiety cues and calming a fussy baby 
2. Parents will be given a digital streaming copy of the video, “Happiest Baby on the Block” 
available at: https://www.happiestbaby.com/products/baby-streaming-video-english 
3. Parents will be given a copy of a video demonstrating responsive bottle feeding: 
https://youtu.be/NLnPGJKdPUw 78 
4. Parents will be given a copy of Bottle Feeding Basics video: 
https://360.articulate.com/review/content/99a63b9a-184c-474e-b836-
7d8cd8aa1652/review 
5. Study coordinators will provide parents with a range of formula volume to be consumed 
based upon research conducted by Butte:79 
 
 
Recommended formula volumes will be calculated based on data from the table above 
informing parents of the recommended formula volume based on 19/20 kcal/ounce formula at 
the infant’s current age as well as the anticipated volume at the infant’s next visit as described 
below.  
 
For those with weight-for-length (WFL) <75th percentile on the WHO WFL growth chart, 
recommended daily formula volumes will be calculated based upon the infant’s sex, current age, 
weight, and energy requirement (kcal/kg/day). Further, parents will be informed of the volume 
to expect at the subsequent visit in one month should the child maintain the same weight-for-
age percentile. 
 
For those with WFL ≥75th percentile on the WHO WFL growth chart, recommended daily 
formula volumes will be calculated based upon the child’s current age, weight, and energy 
requirement (kcal/kg/day) with a 10% reduction in daily volume. Further, parents will be 

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informed of the volume to expect at the subsequent visit in one month should the child 
maintain the same weight-for-age percentile, again with a 10% reduction. 
 
10% was chosen for this pilot because it balances feasibility (relatively likely that parents can 
comply) and safety (unlikely to cause failure-to-thrive by reducing total daily formula volume by 
~3 ounces) 
 
6. Parents will be given instruction to prepare the formula volume in each bottle on the lower 
end of what they anticipate the infant will eat. For example, if they anticipate the infant will 
consume 3-4 ounces per feed, they will prepare 3 ounces at first. If hunger cues persist, they 
will then prepare an additional 1-2 ounces of formula. 
 
7.2.3 
Visit 3  
 
Age 2 Month Visit (42-77 days) 
 
Both study groups: 
1. Anthropometrics of infant (weight, recumbent length) 
2. Diary cards to be completed for the 3 days following the visit 
3. Diary cards to be completed x 3 days prior to next study visit 
 
Intervention group only: 
1. Recommend formula volumes for the next month based on Visit 2 procedures 
2. If, for a second consecutive month, the child has WFL ≥75th percentile on the WHO WFL 
growth chart, recommended daily formula volumes will be calculated based upon the 
child’s current age, weight, and energy requirement (kcal/kg/day) with a 15% reduction in 
daily volume. Further, parents will be informed of the volume to expect at the subsequent 
visit in one month should the child maintain the same weight-for-age percentile, again with 
a 15% reduction. 
 
 
 
7.2.4 
Visit 4 
 
Age 3 Month Visit (78-109 days): Intervention group only 
 
1. Anthropometrics of infant (weight, recumbent length) 
2. Diary cards to be completed for the 3 days following the visit 
3. Diary cards to be completed x 3 days prior to next study visit 
4. Recommend formula volumes for the next month based on Visit 2 and 3 procedures 
 
 
7.2.5 
Visit 5 
 
Age 4 Month Visit (110-140 days) 
 
Both study groups: 
1. Anthropometrics of infant (weight, recumbent length) 
2. Diary cards to be completed for the 3 days following the visit 
3. Diary cards to be completed x 3 days prior to next study visit 
 
Intervention group only: 
4. Recommend formula volumes for the next month based on Visit 2 and 3 procedures 

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5. Provide handouts on soothing fussy infants, feeding 
 
7.2.6 
Visit 6 
 
Age 5 Month Visit (141-171 days) – Intervention Group Only 
 
1. Anthropometrics of infant (weight, recumbent length) 
2. Diary cards to be completed for the 3 days following the visit 
3. Diary cards to be completed x 3 days prior to next study visit 
4. Recommend formula volumes for the next month based on Visit 2 and 3 procedures 
 
7.2.7 
Visit 7 
 
Age 6 Month Visit (172-210 days) 
 
Both study groups: 
1. Anthropometrics of infant (weight, recumbent length) 
2. Parent completed surveys 
a. Baby Eating Behavior Questionnaire 
b. Infant Feeding Styles Questionnaire 
c. Baby’s Basic Needs Questionnaire 
d. Infant Behavior Questionnaire 
 
7.3 
Duration of Participation 
Describe how long subjects will be involved in this research study.  Include the number of sessions and 
the duration of each session - consider the total number of minutes, hours, days, months, years, etc.   
 
Participants will be enrolled in the study for 6 months. Most study visits will occur in conjunction with 
regular well child care, adding ~15 minutes to each visit. 
 
8.0 
Number of Subjects and Statistical Plan 
 
8.1 
Number of Subjects 
Indicate the maximum number of subjects to be accrued/enrolled. Distinguish between the number of 
subjects who are expected to be enrolled and screened, and the number of subjects needed to 
complete the research procedures if applicable (i.e., numbers of subjects excluding screen failures.) 
 
For this pilot study, 60 infants will be recruited. We believe that this number of infants who meet the 
inclusion/exclusion criteria can feasibly be recruited over a 6 month period. 
 
8.2 
Sample size determination 
If applicable, provide a justification of the sample size outlined in section 8.1 to include reflections on, or 
calculations of, the power of the study. 
 
The sample size for this pilot study is based upon the number of participants that we felt we could 
feasibly recruit given the time and resources available for recruitment. As this pilot is going to determine 
feasibility, 60 participants should be adequate. Further, we will use the data generated to determine the 
sample size necessary for a fully powered subsequent trial. 
 

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8.3 
Statistical methods 
Describe the statistical methods (or non-statistical methods of analysis) that will be employed. 
 
We will assess conditional weight gain from birth to 6 months to assess rapid infant growth.80,81 
Conditional weight gain will be calculated as standardized residuals from the linear regression of weight 
for age at 6 months on weight for age at birth, with length for age at birth and 6 months and infant age 
at the 6-month visit entered as covariates. We will explore the moderating role of child sex, delivery 
mode, and maternal parity on intervention effects. Similar analyses will be conducted for the 
intervention period spanning ages 1-6 months. 
 
For cross-sectional analyses at age 6 months, ANOVA will estimate the effects of intervention group on 
mean weight-for-length. Logistic regression will be used to compare intervention effects on the 
dichotomous outcome of overweight at 6 months. 
 
For growth from 1-6 months, we will fit a repeated measures ANOVA of BMI, with visit and study group 
as within and between factors, respectively. 
9.0 
Data and Safety Monitoring Plan 
This section is required when research involves more than Minimal Risk to subjects as defined in “HRP-001 
SOP- Definitions.” 
 
Minimal Risk is defined as the probability and magnitude of harm or discomfort anticipated in the research that 
are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of 
routine physical or psychological examinations or tests.  For research involving prisoners, Minimal Risk is the 
probability and magnitude of physical or psychological harm that is normally encountered in the daily lives, or in 
the routine medical, dental, or psychological examination of healthy persons.  
 
Please complete the sections below if the research involves more than minimal risk to subjects, otherwise 
indicate each section as not applicable.  
[Do not type here] 
 
9.1 
Periodic evaluation of data 
Describe the plan to periodically evaluate the data collected regarding both harms and benefits to 
determine whether subjects remain safe. 
 
Growth charts will be reviewed in real time at patient visits. Those meeting criteria for growth failure 
(failure-to-thrive) described above will be immediate flagged and discussed with Dr. Paul. 
 
9.2 
Data that are reviewed 
Describe the data that are reviewed, including safety data, untoward events, and efficacy data. 
 
For this 6 month trial, growth charts are the data that will be reviewed. 
 
9.3 
Method of collection of safety information 
Describe the method by which the safety information will be collected (e.g., with case report forms, at 
study visits, by telephone calls and with subjects). 
 

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Any growth failure event will be considered an adverse event, and these will be captured with a case 
report form. 
 
9.4 
Frequency of data collection 
Describe the frequency of data collection, including when safety data collection starts. 
 
Data are collected per the visit schedules for the intervention and control groups. 
9.5 
Individuals reviewing the data 
Identify the individuals who will review the data. The plan might include establishing a data and safety 
monitoring committee and a plan for reporting data monitoring committee findings to the IRB and the 
sponsor. 
 
The study coordinators and PI will be the ones reviewing the data. 
9.6 
Frequency of review of cumulative data 
Describe the frequency or periodicity of review of cumulative data. 
 
Cumulative data will be reviewed at the end of the trial. 
9.7 
Statistical tests 
Describe the statistical tests for analyzing the safety data to determine whether harms are occurring. 
 
As we expect adverse events to be infrequent, we are not planning to do any interim safety analyses. 
9.8 
Suspension of research 
Describe any conditions that trigger an immediate suspension of research. 
 
Suspension of the research would occur if: 
1. >33% of participants are not adhering to the data collection procedures 
2. >33% of intervention group participants meet criteria for failure-to-thrive 
3. Attrition exceeds 33% after Visit 2 
10.0 Risks 
List the reasonably foreseeable risks, discomforts, hazards, or inconveniences to the subjects related the 
subjects’ participation in the research. Include as may be useful for the IRB’s consideration, a description of the 
probability, magnitude, duration and reversibility of the risks. Consider all types of risk including physical, 
psychological, social, legal, and economic risks.  Note: Loss of confidentiality is a potential risk when conducting 
human subject research. 
• 
If applicable, indicate which procedures may have risks to the subjects that are currently unforeseeable. 
• 
If applicable, indicate which procedures may have risks to an embryo or fetus should the subject be or 
become pregnant. 
• 
If applicable, describe risks to others who are not subjects. 
 
It is possible that a reduction in formula intake could lead to temporary growth faltering (i.e. failure-to-thrive), 
though this would be self-limited and could be addressed by subsequently increasing formula intake. 

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11.0 Potential Benefits to Subjects and Others  
11.1 
Potential Benefits to Subjects 
Describe the potential benefits that individual subjects may experience from taking part in the research. 
If there is no direct benefit to subjects, indicate as such. Compensation is not considered a benefit. 
Compensation should be addressed in section 13.0. 
 
The study intervention could improve infant growth trajectories, reduce rapid infant weight gain, and 
reduce likelihood of overweight during infancy and beyond for participants. 
11.2 
Potential Benefits to Others 
Include benefits to society or others.  
 
This pilot could inform formula feeding guidelines for infants in clinical care and in clinical research trials. 
12.0 Sharing Results with Subjects 
Describe whether results (study results or individual subject results, such as results of investigational diagnostic 
tests, genetic tests, or incidental findings) will be shared with subjects or others (e.g., the subject’s primary care 
physicians) and if so, describe how information will be shared.  
 
Parents of individual participants will receive real-time data on their infant’s growth, consistent with clinical 
care. 
13.0 Subject Payment and/or Travel Reimbursements 
Describe the amount, type (cash, check, gift card, other) and timing of any subject payment or travel 
reimbursement. If there is no subject payment or travel reimbursement, indicate as not applicable.  
 
Extra or Course Credit:  Describe the amount of credit and the available alternatives. Alternatives should be 
equal in time and effort to the amount of course or extra credit offered. It is not acceptable to indicate that the 
amount of credit is to be determined or at the discretion of the instructor of the course.  
 
Approved Subject Pool: Indicate which approved subject pool will be used; include in response below that 
course credit will be given and alternatives will be offered as per the approved subject pool procedures.  
 
Participating parents randomized to the intervention group will receive up to $300 for participation in the study; 
control participants who have 2 less study visits will receive up to $250 for participation. Following Visit 2, they 
will receive $50 for successful completion of the visit and study surveys. $25 will be given following visits 3-6 
(note no visit 4 and 6 for controls). Upon completion of Visit 7’s anthropometrics and survey data collection, 
participants will receive $150. 
14.0 Economic Burden to Subjects 
14.1 
Costs 
Describe any costs that subjects may be responsible for because of participation in the research. 
 
Research participants will not accrue any additional costs as a result of their participation. 
 
14.2 
Compensation for research-related injury 
If the research involves more than Minimal Risk to subjects, describe the available compensation in 
the event of research related injury. 

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If there is no sponsor agreement that addresses compensation for medical care for research subjects 
with a research-related injury, include the following text as written - DO NOT ALTER OR DELETE: 
It is the policy of the institution to provide neither financial compensation nor free medical treatment 
for research-related injury. In the event of injury resulting from this research, medical treatment is 
available but will be provided at the usual charge. Costs for the treatment of research-related injuries 
will be charged to subjects or their insurance carriers.  
 
For sponsored research studies with a research agreement with the sponsor that addresses 
compensation for medical care for research-related injuries, include the following text as written - DO 
NOT ALTER OR DELETE: 
It is the policy of the institution to provide neither financial compensation nor free medical treatment 
for research-related injury. In the event of injury resulting from this research, medical treatment is 
available but will be provided at the usual charge. Such charges may be paid by the study sponsor as 
outlined in the research agreement and explained in the consent form. 
 
It is the policy of the institution to provide neither financial compensation nor free medical treatment 
for research-related injury. In the event of injury resulting from this research, medical treatment is 
available but will be provided at the usual charge. Costs for the treatment of research-related injuries 
will be charged to subjects or their insurance carriers. 
15.0 Resources Available  
 
15.1 
Facilities and locations 
Identify and describe the facilities, sites and locations where recruitment and study procedures will be 
performed.  
 
If research will be conducted outside the United States, describe site-specific regulations or customs 
affecting the research, and describe the process for obtaining local ethical review. Also, describe the 
principal investigator’s experience conducting research at these locations and familiarity with local 
culture. 
 
This research will be conducted on the maternity/nursery floors of Penn State Children’s Hospital and at 
the ambulatory clinics affiliated with the Division of Academic General Pediatrics. 
Penn State Children’s Hospital maternity/nursery floors - ~2000 infants are delivered annually on the 
floor. All mother-baby dyads on the well newborn service have private rooms. Recruitment and 
enrollment procedures are expected to occur frequently on this unit (6th and 7th floors). 
Ambulatory Clinics – The Division of Academic General Pediatrics performs >50,000 visits annually at its 
clinics located at Hope Drive, Elizabethtown, and Nyes Road. These clinics are accustomed to research. 
Recruitment and enrollment may also occur at the clinics, and monthly anthropometrics and data 
collection will occur, typically as part of well child care visit. 
15.2 
Feasibility of recruiting the required number of subjects 
Indicate the number of potential subjects to which the study team has access.  Indicate the percentage 
of those potential subjects needed for recruitment. 
 
With ~2000 well newborns delivered annually, it is expected that ~30% will be exclusively formula fed. 
Among these 600, it is expected that ~200-300 will meet the remaining inclusion/exclusion criteria, 
providing an ample pool of participants. 

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15.3 
PI Time devoted to conducting the research 
Describe how the PI will ensure that a sufficient amount of time will be devoted to conducting and 
completing the research. Please consider outside responsibilities as well as other on-going research for 
which the PI is responsible. 
 
Dr. Paul has a long track-record of conducting clinical research and devoting appropriate time to his 
research studies despite other obligations including patient care and administration. 
15.4 
Availability of medical or psychological resources 
Describe the availability of medical or psychological resources that subjects might need as a result of 
their participation in the study, if applicable. 
 
Participating infants will receive their typical infant well child care from their pediatricians. 
15.5 
Process for informing Study Team 
Describe the training plans to ensure members of the research team are informed about the protocol 
and their duties, if applicable. 
 
All study team members will have completed the appropriate training prior to the initiation of the study. 
Team meetings will occur at least monthly via Zoom. 
16.0 Other Approvals 
16.1 
Other Approvals from External Entities 
Describe any approvals that will be obtained prior to commencing the research (e.g., from engaged 
cooperating institutions IRBs who are also reviewing the research and other required review 
committees, community leaders, schools, research locations where research is to be conducted by the 
Penn State investigator, funding agencies, etc.). 
 
N/A 
16.2 
Internal PSU Committee Approvals 
 
Check all that apply: 
  Anatomic Pathology – Penn State Health only – Research involves the collection of tissues or use of 
pathologic specimens. Upload a copy of “HRP-902 - Human Tissue For Research Form” in CATS IRB.  
 
  Animal Care and Use – All campuses – Human research involves animals and humans or the use of 
human tissues in animals 
 
  Biosafety – All campuses – Research involves biohazardous materials (human biological specimens 
in a PSU research lab, biological toxins, carcinogens, infectious agents, recombinant viruses or DNA 
or gene therapy). 
 
  Clinical Laboratories – Penn State Health only – Collection, processing and/or storage of extra tubes 
of body fluid specimens for research purposes by the Clinical Laboratories; and/or use of body fluids 
that had been collected for clinical purposes but are no longer needed for clinical use. Upload a copy 
of “HRP-901 - Human Body Fluids for Research Form” in CATS IRB.  
 

Page 26 of 32 (IRB USE ONLY: V. 03/01/2021)  
  Clinical Research Center (CRC) Advisory Committee – All campuses – Research involves the use of 
CRC services in any way. 
 
  Conflict of Interest Review – All campuses – Research has one or more of study team members 
indicated as having a financial interest. 
 
  Radiation Safety – Penn State Health only – Research involves research-related radiation 
procedures. All research involving radiation procedures (standard of care and/or research-related) 
must upload a copy of “HRP-903 - Radiation Review Form” in CATS IRB.  
 
  IND/IDE Audit – All campuses – Research in which the PSU researcher holds the IND or IDE or 
intends to hold the IND or IDE. 
 
  Scientific Review – Penn State Health only – All investigator-written research studies requiring 
review by the convened IRB must provide documentation of scientific review with the IRB 
submission. The scientific review requirement may be fulfilled by one of the following: (1) external 
peer-review process; (2) department/institute scientific review committee; or (3) scientific review by 
the Clinical Research Center Advisory committee.  NOTE: Review by the Penn State Health Cancer 
Institute (PSCI) Protocol Review Committee or the PSCI Disease Team is required if the study 
involves cancer prevention studies or cancer patients, records and/or tissues. For more information 
about this requirement see the IRB website. 
 
  St. Joseph Administrative Review – Penn State Health only – Penn State Health Research that will be 
conducted at St. Joseph Medical Center or St. Joseph Community Medical Groups.  
17.0 Multi-Site Study 
If this is a multi-site study (i.e., a study in which two or more institutions coordinate, with each institution 
completing all research activities outlined in a specific protocol) and the Penn State PI is the lead investigator, 
describe the processes to ensure communication among sites in the sections below. 
[Do not type here] 
 
17.1 
Other sites  
List the name and location of all other participating sites. Provide the name, qualifications and contact 
information for the principal investigator at each site and indicate which IRB will be reviewing the study 
at each site. 
 
 
 
 
N/A 
 
17.2 
Communication Plans 
Describe the plan for regular communication between the overall study director and the other sites to 
ensure that all sites have the most current version of the protocol, consent document, etc.  Describe the 
process to ensure all modifications have been communicated to sites. Describe the process to ensure 
that all required approvals have been obtained at each site (including approval by the site’s IRB of 
record).   Describe the process for communication of problems with the research, interim results and 
closure of the study. 
 
N/A 
 

Page 27 of 32 (IRB USE ONLY: V. 03/01/2021)  
17.3 
Data Submission and Security Plan 
Describe the process and schedule for data submission and provide the data security plan for data 
collected from other sites.  Describe the process to ensure all engaged participating sites will safeguard 
data as required by local information security policies. 
 
N/A 
 
17.4 
Subject Enrollment 
Describe the procedures for coordination of subject enrollment and randomization for the overall 
project. 
 
N/A 
 
17.5 
Reporting of Adverse Events and New Information 
Describe how adverse events and other information will be reported from the clinical sites to the overall 
study director. Provide the timeframe for this reporting. 
 
N/A 
 
17.6 
Audit and Monitoring Plans 
Describe the process to ensure all local site investigators conduct the study appropriately. Describe any 
on-site auditing and monitoring plans for the study. 
 
N/A 
18.0 Adverse Event Reporting 
18.1 
Reporting Adverse Reactions and Unanticipated Problems to the Responsible IRB 
By submitting this study for review, you agree to the following statement – DO NOT ALTER OR DELETE:  
 
In accordance with applicable policies of The Pennsylvania State University Institutional Review Board 
(IRB), the investigator will report, to the IRB, any observed or reported harm (adverse event) experienced 
by a subject or other individual, which in the opinion of the investigator is determined to be (1) 
unexpected; and (2) probably related to the research procedures. Harms (adverse events) will be 
submitted to the IRB in accordance with the IRB policies and procedures. 
 
19.0 Study Monitoring, Auditing and Inspecting 
 
19.1 
Auditing and Inspecting 
By submitting this study for review, you agree to the following statement – DO NOT ALTER OR DELETE:  
 
The investigator will permit study-related monitoring, audits, and inspections by the Penn State quality 
assurance program office(s), IRB, the sponsor, and government regulatory bodies, of all study related 
documents (e.g., source documents, regulatory documents, data collection instruments, study data etc.).  
The investigator will ensure the capability for inspections of applicable study-related facilities (e.g., 
pharmacy, diagnostic laboratory, etc.). 

Page 28 of 32 (IRB USE ONLY: V. 03/01/2021)  
20.0 Future Undetermined Research: Data and Specimen Banking 
If this study is collecting identifiable data and/or specimens that will be banked for future undetermined 
research, please describe this process in the sections below.  This information should not conflict with 
information provided in section 22 regarding whether or not data and/or specimens will be associated with 
identifiers (directly or indirectly).  If NOT applicable, indicate as such below in all sections. 
[Do not type here] 
20.1 
Data and/or specimens being stored 
Identify what data and/or specimens will be stored and the data associated with each specimen. 
 
Files will be stored on the IT file server (hersheymed.net\files). We will also be utilizing Penn State’s 
RedCap EDC system to store all study data. 
 
20.2 
Location of storage 
Identify the location where the data and/or specimens will be stored. 
 
Files will be stored on the IT file server (hersheymed.net\files). We will also be utilizing Penn State’s 
RedCap EDC system to store all study data.  
 
20.3 
Duration of storage 
Identify how long the data and/or specimens will be stored. If data and/or specimens will be stored 
indefinitely, indicate as such.  
 
5 years following the completion of the study. 
 
20.4 
Access to data and/or specimens 
Identify who will have access to the data and/or specimens. 
 
The investigators and the study sponsor. 
 
20.5 
Procedures to release data or specimens 
Describe the procedures to release the data and/or specimens, including: the process to request a 
release, approvals required for release, who can obtain data and/or specimens, and the data to be 
provided with the specimens. 
 
N/A 
 
20.6 
Process for returning results 
Describe the process for returning results about the use of the data and/or specimens. 
 
N/A 
21.0 References 
List relevant references in the literature which highlight methods, controversies, and study outcomes. 
 
1. 
Dennison BA, Edmunds LS, Stratton HH, Pruzek RM. Rapid infant weight gain predicts childhood overweight. Obesity 
(Silver Spring). 2006;14(3):491-499. 
2. 
Dubois L, Girard M. Early determinants of overweight at 4.5 years in a population-based longitudinal study. Int J Obes 
(Lond). 2006;30(4):610-617. 

Page 29 of 32 (IRB USE ONLY: V. 03/01/2021)  
3. 
Stettler N, Kumanyika SK, Katz SH, Zemel BS, Stallings VA. Rapid weight gain during infancy and obesity in young 
adulthood in a cohort of African Americans. Am J Clin Nutr. 2003;77(6):1374-1378. 
4. 
Nader PR, O'Brien M, Houts R, et al. Identifying risk for obesity in early childhood. Pediatrics. 2006;118(3):e594-601. 
5. 
Ong KK, Ahmed ML, Emmett PM, Preece MA, Dunger DB. Association between postnatal catch-up growth and obesity in 
childhood: prospective cohort study. BMJ. 2000;320(7240):967-971. 
6. 
Stettler N, Zemel BS, Kumanyika S, Stallings VA. Infant weight gain and childhood overweight status in a multicenter, 
cohort study. Pediatrics. 2002;109(2):194-199. 
7. 
Peto R, Whitlock G, Jha P. Effects of obesity and smoking on U.S. life expectancy. N Engl J Med. 2010;362(9):855-856; 
author reply 856-857. 
8. 
Xi B, Mi J, Duan JL, et al. [Familial clustering of obesity and the role of lifestyle factors among children in Beijing]. 
Zhonghua Yu Fang Yi Xue Za Zhi. 2009;43(2):122-127. 
9. 
Burke V, Beilin LJ, Dunbar D. Family lifestyle and parental body mass index as predictors of body mass index in Australian 
children: a longitudinal study. Int J Obes Relat Metab Disord. 2001;25(2):147-157. 
10. 
Swinburn BA, Sacks G, Lo SK, et al. Estimating the changes in energy flux that characterize the rise in obesity prevalence. 
Am J Clin Nutr. 2009;89(6):1723-1728. 
11. 
Swinburn B, Sacks G, Ravussin E. Increased food energy supply is more than sufficient to explain the US epidemic of 
obesity. Am J Clin Nutr. 2009;90(6):1453-1456. 
12. 
Swinburn BA, Jolley D, Kremer PJ, Salbe AD, Ravussin E. Estimating the effects of energy imbalance on changes in body 
weight in children. Am J Clin Nutr. 2006;83(4):859-863. 
13. 
Scarborough P, Burg MR, Foster C, et al. Increased energy intake entirely accounts for increase in body weight in women but 
not in men in the UK between 1986 and 2000. Br J Nutr. 2011;105(9):1399-1404. 
14. 
Hagan S, Niswender KD. Neuroendocrine regulation of food intake. Pediatr Blood Cancer. 2012;58(1):149-153. 
15. 
Contu L, Hawkes CA. A Review of the Impact of Maternal Obesity on the Cognitive Function and Mental Health of the 
Offspring. Int J Mol Sci. 2017;18(5). 
16. 
Sullivan EL, Riper KM, Lockard R, Valleau JC. Maternal high-fat diet programming of the neuroendocrine system and 
behavior. Horm Behav. 2015;76:153-161. 
17. 
Rivera HM, Christiansen KJ, Sullivan EL. The role of maternal obesity in the risk of neuropsychiatric disorders. Front 
Neurosci. 2015;9:194. 
18. 
Satpathy HK, Fleming A, Frey D, Barsoom M, Satpathy C, Khandalavala J. Maternal obesity and pregnancy. Postgrad Med. 
2008;120(3):E01-09. 
19. 
Kaul P, Bowker SL, Savu A, Yeung RO, Donovan LE, Ryan EA. Association between maternal diabetes, being large for 
gestational age and breast-feeding on being overweight or obese in childhood. Diabetologia. 2019;62(2):249-258. 
20. 
Van Eerden P. Obesity in pregnancy. S D Med. 2011;Spec No:46-50. 
21. 
Davenport MH, Cabrero MR. Maternal nutritional history predicts obesity in adult offspring independent of postnatal diet. J 
Physiol. 2009;587(Pt 14):3423-3424. 
22. 
Catalano P, deMouzon SH. Maternal obesity and metabolic risk to the offspring: why lifestyle interventions may have not 
achieved the desired outcomes. Int J Obes (Lond). 2015;39(4):642-649. 
23. 
Guo SS, Wu W, Chumlea WC, Roche AF. Predicting overweight and obesity in adulthood from body mass index values in 
childhood and adolescence. Am J Clin Nutr. 2002;76(3):653-658. 
24. 
Drake AJ, Reynolds RM. Impact of maternal obesity on offspring obesity and cardiometabolic disease risk. Reproduction. 
2010;140(3):387-398. 
25. 
Catalano PM. Obesity and pregnancy--the propagation of a viscous cycle? JClinEndocrinolMetab. 2003;88(8):3505-3506. 
26. 
Oken E, Rifas-Shiman SL, Field AE, Frazier AL, Gillman MW. Maternal gestational weight gain and offspring weight in 
adolescence. Obstetrics and Gynecology. 2008;112(5):999-1006. 
27. 
Lake JK, Power C, Cole TJ. Child to adult body mass index in the 1958 British birth cohort: associations with parental 
obesity. ArchDisChild. 1997;77(5):376-381. 
28. 
Wrotniak BH, Shults J, Butts S, Stettler N. Gestational weight gain and risk of overweight in the offspring at age 7 y in a 
multicenter, multiethnic cohort study. AmJClinNutr. 2008;87(6):1818-1824. 
29. 
Smith J, Cianflone K, Biron S, et al. Effects of maternal surgical weight loss in mothers on intergenerational transmission of 
obesity. J ClinEndocrinolMetab. 2009;94(11):4275-4283. 
30. 
Desai M, Jellyman JK, Han G, Beall M, Lane RH, Ross MG. Maternal obesity and high-fat diet program offspring metabolic 
syndrome. Am J Obstet Gynecol. 2014;211(3):237-237. 
31. 
Hermann GM, Dallas LM, Haskell SE, Roghair RD. Neonatal macrosomia is an independent risk factor for adult metabolic 
syndrome. Neonatology. 2010;98(3):238-244. 
32. 
Sherman M, Liu MM, Birnbaum S, Wolf SE, Minei JP, Gatson JW. Adult obese mice suffer from chronic secondary brain 
injury after mild TBI. J Neuroinflammation. 2016;13(1):171. 
33. 
Wang Q, Yuan J, Yu Z, et al. FGF21 Attenuates High-Fat Diet-Induced Cognitive Impairment via Metabolic Regulation and 
Anti-inflammation of Obese Mice. Mol Neurobiol. 2018;55(6):4702-4717. 
34. 
Baufeld C, Osterloh A, Prokop S, Miller KR, Heppner FL. High-fat diet-induced brain region-specific phenotypic spectrum 
of CNS resident microglia. Acta Neuropathol. 2016;132(3):361-375. 

Page 30 of 32 (IRB USE ONLY: V. 03/01/2021)  
35. 
Sriram K, Benkovic SA, Miller DB, O'Callaghan JP. Obesity exacerbates chemically induced neurodegeneration. 
Neuroscience. 2002;115(4):1335-1346. 
36. 
Desai M, Han G, Ross MG. Programmed hyperphagia in offspring of obese dams: Altered expression of hypothalamic 
nutrient sensors, neurogenic factors and epigenetic modulators. Appetite. 2016;99:193-199. 
37. 
Chang GQ, Gaysinskaya V, Karatayev O, Leibowitz SF. Maternal high-fat diet and fetal programming: increased 
proliferation of hypothalamic peptide-producing neurons that increase risk for overeating and obesity. Journal of 
Neuroscience. 2008;28(46):12107-12119. 
38. 
Lemes SF, de Souza ACP, Payolla TB, et al. Maternal Consumption of High-fat Diet in Mice Alters Hypothalamic Notch 
Pathway, NPY Cell Population and Food Intake in Offspring. Neuroscience. 2018;371:1-15. 
39. 
Rajia S, Chen H, Morris MJ. Voluntary post weaning exercise restores metabolic homeostasis in offspring of obese rats. Nutr 
Metab Cardiovasc Dis. 2013;23(6):574-581. 
40. 
Guberman C, Jellyman JK, Han G, Ross MG, Desai M. Maternal high-fat diet programs rat offspring hypertension and 
activates the adipose renin-angiotensin system. Am J Obstet Gynecol. 2013;209(3):262-268. 
41. 
Tamashiro KL, Terrillion CE, Hyun J, Koenig JI, Moran TH. Prenatal stress or high-fat diet increases susceptibility to diet-
induced obesity in rat offspring. Diabetes. 2009;58(5):1116-1125. 
42. 
Seet EL, Yee JK, Jellyman JK, Han G, Ross MG, Desai M. Maternal high-fat-diet programs rat offspring liver fatty acid 
metabolism. Lipids. 2015;50(6):565-573. 
43. 
Bautista CJ, Montano S, Ramirez V, et al. Changes in milk composition in obese rats consuming a high-fat diet. Br J Nutr. 
2016;115(3):538-546. 
44. 
Chen H, Simar D, Morris MJ. Hypothalamic neuroendocrine circuitry is programmed by maternal obesity: interaction with 
postnatal nutritional environment. PLoSONE. 2009;4(7):e6259. 
45. 
Kozak R, Richy S, Beck B. Persistent alterations in neuropeptide Y release in the paraventricular nucleus of rats subjected to 
dietary manipulation during early life. European Journal of Neuroscience. 2005;21(10):2887-2892. 
46. 
Ross MG, Han G, Beall MH, Desai M. Maternal obesity programs offspring hyperphagia via reduced anorexigenic neurons. 
Repro Sci suppl. 2015;22:S-198  
47. 
Paul IM, Savage JS, Anzman SL, et al. Preventing obesity during infancy: a pilot study. Obesity (Silver Spring). 
2011;19(2):353-361. 
48. 
Paul IM, Savage JS, Anzman-Frasca S, et al. Effect of a Responsive Parenting Educational Intervention on Childhood 
Weight Outcomes at 3 Years of Age: The INSIGHT Randomized Clinical Trial. JAMA. 2018;320(5):461-468. 
49. 
Trak-Fellermeier MA, Campos M, Melendez M, et al. PEARLS randomized lifestyle trial in pregnant Hispanic women with 
overweight/obesity: gestational weight gain and offspring birthweight. Diabetes Metab Syndr Obes. 2019;12:225-238. 
50. 
Thangaratinam S, Rogozinska E, Jolly K, et al. Effects of interventions in pregnancy on maternal weight and obstetric 
outcomes: meta-analysis of randomised evidence. BMJ. 2012;344:e2088. 
51. 
Dodd JM, Deussen AR, Mohamad I, et al. The effect of antenatal lifestyle advice for women who are overweight or obese on 
secondary measures of neonatal body composition: the LIMIT randomised trial. BJOG. 2016;123(2):244-253. 
52. 
LeBlanc ES, Smith NX, Vesco KK, Paul IM, Stevens VJ. Weight loss prior to pregnancy and subsequent gestational weight 
gain: Prepare, a randomized clinical trial. Am J Obstet Gynecol. 2021;224(1):99 e91-99 e14. 
53. 
Kashaki M, Samghabadi FM, Bordbar A. Effect of Fortification of Breast Milk in Conjugation with Protein Supplement on 
Neurodevelopment of Preterm Low Birth Weight Infants at 3 Years. Med Arch. 2019;73(5):344-350. 
54. 
Granado M, Fuente-Martin E, Garcia-Caceres C, Argente J, Chowen JA. Leptin in early life: a key factor for the development 
of the adult metabolic profile. Obes Facts. 2012;5(1):138-150. 
55. 
Simmons D, Breier BH. Fetal overnutrition in polynesian pregnancies and in gestational diabetes may lead to dysregulation 
of the adipoinsular axis in offspring. Diabetes Care. 2002;25(9):1539-1544. 
56. 
Kelly AS, Metzig AM, Schwarzenberg SJ, Norris AL, Fox CK, Steinberger J. Hyperleptinemia and hypoadiponectinemia in 
extreme pediatric obesity. Metab Syndr Relat Disord. 2012;10(2):123-127. 
57. 
Frithioff-Bojsoe C, Lund MAV, Lausten-Thomsen U, et al. Leptin, adiponectin, and their ratio as markers of insulin 
resistance and cardiometabolic risk in childhood obesity. Pediatr Diabetes. 2019. 
58. 
Safahani M, Aligholi H, Noorbakhsh F, et al. Switching from high-fat diet to foods containing resveratrol as a calorie 
restriction mimetic changes the architecture of arcuate nucleus to produce more newborn anorexigenic neurons. Eur J Nutr. 
2019;58(4):1687-1701. 
59. 
Safahani M, Aligholi H, Noorbakhsh F, et al. Resveratrol promotes the arcuate nucleus architecture remodeling to produce 
more anorexigenic neurons in high-fat-diet-fed mice. Nutrition. 2018;50:49-59. 
60. 
McNay DE, Briancon N, Kokoeva MV, Maratos-Flier E, Flier JS. Remodeling of the arcuate nucleus energy-balance circuit 
is inhibited in obese mice. J ClinInvest. 2012;122(1):142-152. 
61. 
Sun X, Fukami T, Li T, Desai M, Ross MG. Preferential development of neuropeptide Y/GABA circuit in hypothalamic 
arcuate nucleus in postnatal rats. Brain Res. 2016;1635:27-40. 
62. 
Gluckman PD, Hanson MA, Cooper C, Thornburg KL. Effect of in utero and early-life conditions on adult health and 
disease. N Engl J Med. 2008;359(1):61-73. 
63. 
Ogden CL, Carroll MD, Lawman HG, et al. Trends in Obesity Prevalence Among Children and Adolescents in the United 
States, 1988-1994 Through 2013-2014. JAMA. 2016;315(21):2292-2299. 

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64. 
Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of childhood and adult obesity in the United States, 2011-2012. 
JAMA. 2014;311(8):806-814. 
65. 
Hales CM, Fryar CD, Carroll MD, Freedman DS, Ogden CL. Trends in Obesity and Severe Obesity Prevalence in US Youth 
and Adults by Sex and Age, 2007-2008 to 2015-2016. JAMA. 2018;319(16):1723-1725. 
66. 
Ward ZJ, Long MW, Resch SC, Giles CM, Cradock AL, Gortmaker SL. Simulation of Growth Trajectories of Childhood 
Obesity into Adulthood. N Engl J Med. 2017;377(22):2145-2153. 
67. 
Farrow C, Haycraft E, Mitchell G. Milk Feeding, Solid Feeding, and Obesity Risk: A Review of the Relationships Between 
Early Life Feeding Practices and Later Adiposity. Current Obesity Reports. 2013;2:58-64. 
68. 
Armstrong J, Reilly JJ, Child Health Information T. Breastfeeding and lowering the risk of childhood obesity. Lancet. 
2002;359(9322):2003-2004. 
69. 
Yan J, Liu L, Zhu Y, Huang G, Wang PP. The association between breastfeeding and childhood obesity: a meta-analysis. 
BMC Public Health. 2014;14:1267. 
70. 
Hancox RJ, Stewart AW, Braithwaite I, et al. Association between breastfeeding and body mass index at age 6-7 years in an 
international survey. Pediatr Obes. 2015;10(4):283-287. 
71. 
Owen CG, Martin RM, Whincup PH, Davey-Smith G, Gillman MW, Cook DG. The effect of breastfeeding on mean body 
mass index throughout life: a quantitative review of published and unpublished observational evidence. Am J Clin Nutr. 
2005;82(6):1298-1307. 
72. 
Appleton J, Russell CG, Laws R, Fowler C, Campbell K, Denney-Wilson E. Infant formula feeding practices associated with 
rapid weight gain: A systematic review. Matern Child Nutr. 2018;14(3):e12602. 
73. 
Huang J, Zhang Z, Wu Y, et al. Early feeding of larger volumes of formula milk is associated with greater body weight or 
overweight in later infancy. Nutr J. 2018;17(1):12. 
74. 
Ferguson MC, O'Shea KJ, Hammer LD, et al. Can following formula-feeding recommendations still result in infants who are 
overweight or have obesity? Pediatr Res. 2020;88(4):661-667. 
75. 
Ventura AK, Li R, Xu X. Associations between Bottle-Feeding during Infancy and Obesity at Age 6 Years Are Mediated by 
Greater Infancy Weight Gain. Child Obes. 2020;16(5):316-326. 
76. 
Llewellyn CH, van Jaarsveld CH, Johnson L, Carnell S, Wardle J. Development and factor structure of the Baby Eating 
Behaviour Questionnaire in the Gemini birth cohort. Appetite. 2011;57(2):388-396. 
77. 
Fein SB, Labiner-Wolfe J, Shealy KR, Li R, Chen J, Grummer-Strawn LM. Infant Feeding Practices Study II: study methods. 
Pediatrics. 2008;122 Suppl 2:S28-35. 
78. 
Ventura AK, Silva Garcia K, Meza M, Rodriguez E, Martinez CE, Whaley SE. Promoting Responsive Bottle-Feeding Within 
WIC: Evaluation of a Policy, Systems, and Environmental Change Approach. J Acad Nutr Diet. 2021. 
79. 
Butte NF. Energy requirements of infants. Public Health Nutr. 2005;8(7A):953-967. 
80. 
Savage JS, Birch LL, Marini M, Anzman-Frasca S, Paul IM. Effect of the INSIGHT Responsive Parenting Intervention on 
Rapid Infant Weight Gain and Overweight Status at Age 1 Year: A Randomized Clinical Trial. JAMA Pediatr. 
2016;170(8):742-749. 
81. 
Griffiths LJ, Smeeth L, Hawkins SS, Cole TJ, Dezateux C. Effects of infant feeding practice on weight gain from birth to 3 
years. Arch Dis Child. 2009;94(8):577-582. 
 
22.0 Confidentiality, Privacy and Data Management  
IMPORTANT: The following section is required for all locations EXCEPT Penn State Health and the College of 
Medicine.  Penn State Health and College of Medicine should skip this section and complete “HRP-598 
Research Data Plan Review Form.” In order to avoid redundancy, for this section state “See the Research Data 
Plan Review Form” if you are conducting Penn State Health research. Delete all other sub-sections of section 
22. 
 
For research being conducted at Penn State Health or by Penn State Health researchers only: The research 
data security and integrity plan is submitted using “HRP-598 – Research Data Plan Review Form.”   
 
Refer to Penn State College of Medicine IRB’s “Standard Operating Procedure Addendum: Security and 
Integrity of Human Research Data,” which is available on the IRB’s website. In order to avoid redundancy, for 
this section state “See the Research Data Plan Review Form” if you are conducting Penn State Health 
research. Delete all sub-sections of section 22.  
 
For all other research: complete the following section.  Please refer to PSU Policy AD95 for information 
regarding information classification and security standards and requirements.  It is recommended that you work 
with local IT staff when planning to store, process, or access data electronically to ensure that your plan can be 

Page 32 of 32 (IRB USE ONLY: V. 03/01/2021)  
carried out locally and meets applicable requirements.   If you have questions about Penn State’s Policy AD95 or 
standards or need a consultation regarding data security, please contact security@psu.edu.  
 
See the Research Data Plan Review Form 

 
Version Date: 09/27/21 
 
 
Page 1 of 11 (v.08/30/2021) 
 
 
 
CONSENT FOR RESEARCH 
Penn State College of Medicine 
Penn State Health 
 
 
Title of Project:   
 
Califormula Study: Calibrated Formula Feeding to Optimize Infant Growth  
 
 
Principal Investigator:  
Ian M. Paul, MD, MSc 
 
Address:  
500 University Drive 
 
Hershey, PA 17033 
 
Telephone Numbers:  
Weekdays: 8:00 a.m. to 5:00 p.m. (717) 531-5656.  After hours call (717) 531-8521. 
Ask for the Pediatrics doctor on 24-hour call. 
 
Subject’s Printed Name: _____________________________ 
 
We are asking you to be in a research study. 
Whether or not you take part is up to you. You can choose not to take part. You can agree to take part 
and later change your mind. Your decision will not be held against you, and there will be no penalty or 
loss of benefits to which you are entitled. 
This form gives you information about the research. Please ask questions about anything that is 
unclear to you and take your time to make your choice. 
Some of the people who are eligible to take part in this research study may not be able to give consent 
because they are less than 18 years of age (a minor).  Instead we will ask their parent(s)/guardian(s) to 
give permission for their participation in the study, and we may ask them to agree (give assent) to take 
part.  Throughout the consent form, when we say “you”, we mean you or your child.   
 
KEY INFORMATION   
The following is a short summary of this study to help you decide whether or not to be a part of this 
research. More detailed information is provided later in this form. If you have any questions, be sure to 
ask the study team.  
 
Why am I being invited to take part in this research study? 
We are asking you to take part in this voluntary research study because we are trying to learn how to 
promote optimal growth for exclusively formula fed babies for mothers with a pre-pregnancy body mass 
index of 25 or more. 
 
What is the purpose of this research study? 
The purpose of this voluntary research study is to determine if calibrated formula feeding recommendations 
can promote optimal growth for the first 6 months after birth for mothers with a pre-pregnancy 
body mass index of 25 or more. . 
 
How long will the research study last? 
Your participation in this study will last approximately 6 months. 

 
Version Date: 09/27/21 
 
 
Page 2 of 11 (v.08/30/2021) 
 
 
What will I need to do? 
Participating infants in the intervention group will be seen monthly until age 6 months where they will be 
weighed and measured, and parents will complete surveys related to volume of formula consumed, infant 
appetite, parent feeding style, and infant temperament. Control group infants will follow the same 
procedures, but will not have scheduled visits at ages 3 and 5 months. Instead their visits will correspond to 
well child clinic visits at ages 1, 2, 4, and 6 months. 
  
What are the main risks of taking part in the study? 
For this study, the main risks to know about are: There is an unlikely risk that a reduction in formula intake 
could lead to temporary growth faltering (i.e. failure-to-thrive), though this would be self-limited and could 
be addressed by subsequently increasing formula intake. There is also a risk of loss of confidentiality if your 
information or your identity is obtained by someone other than the investigators, but precautions will be 
taken to prevent this from happening. The confidentiality of your electronic data created by you or by the 
researchers will be maintained to the degree permitted by the technology used. Absolute confidentiality 
cannot be guaranteed. 
 
What are the possible benefits to me that may reasonably be expected from being in the research?  
We cannot promise any benefits to you from taking part in this study. However, possible benefits include 
the improvement of infant growth trajectories, reduction of rapid infant weight gain, and reduction of the 
likelihood of overweight during infancy and beyond for participants. Results of the study may benefit other 
people in the future by helping us learn more about formula feeding guidelines for infants at risk of 
becoming overweight. 
 
What happens if I do not want to be in this research? 
Participation in research is completely voluntary. You can decide to participate or not to participate.  
You may choose not to take part in this research study.  
 
DETAILED INFORMATION 
The following is more detailed information about this study in addition to the information listed above. 
 
1.   Why is this research study being done?    
This research is being done to find out if formula feeding recommendations that are calibrated using age 
and weight specific caloric intake recommendations can prevent excessive infant weight gain and reduce 
overweight in the first 6 months after birth among infants born to mothers with a pre-pregnancy body 
mass index of 25 or more electing to exclusively formula feed their infants. 
 
Approximately 60 people will take part in this research study at Penn State Health.  
 
2.   What will happen in this research study? 
If you agree to be in this research, you will first review and sign this consent form before any research 
procedures or tests are performed. You will be given a copy of the signed consent form for your records.  
 
Research Procedures and Data Collection: 
Visit 1: Birth – 1 month of age 
This visit will occur during the birth hospitalization or at an outpatient clinic prior to the 1 month well child 
visit. 
• 
Your child’s weight and length will be obtained and recorded for the research.  

 
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Page 3 of 11 (v.08/30/2021) 
 
• 
You will be asked for demographic data through an electronic REDCap survey. 
• 
A study team member will obtain your contact information.  
• 
You will be given a diary card to record volume of infant formula consumed for the three days prior 
to the 1 month well child visit (Visit 2) and all subsequent visits. 
 
Visit 2: 1 Month Visit (24-41 days) 
• 
Your child’s weight and length will be obtained and recorded for the research.  
• 
You will be asked some survey questions; 
o Baby Eating Behavior Questionnaire 
o Babies Basic Needs Questionnaire 
o Infant Feeding Practices 
• 
You will complete your diary cards for the 3 days following the visit 
• 
You will complete your diary cards each day for the 3 days prior to the next study visit 
 
For the intervention group only: 
• 
Study coordinators will provide you with a range of formula volume to be consumed 
• 
You will be given instruction to prepare the formula volume in each bottle on the lower end of what 
you anticipate the infant will eat. 
• 
You will be provided with handouts on hunger/satiety cues and calming a fussy baby 
• 
You will be given a copy of a Bottle Feeding Basics video, “Happiest Baby on the Block”, and a video 
demonstrating responsive bottle feeding 
 
Visit 3: 2 Month Visit (42-77 days) 
• 
Your child’s weight and length will be obtained and recorded for the research.  
• 
You will complete your diary cards for the 3 days following the visit 
• 
You will complete your diary cards each day for the 3 days prior to the next study visit 
 
For the intervention group only:  
• 
You will be given recommended formula volumes for the next month based on Visit 2 procedures 
 
Visit 4: 3 Month Visit (78-109 days)  
For the intervention group only: 
• 
Your child’s weight and length will be obtained and recorded for the research.  
• 
You will complete your diary cards for the 3 days following the visit 
• 
You will complete your diary cards each day for the 3 days prior to the next study visit 
• 
You will be given recommended formula volumes for the next month based on Visit 2 and 3 
procedures 
 
Visit 5: 4 Month Visit (110-140 days) 
• 
Your child’s weight and length will be obtained and recorded for the research.  
• 
You will complete your diary cards for the 3 days following the visit 
• 
You will complete your diary cards each day for the 3 days prior to the next study visit 
 
For the intervention group only: 
• 
You will be given recommended formula volumes for the next month based on Visit 2 and 3 
procedures 
• 
You will be provided with handouts on soothing fussy infants and feeding recommendations 

 
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Visit 6: 5 Month Visit (141-171 days) 
For the intervention group only: 
• 
Your child’s weight and length will be obtained and recorded for the research.  
• 
You will complete your diary cards for the 3 days following the visit 
• 
You will complete your diary cards each day for the 3 days prior to the next study visit 
• 
You will be given recommended formula volumes for the next month based on Visit 2 and 3 
procedures 
 
Visit 7: 6 Month Visit (172-210 days) 
• 
Your child’s weight and length will be obtained and recorded for the research.  
• 
You will be asked some survey questions; 
o Baby Eating Behavior Questionnaire 
o Infant Feeding Styles Questionnaire  
o Baby’s Basic Needs Questionnaire 
o Infant Feeding Practices 
 
What are my responsibilities if I take part in this research?  
If you take part in this research, your major responsibilities will include: Participating infants in the 
intervention group will be seen monthly until age 6 months where they will be weighed and measured, and 
parents will complete surveys related to volume of formula consumed, infant appetite, parent feeding style, 
and infant temperament. Control infants will follow the same procedures, but will not have scheduled visits 
at ages 3 and 5 months. Instead their visits will correspond to well child clinic visits at ages 1, 2, 4, and 6 
months. Most study visits, with the exception of Visits 4 and 6, will occur in conjunction with regular well 
child care, adding ~15 minutes to each visit. 
 
3.   What are the risks and possible discomforts from being in this research study?   
Loss of Confidentiality: There is a risk of loss of confidentiality if your information or your identity is obtained 
by someone other than the investigators, but precautions will be taken to prevent this from happening. The 
confidentiality of your electronic data created by you or by the researchers will be maintained as required by 
applicable law and to the degree permitted by the technology used. Absolute confidentiality cannot be 
guaranteed. 
 
Growth Faltering: There is an unlikely risk that a reduction in formula intake could lead to temporary growth 
faltering (i.e. failure-to-thrive), though this would be self-limited and could be addressed by subsequently 
increasing formula intake. 
 
4.   What are the possible benefits from being in this research study?    
4a.  What are the possible benefits to me? 
There is no guarantee that you will benefit from this research. The possible benefits you may 
experience from this research study include the improvement of infant growth trajectories, reduction of 
rapid infant weight gain, and reduction in the likelihood of overweight during infancy and beyond for 
participants. 
  
4b. What are the possible benefits to others? 
Medical science may gain further understanding of formula feeding guidelines for infants at risk of 
becoming overweight.  
  

 
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5.   What other options are available instead of being in this research study? 
You may choose not to be in this research study. 
 
6.   How long will I take part in this research study? 
If you agree to take part, it will take you about 6 months to complete this research study. For the 
intervention group, you will be asked to visit the research site 2 times.  
 
7.   How will you protect my privacy and confidentiality if I decide to take part in this research study? 
7a.  What happens to the information collected for the research? 
Efforts will be made to limit the use and sharing of your personal research information to people who 
have a need to review this information. Reasonable efforts will be made to keep the personal 
information in your research record private. However, absolute confidentiality cannot be guaranteed, 
and there may be situations where disclosure is required by law.  
 
In our research files at Penn State Health (PSH) and Penn State College of Medicine (PSU) we will 
include these identifiers: you and your child’s name/initials, street address, telephone number, date of 
birth, medical record number, electronic mailing address, and a code. 
• 
 A list that matches your name with your code number will be kept in a locked file in the Pediatric 
Research Recourse Office 
• 
Your research records will be labeled with a code number and your initials and will be kept in a safe 
area in the Pediatric Research Resource Office 
• 
A copy of this signed consent form will be included in your PSH medical record. This means that 
other PSH healthcare providers will know you are in this study.  
 
For research records sent to UCLA, you will be identified by a study code number and all elements of 
dates. 
 
This research is covered by a Certificate of Confidentiality from the National Institutes of Health. This 
means that the researchers cannot disclose information that identifies you to anyone not connected 
with the research.  This protection also prevents this information from being used or disclosed for legal 
proceedings, such as being accessed through a court order. The Certificate of Confidentiality however 
does not prevent disclosures required by law, such as information about child abuse or neglect and 
harm to yourself or others.  Also, your information may be disclosed in accordance with any consent 
you provide, including for your medical treatment or use in other research. 
 
In the event of any publication or presentation resulting from the research, no personally 
identifiable information will be shared. 
 
7b. What will happen to my research information and/or samples after the study is completed? 
We may use your research information in future studies or may share your information with other 
investigators for future research without your additional informed consent. Before we use or share 
your information or samples we will remove any information that shows your identity. 
 
7c. How will my identifiable health information be used? 
Instructions: Include the following information in this section: 
• 
Section 7c is mandatory if the research creates, obtains, uses, and/or discloses protected 
health information (PHI) about the research subjects.   

 
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• 
Do not include any part of Section 7c unless the research fits the above criteria. 
• 
If the research involves prisoners, add the following statement: “If you are a prisoner, your 
medical records may also be given to officials and agencies within the criminal justice system 
when necessary and permitted by law.” 
• 
If applicable, describe any limitations on confidentiality based on possible legal issues. For 
example, if the research team is likely to uncover abuse, neglect, or reportable diseases, 
explain that this information may be disclosed to appropriate authorities. For example, “As 
with information contained in research records generally, we will use and disclose your 
identifiable health information  when we are required to do so by law, such as for laws that 
require us to report child abuse or abuse of elderly or disabled adults. Additionally, unless 
this study is covered by a Certificate of Confidentiality, we will also comply with legal 
request or orders that require us to disclose your identifiable health information.” 
If you give your consent, health information that can be traced to you will be collected for this research 
study. In general, under federal law, health information is private. However, there are exceptions to this 
rule, and you should know who may be able to see, use, and share your health information for research 
and why they may need to do so. We will use and disclose your information only as described in this 
form and in the PSH Privacy Notice. 
The research team may use the following health information: 
• 
Past, present, and future medical records, including identifiable information 
• 
New health information from tests, procedures, visits, interviews, or forms filled out as part of 
this research study. 
 
The following people/groups may see, use, and share your identifiable health information: 
• 
PSH/PSU research staff involved in this study 
• 
The PSH/PSU Institutional Review Board (IRB), a group of people who review the research study 
to protect subjects’ rights and welfare 
• 
The PSH/PSU Human Research Protection Program (HRPP) 
• 
The PSH/PSU Research Quality Assurance Office 
• 
Non-research staff within PSH/PSU who need this information to do their jobs (such as for 
treatment, payment (billing), or health care operations) 
• 
Federal and state agencies (such as the U.S. Food and Drug Administration, the Office for 
Human Research Protections, the Department of Health and Human Services, the National 
Institutes of Health, and other U.S. or foreign government bodies that oversee or review 
research) 
• 
People or groups that we hire to do work for us, such as data storage companies, insurers, and 
lawyers 
• 
Organizations that provide independent accreditation and oversight of hospitals and research 
• 
Public health and safety authorities (for example, if we learn information that could mean harm 
to you or others, we may need to report this, as required by law) 
• 
The sponsor(s) of this study, monitors and auditors, and other people or groups it hires to help 
perform this research 
• 
Other researchers and medical centers outside of PSU and Penn State Health that are part of 
this study and their IRBs 
• 
Researchers from other campuses of Penn State University who are part of this study  
• 
A group that oversees the data (study information) and safety of this research 
 

 
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These groups may also review and/or copy your original PSH/PSU records while looking at the results of 
the research study.  It is possible that some of the other people/groups who receive your health 
information may not be required by Federal privacy laws to protect your information. We share your 
information only when we must, and we ask anyone who receives it from us to protect your privacy.  
 
{Add the following paragraph for investigator-initiated research studies if applicable.}  
Sometimes a Principal Investigator or other researcher moves to a different institution. If this happens, 
your identifiable health information and samples may be shared with that new institution and their 
oversight offices. PHI will be shared securely and under a legal agreement to ensure it continues to be 
used under the terms of this consent and HIPAA authorization. 
 
We may remove identifying information from your protected health information.  Once we do this, the 
remaining information will not be subject to the privacy laws.  Information without identifiers may be 
used or disclosed with other people or organizations for purposes besides this study. 
 
Because research is an ongoing process, your permission for the use, storage and sharing of your health 
information will continue indefinitely.  
 
Your privacy rights: 
• 
You have the right to refuse to sign this form that allows us to use and share your health 
information for research; however, if you don’t sign it, you will not be able to take part in this 
research study. 
• 
You have the right to withdraw your permission for us to use or share your health information 
for this research study. If you want to withdraw your permission, you must notify the person in 
charge of this research study in writing using the address on the front of this form. Once 
permission is withdrawn, you cannot continue to take part in the study.  
• 
If you withdraw your permission, we will stop collecting health information about you for this 
study; we may continue to use and share your health information that we already have if it is 
necessary for safety and scientific soundness of the research study; and we will not be able to 
take back information that has already been used or shared with others.  
• 
You have the right to see and get a copy of your health information that is used or shared for 
treatment or for payment. However, you may not be allowed to see or copy certain health 
information that is a part of this research study. This is only for the period of the study. You will 
be allowed to see that information when the entire research study is complete.  
            
8.   What are the costs of taking part in this research study? 
8a. What will I have to pay for if I take part in this research study?  
For costs of tests and procedures that are only being done for the research study: 
• 
You and/or your insurance company will not be charged for the cost of any tests or procedures that 
are required as part of the research and are outside the standard of care (what is normally done) 
for your condition.  
• 
Examples of research-related tests and procedures that may be provided at no cost to you may 
include: visits to the study site, procedures, and/or questionnaires. Talk to the study team about 
which items and procedures this includes. 
 
For costs of medical services for care you would receive even if you were not in this research study: 
• 
You and/or your insurance company will be responsible for the cost of routine medications, 
tests and procedures that you would receive even if you were not in this research. 

 
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• 
You and/or your insurance company will be billed for the costs of these routine tests and 
procedures in the usual manner. 
• 
You will be responsible for any co-payments, co-insurance and deductibles that are standard 
for your insurance coverage.  
• 
You will be responsible for any charges not reimbursed by your insurance company. 
• 
Some insurance companies may not pay for routine costs for people taking part in research 
studies. Before deciding to be in this research you should check with your insurance company 
to find out what they will pay for. 
 
If you have any questions about costs and insurance, ask the research study doctor or a member of the 
research team.  
 
8b. What happens if I am injured as a result of taking part in this research study? 
It is possible that you could develop complications or injuries as a result of being in this research study. 
If you experience a side effect or injury and emergency medical treatment is required, seek 
treatment immediately at any medical facility. If you experience a side effect or injury and you 
believe that emergency treatment is not necessary, you should contact the principal investigator 
listed on the first page of this consent form as soon as possible and the principal investigator will 
arrange for medical treatment. You should also let any health care provider who treats you know 
that you are in a research study. 
 
PSH/PSU compensation for injury 
 
There are no plans for PSH/PSU to provide financial compensation or free medical treatment 
for research-related injury.  
 
If an injury occurs, medical treatment is available at the usual charge.  
 
Costs will be charged to your insurance carrier or to you.  
 
Some insurance companies may not cover costs associated with research injuries.  
 
If these costs are not covered by your insurance, they will be your responsibility. 
 
When you sign this form you are not giving up any legal right to seek compensation for injury.  
 
9. Will I be paid to take part in this research study? 
You will receive $50 for each study visit completed for your participation in this research study for a 
total of $250-$300 depending on which study group you are assigned to (control vs. intervention).  If you 
do not complete the study for any reason, you will be paid for the visits you have completed. The 
payment will be provided by Greenphire Clincard. 
 
This reimbursement will be issued by an external company called Greenphire, which will issue your 
reimbursement. You will be issued a ClinCard, which is a debit card that your funds are loaded onto and 
can be used at your discretion. The research team will give Greenphire some personal information about 
you, as described below. Greenphire will only use your personal information to process this 
reimbursement and will not share it with anyone for any other purpose. Details of the debit card 
system are explained on an additional sheet. If you lose the card, you may be responsible for 
the replacement fee.  
  
When a visit is completed, funds will be approved and loaded onto your card. The funds will be available 
within 2-3 business days. In order to assign a ClinCard to you and load funds onto 

 
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the ClinCard, Greenphire will need your Study/Subject ID, Name, Address, Social Security Number, and 
date of birth. 
 
You will have the option to receive updates related to payment alerts via text message and/or email 
message. Standard text messaging rates will apply. In order to send you messages Greenphire will need 
your Mobile Phone Number and/or E-mail Address.  
 
Payment received as compensation for participation in research is considered taxable income.  If 
payments from Greenphire exceed $600 in any one calendar year, you will be required to provide your 
social security number so that Greenphire can file a 1099 (Miscellaneous Income) form on behalf of 
Penn State. Payment totals are calculated across all research participation at Penn State if you 
participate in multiple studies.   
 
10. Who is paying for this research study? 
Instructions: Include the following information in this section: 
• 
Funding disclosure: Disclose what grantors, institution(s) (e.g., NIH) or companies are 
involved in the research through funding or grants. If none, say so.  
• 
Conflict of Interest: Include information about any consultative relationships with the 
sponsor or financial or business interests the investigators may have related to this 
research.  
 
 
The institution and investigators are receiving a grant from The Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD) and the University of California at Los 
Angeles (UCLA) to support this research.  
 
The sponsors, NICHD and UCLA are paying PSH/PSU for the research to be done.  
 
11.  What are my rights if I take part in this research study? 
Taking part in this research study is voluntary.  
 
You do not have to be in this research.  
 
If you choose to be in this research, you have the right to stop at any time.  
 
If you decide not to be in this research or if you decide to stop at a later date, there will be no 
penalty or loss of benefits to which you are entitled.  
 
You may withdraw your participation from this study at any time. We will collect and use all of the data 
collected up to the point of withdrawn participation.  
 
During the course of the research you will be provided with any new information that may affect your 
health, welfare or your decision to continue participating in this research. 
 
12. If I have questions or concerns about this research study, whom should I call?     
Please call the head of the research study Dr. Ian Paul, at (717) 531-5656 or the Pediatric doctor on 24-hour 
call at (717) 531-8521 if you: 
 
Have questions, complaints or concerns about the research. 
 
Believe you may have been harmed by being in the research study.   
 

 
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Page 10 of 11 (v.08/30/2021) 
 
You may also contact the research protection advocate in the PSU Human Research Protection Program 
(HRPP) at (814) 865-1775 if you: 
 
Have questions regarding your rights as a person in a research study. 
 
Have concerns, complaints or general questions about the research.  
 
Have questions about your privacy and the use of your personal health information.  
 
You may also call this number if you cannot reach the research team or wish to offer input or to talk 
to someone else about any concerns related to the research.  
 
You may visit the Penn State College of Medicine’s Clinical Research web site at 
http://med.psu.edu/clinical-research/faqs  for: 
 
Information about your rights when you are in a research study;  
 
Information about the Institutional Review Board (IRB), a group of people who review the research 
to protect your rights; and  
 
Links to the federal regulations and information about the protection of people who are in research 
studies. If you do not have access to the internet, copies of these federal regulations are available 
by calling the HRPP at (814) 865-1775. 
 
A description of this clinical trial will be available on https://www.ClinicalTrials.gov, as required by U.S. Law. 
This Web site will not include information that can identify you. At most, the Web site will include a 
summary of the results. You can search this Web site at any time. 
 
INFORMED CONSENT AND AUTHORIZATION TO TAKE PART IN RESEARCH  
 
Signature of Person Obtaining Informed Consent 
 
Your signature below means that you have explained the research to the subject or subject 
representative, provided the subject or subject representative an opportunity to discuss and consider 
whether or not to participate in the research, and have answered any questions about the research. 
 
______________________________ 
 
__________ 
______  
________________ 
Signature of person who explained this research Date 
 
Time 
 
Printed Name 
 
(Only approved investigators for this research may explain the research and obtain informed consent.)   
 
Signature of Person Giving Informed Consent and Authorization 
Before making the decision about being in this research you should have: 
• 
Discussed this research study with an investigator,  
• 
Read the information in this form, and 
• 
Had the opportunity to ask any questions you may have.  
Your signature below means that you have received this information, have asked the questions you currently 
have about the research and those questions have been answered. You will receive a copy of the signed and 
dated form to keep for future reference. 
 
Signature of Subject 
 
By signing this consent form, you indicate that you voluntarily choose to be in this research and authorize 
your information to be used and shared as described above.  
 
 

 
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___________________________ 
__________ 
______  
________________  
Signature of Subject 
 
 
Date 
 
Time 
 
Printed Name 
 
 
Signature of Parent(s)/Guardian for Child 
 
By signing this consent form, you indicate that you permit your child to be in this research and authorize 
your child’s information to be used and shared as described above.  
 
 
_____________________________________________ 
Printed name of child 
 
 
___________________________ 
__________ 
______  
________________  
Signature of Parent/Guardian 
 
Date 
 
Time 
 
Printed Name 
 
 Parent 
 Individual legally authorized to consent to the child’s general medical care. (See note below.) 
 
Note:  Investigators are to ensure that individuals who are not parents can demonstrate their legal authority to 
consent to the child’s general medical care. Contact legal counsel if any questions arise.