Mobile Health Intervention to Promote Positive Infant Health Outcomes in Guatemala
Phase: NA
Conditions: Infant Development
Sponsor: Children's Hospital Los Angeles

Title: Mobile Health IntervenƟon to Promote PosiƟve Infant Health Outcomes in Guatemala 
NCT Number: NCT05106894 
Date of Document: 8/9/2023  
PI: Beth A. Smith, PT, DPT, PhD, Email: bsmith@chla.usc.edu , Children’s Hospital Los Angeles 

Protocol Amendment, dated August 9, 2023 
 
Wuqu’ Kawoq | Maya Health Alliance (Maya Health Alliance or MHA) 
Protocol Summary Form 
 
NAME OF PRINCIPAL INVESTIGATOR: 
 
Beth Smith (CHLA) 
Peter Rohloff (WK) 
 
PROTOCOL TITLE: Mobile Health to Promote Positive Infant Outcomes in Guatemala 
 
SOURCE OF FUNDING: United States National Institutes of Health 
 
SPECIFIC AIMS: 
(State objectives concisely, describe hypothesis tested) 
 
Investments made early in the life course—especially efforts directed at supporting 
development in the first two years of life—are more cost-effective than interventions later 
in childhood and can permanently enhance development (5-9). Consequently, one of the 
most effective and evidence-based interventions for ensuring healthy child development is 
the promotion of high-quality, nurturing care by primary caregivers in the first months of 
life (10) (See Table 1). 
 
Table 1 
STUDY AIMS 
  
Aim 1 
Aim 2 
Aim 3 
Study Design 
Prospective single 
visit or repeated visit 
small group 
interviews 
Two-arm prospective, 
longitudinal, 
randomized, 6-month 
pilot intervention to 
assess the 
implementation 
characteristics of the 
technology—usability, 
acceptability, and 
sustainability.  
Outcomes assessed at 6 
months. 
Two-arm prospective, 
longitudinal, 
randomized 18-month 
intervention with 
developmental 
outcomes assessed at 
18 months to help 
determine the 
effectiveness of a 
smartphone-based, 
real-time caregiver 
feedback intervention.   
Study 
Procedures 
Focus groups 
The intervention arm 
(n=20) will receive the 
smartphone 
application.  The control 
arm (n=20) will receive 
printed caregiving 
materials.  
The intervention arm 
(n=110) will receive 
the smartphone 
application.  The 
control arm (n=110) 
will receive printed 
caregiving materials.  
Recruitment 
Up to 20 caregivers 
and up to 20 Maya 
Health Alliance staff 
will be recruited for 
formative focus 
groups 
40 caregivers and their 
infants from birth to 4 
weeks of age  
220 first-time 
caregivers and their 
infants from birth to 4 
weeks of age  

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Duration 
Focus groups will be 
1-2 hours in 
duration. 
6 months with 7 home 
visits by research staff 
(initial visit and monthly 
follow-up visits months 
1-6) 
18 months with 8 
home visits by 
research staff (initial 
visit, follow-up visits 
every 3 months and 1 
visit at the end of the 
study for BSID 4). 
Outcome 
Measures 
To develop a new 
mHealth smartphone 
application to engage 
primary caregivers 
directly in the active 
monitoring of their 
infants’ 
development, and to 
provide tailored 
feedback and 
support for the 
provision of 
nurturing care. 
To collect data on 
usability and 
acceptability of the 
technology to end users 
and determine effect 
size of clinical 
effectiveness (infant 
development 
outcomes).  The 
primary outcome is 
BSID-4 as a measure of 
infant developmental 
outcomes.  
To test clinical 
effectiveness 
(improved infant 
development 
outcomes and 
caregiving behaviors). 
The primary outcome 
is BSID-4 as a measure 
of infant 
developmental 
outcomes. The 
secondary outcomes 
are quality of infant-
caregiver interaction 
(NCAST feeding scale) 
and quality of the 
home environment 
(HOME scale).   
 
 
• 
In Aim 1, we will develop a new mHealth smartphone application which can be used 
to engage primary caregivers directly in the active monitoring of their infants’ 
development, and to provide tailored feedback and support for the provision of 
nurturing care. Aim 1 will use focus groups, an Agile Design process, and the RE-AIM 
framework for assessment.  
• 
In Aim 2, we will prospectively assess the implementation characteristics of the 
technology—usability, acceptability, and sustainability—for caregivers over time for 
different periods of infant development. Aim 2 will use a prospective, longitudinal, six-
month pilot intervention, enrolling 40 caregivers and their infants from birth to 4 weeks 
of age (using simple randomization to assign them to either the 6-month smartphone 
intervention (n=20) or control (receipt of printed parenting materials, n=20).  
• 
Aim 3 is similar to Aim 2 only 1) it is adequately powered based on Aim 2 results with 
110 participants per group, 2) the developmental outcome (BSID-4) will be measured 
at 18 months in Aim 3 instead of 6 months in Aim 2, and 3) we will add assessment of 
quality of infant-caregiver interaction as measured by the Nursing Child Assessment 
Satellite Training (NCAST) feeding scale and Home Observation for the Measurement 
of the Environment (HOME scale).    
 
 
 
BACKGROUND AND SIGNIFICANCE: 
(Brief paragraph summarizing any information important for understanding the study and proposed 
research procedures) 

Protocol Amendment, dated August 9, 2023 
 
 
According to recent estimates, 43% of children under age 5 residing in low- and middle-
income countries (LMICs)—250 million children in total—are at risk of not reaching their 
developmental potential due to living in environments with malnutrition, poverty, and lack 
of early stimulation. (3-5) Most community programs rely on basic growth indicators or 
parent-reported concerns, techniques which are indirect measures of development and not 
sensitive in infancy. As a result, data on the onset of developmental disabilities in infants 
are almost completely missing, and early interventions are begun well after significant 
effects have already occurred. Technologies to support earlier identification of atypical 
development 
would 
therefore 
support 
earlier 
intervention 
and 
improved 
neurodevelopmental outcomes. 
 
Numerous studies in LMICs have intervened with caregivers to promote infant 
development. However, most have involved face-to-face interactions between frontline 
staff--usually community health workers--and caregivers (6,11-14). While this is an 
effective strategy, it may cause health system strain, as it relies on health workers who have 
many competing demands on their time. This “task-shifting” can lead to overburdening 
and deterioration of intervention quality (15-18). For infant development, mHealth 
technologies have the potential to solve this problem by providing tailored content directly 
to caregivers, involving and empowering them to promote infant development, promoting 
and facilitating interactions with health workers when areas of concern are identified and, 
therefore, expanding the reach of healthcare systems.  
 
This project will use mHealth to provide caregiver feedback and anticipatory guidance 
around three key infant caregiving domains: sleep, feeding, and activity/caregiver 
interaction. For each of these domains, evidence-based international guidelines exist, 
published by the World Health Organization (WHO) and UNICEF (63). Recent efforts by 
our team have included cultural adaptations of these guidelines to Guatemala, including 
UNICEF/WHO/s Care for Child Development (63). These adapted caregiver 
recommendations will form the basis for the content to be incorporated into the smartphone 
app during this project. 
 
The purpose of this Android app is to provide general anticipatory age-based guidance to 
caregivers in Guatemala on infant growth, nutrition, sleep, and development. The app is 
intended to increase patient awareness, education, and empowerment, and support 
patient-centered health-care. The app is not intended for use in the diagnosis of diseases 
or conditions, or in the cure, mitigation, treatment, or prevention of disease by aiding 
clinical decision making. Reinforcing feedback based on the entered data will be 
provided via direct interaction (by phone/text) with health workers from Maya Health 
Alliance for problem areas. No data will be used clinically. The intended users of the app 
are caregivers in rural Guatemala.  The app uses a standard Android registration 
workflow. A caregiver (end user) registers using their name and a password. Either 
preferred phone number or email is also collected to assist the end user with password 
recovery if they forget their password. After registering as a user, the caregiver (end user) 
can then enter their infant child's information into the app (name, sex, date of birth).   
Data collected on the app will sync to a secure cloud-based server backend  at the project 
partner Wuqu' Kawoq in Guatemala. Only implementing staff at Wuqu' Kawoq have 

Protocol Amendment, dated August 9, 2023 
 
direct access to this data. Deidentified data (i.e. survey responses)from the server will be 
shared by Wuqu' Kawoq staff with the study team. Information from the mobile app will 
not be placed in medical records. The mobile app will be available in Spanish and not in 
Kaqchikel since this language is mostly an oral language read by very few.  
 
 
RESEARCH DESIGN AND METHODS: 
(Briefly describe study design, anticipated enrollment, eligibility criteria, study procedures. If study 
involves a medical intervention, describe standard of care and how study procedures differ from 
standard of care. Explicitly describe how risk to subjects is being minimized. Explicitly describe 
methods being used to ensure subject safety, including criteria for removing a subject from the 
study if applicable) 
 
Study Design: 
This research will be conducted in Tecpán, Guatemala where Wuqu’ Kawoq | Maya 
Health Alliance has its main clinical office.  
 
Aim 1 Study Design: Prospective single visit or repeated visit small group interviews. We 
will conduct focus groups to gather end-user perspectives on a smartphone application to 
support caregivers.  
 
Aim 2 Study Design. Two-arm prospective, longitudinal, randomized 6-month pilot 
intervention. We will assess the implementation characteristics of the smartphone 
application through a longitudinal, six-month usability trial, to determine caregiver 
engagement over time and to assess the perceived usefulness of the application.  Aim 2 
will complement the technical work in Aim 1 by conducting a larger-scale pilot 
implementation of the caregiver smartphone application. Aim 2 is designed to collect data 
on usability and acceptability of the technology to end users and determine effect size of 
clinical effectiveness (infant development outcomes). 
 
Aim 3 Study Design. Two-arm prospective, longitudinal, randomized 18-month 
intervention with developmental outcomes assessed at 18 months. Aim 3 will determine 
the effectiveness of a smartphone-based, real-time caregiver feedback intervention to 
promote positive infant developmental outcomes and improved caregiving behaviors.  Aim 
3 will test clinical effectiveness (improved infant development outcomes and caregiving 
behaviors).  
 
Eligibility criteria: 
  
Criteria for all aims of the study will be as follows:  
 
Inclusion Criteria: Consenting first-time caregivers with an infant in the eligible 
age range (0-4 weeks), singleton, full-term (>37 weeks) birth. For stakeholder 
interviews and application testing phases, any consenting caregiver with an infant 
less than 6 months of age and a smartphone, or any Maya Health Alliance staff 
member who works with infants will be eligible to participate.   
 

Protocol Amendment, dated August 9, 2023 
 
Exclusion Criteria: Presence of acute malnutrition/wasting or severe medical illness 
(heart disease, kidney disease, congenital abnormality), medical need for 
supplementation of breastfeeding, caregiver not literate (our exploratory feasibility 
data in preparation for this proposal shows that >95% of first time caregivers in the 
region are now literate).  
 
 
Recruitment:  
 
The caregivers participating in both phases (Aim 1, design/formative phase; Aim 2, 
implementation/trial phase) will be recruited from among first-time caregivers receiving 
services at a major maternal-child wellness clinic run by Maya Health Alliance out of their 
main office in Tecpán Guatemala. 
 
For Aim 1, up to 20 caregivers will be recruited in this fashion for formative focus 
groups. Up to 20 Maya Health Alliance staff will be recruited.  All staff who work in 
early child development and nutrition programs will be eligible. Recruitment will be by 
word of mouth.  
 
These participants will then be invited, as they are willing, to participate in the formative 
agile design phase of the app. Subsequently, in Aims 2 and 3, 40 and 220 (respectively) 
additional caregiver/infant dyads will be recruited in the same fashion into participate in 
the prospective implementation trial. 
 
Study Procedures: 
 
Aim 1: Focus groups: User perspectives will be collected using a focus group format, 
facilitated by a research staff at Maya Health Alliance under the supervision of Dr. 
Rohloff, who is fluent in Spanish and Kaqchikel Maya, so that speakers who prefer either 
language can be included. Convenience samples of caregivers who own smartphones and 
have infants 0-6 months old will be recruited from Maya Health Alliance clinics, taking 
care to recruit both male and female caregivers. These will be supplemented by additional 
focus groups with Maya Health Alliance early child development staff (nurses, 
technicians, physicians). Four focus groups (1-2 hours in duration) will be conducted, 
with 5-10 participants each (2 groups caregivers, 2 groups staff). Additional focus 
groups, up to 5 total, will be held as needed so that preference can be given to those who 
prefer to conduct the sessions in Spanish or Kaqchikel.  During the focus groups, 
participants will be asked about their opinions around their experience with smartphone 
applications and understanding of an mHealth application in supporting caregiving. 
Participants will also be shown and have the opportunity to work with examples of 
existing parenting/caregiving applications and will be asked to provide feedback on the 
usefulness of these existing applications. 
 
Aim 
2: 
Two-arm 
prospective, 
longitudinal, 
randomized 
6-month 
pilot 
intervention. Recruited caregivers/infants will undergo simple randomization to one of 2 
arms. The control arm (n=20) will receive printed caregiving materials based on 
recommendations outlined in Table 2. The intervention group (n=20) will receive the 

Protocol Amendment, dated August 9, 2023 
 
smartphone application. Study staff will make an initial home visit (less than an hour) to 
install the application on the caregiver phone and demonstrate use and collect baseline data. 
The baseline data will include: infants/caregivers demographics, poverty scorecard, 
infant’s pre- and post-natal medical history and anthropometrics. The baseline data will be 
collected using an electronic RedCap form. “Teach back” demonstration will be used to 
assure understanding. Subsequently, in the intervention arm, staff will make monthly visits 
(approximately 15 minutes duration) to assess functionality of the smartphone and answer 
questions/reinforce use. In the control arm, staff will make monthly visits (approximately 
15 minutes duration) to ask if there are questions about the printed caregiving materials. 
The smartphone app in the intervention arm will function as follows. On 3 consecutive 
days per week it will query caregivers to complete a 20-second survey that asks about 1) 
frequency, amount and type of feeding, 2) frequency and duration of sleeping, or 3) 
frequency, duration and type of activity and interaction, subsequently providing reinforcing 
feedback based on entered data and permitting direct interaction (by phone/text) with 
health workers from Maya Health Alliance for problem areas identified as described above. 
On non-survey days, the app will provide age-based anticipatory guidance (Table 2). For 
the 6-month study, there will be a total of 9 visits.  The study will last 6 months and consist 
of 7 home visits by research staff (initial visit and monthly follow-up visits months 1-6) 
and 2 BSID-4 assessment visits (at baseline and conclusion). The BSID-4 can be completed 
in a space provided by the institution or close to where the subject lives to ensure comfort 
for their child.  During the home visits, research staff will also collect the following 
information from all subjects (intervention and control): Infant/caregiver demographics 
(first visit), infant’s medical history (first visit), caregiver poverty scorecard (first visit),  
infant’s height and weight (each visit)  For the intervention arm, app usability (System 
Usability Scale Survey) and usefulness and satisfaction (Usefulness and Satisfaction 
Survey) scales  will be done at the first and last visit.  These surveys will be collected using 
an electronic RedCap form. This information will be collected for research purposes only 
and will be obtained directly from the caregiver.  The BSID-4 will be measured at 
enrollment and study conclusion during a separate assessment visit (less than an hour in 
duration).  A semi-structured interview with subjects enrolled in the intervention group at 
the last visit will be used to qualitatively assess interest, engagement, and perceptions of 
the app technology. This interview will be audio-recorded to accurately capture each 
subjects response. The audio-recordings will not be shared outside the research team and 
will be destroyed once they have been transcribed. 
 
Aim 3: Two-arm prospective, longitudinal, randomized 18-month intervention with 
developmental outcomes assessed at 18 months.  Recruited caregivers/infants will undergo 
simple randomization to one of 2 arms. The control arm will receive printed caregiving 
materials based on recommendations outlined in Table 1. The intervention group will 
receive the smartphone application. Study staff will make an initial home visit (less than 
an hour) to install the application on the caregiver phone and demonstrate use. “Teach 
back” demonstration will be used to assure understanding.  
 
Subsequently, in the intervention arm, staff will make visits every 3 months (less than 1 
hour duration) to assess functionality of the smartphone and answer questions/reinforce 
use.  

Protocol Amendment, dated August 9, 2023 
 
 
In the control arm, staff will conduct visits every 3 months (less than 1 hour duration) to 
ask if there are questions about the printed caregiving materials. The smartphone app in 
the intervention arm will function as described above in Aim 2, including the semi-
structured interview. This intervention phase of the study will last 18 months. The NCAST 
feeding scale and HOME scale will be administered at visits 0, 6 months, 12 months, and 
18 months. The BSID-4 will be measured at 18 months (less than an hour in duration).  
BSID-4 will be completed during separate assessment visits. There will be a total of 8 home 
visits by research staff (initial visit, 3 month follow-up visits months 1-6 and 1 visit at the 
end of the study for BSID-4).  Also, during the home visits, research staff will also collect 
the following information: Infant/caregiver demographics, infant’s medical history, 
caregiver poverty scorecard, and infant’s measurements and weight.  This information will 
be collected for research purposes only and will be obtained directly from the caregiver.   
 
 
Primary Outcome:  
The primary outcome is BSID-4 as a measure of infant developmental outcomes. It is a 
standardized assessment of cognitive, motor, and language development. Research staff 
interact with the child in a standardized way and observe his or her behavior.  
 
Secondary Outcomes: 
The secondary outcomes are quality of infant-caregiver interaction (NCAST feeding scale) 
and quality of the home environment (HOME scale). The NCAST is a standardized, 
reliable assessment of quality of caregiver-infant interaction. Administration consists of 
videotaping up to 5 minutes of the caregiver feeding the infant. The HOME is a 45-item 
yes/no checklist completed by an observer to measure the quality and quantity of 
stimulation and support available to a child in the home environment, which we have 
validated extensively already in rural Guatemala.  
 
Table 2. Evidence-based guidance for infant care domains to be incorporated into smartphone 
application.  
Care 
Domain 
Key Guidance 
Source 
Sleep 
* Infants sleep around 14-16 hours per day during the first 6 
months 
* Sleep in the supine position 
* Sleep in the same room as the mother to support responsive 
breastfeeding  
UNICEF - Guidance on 
Infant Care at Night  
Feeding 
* Exclusive breastfeeding for first 6 months (following WHO 
guidelines for acceptable medical reasons for substitute feeding) 
* Breastfeeding on demand (on average approximately 8-12 
times/day) 
* Avoid additional food or drink other than breastmilk 
* Sleep in the same room as the mother to support responsive 
breastfeeding 
WHO - Infant and 
Young Child Feeding  
Activity 
* Play: “Provide ways for your child to see, hear, feel, move 
freely, and touch you. Slowly move colourful things for your child 
to see and reach for. Sample toys: shaker rattle, big ring on a 
string.” 
* Communication: “Smile and laugh with your child. Talk to your 
child. Get a conversation going by copying your child’s sounds 
or gestures.” 
UNICEF – Care for 
Child Development  

Protocol Amendment, dated August 9, 2023 
 
 
Standard of Care 
Aim 1 (Focus Groups) does not involve an intervention. Aims 2 and 3 will compare 2 
interventions: printed caregiving materials and a smartphone application. Both 
interventions will be provided in addition to standard care. All subjects will be recruited 
from MHA clinics and will continue to be eligible for all standard of care health 
maintenance services in those settings, regardless of their decision to participate in the 
study. BSID-4 results will be discussed with the parent or legal guardian and any standard 
of care recommendations made. 
 
Minimization of Risk 
 
To protect confidentiality, the following steps will be taken:  
 
Redcap, a secure web-based storage system for research data, will be used for all subject 
information except for smartphone and video data (described below). All paper research 
forms from research visits conducted by RAs will be kept in locked file cabinets on site in 
Guatemala and will be available only to research staff directly involved in this project. All 
research forms will have a cover sheet that codes identifying information to a unique 
number. This number will be transcribed to Redcap, and the cover sheet will then be 
removed and destroyed. Data from paper observational forms will be double-entered into 
Redcap, linked only to subject identifying numbers, and these will be stored separately 
from the key that identifies subjects. Laboratory members will have access to data 
identified by code for analysis and manuscript preparation, while only the PI’s and the staff 
RA collecting it will have access to identifying information for participant tracking 
purposes. Once data extraction and cleaning has been completed, this key will be 
destroyed, and data in the analysis phase will be completely de-identified. Laptop 
computers used for data entry will be routinely backed-up and will be password-protected 
and full-disk encrypted.   
  
For key stakeholders involved in the project, loss of confidentiality is also a concern. This 
is especially the case for employees of Maya Health Alliance involved in the project. To 
protect against this concern, the same study ID protection procedures used for 
children/caregivers will also be employed for the stakeholder interviews. In the monthly 
Implementation Team Meetings, only de-identified data from these interviews will be 
reviewed as relevant implementation feedback.  
 
Smartphone Data: Our smartphone development process for this project will include end-
to-end EMR integration with OpenMRS through the SanaMobile infrastructure, which 
integrates mHealth applications with EMRs.  Both of these technologies are hosted on 
Maya Health Alliance secure web-based server architecture. Designing to include EMR-
integration with OpenMRS will make our technology immediately applicable to numerous 
other global contexts where OpenMRS is in use. This platform integration also facilitates 
linkages between caregivers using the application and health workers, who can review 
incoming data and provide support to caregivers. In addition, the SanaMobile infrastructure 
provides a secure channel for transmission of identifiable data between end-users and 
clinicians. Our use of SanaMobile for collection and transmission of electronic smartphone 

Protocol Amendment, dated August 9, 2023 
 
data will minimize risks related to privacy and security. Dr. Rohloff controls access to 
SanaMobile, and access will only be granted to study staff involved in the collection or analysis of 
smartphone data. 
 
Video Data: video data will be stored on CHLA One Drive, a secure storage option for 
identifiable research data. Dr. Smith controls access to CHLA One Drive, and access will 
only be granted to study staff involved in the collection or analysis of video data. 
 
Ensuring Safety of Subjects 
This research meets minimal risk criteria for research with children. These intervention 
components involve basic interviewing, observation, and survey procedures which are 
unlikely to cause any degree of distress or harm to participants greater than those 
encountered in everyday life. No medical or invasive procedures are involved. No direct 
adverse events attributable to this study are anticipated, since it is a minimal risk 
intervention involving observation and survey procedures. The most likely adverse 
outcome is the potential for psychological trauma for caregivers based on 
assessment/interaction data with staff suggesting that their child suffers from some degree 
of developmental delay, which can be stigmatizing and disempowering. However, we 
anticipate that this risk will actually be considerably less than is the case in other existing 
standard of care developmental assessments and interventions, since the tool we will use 
here is specifically designed to be participatory and non-stigmatizing. In particular 
it doesn’t seek to “label” children as delayed but, rather, to establish a starting point of each 
child on a developmental trajectory and foster progress. Nevertheless, study staff will 
closely track data from caregivers or staff registering dissatisfaction with or complaints 
about the study. PI Rohloff will review this data at least every 3 months, in order to assess 
whether changes to the study protocol are needed. Any potential adverse events will be 
reported to the Institutional Review Board. Unexpected safety concerns will also be 
communicated with the NIH Program Official in accordance with study regulations. 
 
FORESEEABLE RISKS: 
(Brief description of any foreseeable risks to subjects. These should include not only biomedical 
risks but also any and all psychosocial risks or risks related to privacy/confidentiality) 
 
There are 5 foreseeable risks:  
 
1. For participating infants and caregivers the primary risk is one of lost productivity 
or perceived interference with domestic routines and other responsibilities. Staff 
members may also experience a loss of productivity.  
2. There is also risk of psychological stress or stigma to caregivers if protected health 
information is accidentally disclosed by the research team. 
3. There is the risk that patients will feel compelled to participate in the research 
project as a condition of receiving care from MHA or to receive a good performance 
review if they are a staff member at MHA 
4. There is the risk that there will be discordant interest between a caregiver and other 
family members about wanting to participate in the study which might cause 
conflict, particular in the case of a single mother or where other extended family 
members exercise significant decision making power over the primary caregiver 

Protocol Amendment, dated August 9, 2023 
 
5. Some of the questions may make the participant feel uneasy or embarrassed. 
However, participants may choose to skip or stop answering questions at any time. 
 
EXPECTED BENEFITS: 
(Describe expected benefits to subjects as well as the benefit to society that may result through an 
increase in knowledge) 
 
Stakeholder participants will benefit mostly indirectly from this project by helping to improve 
implementation knowledge around mHealth and infant development interventions in Guatemala. 
However, they may also benefit directly from a greater sense of empowerment and job satisfaction, 
by participating. 
 
Children and caregivers enrolled in the study may benefit directly from participation. Potential 
benefits include improvements in developmental and growth outcomes. For caregivers, an 
enhanced knowledge of early child development and improved self-efficacy as caregivers are other 
potential benefits. Caregivers’ may see improvement in some or all their child’s symptoms. 
 
The information gained through this project will contribute important, practical insights into the 
implementation of mHealth interventions in LMIC, at minimal risk to participants. The results of 
this project will develop mHealth smartphone technology which can be used to engage primary 
caregivers directly in the active monitoring of their infants’ development, and to provide tailored 
feedback and support for the provision of nurturing care. In addition to design of the technology, 
we will also prospectively assess the implementation characteristics of the technology—usability, 
acceptability, and sustainability—for caregivers in a rural Guatemalan population which is at high 
risk for impaired infant growth and development. Following successful implementation in 
Guatemala, this mHealth method could then be expanded to families with at-risk infants worldwide.  
 
EQUITABLE SELECTION OF SUBJECTS: 
(No group of persons should be excluded from research, with its associated risks and benefits, 
without justification. Provide a justification for your selection criteria. Also, explicitly address your 
plan for overcoming any cultural or language barriers that pertain) 
 
The population study sample is a convenience sample of infants and their caregivers from 
Tecpán, Guatemala. This population is more than 95% indigenous Maya, and many may 
not speak Spanish as a first language. In order to ensure equitable access to the research, 
the research assistants conducting visits and obtaining consent will be bilingual native 
speakers of Spanish and Kaqchikel Maya, the language spoken in Tecpán.  
 
RECRUITMENT PROCEDURES: 
(Provide a specific methodology that will be used for subject recruitment. Make sure to explicitly 
address how and by whom subjects will be approached. Also provide any details regarding efforts 
to enhance recruitment of minorities or women, as well as any details about remuneration) 
 
The caregivers participating in both phases (Aim 1, design/formative phase; Aim 2, 
implementation/trial phase) will be recruited from among first-time caregivers receiving 
services at a major maternal-child wellness clinic run by Maya Health Alliance out of their 
main office in Tecpán Guatemala. A full time research staff member (from Maya Health 
alliances research core staff) will be tasked with recruitment activities. This research staff 
member will review planned clinical activities with maternal-child clinical team managers 

Protocol Amendment, dated August 9, 2023 
 
on a monthly basis to ensure that they can be physically present during wellness clinic 
days. The research staff member will then approach caregivers in the waiting room to 
describe the details of the study to potential participants, including the nature of their 
requested involvement in the study, the possible risks and benefits of participation, and the 
individual capacity to withdraw from the study at any time without consequence.  
  
We anticipate that this recruitment strategy will be successful for two reasons. First, Maya 
Health Alliance has successfully used this “waiting room” approach for recruitment in 
numerous other studies, with high success rate and meeting of recruitment targets. Second, 
because the research study staff conducting this recruitment will be natively fluent in both 
Spanish and Kaqchikel Maya, they will be able to conduct recruitment in either language, 
as caregivers prefer, overcoming this potential barrier to recruitment. The staff member 
will be able to provide details of the study and administer informed consent in either 
language, therefore fostering trust and improving subjects’ interest in participation.   
  
For Aim 1, up to 20 caregivers will be recruited in this fashion for formative focus groups. 
These participants will then be invited, as they are willing, to participate in the formative 
agile design phase of the app. Subsequently, in Aims 2 and 3, 40 and 220 (respectively) 
additional caregivers will be recruited in the same fashion into participate in the prospective 
implementation trial. Given cultural patterns around caregiving in Guatemala, we 
anticipate that most participants will be female caregivers, but we will make every effort 
to include male caregivers, including extending joint invitations to both caregivers, making 
follow-up phone calls to male caregivers when only female caregivers present to clinics, 
and making research home visits.  
  
The study co-PI (Rohloff) will monitor recruitment numbers on a biweekly basis, in 
collaboration with the Maya Health Alliance study team, reporting to the PI Smith. If 
recruitment numbers are unexpectedly low, the team will consider additional strategies, 
such as visiting other primary care clinics in town to solicit participation of caregivers 
referred by other providers and distributing materials announcing the purpose of the study 
to civic support groups (mothers groups, church groups).   
  
Study retention in rural Guatemala, primarily because of competing demands on time, is at 
times a concern. For the components of the study requiring longitudinal involvement (Aims 
2 and 3), study staff will use three strategies to ensure retention: (1) collect multiple 
telephone contact numbers, including alternate family member contacts; (2) collect detailed 
information on location of subject’s home, so that follow-up visits can  easily be made to 
reestablish contact if necessary; (3) develop a formal protocol within the study operating 
manual, requiring multiple phone calls and at least two attempts at repeat home visits prior 
to considering a subject lost to follow-up. Taken together, Maya Health Alliance has used 
these strategies successfully in multiple other projects and are confident they will ensure a 
high rate of subject retention.  
 
At each study visit, each participant will receive a small care package to compensate for 
their time. This will contain items commonly provided to participants in other research 
study and clinical nutrition encounters at Maya Health Alliance (such as high-quality food 

Protocol Amendment, dated August 9, 2023 
 
items for family home consumption like eggs and beans, infant diapers and hygiene 
supplies, infant toys. Care will be taken to avoid toxic items and choking hazards). The 
approximate value of these items will be US $5 for each visit.  
 
CONSENT PROCEDURES: 
(Explain in detail how, where, when, and by whom consent will be obtained. Describe how coercion 
in the consent process will be avoided.  If research involves children, make certain to fill out the 
supplementary form on Research involving Children) 
 
After ascertaining initial interest in participation, a research assistant will then make a visit 
to the primary caregiver at their home (or in another confidential setting, as appropriate) to 
explain the details of the study, including the nature of the requested involvement in the 
study, the possible risks and benefits of participation, and the individual capacity to 
withdraw from the study at any time without consequence. Specific mention will be made 
of the fact that accessing care from MHA is not conditional on participation in the study, 
and that there will be no repercussions for declining to participate.   
 
Verbal informed consent will be obtained from all participating caregivers. A verbal 
consent script will be read to the caregiver, and a copy of the script (in Spanish, as 
Kaqchikel is mostly an oral language read by very few) will also be provided. Effort will 
be made to obtain permission from both biological parents or legal guardians if present. 
However, consent from one parent/guardian will be sufficient to enroll in the trial. Assent 
will not be sought from enrolled children, as the participating infants (0-18 months of age) 
are not capable of providing assent. 
 
In addition, given concerns that some caregivers (especially younger women or single 
mothers) may have restricted agency within their home and might choose to participate but 
have a family member countervene their decision, we will ask all caregivers if there is 
another individual who we should discuss the study with to get their permission and, if so, 
the research assistant will also explain the study to that individual and obtain their assent. 
In addition, for underage adolescent caregivers (<18 years), assent from the caregiver will 
be obtained, but consent from the adolescent’s legal guardian or parent, since Guatemalan 
law does not recognize emancipation of minors on the basis of parenthood.  
 
All consent procedures will occur in the language of the participant’s choosing. Research 
staff in Guatemala will be natively fluent in Kaqchikel Maya and Spanish. Finally, research 
staff will have no clinical role in the care of potential subjects.  
 
DATA SAFETY AND MONITORING: 
(Describe the plan for monitoring data to ensure the safety of the subjects. This should include a 
description of which data will be reviewed, at what frequency, and by whom. Stopping rules should 
also be detailed. Describe the plan for reviewing and reporting adverse events. Consultation with 
an WK IRB staff member prior to filling out this section may be helpful because, based on the 
complexity of the protocol, an independent Data Monitoring Committee may be mandated) 
 
No direct adverse events attributable to this study are anticipated since it is a minimal risk 
intervention involving observation and survey procedures. As such, no specific safety or 

Protocol Amendment, dated August 9, 2023 
 
efficacy outcomes will be reviewed as stopping criteria.  
 
However, the PIs will have regular meetings (biweekly) with the field team to solicit 
feedback on the study and identify any areas of concern that might require modification of 
the protocol.  
 
MONITORING AND QUALITY ASSURANCE: 
(Detail the plan to assure the validity and integrity of the data and adherence to the approved 
research protocol. Detail who will be responsible for this monitoring, and at what frequency.) 
 
Study staff at Wuqu’ Kawoq | Maya Health Alliance will be responsible for all initial data 
collection and coding. Data will be collected and uploaded to CHLA OneDrive (for video 
data) and MHA Redcap (for HOME score, growth data, NCAST score, BSID-4 data) 
applications. Both are HIPAA compliant.   
 
The investigator team will review the rate of subject accrual, compliance with 
inclusion/exclusion criteria, and informed consent procedures on a monthly basis during 
the recruitment phase, to ensure sufficient enrollment as per the planned study protocol.  
 
PRIVACY AND CONFIDENTIALITY: 
(Detail the methods that will be used to protect the privacy of subjects and to maintain 
confidentiality. This should include all techniques such as deidentifying or coding data, removing 
health identifiers, storage and security of electronic and paper records, and the like) 
 
To protect confidentiality, the following steps will be taken: All paper research forms from 
research visits conducted by RAs will be kept in locked file cabinets locally in Guatemala 
and will be available only to research staff directly involved in this project. All research 
forms will have a cover sheet that codes identifying information to a unique number. This 
number will be transcribed to Redcap, and the cover sheet will then be removed and 
destroyed. Data from paper observational forms will be double-entered into Redcap, linked 
only to subject identifying numbers, and these will be stored separately from the key that 
identifies subjects. Laboratory members will have access to data identified by code for 
analysis and manuscript preparation, while only the PI’s and the staff RA collecting it will 
have access to identifying information for participant tracking purposes.  One data 
extraction and cleaning has been completed, this key will be destroyed, and data in the 
analysis phase will be completely de-identified. Laptop computers used for data entry will 
be routinely backed-up and will be password-protected and full-disk encrypted.  
 
 
DATA SHARING: 
(Detail any plans to share data with collaborators outside WK, including what information will be 
shared and what measures will be taken to protect privacy and confidentiality) 
 
The study involves collaborating researchers from CHLA and MHA. All identifiable data 
will be shared only through secure applications (OneDrive, Redcap) hosted at MHA 
(Redcap) or CHLA (One Drive).  
 
Only the PIs or their delegate will have access to the study spreadsheet linking unique study 

Protocol Amendment, dated August 9, 2023 
 
IDs to individual subjects.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Bibliography/References 
 
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income and middle-income countries: an estimation and analysis at the global, 
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McCoy DC, Peet ED, Ezzati M, Danaei G, Black MM, Sudfeld CR, et al. Early 
Childhood Developmental Status in Low- and Middle-Income Countries: National, 

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Regional, and Global Prevalence Estimates Using Predictive Modeling. PLoS 
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Richter LM, Daelmans B, Lombardi J, Heymann J, Boo FL. Investing in the 
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Huebner G, Boothby N, Aber L, Darmstadt G, Diaz A, Masten A, et al. Beyond 
Survival: The Case for Investing in Young Children Globally. Discussion Paper, 
National Academy of Medicine, Washington, DC. Retrieved from: 
https://www.researchgate.net/publication/304011414_Beyond_Survival_The_Cas
e_for_Investing_in_Young_Children_Globally (last accessed 08/25/17). 
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Carneiro PM, Heckman JJ. Human Capital Policy. 2003 Jul 1. Discussion Paper 
No. 821. 2003 Jul 1. Retrieved from: http://ssrn.com/abstract=434544 (last 
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10. 
Britto PR, Lye SJ, Proulx K, Yousafzai AK, Matthews SG. Nurturing care: 
promoting early childhood development. Lancet. 2017;389:91–102.  
11. 
Black MM, Perez-Escamilla R, Fernandez Rao S. Integrating Nutrition and Child 
Development Interventions: Scientific Basis, Evidence of Impact, and 
Implementation Considerations. Adv Nutr. 2015 Nov 13;(6):852–9. 
12. 
Grantham-McGregor SM, Fernald LCH, Kagawa RMC, Walker S. Effects of 
integrated child development and nutrition interventions on child development and 
nutritional status. Black MM, Dewey KG, editors. Ann. N.Y. Acad. Sci. 2014 Nov 
4;(1308):11–32.  
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Nahar B, Hossain MI, Hamadani JD, Ahmed T, Huda SN, Grantham-McGregor 
SM, et al. Effects of a community-based approach of food and psychosocial 
stimulation on growth and development of severely malnourished children in 
Bangladesh: a randomised trial. Eur J Clin Nutr. 2012 Feb 22;66(6):701–9.  
14. 
Yousafzai AK, Rasheed MA, Rizvi A, Armstrong R, Bhutta ZA. Effect of integrated 
responsive stimulation and nutrition interventions in the Lady Health Worker 
programme in Pakistan on child development, growth, and health outcomes: a 
cluster-randomised factorial effectiveness trial. Lancet. 2014;(384):1282–93.  
15. 
Smith S, Deveridge A, Berman J, Negin J, Mwambene N, Chingaipe E, et al. 
Task-shifting and prioritization: a situational analysis examining the role and 
experiences of community health workers in Malawi. Hum Resour Health. 2014 
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16. 
Okyere E, Mwanri L, Ward P. Is task-shifting a solution to the health workers’ 
shortage in Northern Ghana? PLoS ONE. 2017 Mar 30;12(3):e0174631–22.  
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STUDY PROTOCOL 
 
Study context and ethics oversight 
This trial was conducted in collaboration with Maya Health Alliance, a primary care organization 
working in rural Indigenous Maya communities in Guatemala. The study was conducted in the 
municipality of Tecpán, Chimaltenango (population 95 000), a semi-rural community where more 
than 95% of the population is of Indigenous Kaqchikel Maya ancestry.  The trial was conducted 
according to the principles in the Declaration of Helsinki, prospectively registered 
(NCT05106894), and approved by the Institutional Review Boards of Children’s Hospital Los 
Angeles (CHLA-21-00168) and Maya Health Alliance (WK 2021 002). 
 
Smartphone app design 
We employed an agile design framework to develop an Android-based app. The design team 
included app programmers, investigators, clinical staff at Maya Health Alliance, and volunteer 
caregivers/end users. End users provided feedback in both focus groups and one-on-one after 
codesign sessions and extensive in-home usability tests. Although target participants were 
primarily speakers of Kaqchikel Maya the app was developed in Spanish as Kaqchikel Maya is 
not widely written or read. Participants who speak Kaqchikel Maya typically read and write in 
Spanish. App design included built-in multilingual support to permit future additions of various 
languages, and as many images as possible. Evidence-based caregiver recommendations in the 
app for breastfeeding and complementary feeding, sleep, and developmental support were 
selected from evidence-based sources. 
 
Trial design and participants 
This was a single-center, individually randomized (1:1 allocation ratio), parallel-group pilot trial to 
compare use of the smartphone app to printed educational materials. First-time primary 
caregivers and their infant were eligible to participate if the infant was 0-28 days old at the time of 
recruitment and a singleton full-term (³ 37 weeks) birth. Infant exclusion criteria were acute 
malnutrition (weight-for-length/height Z score £ −2 SD using WHO standards), severe medical 
illness, or medical contraindication to breastfeeding. Caregiver exclusion criteria were inability to 
read or speak Spanish. Eligible caregivers who did not possess a functioning Android smartphone 
were given a phone for the duration of the study.  
Subjects were recruited by trained research nurses within usual clinical care settings after referral 
by healthcare providers working at Maya Health Alliance. Verbal consent was obtained following 
Maya Health Alliance protocol for a minimal-risk study with Indigenous populations as obtaining 
signatures is not a culturally common practice. Study visits and data collection occurred in the 
home by trained research nurses, except for the secondary outcome variable (Bayley Scales of 
Infant Development, Version 4; BSID4; Pearson Assessments, San Antonio, TX, USA) which was 
collected by consulting psychologists in clinical spaces at Maya Health Alliance.  

 
After enrollment and randomization, caregivers received either the smartphone app, installed with 
assistance from a study nurse, or printed materials. Brief monthly visits (~ 15 minutes) were 
conducted monthly for 5 consecutive visits by a study nurse to resolve questions about the app 
or, in the comparator arm, to resolve any caregiver questions about the printed materials. BSID4 
data was collected at enrollment and study exit at 6 months post enrollment. 
 
STATISTICAL ANALYSIS PLAN 
Quantitative statistical analysis was conducted using Stata Version 17. Demographic and clinical 
characteristics of study participants were summarized using means and standard deviations; 
median and interquartile range; or percentages, as appropriate. For BSID4 outcomes, raw 
differences between intervention and control arms in composite scores were summarized and 
adjusted differences calculated using linear regression with adjustments chosen a priori for sex 
of child, caregiver educational level, poverty score, birth weight and change in length for age Z 
score from 0 to 6 months.