Mobile WACh NEO Randomized Clinical Trial: Mobile Phone 2-Way Short Message Service (SMS) Versus Control to Reduce Neonatal Mortality in Kenya
Phase: NA
Conditions: Neonatal Death, Perinatal Death, Depression
Sponsor: Women and Infants Hospital of Rhode Island

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TITLE: 
 
Mobile WACh NEO: Mobile Solutions for Neonatal Health and Maternal Support 
NCT04598165 
 
 
 

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Contents 
 
1. LIST OF ABBREVIATIONS ........................................................................................................................................3 
2. INVESTIGATORS .........................................................................................................................................................3 
3. COLLABORATING INSTITUTIONS ........................................................................................................................6 
4. FUNDING AGENCY ......................................................................................................................................................6 
5. SUMMARY .....................................................................................................................................................................6 
6. INTRODUCTION/ BACKGROUND .........................................................................................................................7 
7. LITERATURE REVIEW ..............................................................................................................................................8 
Table 1.  UW-Kenya mHealth Studies Support the Reproductive Health Continuum ............................ 11 
8. RATIONALE ............................................................................................................................................................... 13 
9. HYPOTHESIS & STUDY QUESTIONS: ................................................................................................................ 13 
10. OBJECTIVES ............................................................................................................................................................ 13 
10.1 Broad Objectives .......................................................................................................................................... 13 
10.2 Specific Objectives ....................................................................................................................................... 14 
11. METHODOLOGY .................................................................................................................................................... 14 
11.1 Study Design ................................................................................................................................................... 14 
11.2 Study Area Description .............................................................................................................................. 14 
11.3 Study Population .......................................................................................................................................... 14 
Table 2. Summary of proposed eligibility, procedures and outcomes for study aims ........................... 14 
11.4 Sample Size Determination ...................................................................................................................... 15 
Table 3. Power and sample size ranges. .................................................................................................................... 16 
11.5 Recruitment, Screening and Consent Procedures ............................................................................ 16 
11.6 Data Collection Procedures ...................................................................................................................... 17 
11.7 Data Analysis ................................................................................................................................................. 19 
Table 4: RCT outcomes ..................................................................................................................................................... 19 
11.8 Study Materials ............................................................................................................................................. 20 
11.9 Training Procedures ................................................................................................................................... 20 
11.10 Quality Assurance Procedures .............................................................................................................. 20 
12. ETHICAL CONSIDERATIONS ............................................................................................................................. 20 
12.1 Consent explanation ................................................................................................................................... 20 
12.2 Institutional Review Board ....................................................................................................................... 21 
12.3 Risks to subjects ........................................................................................................................................... 21 
12.4 Protection against risks ............................................................................................................................. 21 
12.5 Potential benefits ......................................................................................................................................... 22 
12.6 Compensation ................................................................................................................................................ 22 
12.7 Importance of the knowledge to be gained ........................................................................................ 22 
13. DATA MANAGEMENT .......................................................................................................................................... 22 
14. RESULTS DISSEMINATION ................................................................................................................................ 23 
15. STUDY LIMITATIONS .......................................................................................................................................... 23 
16. STUDY TIMELINE ................................................................................................................................................. 23 
17. REFERENCES .......................................................................................................................................................... 24 
APPENDIX I COVID-19 RESPONSE PROCEDURES ............................................................................................. 30 
 
 
 

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1. LIST OF ABBREVIATIONS 
 
ANC 
 
Antenatal Care 
CHW  
Community Health Worker  
ERC 
 
Ethics Review Committee 
FP  
 
Family planning 
HIV 
 
Human Immunodeficiency Virus 
HW 
 
Health Worker 
IDI 
 
In-depth interview 
IRB 
 
Institutional Review Board 
KNH 
 
Kenyatta National Hospital 
M&E   
Monitoring and evaluation  
MCH  
Maternal and Child Health 
MNCH  
Maternal, newborn and child health  
MOH  
Ministry of Health 
MWN  
Mobile WACh NEO  
MW 
 
Mobile WACh (Mobile Solutions for Women’s, Adolescent’s and Child Health)  
RCT 
 
Randomized controlled trial   
SMS 
 
Short message service 
SOP 
 
Standard operating procedure 
UoN 
 
University of Nairobi 
UW 
 
University of Washington 
WHO  
World Health Organization 
 
2. INVESTIGATORS 
 
 
Jennifer A. Unger, MD, MPH (PRINCIPAL INVESTIGATOR) 
(Responsible for the development, oversight and evaluation of the project)   
Associate Professor 
Department of Obstetrics and Gynecology 
Warren Alpert Medical School of Brown University 
Women and Infants Hospital 
401-274-1122; fax  
Tel: +1-206-388-8141 
Fax: +1-401-276-7871 
Email: jennifer_unger@brown.edu 
 
John Kinuthia, MBChB, MMed, MPH (SITE PRINCIPAL INVESTIGATOR)  
(Responsible for the assistance in development, oversight and science of the project) 
Head, Department of Research & Programs, Kenyatta National Hospital 
PO Box 20723-00202, Nairobi, Kenya 
Tel: +254 0722 799-052 
Email: kinuthia@uw.edu 
 
Keshet Ronen, PhD (CO-INVESTIGATOR, Project epidemiologist) 
(Responsible for protocol, data and analysis plan, and evaluation of the project)  
Research Scientist 
Department of Global Health, University of Washington 
Harborview Medical Center, 325 Ninth Ave., Box 359909, Seattle, WA 98104 
Tel: +1-206-685-4363 
Fax: +1-206-543-4818 
Email: keshet@uw.edu   
 
Brenda Wandika (STUDY CLINICIAN COORDINATOR) 

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(Responsible for daily medical oversight, message review, staff education, study coordination and 
oversight, protocol development and collaborations with MOH staff)  
Department of Obstetrics and Gynecology 
University of Nairobi 
Nairobi, Kenya 
Tel: +254725297691 
Email: brandarl@gmail.com   
 
Peninah Kithao  (ASSISTANT STUDY COORDINATOR) 
(responsible for message development, staff training, study approvals at local/county levels, inputting  
SMS system with patient information, supplies at the study sites, daily summary of study progress) 
Department of Obstetrics and Gynecology 
University of Nairobi 
Kisumu - Kenya 
Tel; +254 722409897 
Email; peshkithao@yahoo.com 
June Moraa  (ASSISTANT STUDY COORDINATOR) 
(responsible for message development, staff training, study approvals at local/county levels, inputting  
SMS system with patient information, supplies at the study sites, daily summary of study progress) 
Department of Obstetrics and Gynecology 
University of Nairobi 
Nairobi - Kenya 
Tel; +254 705549792 
Email: junemoraa@gmail.com  
 
Daniel Matemo (PROJECT SITE COORDINATOR) 
(Responsible for study site coordination, MOH collaboration)  
Research & Program Manager 
Ahero sub-district Hospital, Ahero, Kenya 
Tel: +254 725 662 840 
 
Dalton Wamalwa, MBChB, MMed, MPH (CO-INVESTIGATOR)  
(Responsible for scientific mentorship of the project) 
Associate Professor, Department of Paediatrics & Child Health, University of Nairobi 
PO Box 20723-00202, Nairobi, Kenya 
Tel: +254 0722 799-052 
Email: Dalton@africaonline.co.ke  
 
Manasi Kumar, PhD (CO-INVESTIGATOR)  
(Responsible for scientific mentorship of the project) 
Senior Lecturer and Clinical Psychologist  
Department of Psychiatry, University of Nairobi.  
PO Box 20723-00202, Nairobi, Kenya 
Email: m.kumar@ucl.ac.uk  
 
Grace John-Stewart, MD, PhD (CO-INVESTIGATOR, Scientific mentor) 
(Responsible for scientific mentorship of the project) 
Professor 
 
 
 
  
Departments of Medicine, Epidemiology, Global Health, Pediatrics, University of Washington 
Harborview Medical Center, 325 Ninth Ave., Box 359909, Seattle, WA 98104 
Tel: +1-206-543-4278 
Email: gjohn@uw.edu 
 
Barbra Richardson PhD (CO-INVESTIGATOR, Scientific mentor) 
(Responsible for biostatistic mentorship of the project) 

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Professor 
 
 
 
  
Departments of Biostatistics, Global Health, Pediatrics, University of Washington 
Harborview Medical Center, 325 Ninth Ave., Box 359909, Seattle, WA 98104 
Tel: +1-206-543-4278 
Email: barbrar@uw.edu  
 
Anna Hedstrom, MD, (CO-INVESTIGATOR, Scientific mentor) 
(Responsible for scientific mentorship of the project) 
Assistant Professor 
Department of Pediatrics, Neonatology Division, University of Washington  
1959 NE Pacific Street, RR542 HSB, Box 356320, Seattle WA 98195-6320 
Tel: +1-206-543-3200 
Fax: +1-206-987-2685 
Email: hedstrom@uw.edu    
 
Maneesh Batra, MD, MPH (CO-INVESTIGATOR, Scientific mentor) 
(Responsible for scientific mentorship of the project) 
Professor 
Department of Pediatrics, University of Washington  
1959 NE Pacific Street, RR542 HSB, Box 356320, Seattle WA 98195-6320 
Tel: +1-206-987-6556  
Fax: +1-206-985-3157  
Email: maneesh.batra@seattlechildrens.org  
 
Brian DeRenzi, PhD (MHEALTH CONSULTANT) 
(Responsible for mHealth system development and evaluation of the project)   
Director of Research Strategy  
Dimagi South Africa  
Cape Town, South Africa 
Tel: +27-79-689-0574 
Email: bderenzi@dimagi.com  
 
Wangui Muthigani, MD, MS (Ministry of Health (MOH) Consultant) 
(Responsible for project consultation to ensure consistency with MOH policy) 
Reproductive and Maternal Health Services Unit - Maternal Newborn Health Manager 
Kenya Ministry of Health 
Afya House, Cathedral Road 
P.O Box 30016-00100, Nairobi, Kenya 
Tel: +254725510510 
Email: kuimuthigani@gmail.com  
 
Lusi Osborn (DATA MANAGEMENT SPECIALIST) 
(Responsible for data collection, data analysis management and scientific plans)  
Ahero sub-district Hospital 
Ahero, Kenya 
Tel: +254 725 662 840 
Email: lusiosborn@gmail.com  
 
 
Jenna Udren, MPH (RESEARCH COORDINATOR, Seattle ) 
(Responsible for study coordination, ERC/IRB communication, protocol development and analysis)  
Department of Global Health, University of Washington 
Harborview Medical Center, 325 Ninth Ave., Box 359931, Seattle, WA 98104 
Tel: +1-206-221-4156 
Fax: +1-206-543-4818 

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Email: jennaiu@uw.edu   
 
3. COLLABORATING INSTITUTIONS 
University of Nairobi 
Kenyatta National Hospital 
University of Washington 
 
4. FUNDING AGENCY 
 
Funding type: Grant 
Name of Funding agency: NIH/ NICHD 
Grant Number: 1R01HD098105-01 
Principal Investigator on Proposal: Jennifer Unger  
Title of Proposal: Mobile WACh NEO: Mobile Solutions for Neonatal Health and Maternal Support 
Dates: 01/06/2019-31/3/2024 
 
5. SUMMARY 
 
High-impact essential newborn care practices and interventions are available to support neonatal 
survival, but coverage remains a challenge in sub-Saharan Africa, where neonatal mortality is 
unacceptably high. Adherence to these practices and uptake of life-saving interventions requires that 
a mother understands neonatal care and illness and that she is supported to implement care. It is 
estimated that up to 80% of neonatal deaths occur as a result of delays in mothers’ recognition of 
infant illness and decision to seek care. Two-way mobile health (mHealth) communication strategies 
can enable mothers to remotely interact with a healthcare worker (HCW) and receive real-time 
education, counseling, encouragement, motivation and decisional guidance to support neonatal 
health. We hypothesize that two-way SMS communication in late pregnancy and the neonatal period 
can prevent neonatal mortality by (1) supporting maternal implementation of essential newborn care 
(early and exclusive breastfeeding, cord care, and thermal care), (2) improving identification of 
neonatal danger signs and care seeking, and (3) augmenting maternal social support and self-
efficacy, and reducing depressive symptoms. We have developed a unique two-way SMS platform 
(Mobile WACh) that combines automated bulk SMS messaging and dialogue with a HCW. We have 
adapted this approach for intensive neonatal support and evaluations (Mobile WACh-NEO). Mobile 
WACh NEO (MWN) enhances the benefits of SMS messaging by engaging mothers with SMS 
communication and bringing timely information and support - asking critical questions at crucial times 
in order to assess the needs and health of newborns.  Our overarching aim is to determine the effect 
of Mobile WACh NEO on neonatal mortality and understand the mechanisms by which this innovation 
impacts neonatal health.  
 
We will conduct a randomized controlled trial of the MWN intervention among 5020 women (2510 
MWN arm, 2510 control arm) to determine the effect of MWN on neonatal mortality, essential newborn 
care, care seeking, and maternal mental health in the first 6 weeks postpartum. In AIM 1 we will 
determine the effect of Mobile WACh NEO on neonatal mortality, compared to no SMS control. In 
AIM 2, we will examine the effect of Mobile WACh NEO on maternal implementation of essential 
newborn care and care seeking behavior. In AIM 3 we will examine the effects of Mobile WACh NEO 
on maternal social support, self-efficacy and depression. Finally, we will explore the associations 
between maternal mental health, implementation of essential newborn care, neonatal care seeking 
and participant engagement by SMS. 
 
This study will evaluate a novel intervention to address a crucial gap in supporting mothers to care for 
their neonates and seek care when needed, and has the potential to make a significant contribution 
to the World Health Organization’s Every Newborn Action Plan to end preventable neonatal death 
and stillbirth. 
 

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6. INTRODUCTION/ BACKGROUND 
 
Prevention of Neonatal Deaths Remains a 
Challenge in Low-to-Middle Income Countries 
(LMICs)  
Despite recent achievements in reducing child 
mortality, neonatal deaths remain high, accounting 
for 46% of all deaths in children under 5 worldwide 
(Figure 1) (2). The average annual rate reduction 
in under 5 mortality in 1990-2012 was 3.4%, 
compared to 2.1% in neonates (1st 28 days of life) 
(3). Neonatal morality in Kenya is reported to be 
22.6 per 1000 live births (4), ranking among the 
countries with the highest number of neonatal 
deaths (~40,000) (5). Rates are higher among 
rural and urban poor. Achieving the World Health Organization’s Every Newborn Action Plan (ENAP) 
target of ≤10 neonatal and stillbirths per 1000 live births (6) will require rapid scale-up of, and access 
to, effective, evidence-based interventions targeting the major causes of neonatal mortality.   
 
Essential newborn practices have impact on adverse neonatal 
outcomes but are underutilized 
Of the 2.8 million neonates who die each year, almost 75% die 
within the first week of life (7). Eighty percent of reported neonatal 
deaths are from complications of preterm birth (PTB), intrapartum 
deaths (including birth asphyxia) and serious neonatal infections 
(sepsis, meningitis, pneumonia and diarrhea) (Figure 2). For each 
of the major causes of deaths, evidence-based prevention and 
management solutions exist. High coverage with existing 
interventions could reduce deaths from these common 
causes by 58% (preterm), 79% (intrapartum) and 84% 
(infection) (8).  
 
Families, particularly mothers, are vital for providing newborn care, 
especially after the first day of life when most babies are sent 
home.  High-impact cost-effective, mother-centered, practices are available for newborn health 
including essential newborn care (ENC): early initiation of exclusive breastfeeding (EBF), hygienic 
cord care, and thermal control (6).  Evidence from pooled data show early initiation of breastfeeding 
(within 1 hour of life) and EBF are independently associated with lower neonatal mortality (9).  Clean 
cord care in the days following birth is effective in preventing cord infections (10), and neonatal 
mortality (11) mainly due to Clostridium 
tetani. Thermal care includes birth 
practices such as skin-to-skin contact 
with the mother, drying and wrapping 
immediately after birth, and delaying a 
bath for at least 24 hours. Appropriate 
thermal 
protection 
prevents 
hypothermia and associated morbidity 
and mortality particularly in the context 
of prematurity (12).   
 
Although evidence for the efficacy of these interventions is substantial, coverage remains low.  Large 
population-based surveys and smaller investigations in Uganda found sub-optimal practices of cord 
care, thermal protection and breastfeeding (13-15). Practice of appropriate cord care ranged from 31-
39%, optimal thermal care from 42-67%, and appropriate neonatal feeding from 57-62%; women cited 
conflict between the recommended ENC and traditional beliefs and practices, especially delayed 
Figure 1: Comparison of under-5 and neonatal mortality 
rates by region, 2015.   
Figure 2: Causes of neonatal death, 
2015 WHO (1)  
Figure 3: Number of deaths by day in the first 
28 days of life, 2013. UNICEF  

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bathing and dry cord care. There is promising evidence that ENC practices may be accepted after 
behavior change communication messages from community health workers (CHWs) and facility-
based health care workers (HCWs) (16) but these interventions are both intermittent and costly, and 
do not address the problem of workforce constraints.  A systematic assessment of 8 of 13 countries 
with the most neonatal deaths found significant bottlenecks across the health workforce, service 
delivery, financing and community ownership and partnership (17). All 8 countries, including Kenya, 
were found to have bottlenecks in community-based information, education and behavioral change 
communication strategies, as well as delays in seeking care. 
 
Neonatal clinical care seeking is inadequate, often delayed, and requires more real-time support    
Many newborns continue to die at home without health care services being sought (18). The reasons 
are multifactorial, at the societal, health system, and family levels. Strategic Objective 4 of the Every 
Newborn Action Plan is to “harness the power of parents, families and communities” by engaging 
them to seek care throughout pregnancy, birth and the first days and weeks of their children’s lives. 
Improved identification and management of neonates with potentially life-threatening illness at home 
is critically needed to significantly reduce neonatal mortality (19, 20).  Decisions made within the 
household and the family’s ability to reach care play a large part in determining neonatal 
outcomes. The “three delays model”, originally developed to understand maternal deaths (21), has 
been adapted to assess the missed opportunities leading to neonatal deaths. The model identifies 
delays in: (1) identifying illness and deciding to seek care, (2) reaching the health facility, and (3) in 
receiving quality care once a facility is reached. Delays 
recognizing illness and deciding to seek care (delay 1) are a 
major contributor to neonatal and child deaths, up to 80% 
(18, 19, 22, 23). In research from Kenya, Uganda, and Ethiopia, 
mothers had difficulty identifying serious illness in newborns, and 
they often did not seek care outside the home even when illness 
was recognized (24-26). Knowledge of danger signs is 
associated with fewer delays in identifying illness and seeking 
care (27). In addition, preventative postnatal care (PNC) is 
underutilized. In Kenya 50% of newborns in the richest 
households receive PNC within 2 days after birth, and 24% of 
those in the poorest households (4). 
 
7. LITERATURE REVIEW 
 
Maternal empowerment affects neonatal care and care seeking and can be supported by novel 
interventions  
Maternal and neonatal health and well-being are inextricably linked. Maternal self-efficacy is an 
important determinant of positive parenting behaviors and infant attachment (28).  A mother with low 
parenting self-efficacy may delay seeking care due to lack of confidence in making healthcare 
decisions, thus allowing the neonate’s condition to worsen. Conversely, higher self-efficacy can lead 
to greater social and interpersonal connectedness, decision-making autonomy, and problem-solving. 
Although many factors determine parenting self-efficacy, maternal mental health (depression and 
anxiety) and social support are major predictors (28). In addition, maternal depression has been 
associated with adverse infant outcomes including PTB (29) low birth weight (LBW) (30), infant illness 
(31), poor social engagement (32) and developmental delay (33, 34) and is also predictive of poorer 
safe child practices (35).  Even depressive symptoms alone, without a clear diagnosis, correlate with 
lower care seeking and preventive practices (36). It is not well understood how maternal depression 
affects neonatal survival, but it is plausible that parenting self-efficacy may affect neonatal outcomes. 
Interventions that support maternal mental health by reducing depressive symptoms and 
increasing social support will bolster maternal/parental self-efficacy and improve neonatal 
outcomes.   
 
Community-based interventions work but are not accessible in real time  
Figure 4: Three delays model for neonatal 
care   

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Clinic-based counselling during pregnancy and postpartum may increase uptake of effective practices 
and appropriate health care seeking (37), but high clinic volume and HCW shortages limit counselling 
time. Additionally, health concerns and challenges often occur between visits. Studies from LMICs 
demonstrate that home visits and assessments by CHWs can improve maternal and neonatal 
outcomes (38). However, home visits are not ‘on-call’ and may miss critical periods when neonates 
become ill. Trials from South Asia also suggest that women’s community groups improve ENC 
practices and neonatal mortality rates, although these groups may not be as effective in transient or 
dispersed populations and sufficient intervention coverage is a challenge (39, 40). Testing novel 
strategies in the form of accessible, acceptable digital interventions can strengthen the base of 
community care. 
 
Mobile health (mHealth) interventions can provide support and information on-demand  
mHealth tools, those that utilize mobile phones and other wireless technologies to support health, 
provide an attractive strategy to augment clinic-based care and efficiently connect households to 
support. More households in low-income countries own a mobile phone than have access to electricity 
or adequate sanitation (Figure 5) (41). The rate of mobile phone penetration in Kenya is over 88 per 
100 inhabitants, with an estimated 37 million mobile phones in a national population of 43 million (42). 
A World Bank report found that Kenyans living at the so-called “[economic] bottom of the 
pyramid” reported health information and communication as the service they would most like 
to receive with their mobile phones (43). The ideal mHealth approach increases efficiency rather 
than adding to healthcare workforce burden.   
 
mHealth approaches such as short message service (SMS) 
messaging could provide guidance and support to mothers and 
families between clinic visits. There is evidence that mHealth 
can be used to educate, provide reminders for visits and 
medications, improve communication between HCWs and 
patients, and improve self-efficacy and depressive symptoms, 
all potentially leading to better outcomes (44-48).  SMS 
programs for maternal, neonatal and child health (MNCH) have 
been implemented in South Africa, Bangladesh, India, Nigeria 
and the United States (49, 50). However, program efficacy data 
are lacking, and these programs are varied and often limited to 
education, encouragement and visit reminders rather than 
decision support (51, 52). There is some evidence that mHealth interventions improve antenatal care 
(ANC) attendance and skilled delivery uptake (53-56). Few studies have examined mHealth 
approaches for neonatal outcomes. One randomised controlled trial (RCT) observed a significant 
decrease in perinatal mortality with a combined unidirectional SMS and voucher intervention(57). 
These studies suggest mHealth may improve MNCH outcomes but more evidence is needed on 
efficacy, mechanisms, and best implementation approach. To our knowledge, no study has directly 
compared the effect of bidirectional SMS approaches, in which mothers can engage in interactive 
conversation with HCW by SMS, on neonatal outcomes. We hypothesize that an interactive 
mHealth intervention has the potential to: 1) provide education and support with sustained 
practices of ENC, 2) provide education and decision support with identifying neonatal danger 
signs and seeking clinical care, and 3) provide emotional and social support for mothers to 
improve self-efficacy and decrease depressive symptoms.   
 
UW-Kenya mHealth Studies Human Centered Design Approach 
Over the last 6 years, our collaborative team has developed an open-source human-computer hybrid 
communication platform, Mobile WACh (Mobile Solutions for Women’s and Children’s Health). This 
internet-based two-way SMS communication system is tailored to engage Kenyan mothers by SMS 
and improve maternal and child health (MCH) outcomes. The system contains a user interface 
designed for HCW management and patient tracking. Through extensive formative testing with 
Kenyan mothers and HCWs, the Mobile WACh team has developed over 3000 personalized, 
actionable, encouraging, and time sensitive SMS messages.  Development of SMS messages in 
Figure 5: Digital technology spread in low-
income countries  

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all studies was based on focus group discussions and interviews with the target population (58-60). 
The messaging platform was developed for management of SMS communications (61), with 
significant input from Kenyan nurses on features to improve usability and streamline workflow (Figure 
6). The interface was designed to enable HCWs to triage and counsel on potential medical 
conditions or concerns in a timely manner (Figure 7). It includes features that motivate completion 
of tasks such as message responses, patient tracking updates, and coding of messaging for 
streamlined monitoring and evaluation. The system also enables collection of data on participant 
interaction (paradata) (62). Paradata from previous implementations of the Mobile WACh system (see 
section 3.3) have enabled us to understand effects of different messaging strategies (e.g. content, 
personalization, timing of messages, speed of response) to optimize the mHealth package. For 
example, we have analyzed messaging volume as a function of time and have found that participant 
messaging volume peaks in response to automated system messages. Interestingly, while many of 
the responses are related to the system message topics, many responses are on unrelated topics, 
which indicates that system messages can be used to trigger participant engagement, enabling HCWs 
to address issues without a clinic visit. The system is poised to reach large numbers of women with 
many flexible capabilities including different languages and diverse conditions (pregnancy, 
postpartum, infant growth and development, infant deaths, HIV). Currently the Mobile WACh platform 
is deployed in 8 sites in Kenya and has been used in 7 individual implementations to support mainly 
reproductive, maternal, newborn and child health (RMNCH) and HIV prevention and care in Kenya. 
 
Preliminary studies: RCTs of Mobile WACh to improve MCH. Our collaborative research team has 
conducted 3 RCTs of interventions employing the Mobile WACh system (Table 1). The first Mobile 
WACh trial (NICHD, WRHR K12 PI: Unger) (63) was a 3-arm RCT to determine the effect of weekly 
1-way (push) versus two-way (dialogue) SMS communication with a nurse versus control on uptake 
of maternal and neonatal services including facility delivery, EBF and postpartum contraception in the 
first 24 weeks postpartum (63). We found that both SMS intervention arms demonstrated higher rates 
of EBF through 10 and 16 weeks, and women in the two-way SMS arm were significantly more likely 
to adhere to recommendations to EBF through 24 weeks (Figure 8). The probability of contraceptive 
use by 16 weeks postpartum was significantly higher in both SMS groups than control. We received 
over 1100 messages from 83% of 
women in the two-way arm who 
engaged with the nurse (n=83). Infant 
health and breastfeeding were topics 
that 
compromised 
20% 
of 
all 
messages received. Overall, there 
were 16 stillbirths and neonatal 
deaths (5%); 14 occurred prior to the 
first postpartum follow-up visit at 2 
weeks. There were fewer stillbirths 
and infant deaths in the two-way 
group compared to the control group 
(3.1% versus 8.0%, p=0.21); although this was not significant, the study was not designed or powered 
to determine an effect on these outcomes. 
 
The success of the Mobile WACh 
approach 
was 
leveraged 
for 
2 
subsequent RCTs: Mobile WACh-X 
(NICHD, PI: John-Stewart) (64) and 
Mobile WACh-XY (Society for Family 
Planning, PI: Harrington) (58). Mobile 
WACh XY evaluated the effect of two-
way 
SMS 
messaging 
on 
highly 
effective contraceptive (HEC) use at 
six months postpartum versus control among 260 Kenyan women. HEC use was significantly higher 
among women in the SMS group (69.9%) compared to  controls (57.4%) with 94.6% of the 130 women 
Figure 7: Effect of SMS interventions on primary outcomes among 
Mobile WACh participants (Unger BJOG 2018)   
Figure 6: Mobile WACh messaging identifying a critically ill infant 

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receiving the intervention interacting with the intervention and sending 3188 messages (58). Mobile 
WACh-X is ongoing and expected to be completed in late 2019. 
Table 1.  UW-Kenya mHealth Studies Support the Reproductive Health Continuum 
Investigator, 
location, year  
Study 
Name  
Number 
and 
Characteristics  
Intervention  
Study 
Design  
Outcomes 
Measured  
Results  
Unger, Kenya 
2013 (60, 61, 
63, 65) 
 
Mobile 
WACh  
300 
peripartum 
women and their 
infants 
1-way 
SMS 
versus 2-way 
dialogue  
RCT 
Facility 
delivery 
contraption 
EBF  
Improved 
early 
contraceptiv
e uptake 
Improved 
EBF  
John-Stewart, 
Kenya 
2015 
(59, 60, 64) 
 
Mobile 
WACh 
X 
875 HIV infected 
peripartum 
women 
and 
infants 
1-way 
SMS 
versus 2-way 
dialogue 
RCT  
Retention 
ART 
Adherence 
Viral 
suppression  
Drug 
resistance 
Infant HIV  
Ongoing  
Harrington, 
Kenya 
2016 
(58) 
 
Mobile 
WACh 
XY  
260 postpartum 
women and male 
partners  
2-way SMS  
RCT  
Highly 
effective 
contraceptiv
e (HEC) use 
 
Improved 
HEC 
use 
postpartum  
Ronen, Kenya 
2017  
Vijana
-
SMAR
T  
110 HIV-infected 
adolescents  
WhatsApp 
peer 
group 
intervention  
Pilot  
Retention  
ART 
adherence  
Ongoing  
Bhat, US 2016 
(66) 
 
DAWN 25 women with 
perinatal 
depression 
in 
collaborative 
care  
2-way SMS  
Pilot  
Process 
outcomes  
Use of SMS 
for 
depression 
support 
acceptable 
and feasible  
Unger, Kenya 
2016  
Mobile 
WACh 
NEO  
800 
peripartum 
women and their 
infants  
2-way SMS  
Demonstr
ation 
project  
Process 
outcomes  
Facility 
delivery 
Contracepti
on 
Neonatal 
mortality  
Ongoing  
John-Stewart, 
Kenya 2017  
Mobile 
WACh 
PrIYA  
300 
young 
women 
and 
adolescent girls  
2-way SMS  
Demonstr
ation 
project  
Process 
outcomes  
PrEP 
adherence  
Ongoing  

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Additionally, we have adapted Mobile WACh for 3 pilot projects: Mobile WACh NEO (Saving Lives at 
Birth, PI: Unger), Mobile WACh PrIYA (Pre-exposure prophylaxis implementation in young women 
and adolescents) (sub-aim) (DREAMS, PI: John-Stewart), and DAWN, a project for peripartum 
depression (sub-aim) (NIMH, PI: Bhat)  (66). In each instance we have accrued extensive experience 
adapting the platform for use among vulnerable populations and handling sensitive information such 
SMS related to HIV management (59), depression (66) and adverse outcomes such as infant death 
(65).  
 
Preliminary studies: mHealth and neonatal health 
As a result of the findings from the 
original Mobile WACh RCT, and our 
interest in innovations to support 
neonatal survival, we initiated a pilot 
project, Mobile WACh NEO (Figure 8), 
with 
the 
Saving 
Lives 
at 
Birth 
consortium.  We modified the Mobile 
WACh 
system 
and 
messaging 
approach to deliver messaging in late 
pregnancy and the first 2 months 
postpartum 
focused 
on 
providing 
tailored support by SMS in 3 strategic 
domains which have the greatest 
impact on maternal and neonatal 
health: facility delivery planning, clinical 
assessment of neonates and the 
postpartum mother, and contraceptive 
decision support. We launched our 
pilot project in two high volume 
clinics in Kenya and have enrolled 
800 women in 5 months, received thousands of SMS to date, triaged hundreds of concerns 
about maternal and neonatal health, and received timely reports of over 200 births and 20 
adverse events.  Nurses and community health workers manage the messaging demand with 91% 
of women engaging with the messaging and sending on average 14 messages per woman to date, 
although most women are still in follow-up. We have noted several messages reporting depressive 
symptoms, and seeking assistance in practicing essential neonatal care and identifying infant illness. 
In exit interviews, women have almost unanimously requested continuation of the intervention. 
Although there is tremendous enthusiasm and demand for the intervention, and potential for impact, 
the pilot has no control arm and is not powered to determine clinical impact. As a result, we propose 
to conduct a rigorous trial of Mobile WACh NEO to determine the effect of this two-way SMS 
intervention on neonatal mortality. We will utilize paradata, process indicators, outcome data and 
exit interviews from the Mobile WACh NEO pilot to inform SMS message content development and 
approach. 
 
Conceptual framework 
Drake, Kenya 
2017  
mCub
e 
1,000 
adolescents and 
adult women  
Smart 
logic 
2-way 
SMS 
for 
data 
collection 
Pilot  
Process 
outcomes 
Contracepti
ve 
use 
Discontinuat
ion 
Side effects  
Ongoing  
Figure 8: Components of the Mobile WACh NEO pilot  

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Figure 9 summarizes the conceptual framework that guides design and evaluation of the Mobile 
WACh NEO intervention. This framework is based on the Information-Motivation-Behavioral Skills 
(IMB) model of behavioral change, which posits that individual health behavior is predicted by the 
individual’s access to information about the behavior, motivation, and behavioral skills to perform the 
behavior (67). Our overall hypothesis is that the Mobile WACh NEO intervention improves neonatal 
health through two complementary mechanisms. First, it provides mothers with Information and Skills 
through education, actionable SMS, instrumental support, and interactive triage to prevent, identify, 
and seek care for neonatal illness. Second, it provides mothers with Motivation though social and 
emotional support and psychoeducation to improve their mental health and self-efficacy, which in turn 
reinforces their ability to successfully implement protective essential neonatal care.  
 
 
8. RATIONALE 
 
Despite recent achievements in reducing child mortality, neonatal deaths remain high, accounting for 
46% of all deaths in children under 5 worldwide. Neonatal morality in Kenya is reported to be 22.6 per 
1000 live births, ranking among the countries with the highest number of neonatal deaths. Addressing 
the high neonatal mortality demands efforts focused on getting proven interventions to at-risk 
neonates and their families.  Bidirectional two-way SMS communication with a HCW presents a 
unique opportunity to connect mothers to a HCW, increase “real-time” identification of neonatal 
danger signs and guide appropriate care seeking. At the same time, this communication can provide 
support to women during the critical peripartum period, increase self-efficacy and social support, and 
contribute to decreasing depressive symptoms, which may further improve care seeking. SMS 
communication is designed to supplement, not to replace, in person health care delivery.  We propose 
a randomized controlled trial (RCT) of a semi-automated, two-way SMS intervention, Mobile WACh 
NEO, to determine its effect on neonatal mortality, implementation of ENC, identification of and 
appropriate care seeking for neonatal illness, and maternal mental health.   
 
9. HYPOTHESIS & STUDY QUESTIONS: 
 
Our overarching hypothesis is that Mobile WACh NEO, a theoretically grounded two-way SMS 
intervention that connects women with healthcare workers in the critical period surrounding delivery 
of their babies, will improve their knowledge, skills and motivation to prevent, identify and seek care 
for neonatal illness, leading to improved maternal and neonatal health.  
 
10. OBJECTIVES 
10.1 Broad Objectives 
Our overarching aim is to determine the effect of Mobile WACh NEO SMS on neonatal mortality and 
understand the mechanisms by which this innovation impacts neonatal health. We propose to 
determine the effect of Mobile WACh NEO SMS on neonatal mortality, essential newborn care, 
care seeking, and maternal mental health in the first 6 weeks postpartum, in a 2-armed 
randomized controlled trial (RCT), comparing essential newborn care SMS versus no SMS control. 
Figure 9. Mobile WACh NEO 
conceptual framework 

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10.2 Specific Objectives 
Aim 1: To determine the effect of tailored, systematic two-way Mobile WACh NEO SMS on neonatal 
mortality. 
Hypothesis: Women randomized to Mobile WACh NEO will have lower neonatal mortality than 
women randomized to control. 
 
Aim 2: To determine the effect of Mobile WACh NEO SMS on maternal implementation of essential 
newborn care and care seeking behavior. 
2a. To compare practices of early and exclusive breastfeeding, cord care and thermal care among 
mothers randomized to Mobile WACh NEO versus control. 
2b. To compare knowledge of infant danger signs and care seeking for neonatal illness among 
mothers randomized to Mobile WACh NEOv ersus control. 
Hypothesis: Implementation of essential newborn care, knowledge of neonatal danger signs, 
and clinic attendance will be higher in mothers randomized to Mobile WACh NEO SMS than 
control. 
 
Aim 3: To determine the effect of Mobile WACh NEOSMS on longitudinal maternal social 
support, self-efficacy and depression among mothers randomized to Mobile WACh 
NEOversus control. 
Hypothesis: Maternal self-efficacy and social support will be higher and depression will be 
lower among women randomized to Mobile WACh NEO than control. 
 
Exploratory aim: To determine associations between maternal mental health, implementation of 
essential newborn care, care seeking and SMS engagement. 
 
11. METHODOLOGY 
11.1 Study Design 
The study is a non-blinded randomized controlled trial. 
11.2 Study Area Description 
 
Study sites:  The proposed study will be conducted at 11 sites in Kenya: Mathare North City Health 
Centre, Riruta Health Centre, Rachuonyo South County Hospital, Ahero sub-District Hospital, Bondo 
District Hospital, Kisumu County Hospital, Migosi Sub-County Hospital, Lumumba Sub-County 
Hospital, Homa Bay County Referral Hospital, Rangwe Sub County Hospital and Rachuonyo North 
Sub County Hospital. Neonatal mortality in the Nairobi slum areas, Kisumu and Homa Bay counties 
is particularly high (4) so communities in these areas stand to benefit the most from the Mobile WACh 
NEO intervention. These facilities represent a mix of rural and urban facilities, all with sufficient patient 
volume to assure feasibility of recruitment. From our ongoing studies at these sites we estimate ~260 
women attend ANC per month at each site. 
 
Letters of cooperation will be submitted in a subsequent modification to this application.  
 
11.3 Study Population 
Population 
N 
Inclusion Criteria 
Data Collection 
Table 2. Summary of proposed eligibility, procedures and outcomes for study aims 

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15 
 
RCT 
Pregnant women 
5020 
• 
Pregnant 
• 
28-36 weeks gestation 
• 
Daily access to a mobile phone 
(own or shared) on the Safaricom 
network 
• 
Willing to receive SMS 
• 
Age ≥14 years 
• 
Able to read and respond to text 
messages in English, Kiswahili or 
Luo, or have someone in the 
household who can help 
• 
 
• 
Screening 
questionnaire 
• 
Enrolment and follow-
up questionnaires 
• 
Content 
of 
SMS 
conversations 
with 
Mobile WACh system 
Post-RCT IDIs 
Postpartum 
women 
60 
Intervention RCT participant 
• 
IDI 
 
Study populations for each of the aims are summarized in Table 2. Two study populations will be 
included in the study:  
1. Pregnant women (Randomized controlled trial) (N=5020) 
Inclusion criteria: 
o Age ≥14 
o Pregnant 
o 28-36 weeks gestation 
o Daily access to a mobile phone on the Safaricom network 
o Able to read and respond to text messages in English, Kiswahili or Luo, or have 
someone in the household who can help 
Exclusion criteria: 
• 
Currently enrolled in another research study 
• 
Previous participant in the Mobile WACh NEO RCT (i.e. with a new pregnancy) 
To enhance generalizability, literacy will not be required if women have access to a partner or family 
member whom she would be comfortable to have read her the messages. This approach was 
developed in consultation with mothers in Kenya, who felt that involving their partner was acceptable 
and may engage more support, and has been successfully implemented in our previous Mobile WACh 
studies. 
2. Postpartum women (post-RCT IDIs) (N=60) 
A subset of intervention RCT participants will be invited to participate in IDIs after they 
complete the intervention to evaluate their experiences with the intervention. 
11.4 Sample Size Determination 
 
11.4.i. RCT 
Table 4 summarizes detectable differences based on the expected outcomes, assuming α=0.0055 
(Bonferroni-adjusted for 9 hypothesis tests) and sample size 5020 (2510 per arm).  Expected 
outcomes are based on those observed in our previous work in Kenyan pregnant women (unpublished 
data) (58, 64) or other publications (68). 
 
 

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Indicator 
Outcomes 
(control) 
Outcomes 
(intervention) 
Absolute 
difference 
Relative  
difference 
Neonatal mortality per 1000 births1 
25.0 
23.0 
13.8 
12.2 
11.2 
10.8 
0.55 
0.53 
20.0 
10.0 
10.0 
0.50 
Initiation of BF within 1h; 
EBF for 6 weeks2 
90.0% 
93.0% 
3.0% 
1.03 
80.0% 
84.1% 
4.1% 
1.05 
Application of substances to cord; 
Bath within 24h2 
40.0% 
45.3% 
5.3% 
1.13 
50.0% 
55.4% 
5.4% 
1.11 
Number of clinic visits in first 6 weeks2 
0.5 
0.6 
0.1 
1.22 
1.0 
1.1 
0.1 
1.11 
Number of danger signs correctly 
named2  
3.0 
5.0 
3.1 
5.1 
0.1 
0.1 
1.03 
1.02 
Maternal depression2 
19.0% 
14.6% 
4.4% 
0.77 
Maternal social support score; 
Maternal self-efficacy score (max 4.0)2 
2.5 
3.5 
2.6 
3.6 
0.1 
0.1 
1.04 
1.03 
1α=0.05,2Adjusted α=0.0055, β=0.8, 2-sided tests 
 
11.4.ii. IDIs 
Sample size for qualitative data collection was determined based on the number of interviews needed 
to achieve saturation of concepts. It is estimated that 60 interviews will be sufficient to achieve 
saturation. 
11.5 Recruitment, Screening and Consent Procedures 
 
11.5.i. RCT  
Recruitment: Women will be recruited when attending routine ANC, through in-person outreach by 
study staff.  
 
Screening and consent: Interested patients will be asked to provide verbal consent for screening 
(see screening consent script), consenting women will be asked screening questions to assess 
eligibility and, if eligible (see inclusion criteria above), be invited to participate in the study. Women 
willing to participate in the study will be asked to provide written informed consent form. The age of 
consent in Kenya is 18, but pregnant women age 14 or older are considered emancipated minors and 
can consent independently. Discussions between study staff and potential participants will be 
conducted in a private secluded place to maintain privacy. 
 
11.5.ii. IDIs  
 
Recruitment: Participants from the intervention arm will be classified into high, medium and low 
interactors based on their engagement or use of the Mobile WACh NEO program i.e. how often they 
send or respond to SMS.  We will then randomly select 10 from each group to participate in interviews 
(IDIs). They will be invited to participate in IDIs while they are still on-study. We will also interview 30 
women among those with neonatal complications or demises.  Based on our previous studies we 
anticipate that half of the women who lose their babies want to remain connected to the program.  We 
Table 3. Power and sample size ranges. 
Minimum detectable difference 

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will select women for IDIs from among those who agree to remain connected to the program even 
after their loss.   
11.6 Data Collection Procedures 
 
11.6.i. RCT  
Intervention package: We propose to utilize Mobile WACh, a human-computer hybrid system used in 
our previous studies, which enables seamless two-way SMS communication and patient tracking, to 
provide consistent support to women and their infants during the peripartum period and 6 weeks into 
the baby’s life. Women will receive automated theoretically grounded SMS messages targeting the 
appropriate peripartum period (Figure 10) and will have the capability to respond and spontaneously 
message a nurse based at the clinic. During pregnancy, automated SMS will be delivered weekly. 
Two weeks prior to the participant’s estimated due 
date (EDD), daily messaging will begin, and will 
continue for two weeks after delivery is ascertained. If 
delivery is not confirmed by 43 weeks gestational age, 
the participant will be automatically moved to the 
postpartum messaging track. Thereafter, SMS will be 
delivered every other day for the remaining four 
weeks. Automated SMS will be delivered at times and 
in languages based on patient preferences. We have 
partnered with a local premium rate service provider (PRSP), Africa’s Talking, to provide SMS 
dialogue free of charge to participants.  Women who experience pregnancy or infant loss will be 
enrolled into an infant loss track where they will receive messages of support. 
 
Randomization: 
Participants will be randomized to 1) Interactive two-
way SMS dialogue or 2) Control (no SMS), using 1:1 
allocation. A randomization list will be generated by the 
study statistician using random block sizes in statistical 
software. Randomization will be stratified by site.  This 
randomization list will be programmed into a computer 
program on an internet-based randomization platform. 
Each study site will be assigned unique user names 
and log in credentials for traceability purposes and 
ensuring that the randomization process is controlled.. 
Study staff will use their unique credentials to log in to 
the randomization program. The program will display 
the allocation after staff have entered the participant ID. The allocation will be recorded in the program 
for further traceability. The study arm will be unblinded to participants and study staff. The control arm 
will receive standard care and education provided in ANC by MCH clinic staff. Because the study 
aims to determine mHealth benefits in addition to routine clinical care, MNCH services will be 
delivered by the MOH programs with minimal clinic interactions with study personnel.  The intervention 
will be delivered between 28 weeks of gestation and 6 weeks postpartum. 
 
Data collection: 
Participants will be followed from enrolment (28-36 weeks gestation) up to 18 weeks postpartum. All 
clinical care will be managed through the existing MCH infrastructure. The study visit schedule will be 
aligned to routine postpartum and infant visits: enrolment visit in pregnancy (28-36 weeks gestation), 
2 weeks postpartum and 6 weeks postpartum. Active tracing will be performed through phone calls 
and home visits to maximize completeness of data at study visits. Participants who do not report their 
delivery by 40 weeks will be contacted by phone, followed by home tracing if not reached by phone. 
Further, participants who are 1 week late for their 2-week or 6-week postpartum visits will be traced 
by phone. Participants who are 1 week late for their 6-week visit and cannot be reached by phone will 
be traced at their home. Participants who do not wish to come to clinic for their 2-week or 6-week visit 
will be offered to complete their visits by phone or at home in locations that ensure participant safety 
Figure 10. Mobile WACh NEO intervention 

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and confidentiality. This approach has been successful and acceptable in our previous studies in this 
population (31, 64, 69).  During the consent process, study staff will collect contact information and 
permission to contact a family member or trusted individual who they may contact in case of long-
term lack of communication from the participant. This person may be contacted as part of active 
tracing. In the case of a maternal death or disappearance, staff will collect information on the event 
from the provided contact. 
 
A tablet-based screening questionnaire will be used to assess eligibility and collect sociodemographic 
characteristics. Following enrolment in the RCT and randomization, a tablet-based enrolment 
questionnaire using an open-source tablet-based data collection system (Open Data Kit)  will be used 
to collect enrolment data including: demographics, clinical and sexual history, family planning, 
experience with SMS and technology, social support, intimate partner violence, and depression.  
 
At each visit, a standardized questionnaire will evaluate self-reported outcomes (Table 4), experience 
with the intervention (for intervention participants) and participant clinical characteristics that may be 
associated with the outcomes, such as delivery experience, maternal and child health status, 
breastfeeding, care-seeking, cord care, depression and social support. Between study visits, data will 
be abstracted from patient clinic records to ascertain clinical outcomes such as deliveries, 
clinic/hospital visits, and infant or maternal deaths (Table 4). The data will be abstracted from available 
facility records including MCH cards, facility registers (hospitalization, ANC, CWC, PNC), and EMR 
systems. The study nurses will review clinic records daily to check for deliveries and clinic visits from 
study participants. We have successfully employed this approach in a previous RCT, Mobile WACh-
X (64).  In addition to contributing to ascertainment of trial outcomes, abstraction of clinic records will 
enable personalization of messaging, for example initiating postpartum messaging after a participant 
delivers. 
 
 
Medical extraction forms will be completed by data teams: delivery information, infant admissions, 
maternal health, infant health, maternal mortality, and infant mortality. 
 
When the study team learns of an infant death through an SMS message, phone call or clinic record 
review, the study team will contact the participant to arrange a visit to conduct a verbal autopsy. Verbal 
autopsies will be performed about 6 weeks after the infant death, either in the clinic or at the 
participant’s home based on their preference.  
 
Participants will be provided Ksh. 400 per visit to compensate for time and transportation expenses 
to participate in the study. We will provide this monetary compensation to each participant at the 
conclusion of each study visit. In the case of a maternal death or disappearance, the contact from 
whom the information on the event was collected will be provided Ksh. 400 to compensate for time. 
 
Data collection instruments 
Data collection instruments will include forms to record data from participant surveys, to include:  
• 
Demographics  
• 
Clinical and sexual history 
• 
FP use 
• 
Experience with SMS and technology  
• 
Intimate partner violence 
• 
Depression 
• 
Social support 
• 
Delivery report 
• 
Infant health 
• 
Maternal health 
 
 
11.6.ii. IDIs 

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IDIs will be performed in a private area within the facility. Participants will meet a trained interviewer 
who will ask questions and take notes. Consent will be obtained from participants to take notes and 
audio record the discussion. The interviewer will describe procedures and norms for discussion and 
participation. Participants will be given a chance to ask questions regarding procedures prior to the 
discussion. Their socio-demographic information will be documented in separate forms. Socio-
demographic information that will be captured include: age, marital status, education level, 
employment, number of children.   
 
We will submit an IDI guide in a future modification.  
 
Interviews will be conducted in English, Kiswahili, or Luo depending on participant preferences. 
Thereafter, notes will be compared to audio-recordings to fill in missing information and transcribed 
to English (if necessary). Transcribed data will be de-identified. Tape-recorded discussions will be 
destroyed no later than 3 years after conducting the IDI. 
 
Participants will be provided refreshments and Ksh. 400 to compensate for time and transportation 
expenses to participate in the study. We will provide this monetary compensation to each participant 
at the conclusion of each interview. 
11.7 Data Analysis 
 
Table 4: RCT outcomes 
Outcome 
Role 
Indicator   
Source   
Timing 
of 
ascertainment 
Statistical 
Analysis  
Aim 1 
Neonatal 
mortality  
Primary 
outcome 
Death during 1st 28 
days of life 
Questionnaire, 
clinic 
records; 
verbal autopsy 
2 and 6 week 
visits, ongoing 
record 
abstraction  
Cox proportiona
hazards  
Aim 2  
Initiation 
of 
early 
breastfeeding 
Secondary 
outcome 
Breastfeeding in 1st 
hour of life 
Questionnaire 
2 week visit  
Poisson 
regression 
(robust standard
errors) 
Exclusive 
breastfeeding 
Secondary 
outcome 
Cessation of EBF in 1st 
6 weeks of life 
Questionnaire 
2 and 6 week 
visits  
Cox proportiona
hazards 
Thermal care   
Secondary 
outcome 
Bath in 1st 24 hours of 
life   
Questionnaire  
2 week visit 
Poisson 
regression 
(robust standard
errors) 
Cord care  
Secondary 
outcome 
No 
application 
of 
substances to cord 
Questionnaire 
2 week visit  
Poisson 
regression 
(robust standard
errors) 
Maternal 
knowledge 
of 
neonatal 
danger signs  
Secondary 
outcome 
Number 
of 
the 
7 
danger 
signs 
or 
symptoms 
successfully named 
Questionnaire  
2 and 6 week 
visits 
Poisson GEE 
 
Appropriate 
care seeking   
Secondary 
outcome 
Number of clinic visits 
with danger sign and/ 
or hospital admissions 
reported in 1st 6 weeks 
Questionnaire, 
clinic records 
2 and 6 week 
visits, ongoing 
record 
abstraction 
Poisson 
regression 
Aim 3  

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For IDI analysis, two analysts will independently code transcripts to identify themes and sub-themes, 
coordinating analyses to create a comprehensive codebook and concept map. We will use domains 
identified under the IMB theory and our conceptual model to categorize participants’ perceived 
intervention functions. 
11.8 Study Materials 
Equipment: The grant award includes support for SMS platform messaging delivery and 
receipt, 6 tablets, field office supplies (stationary, paper, toner), 6 laptop computers. 
 
Personnel: The grant award includes support for KNH, UW and MOH investigators, clinic 
personnel, the data team, and two study coordinators (clinical coordinator (Nairobi based) and 
overall coordination (Seattle based)).  Study personnel working in Kenya will be hired through 
KNH according to standard procedures. 
 
11.9 Training Procedures 
Dr. John Kinuthia, Dr. Jennifer Unger, Dr. Keshet Ronen, Daniel Matemo, Jenna Udren, Brenda 
Wandika, Peninah Kithao and June Moraa will supervise training of clinical personnel in study 
procedures.  This will include research ethics, neonatal health and FP counseling and completion of 
surveys. 
11.10 Quality Assurance Procedures 
 
Clinical care: The study will adhere to Government of Kenya guidelines for the care of 
pregnant/postpartum women and their infants; however, no clinical care will be provided by study 
staff.  Data collected as part of the study will be abstracted from the mother’s “Mother & Child Health 
Booklet” or clinic medical records. 
 
Adherence to protocol: Weekly reporting of enrolment, follow-up, medical complications and results 
will enable us to monitor that the study is running according to approved protocols.  Frequent reporting 
will also enable us to quickly respond to any problems that arise during the study. 
 
12. ETHICAL CONSIDERATIONS 
12.1 Consent explanation 
Please see the attached consent forms: 
Consent 1: RCT study participation  
Depression  
Secondary 
outcome 
Score 
above 
diagnostic threshold 
(≥12) for Edinburgh 
Postnatal 
Depression 
Scale 
(70)   
Questionnaire 
Enrolment, 2 
and 6 week 
visits 
Poisson 
regression (robus
standard errors) 
Social support 
Secondary 
outcome 
Score using MOS 
Social 
Support 
Survey (71) 
 
Questionnaire 
Enrolment, 2 
and 6 week 
visits 
Linear GEE 
Self-efficacy  
Secondary 
outcome 
Score 
using 
Self-
efficacy 
in 
Infant 
Care Scale (68) 
 
Questionnaire  
Enrolment, 2 
and 6 week 
visits 
Linear GEE 

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12.2 Institutional Review Board  
This is a collaborative research proposal that will involve field procedures in Nairobi and data analyses 
in Nairobi and Seattle. The study will be reviewed by the Kenyatta National Hospital/University of 
Nairobi (KNH/UON) Ethics and Research Committee (ERC), and the University of Washington 
Institutional Review Board (IRB). The study will not recruit subjects prior to approval from both the 
UW IRB and the KNH/UON ERC. 
12.3 Risks to subjects 
Physical: The study involves no medical interventions therefore we anticipate no risk of serious harm 
to participants. 
 
Other: SMS: There is a potential risk of disclosure of an individual’s person information to others in 
situations where phones are shared or stolen. We will minimize these risks through counseling in the 
informed consent process and ensuring women understand the type of messaging that will occur.   
 
Access to clinical records: There could be a breach of confidentiality in the process of retrieving 
participants’ medical records. This will be mitigated by training all study staff on data management 
and storage to ensure confidentiality of sensitive data is maintained.  
 
Loss of Confidentiality in IDI: Women will be notified that by participating in the IDI, loss of 
confidentiality is a possible risk of participating. They will be informed that this is very unlikely as every 
measure will be taken to ensure confidentiality. 
 
Alternative treatments or procedures: Not applicable 
 
12.4 Protection against risks 
 
Informed consent: Study staff will give potential participants verbal and written information about the 
study. Consent will be obtained and documented in verbal and written forms.  Participants will have a 
chance to ask questions about the study, and offered participation. They will be enrolled in the study 
after providing written informed consent. Mothers will provide informed consent for study participation 
on behalf of their infants. 
 
SMS: There is a potential risk of disclosure of an individual’s person information to others in situations 
where phones are shared or stolen. However, we will not send any sensitive information via text. 
Study staff will specifically demonstrate example messages, to ensure potential cohort study 
participants agree to receipt of this information. Participants will only be enrolled once they understand 
study procedures and find the messaging acceptable. 
 
Access to clinical records: There is could be a breach of confidentiality in the process of retrieving 
participants’ medical records. This will be mitigated by training all study staff on data management 
and storage to ensure confidentiality of sensitive data is maintained. Databases will not include patient 
identifiers and will be encrypted and password protected.    
 
Loss of confidentiality in IDI: We will assure women of protection of confidentiality. 
 
DSMB: Clinical care will continue to be provided as prescribed.  As this is a clinical trial, we will have 
a DSMB who will regularly monitor protocols and outcomes.    
 

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Undiagnosed conditions: It is possible we will detect previously undiagnosed conditions such as 
depression and intimate partner violence. Participants will be referred for appropriate health and social 
services.   
 
SMS withdrawal: Participants in the intervention group may withdraw from receiving SMS messages 
at any time. Study staff will complete an SMS Withdrawal form for any participants who wish to 
withdraw from the system. Participants who withdraw from SMS can continue or withdraw from the 
study. 
 
Study withdrawal: Participants may withdraw from the study at any time for any reason. The Study or 
Site PI may also terminate a participant from the study at their discretion, if she was enrolled 
inappropriately, or if continued participation would be harmful. Study staff will complete a Study 
Termination form for any participants choosing to terminate early. All data collection and SMS 
messaging will discontinue at that point. 
12.5 Potential benefits 
 
The study will contribute to our understanding of how to deliver education and counseling to help 
women and families. It will also provide information that can be used to improve services to ensure 
more women attend clinic visits, get help with their delivery, and are provided with family planning 
options. It may help get more babies immunized. The study will also shape future SMS programs. 
Participants in the intervention arm may personally benefit from having access to advice about infant 
heath and infant illness. It may lead to improved care of the infants, better identification of infant illness 
and more appropriate care-seeking.  
12.6 Compensation 
A nominal travel reimbursement will be provided for participant travel to the study clinic (see section 
11.6).  
 
12.7 Importance of the knowledge to be gained 
This study will determine the efficacy of 2-way communication to improve neonatal and maternal 
postpartum outcomes.  
 
13. DATA MANAGEMENT  
 
IDIs  
IDI audio recordings and transcripts will be uploaded to a password-protected computer and erased 
from the recorder within one day of interview. Recordings will be erased once transcripts have been 
validated, no more than 6 months after generation of the recording. 
 
Questionnaires 
All questionnaires will be administered using the tablet-based ODK platform. Tablets will be password-
protected and questionnaires will be transmitted to a secure server daily and erased from the tablets. 
Data will be transmitted via secure socket layer (SSL) and only accessible by authenticated users. 
Tablets will be stored in a secure, locked office accessible to study staff only. All participants will be 
assigned a non-identifiable study ID number upon enrolment. All data records will be identified by 
study ID only. The link between identifiable participant information and study IDs will be locked in a 
secure, locked location and destroyed following study completion. Study analysts will receive only 
coded data. 
 
Paper records 
Consent forms and participant locator information will be stored in paper forms. These will be stored 
in a secure, locked location and destroyed following study completion. 
 
Data Ownership 

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The proposed project is a collaborative effort between investigators at the UW and KNH.  The 
aforementioned institutions will jointly share ownership of the data.  Study investigators at the UW 
and KNH will have full access to the data. Authorship on publications, conference presentations, 
abstracts and other materials generated from this study will reflect contribution to design, execution 
and analysis of the study.  
 
Data Release/Sharing Policy 
This study will comply with the NIH Public Access Policy, which ensures that the public has access to 
the published results of NIH funded research. It requires scientists to submit final peer-reviewed 
journal manuscripts that arise from NIH funds to the digital archive PubMed Central upon acceptance 
for publication.   
 
14. RESULTS DISSEMINATION  
 
We will establish 4 community advisory boards, one for each facility. This will include medical 
providers and community members living in the area.  We will disseminate results to this board 
twice a year and ask for guidance if community issues arise.   
 
Study findings will be shared with the participating facilities and Kenyan Ministry of Health at 
its conclusion as a presentation or written report. Findings will be disseminated to the research 
community in the form of conference presentations and journal articles. 
 
15. STUDY LIMITATIONS 
 
SMS alone cannot directly improve the health care system or address the third delay in care (delay 
in receiving quality care). There are many other external factors – partner, socioeconomic factors, 
quality of facility-based care – that may not be modulated by SMS messaging. This may limit our 
ability to detect an impact on the primary outcome of neonatal mortality. Evaluation of the impact of 
SMS on secondary outcomes of ENC, knowledge of warning signs, care seeking and maternal mental 
health will nonetheless enable us to assess whether the SMS intervention has the desired impact and 
has potential to improve mortality in combination with additional health systems strengthening. 
Moreover, these secondary outcomes have value in improving neonatal and maternal health in 
their own right. Fidelity and generalizability of dialogue interventions are challenging. We have 
extensive experience in standardizing messaging dialogue, but it will not be possible to completely 
standardize the nurse responses in the intervention. This challenge however is part of routine medical 
care and any type of behavioral interventions involving health workers. Implementation and evaluation 
in four sites will increase the generalizability of any measured effect. With regards to the care seeking 
outcome, babies in the control arm may have higher numbers of clinic visits and/ or hospitalizations 
if their mothers are less likely to practice ENC or if mothers seek care later in the illness process. If 
we observe this effect we will compare illness severity at presentation between the two arms using a 
validated neonatal illness assessment. Women in the trial cannot be blinded to their assignment, 
which may lead to performance bias. Additionally, outcomes obtained by self-report could introduce 
bias for social desirability, but this will likely occur across all arms. 
 
16. STUDY TIMELINE 
 
The study timeline is summarized in Figure 11. We anticipate that this study will take 5 years to 
complete. In the first year, we will obtain ethical approval from institutional review boards at the 
University of Washington and Kenyatta National Hospital.  During this time, we will develop and refine 
study tools and finalize standard operating procedures and publish the clinical trial protocol. We will 
also adapt the messaging platform technology based on final pilot project data and finalize the 
message bank for the intervention.  Following IRB approval, field site preparation will take 3 months, 
including hiring and training of site staff, and conducting of mock enrolments and messaging. We will 
also conduct community sensitization and outreach to ensure the community is aware of the purpose 
of the project. We will recruit and enroll participants and conduct follow-up over a 24-month period. 

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The last follow-up visit will occur in quarter 1 of year 4.  We will conduct the post RCT interviews in 
Year 4.  Approximately 6 additional months will be needed for data verification and cleaning, 
ascertainment and transcription of any outstanding clinical records. Data analysis and dissemination 
including manuscript submissions will occur in Years 4-5. 
 
 
 
 
17. REFERENCES 
 
1. 
Organization WH. Global Health Observatory Data Repository Geneva: World Health 
Organization 2014 [cited 2018 20 May ]http://apps.who.int/ghodata/]. 
2. 
UNICEF WB, UN DESA/Population Division Levels and Trends in Child Mortality 2017. 
3. 
Lawn JE, Kinney MV, Black RE, Pitt C, Cousens S, Kerber K, Corbett E, Moran AC, Morrissey 
CS, Oestergaard MZ. Newborn survival: a multi-country analysis of a decade of change. Health Policy 
Plan. 2012;27 Suppl 3:iii6-28. Epub 2012/06/22. doi: 10.1093/heapol/czs053. PubMed PMID: 
22692417. 
4. 
Macro KNBoSKaI. Kenya Demographic and Health Survey: Key Indicators 2014. 2015 ed. 
Rockville, MD KNBS and ICF Macro; 2015. 
5. 
IGME) TUNI-aGfCMEU. Level and Trends in Childhood Mortality UNICEF, 2017. 
6. 
World Health Organization U. Every newborn: An action plan to end preventable deaths. 
Geneva WHO, 2014. 
7. 
Lawn JE, Blencowe H, Oza S, You D, Lee AC, Waiswa P, Lalli M, Bhutta Z, Barros AJ, 
Christian P, Mathers C, Cousens SN, Lancet Every Newborn Study G. Every Newborn: progress, 
priorities, and potential beyond survival. Lancet. 2014;384(9938):189-205. Epub 2014/05/24. doi: 
10.1016/S0140-6736(14)60496-7. PubMed PMID: 24853593. 
8. 
Bhutta ZA, Das JK, Bahl R, Lawn JE, Salam RA, Paul VK, Sankar MJ, Blencowe H, Rizvi A, 
Chou VB, Walker N, Lancet Newborn Interventions Review G, Lancet Every Newborn Study G. Can 
available interventions end preventable deaths in mothers, newborn babies, and stillbirths, and at 
what cost? Lancet. 2014;384(9940):347-70. Epub 2014/05/24. doi: 10.1016/S0140-6736(14)60792-
3. PubMed PMID: 24853604. 
9. 
Group NS. Timing of initiation, patterns of breastfeeding, and infant survival: prospective 
analysis of pooled data from three randomised trials. Lancet Glob Health. 2016;4(4):e266-75. Epub 
2016/03/26. doi: 10.1016/S2214-109X(16)00040-1. PubMed PMID: 27013313. 
10. 
Bhutta ZA, Darmstadt GL, Hasan BS, Haws RA. Community-based interventions for improving 
perinatal and neonatal health outcomes in developing countries: a review of the evidence. Pediatrics. 
2005;115(2 Suppl):519-617. Epub 2005/05/04. doi: 10.1542/peds.2004-1441. PubMed PMID: 
15866863. 
Figure 11. Study timeline 

STUDY PROTOCOL                                                                   
 
V2.4 October 1, 2021 
 
25 
 
11. 
Agrawal PK, Agrawal S, Mullany LC, Darmstadt GL, Kumar V, Kiran U, Ahuja RC, Srivastava 
VK, Santosham M, Black RE, Baqui AH. Clean cord care practices and neonatal mortality: evidence 
from rural Uttar Pradesh, India. J Epidemiol Community Health. 2012;66(8):755-8. Epub 2012/04/12. 
doi: 10.1136/jech-2011-200362. PubMed PMID: 22493477. 
12. 
Lunze K, Hamer DH. Thermal protection of the newborn in resource-limited environments. J 
Perinatol. 2012;32(5):317-24. Epub 2012/03/03. doi: 10.1038/jp.2012.11. PubMed PMID: 22382859. 
13. 
Kabwijamu L, Waiswa P, Kawooya V, Nalwadda CK, Okuga M, Nabiwemba EL. Newborn 
Care Practices among Adolescent Mothers in Hoima District, Western Uganda. PLoS One. 
2016;11(11):e0166405. Epub 2016/11/18. doi: 10.1371/journal.pone.0166405. PubMed PMID: 
27855186; PMCID: PMC5113955. 
14. 
Waiswa P, Peterson S, Tomson G, Pariyo GW. Poor newborn care practices - a population 
based survey in eastern Uganda. BMC Pregnancy Childbirth. 2010;10:9. Epub 2010/02/25. doi: 
10.1186/1471-2393-10-9. PubMed PMID: 20178626; PMCID: PMC2834614. 
15. 
Byaruhanga RN, Nsungwa-Sabiiti J, Kiguli J, Balyeku A, Nsabagasani X, Peterson S. Hurdles 
and opportunities for newborn care in rural Uganda. Midwifery. 2011;27(6):775-80. Epub 2010/08/06. 
doi: 10.1016/j.midw.2010.02.005. PubMed PMID: 20685016. 
16. 
Waiswa P, Pariyo G, Kallander K, Akuze J, Namazzi G, Ekirapa-Kiracho E, Kerber K, 
Sengendo H, Aliganyira P, Lawn JE, Peterson S, Uganda Newborn Study T. Effect of the Uganda 
Newborn Study on care-seeking and care practices: a cluster-randomised controlled trial. Glob Health 
Action. 2015;8:24584. Epub 2015/04/07. doi: 10.3402/gha.v8.24584. PubMed PMID: 25843498; 
PMCID: PMC4385212. 
17. 
Dickson KE, Simen-Kapeu A, Kinney MV, Huicho L, Vesel L, Lackritz E, de Graft Johnson J, 
von Xylander S, Rafique N, Sylla M, Mwansambo C, Daelmans B, Lawn JE, Lancet Every Newborn 
Study G. Every Newborn: health-systems bottlenecks and strategies to accelerate scale-up in 
countries. Lancet. 2014;384(9941):438-54. Epub 2014/05/24. doi: 10.1016/S0140-6736(14)60582-1. 
PubMed PMID: 24853600. 
18. 
Bogale TN, Worku AG, Bikis GA, Kebede ZT. Why gone too soon? Examining social 
determinants of neonatal deaths in northwest Ethiopia using the three delay model approach. BMC 
Pediatr. 2017;17(1):216. Epub 2017/12/29. doi: 10.1186/s12887-017-0967-9. PubMed PMID: 
29282018; PMCID: PMC5745914. 
19. 
Waiswa P, Kallander K, Peterson S, Tomson G, Pariyo GW. Using the three delays model to 
understand why newborn babies die in eastern Uganda. Trop Med Int Health. 2010;15(8):964-72. 
Epub 2010/07/20. doi: 10.1111/j.1365-3156.2010.02557.x. PubMed PMID: 20636527. 
20. 
Choi Y, El Arifeen S, Mannan I, Rahman SM, Bari S, Darmstadt GL, Black RE, Baqui AH, 
Projahnmo Study G. Can mothers recognize neonatal illness correctly? Comparison of maternal 
report and assessment by community health workers in rural Bangladesh. Trop Med Int Health. 
2010;15(6):743-53. Epub 2010/04/22. doi: 10.1111/j.1365-3156.2010.02532.x. PubMed PMID: 
20406425. 
21. 
Thaddeus S, Maine D. Too far to walk: maternal mortality in context. Soc Sci Med. 
1994;38(8):1091-110. Epub 1994/04/01. PubMed PMID: 8042057. 
22. 
Kallander K, Hildenwall H, Waiswa P, Galiwango E, Peterson S, Pariyo G. Delayed care 
seeking for fatal pneumonia in children aged under five years in Uganda: a case-series study. Bull 
World Health Organ. 2008;86(5):332-8. Epub 2008/06/12. PubMed PMID: 18545734; PMCID: 
PMC2647445. 
23. 
Wilmot E, Yotebieng M, Norris A, Ngabo F. Missed Opportunities in Neonatal Deaths in 
Rwanda: Applying the Three Delays Model in a Cross-Sectional Analysis of Neonatal Death. Matern 
Child Health J. 2017;21(5):1121-9. Epub 2017/02/20. doi: 10.1007/s10995-016-2210-y. PubMed 
PMID: 28214925. 
24. 
Kibaru EG, Otara AM. Knowledge of neonatal danger signs among mothers attending well 
baby clinic in Nakuru Central District, Kenya: cross sectional descriptive study. BMC Res Notes. 
2016;9(1):481. Epub 2016/10/27. doi: 10.1186/s13104-016-2272-3. PubMed PMID: 27782863; 
PMCID: PMC5078951. 
25. 
Nigatu SG, Worku AG, Dadi AF. Level of mother's knowledge about neonatal danger signs 
and associated factors in North West of Ethiopia: a community based study. BMC Res Notes. 

STUDY PROTOCOL                                                                   
 
V2.4 October 1, 2021 
 
26 
 
2015;8:309. Epub 2015/07/21. doi: 10.1186/s13104-015-1278-6. PubMed PMID: 26188481; PMCID: 
PMC4506763. 
26. 
Sandberg J, Odberg Pettersson K, Asp G, Kabakyenga J, Agardh A. Inadequate knowledge 
of neonatal danger signs among recently delivered women in southwestern rural Uganda: a 
community 
survey. 
PLoS 
One. 
2014;9(5):e97253. 
Epub 
2014/05/16. 
doi: 
10.1371/journal.pone.0097253. PubMed PMID: 24824364; PMCID: PMC4019554. 
27. 
Ekwochi U, Ndu IK, Osuorah CD, Amadi OF, Okeke IB, Obuoha E, Onah KS, Nwokoye I, 
Odetunde OI, Obumneme-Anyim NI. Knowledge of danger signs in newborns and health seeking 
practices of mothers and care givers in Enugu state, South-East Nigeria. Ital J Pediatr. 2015;41:18. 
Epub 2015/04/19. doi: 10.1186/s13052-015-0127-5. PubMed PMID: 25888409; PMCID: 
PMC4372313. 
28. 
Coleman PK KK. Self-Efficacy and Parenting Quality: Findings and Future Applications. 
Developmental Review. 1998;18(1):47-85. 
29. 
Jarde A, Morais M, Kingston D, Giallo R, MacQueen GM, Giglia L, Beyene J, Wang Y, 
McDonald SD. Neonatal Outcomes in Women With Untreated Antenatal Depression Compared With 
Women Without Depression: A Systematic Review and Meta-analysis. JAMA Psychiatry. 
2016;73(8):826-37. Epub 2016/06/09. doi: 10.1001/jamapsychiatry.2016.0934. PubMed PMID: 
27276520. 
30. 
Grote NK, Bridge JA, Gavin AR, Melville JL, Iyengar S, Katon WJ. A meta-analysis of 
depression during pregnancy and the risk of preterm birth, low birth weight, and intrauterine growth 
restriction. 
Arch 
Gen 
Psychiatry. 
2010;67(10):1012-24. 
Epub 
2010/10/06. 
doi: 
10.1001/archgenpsychiatry.2010.111. PubMed PMID: 20921117; PMCID: PMC3025772. 
31. 
Beijers R, Jansen J, Riksen-Walraven M, de Weerth C. Maternal prenatal anxiety and stress 
predict infant illnesses and health complaints. Pediatrics. 2010;126(2):e401-9. Epub 2010/07/21. doi: 
10.1542/peds.2009-3226. PubMed PMID: 20643724. 
32. 
Feldman R, Granat A, Pariente C, Kanety H, Kuint J, Gilboa-Schechtman E. Maternal 
depression and anxiety across the postpartum year and infant social engagement, fear regulation, 
and stress reactivity. J Am Acad Child Adolesc Psychiatry. 2009;48(9):919-27. Epub 2009/07/25. doi: 
10.1097/CHI.0b013e3181b21651. PubMed PMID: 19625979. 
33. 
Huizink AC, Robles de Medina PG, Mulder EJ, Visser GH, Buitelaar JK. Stress during 
pregnancy is associated with developmental outcome in infancy. J Child Psychol Psychiatry. 
2003;44(6):810-8. Epub 2003/09/10. PubMed PMID: 12959490. 
34. 
Deave T, Heron J, Evans J, Emond A. The impact of maternal depression in pregnancy on 
early child development. BJOG. 2008;115(8):1043-51. Epub 2008/07/25. doi: 10.1111/j.1471-
0528.2008.01752.x. PubMed PMID: 18651886. 
35. 
McLearn KT, Minkovitz CS, Strobino DM, Marks E, Hou W. The timing of maternal depressive 
symptoms and mothers' parenting practices with young children: implications for pediatric practice. 
Pediatrics. 2006;118(1):e174-82. Epub 2006/07/05. doi: 10.1542/peds.2005-1551. PubMed PMID: 
16818531. 
36. 
Alhusen JL, Ayres L, DePriest K. Effects of Maternal Mental Health on Engagement in 
Favorable Health Practices During Pregnancy. J Midwifery Womens Health. 2016;61(2):210-6. Epub 
2016/02/06. doi: 10.1111/jmwh.12407. PubMed PMID: 26849176; PMCID: PMC5203698. 
37. 
Cleland J, Shah IH, Daniele M. Interventions to Improve Postpartum Family Planning in Low- 
and Middle-Income Countries: Program Implications and Research Priorities. Stud Fam Plann. 
2015;46(4):423-41. Epub 2015/12/09. doi: 10.1111/j.1728-4465.2015.00041.x. PubMed PMID: 
26643491. 
38. 
Gogia S, Sachdev HS. Home visits by community health workers to prevent neonatal deaths 
in developing countries: a systematic review. Bull World Health Organ. 2010;88(9):658-66B. Epub 
2010/09/25. doi: 10.2471/BLT.09.069369. PubMed PMID: 20865070; PMCID: PMC2930362. 
39. 
Fottrell E, Azad K, Kuddus A, Younes L, Shaha S, Nahar T, Aumon BH, Hossen M, Beard J, 
Hossain T, Pulkki-Brannstrom AM, Skordis-Worrall J, Prost A, Costello A, Houweling TA. The effect 
of increased coverage of participatory women's groups on neonatal mortality in Bangladesh: A cluster 
randomized 
trial. 
JAMA 
Pediatr. 
2013;167(9):816-25. 
Epub 
2013/05/22. 
doi: 
10.1001/jamapediatrics.2013.2534. PubMed PMID: 23689475; PMCID: PMC5082727. 

STUDY PROTOCOL                                                                   
 
V2.4 October 1, 2021 
 
27 
 
40. 
More NS, Bapat U, Das S, Alcock G, Patil S, Porel M, Vaidya L, Fernandez A, Joshi W, Osrin 
D. Community mobilization in Mumbai slums to improve perinatal care and outcomes: a cluster 
randomized 
controlled 
trial. 
PLoS 
Med. 
2012;9(7):e1001257. 
Epub 
2012/07/18. 
doi: 
10.1371/journal.pmed.1001257. PubMed PMID: 22802737; PMCID: PMC3389036. 
41. 
Bank W. World Development Report 2016: Digital Dividends.  . Washington, DC: World Bank 
2016. 
42. 
Kenya CAo. ICT Sector Quarterly Statistics Report. Nairobi, Kenya 2016  
43. 
Research i. Mobile phone usage at the Kenya base of the pyramid Nairobi, Kenya 2012 [cited 
2018 
May 
21 
]. 
Available 
from: 
https://blogs.worldbank.org/ic4d/files/ic4d/mobile_phone_usage_kenyan_base_pyramid.pdf. 
44. 
Boksmati N, Butler-Henderson K, Anderson K, Sahama T. The Effectiveness of SMS 
Reminders on Appointment Attendance: a Meta-Analysis. J Med Syst. 2016;40(4):90. doi: 
10.1007/s10916-016-0452-2. PubMed PMID: 26852337. 
45. 
Lester RT, Ritvo P, Mills EJ, Kariri A, Karanja S, Chung MH, Jack W, Habyarimana J, 
Sadatsafavi M, Najafzadeh M, Marra CA, Estambale B, Ngugi E, Ball TB, Thabane L, Gelmon LJ, 
Kimani J, Ackers M, Plummer FA. Effects of a mobile phone short message service on antiretroviral 
treatment adherence in Kenya (WelTel Kenya1): a randomised trial. Lancet. 2010;376(9755):1838-
45. doi: 10.1016/S0140-6736(10)61997-6. PubMed PMID: 21071074. 
46. 
Jareethum R, Titapant V, Chantra T, Sommai V, Chuenwattana P, Jirawan C. Satisfaction of 
healthy pregnant women receiving short message service via mobile phone for prenatal support: A 
randomized controlled trial. J Med Assoc Thai. 2008;91(4):458-63. PubMed PMID: 18556852. 
47. 
Ross R, Sawatphanit W, Suwansujarid T, Stidham AW, Drew BL, Creswell JW. The effect of 
telephone support on depressive symptoms among HIV-infected pregnant women in Thailand: an 
embedded mixed methods study. J Assoc Nurses AIDS Care. 2013;24(5):e13-24. doi: 
10.1016/j.jana.2012.08.005. PubMed PMID: 23260038. 
48. 
Agyapong VIO, Juhas M, Ohinmaa A, Omeje J, Mrklas K, Suen VYM, Dursun SM, Greenshaw 
AJ. Randomized controlled pilot trial of supportive text messages for patients with depression. BMC 
Psychiatry. 2017;17(1):286. Epub 2017/08/05. doi: 10.1186/s12888-017-1448-2. PubMed PMID: 
28768493; PMCID: PMC5541655. 
49. 
(MAMA) MAfMA. Research Agenda 2015 [cited 2016 March 6]. Available from: 
http://www.mobilemamaalliance.org. 
50. 
Administration USDoHaHSHRaS. Promoting Maternal and Child Health Through Health Text 
Messaging 
An Evaluation of the Text4Baby Program- Final Report. Rockville, Maryland: 2015. 
51. 
Evans WD, Wallace Bihm J, Szekely D, Nielsen P, Murray E, Abroms L, Snider J. Initial 
outcomes from a 4-week follow-up study of the Text4baby program in the military women's population: 
randomized controlled trial. J Med Internet Res. 2014;16(5):e131. doi: 10.2196/jmir.3297. PubMed 
PMID: 24846909; PMCID: PMC4051747. 
52. 
Evans WD, Wallace JL, Snider J. Pilot evaluation of the text4baby mobile health program. 
BMC Public Health. 2012;12:1031. doi: 10.1186/1471-2458-12-1031. PubMed PMID: 23181985; 
PMCID: PMC3570294. 
53. 
Lund S, Hemed M, Nielsen BB, Said A, Said K, Makungu MH, Rasch V. Mobile phones as a 
health communication tool to improve skilled attendance at delivery in Zanzibar: a cluster-randomised 
controlled trial. BJOG. 2012;119(10):1256-64. doi: 10.1111/j.1471-0528.2012.03413.x. PubMed 
PMID: 22805598. 
54. 
Lund S, Nielsen BB, Hemed M, Boas IM, Said A, Said K, Makungu MH, Rasch V. Mobile 
phones improve antenatal care attendance in Zanzibar: a cluster randomized controlled trial. BMC 
Pregnancy Childbirth. 2014;14:29. doi: 10.1186/1471-2393-14-29. PubMed PMID: 24438517; 
PMCID: PMC3898378. 
55. 
Kaewkungwal J, Singhasivanon P, Khamsiriwatchara A, Sawang S, Meankaew P, Wechsart 
A. Application of smart phone in "Better Border Healthcare Program": a module for mother and child 
care. BMC Med Inform Decis Mak. 2010;10:69. doi: 10.1186/1472-6947-10-69. PubMed PMID: 
21047412; PMCID: PMC2989931. 

STUDY PROTOCOL                                                                   
 
V2.4 October 1, 2021 
 
28 
 
56. 
Oyeyemi SO, Wynn R. Giving cell phones to pregnant women and improving services may 
increase primary health facility utilization: a case-control study of a Nigerian project. Reprod Health. 
2014;11(1):8. doi: 10.1186/1742-4755-11-8. PubMed PMID: 24438150; PMCID: PMC3898403. 
57. 
Lund S, Rasch V, Hemed M, Boas IM, Said A, Said K, Makundu MH, Nielsen BB. Mobile 
phone intervention reduces perinatal mortality in zanzibar: secondary outcomes of a cluster 
randomized controlled trial. JMIR Mhealth Uhealth. 2014;2(1):e15. doi: 10.2196/mhealth.2941. 
PubMed PMID: 25098184; PMCID: PMC4114456. 
58. 
Harrington EK ME, Drake AL, Matemo D, John-Stewart G, Kinuthia J, Unger JA. “Kindly tell 
us the truth of that family planning”: men’s and women’s perspectives on a short message service 
(SMS) approach to improve postpartum family planning education and counseling in Kenya. 
Contraception 2017;96(4):301. Epub October 2017. 
59. 
Ronen K, Unger JA, Drake AL, Perrier T, Akinyi P, Osborn L, Matemo D, O'Malley G, Kinuthia 
J, John-Stewart G. SMS messaging to improve ART adherence: perspectives of pregnant HIV-
infected women in Kenya on HIV-related message content. AIDS Care. 2018;30(4):500-5. Epub 
2017/12/20. 
doi: 
10.1080/09540121.2017.1417971. 
PubMed 
PMID: 
29254362; 
PMCID: 
PMC5839109. 
60. 
Fairbanks J B-SK, Akinyi P, Matemo D, Unger JA, Kinuthia J, O’Malley G, Drake Al, John-
Stewart G, Ronen, K. You will know that despite being HIV positive you are not alone: Content 
preferences for an SMS intervention to improve prevention of mother-to-child HIV transmission 
(PMTCT). JMIR Mhealth Uhealth. 2018(forthcoming ). doi: 10.2196/10671. 
61. 
Perrier T DN, DeRenzi B, Anderson R, Kinuthia J, Unger J, John-Stewart G Engaging 
Pregnant Women in Kenya with a Hybrid Computer-Human SMS Communication System.  CHI '15 
Proceedings of the 33rd Annual ACM Conference on Human Factors in Computing Systems; Seoul, 
Republic of Korea ACM 2015. 
62. 
Bauermeister JA, Golinkoff JM, Muessig KE, Horvath KJ, Hightow-Weidman LB. Addressing 
engagement in technology-based behavioural HIV interventions through paradata metrics. Curr Opin 
HIV AIDS. 2017;12(5):442-6. Epub 2017/06/16. doi: 10.1097/COH.0000000000000396. PubMed 
PMID: 28617711; PMCID: PMC5637536. 
63. 
Unger JA RK, Perrier T, DeRenzi B, Slyker J, Drake A, Mogaka D, Kinuthia J, John-Stewart 
G. SMS communication improves exclusive breastfeeding and early postpartum contraception in a 
low to middle income country setting: A randomised trial BJOG. 2018;in press  
64. 
Drake AL, Unger JA, Ronen K, Matemo D, Perrier T, DeRenzi B, Richardson BA, Kinuthia J, 
John-Stewart G. Evaluation of mHealth strategies to optimize adherence and efficacy of Option B+ 
prevention of mother-to-child HIV transmission: Rationale, design and methods of a 3-armed 
randomized controlled trial. Contemp Clin Trials. 2017;57:44-50. Epub 2017/03/21. doi: 
10.1016/j.cct.2017.03.007. PubMed PMID: 28315480; PMCID: PMC5522580. 
65. 
Unger JA, Kinuthia J, John-Stewart G. Texting Condolences: Adapting mHealth Programs 
After Unexpected Pregnancy and Infant Outcomes. JMIR Mhealth Uhealth. 2017;5(12):e176. Epub 
2017/12/10. doi: 10.2196/mhealth.8303. PubMed PMID: 29222078; PMCID: PMC5741824. 
66. 
Bhat A, Mao J, Unutzer J, Reed S, Unger J. Text messaging to support a perinatal 
collaborative care model for depression: A multi-methods inquiry. Gen Hosp Psychiatry. 2018;52:14-
20. Epub 2018/03/02. doi: 10.1016/j.genhosppsych.2018.01.005. PubMed PMID: 29494854; PMCID: 
PMC5936469. 
67. 
Fisher WA FJ, Harman J.  . The information-motivation-behavioral skills model: A general 
social psychological approach to understanding and promoting health behavior. . In: Suls J WK, editor. 
Social Psychological Foundations of Health and Illness Blackwell Publishing Ltd 2003. p. 82-106. 
68. 
Prasopkittikun T, Tilokskulchai F, Sinsuksai N, Sitthimongkol Y. Self-Efficacy in Infant Care 
Scale: development and psychometric testing. Nurs Health Sci. 2006;8(1):44-50. Epub 2006/02/03. 
doi: 10.1111/j.1442-2018.2004.00266.x. PubMed PMID: 16451428. 
69. 
Kinuthia J, Drake AL, Matemo D, Richardson BA, Zeh C, Osborn L, Overbaugh J, McClelland 
RS, John-Stewart G. HIV acquisition during pregnancy and postpartum is associated with genital 
infections and partnership characteristics. AIDS. 2015;29(15):2025-33. Epub 2015/09/10. doi: 
10.1097/QAD.0000000000000793. PubMed PMID: 26352880; PMCID: PMC4692052. 

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V2.4 October 1, 2021 
 
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70. 
Cox JL, Holden JM, Sagovsky R. Detection of postnatal depression. Development of the 10-
item Edinburgh Postnatal Depression Scale. Br J Psychiatry. 1987;150:782-6. Epub 1987/06/01. 
PubMed PMID: 3651732. 
71. 
Sherbourne CD, Stewart AL. The MOS social support survey. Soc Sci Med. 1991;32(6):705-
14. Epub 1991/01/01. PubMed PMID: 2035047. 
 
 
 

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APPENDIX I COVID-19 RESPONSE PROCEDURES 
 
In response to the COVID-19 pandemic and policy changes issued by the Kenyan Ministry of Health 
(MOH), we are ensuring study procedures protect the health and safety of study participants and staff. 
Study visits align with routine patient clinical care schedules, and all participants and staff will follow 
MOH guidelines within the facility to reduce risks of potential exposure i.e. use of personal protective 
equipment, appropriate distancing with participants, reducing contact with commonly touched 
surfaces, handwashing and environmental cleaning. We will provide participant reimbursement via 
M-PESA to minimize tough points between staff and participants. All data will be collected by study 
staff on tablets to which only they will have access and will follow disinfection procedures. Participants 
will not be required to touch any study materials.   
 
Revisions to Data Collection Procedures 
Any in-person home visits for follow-up or infant verbal autopsy, or clinic visits for in-depth interviews 
will be suspended until social distancing measures have been rescinded by the Kenyan government. 
Follow-up data collection will occur via study visits aligned only with routine clinical care or phone as 
already noted in this protocol. Verbal autopsies and in-depth interviews will be conducted via phone 
until in-person study-specific visits are approved by appropriate authorities.