Bowel And Bladder Function in Infant Toilet Training- a Randomized Intervention Study to Investigate the Efficacy of Assisted Infant Toilet Training on Preventing Functional Gastrointestinal and Urinary Tract Disorders up to 4 Years of Age
Phase: NA
Conditions: Infantile Colic, Constipation - Functional, Bladder Dysfunction, Toilet Training
Sponsor: Dalarna County Council, Sweden

Clinical study protocol 
 
 
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Protocol version 2.3  
October 29, 2023 
 
 
 
 
 
Bowel And Bladder function in Infant Toilet Training (BABITT) 
 
 - a randomized multicenter intervention study, to investigate the efficacy of assisted infant toilet 
training on the prevention of functional gastrointestinal and urinary tract disorders in Swedish 
children up to 4 years of age. 
 
 
NCT04082689 
 
 
October 29, 2023, protocol version 2.3  
 
 
 
 

Clinical study protocol 
 
 
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Protocol version 2.3  
October 29, 2023 
1. Title in English 
Bowel And Bladder function in Infant Toilet Training (BABITT) – a randomized multicenter 
intervention study, to investigate the efficacy of assisted infant toilet training on the prevention of 
functional gastrointestinal and urinary tract disorders in Swedish children up to 4 years of age. 
  
Title in Swedish 
Tarm- och blåsfunktion hos barn som startar potträning under det första levnadsåret (BABITT) – en 
randomiserad interventionsstudie 
2. Trial registration 
ClinicalTrials.gov: NCT04082689 
ClinicalTrials.gov protocol ID: BABITT-01 
 
Primary registry and trial 
identification number 
ClinicalTrials.gov: NCT04082689 
 
Date of registration in 
primary registry 
June 12, 2019 
Secondary identification 
numbers 
Not applicable 
Sources of monetary or 
material support 
Region Dalarna, Center for Clinical Research Dalarna, Regional 
Research Council of Uppsala- Örebro, 
The Mayflower Foundation, The Samaritan Foundation, The 
Swedish Enuresis Academy 
Primary sponsor 
Region Dalarna  
Secondary sponsor(s) 
Not applicable 
Contact for public enquiries 
Sara Skoglund (administrative staff) 
Center for Clinical Research (CKF) Dalarna 
Nissers väg 3 
S-791 82 Falun, Sweden 
Telephone number: +46 (0)72-587 56 52 
E-mail: sara.skoglund@regiondalarna.se 
 
Contact for scientific queries 
Barbro Hedin Skogman, PI 
Address: Nissers väg 3, S-791 82 Falun, Sweden 
Telephone: +46 (0)703-09 11 01 
Email: barbro.hedinskogman@regiondalarna.se 
Public title 
Tarm- och blåsfunktion hos barn som pottränas under det första 
levnadsåret  
Scientific title 
Tarm- och blåsfunktion hos barn som pottränas under det första 
levnadsåret (BABITT) – en randomiserad interventionsstudie 
Countries of recruitment 
Sweden 
Health conditions or 
problems studied 
Functional constipation in children, infant colic, infant dyschezia, 
bladder dysfunction, process of infant toilet training, infant-to-
mother attachment, parental stress 
Intervention(s) 
Intervention 1 (Group A):  
Infant toilet training starting at inclusion to the study (but no later 
than the age of 3 months). To be active in assisted infant toilet 
training is defined by the making of at least one attempt a day 

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(without the requirement of a successful outcome) on at least 5 
out of 7 days per week. 
Intervention 2 (Group B):  
Infant toilet training starting at 9-11 months of age. To be active in 
assisted infant toilet training is defined by the making of at least 
one attempt a day (without the requirement of a successful 
outcome) on at least 5 out of 7 days per week. 
Key inclusion and exclusion 
criteria 
Ages eligible for study:  
Infants younger than 2 months, 1 week and 6 days at inclusion.  
Sexes eligible for study:  
Female or male.  
Inclusion criteria:  
 
Full-term infant (born at gestational week 37+0 to 41+6) 
Exclusion criteria: 
 
Infants with malformations or disorders that may affect the 
gastrointestinal or urinary tract in any relevant way 
 
Infants born small for gestational age (SGA), <-2 SD 
 
Parents with insufficient understanding of the Swedish 
language 
 
Infants older than 2 months, 1 week and 6 days at inclusion 
Study type 
Interventional 
Allocation: randomized 
Masking: specialized staff performing objective measurements  
Intervention model: parallel assignment 
Purpose: prevention 
Date of first enrollment 
April 18, 2019 (pilot phase) 
Target sample size 
Total of 268 infants (134 in each intervention group) 
Recruitment status 
Recruiting 
Primary outcomes 
 
Prevalence of functional constipation (defined according to 
ROME IV criteria) up to 9 months of age 
 
Prevalence of infant dyschezia (defined according to ROME IV 
criteria) up to 9 months of age 
 
Prevalence of infant colic (defined according to ROME IV 
criteria) up to 5 months of age 
 
Key secondary outcomes 
 
Prevalence of functional constipation (defined according to 
ROME IV criteria) up to 4 years of age 
 
Prevalence of gastrointestinal symptoms measured with 
Pediatric Quality of Life Inventory Gastrointestinal Symptoms 
Module, (PedsQLGastro) at 4 years of age 
 
Prevalence of stool toileting refusal up to 4 years of age 
 
Prevalence of bladder dysfunction and/or urinary tract 
infections up to 4 years of age 
 
Infant-to-mother attachment measured with Maternal 
Postnatal Attachment Scale (MPAS) up to 9 months of age 
 
Parental stress measured with Swedish Parenthood Stress 
Questionnaire (SPSQ) up to 2.5 years of age 
 
Experiences of the toilet training process up to 2.5 years of age 
 
 
 

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3. Protocol version 
Revision chronology: 
Protocol version 1.0, June 4, 2020, Original 
Protocol version 2.0, May 27, 2021: Amendment 1, Authors: TN, BHS 
Primary reason for amendment: changes in description of intervention, section 11, adjustments 
made due to the corona pandemic: introductory meeting was held as an online video meeting, the 
educational parental forum was cancelled, parents receive additional information about obtaining 
daytime dryness sent as an email. Additional changes (these changes themselves would not justify a 
protocol amendment): update of sponsor contact information in section 5b; clarifying section about 
the pilot phase in section 8; clarifying sentence about day care services in section 9. 
Protocol version 2.2, October 25, 2021: Amendment 2, Authors: TN, BHS 
Primary reason for amendment: further correction in section 8, date for first recruitment of study 
participant in the pilot phase was corrected to April 18, 2019. Appendix in Swedish language (consent 
and participant information forms) was deleted from the study protocol upon request.  
Protocol version 2.3, October 29, 2023: Amendment 3, Authors: TN, BHS 
Primary reason for amendment: patients included in the pilot phase was decided not to be part of 
the full study analysis. The SAP had been adjusted. Also, contact for public enquiries had been 
changed.  
4. Funding 
Region Dalarna, Center for Clinical Research Dalarna, Regional Research Council of Uppsala- Örebro, 
The Majblomman Foundation, The Samaritan Foundation, The Swedish Enuresis Academy. 
5. Roles and responsibilities 
Research group: 
Barbro Hedin Skogman, BHS, senior consultant at the Department of Pediatrics, Falun Hospital, 
Associate professor at Örebro University and post-doctoral researcher at the Center for Clinical 
Research (CKF) Dalarna. Main supervisor to Anna Leijon and Terese Nilsson. 
Anna Leijon, AL, resident in family medicine Dalarna, PhD student at Örebro University and at the 
Center for Clinical Research (CKF) Dalarna. 
Terese Nilsson, TN, resident in family medicine Dalarna, PhD student at Örebro University and at the 
Center for Clinical Research (CKF) Dalarna. 
Ulla Sillén, US, senior consultant and professor emerita, Department for Pediatric surgery, University 
of Gothenburg. Co-supervisor to Anna Leijon and Terese Nilsson.  
Anna-Lena Hellström, ALH, urotherapist and professor emerita, Institute of Health and Care 
Sciences, University of Gothenburg. Co-supervisor to Anna Leijon and Terese Nilsson. 
Cathrine Gatzinsky, CG, consultant and PhD student, Department for Pediatric surgery, University of 
Gothenburg. Responsible for the cohort of children constituting the reference material (Group C).  

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Elisabet Gustavsson, EG, pediatric surgeon and PhD at the Children’s Hospital, Uppsala and at 
Uppsala University. Researcher competent in the field of bowel dysfunction and gastrointestinal 
disorders. 
Malin Borgström, MB, pediatric nurse and urotherapist at the Department of Pediatrics, Falun and 
PhD student (project on enuresis) at Uppsala University and at the Center for Clinical Research (CKF) 
Dalarna. Specialized pediatric nurse performing ultrasound measurements of rectum in the BABITT-
study. 
Co-workers: 
Eva Eriksson, EE, nurse at the Department of Pediatrics, Falun. Study coordinator.  
Lilian Göras, LG, pediatric assistant nurse at the Department of Pediatrics, Falun. Specialized co-
worker performing ultrasound measurements of rectum in the BABITT-study. 
Aldina Pivodic, AP, medical statistician at Statistical consulting group, Gothenburg.  
Patricia Westling, PW, pediatric nurse at the Department of Pediatrics, Mora. 
5a. Authors’ contributions: 
BHS, AL, TN, ALH and US initiated the study and decided on the study design. BHS, AL and TN drafted 
the study protocol. ALH, US and EG revised the study protocol. All authors contributed to refinement 
of the study protocol and approved the final protocol version 1.0. 
5b. Sponsor contact information 
Trial Sponsor: Region Dalarna  
Sponsor’s reference: organization number: VAT SE 232100-0180 
Contact name: Björn Äng, research manager 
Address: Region Dalarna, Vasagatan 27, S-791 37 Falun, Sweden 
Telephone: +46 (0)23-490000 
Email: bjorn.ang@regiondalarna.se 
5c. Sponsor and funder 
Sponsor and funders have not been involved in the design of the study, and will not have any role 
during its execution, analyses, interpretation of the data or decision to submit results to scientific 
journals. 
5d. Committees 
Not applicable. 
 
6. Introduction 
6a. Background and rationale 
In the last decades the average age for toilet training has increased in the western world (1). In the 
1960’s the vast majority of Swedish children were regularly using the potty by their first birthday (2). 
In contrast, being in diapers at the age of three is not unusual today (3). It is suggested that the 
postponed initiation of toilet training is a contributing factor to problems related to bowel and 
bladder control (4-9). 
In Vietnam, toilet training starts in early infancy by tradition. By the age of nine months, the majority 
of children achieve parent-assisted dryness (10). In the western world this technique for early toilet 
training has received attention, by the term "Elimination Communication" or “Infant Toilet Training”. 

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As the caregiver responds to the elimination signals and routines of the child by taking it to a 
designated place to relive itself rather than in a diaper, the baby’s cues and ability to convey 
elimination needs are gradually enhanced. Through this responsive interaction, a two-way 
communication pathway opens between the caregiver and the child (11). In infant toilet training, the 
baby is held in a squat position over some sort of receptacle (e.g. potty or basin). Studies in adults 
have shown that a squat position straightens the rectal angle, thus facilitating fecal evacuation (12). 
The Swedish National Guide to Child Health Care is web-based decision support, providing evidence-
based guidelines for Swedish Child Health Care (CHC) centers. In 2015, a new recommendation was 
published, stating that initiation of toilet training should be encouraged at the 10-month visit and 
preferably before the child can walk (13).  
Infant colic is characterized by inconsolable crying or fussing without obvious cause in infants under 
the age of five months. A recent systematic review found that the overall prevalence of infant colic 
ranged from 17-25% during the first 6 weeks of life (14). Infant colic is a functional disorder that 
often causes great stress for the family while it is ongoing, despite its benign and self-limited 
character. The cause of infant colic is unknown (15).  
Infant dyschezia is a functional condition in children <9 months of age defined by at least 10 minutes 
of straining and crying before successful or unsuccessful passage of soft stools (16). Prevalence varies 
from 0.9-3.9% in children <9 months. The cause is considered to be failure to coordinate increased 
intra-abdominal pressure with relaxation of the pelvic floor muscles (16).  
In the newborn, incomplete voiding and residual urine is normal. This is caused by dyscoordination 
between the expelling bladder muscle and the closing sphincter. As shown by a study on Vietnamese 
and Swedish children (17), coordination develops in association with toilet training and not through 
passive maturation, as previously prevailing opinion has suggested. Symptoms of bladder dysfunction 
are common in school-age children and primarily present as urgency and incontinence (18-20). 
Constipation affects bladder function. This is illustrated by the fact that symptoms of bladder 
dysfunction as well as recurrent urinary tract infections generally disappear with the treatment of 
concomitant constipation (21).  
The prevalence of constipation, as presented in international studies, is very variable (0.7–30%), 
possibly due to the multifactorial nature of the condition, but also due to the lack of uniform 
definitions (22). According to preliminary results from an ongoing Swedish study, the prevalence of 
constipation is estimated to 10-15% during the first year of life (personal communication). In most 
cases of children with constipation (> 90%), the condition is defined as functional constipation, i.e. no 
organic cause is found (22). Despite good treatment options, it has been shown that quality of life in 
constipated children is significantly decreased compared to children without constipation (23, 24). 
Furthermore, children often suffer relapses during childhood and up to a third still experience 
symptoms of constipation in adulthood (25-27).  
The effect of infant toilet training on functional gastrointestinal disorders (functional constipation, 
infant dyschezia and infant colic) or urinary tract disorders (bladder dysfunction and urinary tract 
infection) in children, has not previously been studied. If infant toilet training can prevent functional 
gastrointestinal or urinary tract disorders, significant health benefits are to be expected due to 
reduced suffering for the children and their families, as well as a more effective use of healthcare 
resources. Learning more on when and how it is beneficial to introduce the potty in a modern family 
setting, in a Swedish cultural context, is crucial to elaborate upon appropriate guidelines on toilet 
training. 

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The results of the BABITT-study could lay the foundation for new evidence-based recommendations 
on toilet training carried out by the Swedish Child Health Care centers. Moreover, substantial 
international interest is to be expected, as results could be implemented in other healthcare systems. 
6b. Choice of comparators 
The Swedish National Guide to Child Health Care stated in 2015 that the CHC should encourage 
initiation of toilet training on the 10-month visit (13). Therefore, it was unethical to recruit parents 
who would not receive any advice or intervention on toilet training in children older than 9-11 
months. Consequently, in the BABITT-study, the control group consists of children who have not yet 
been introduced to toilet training (Group B, described below). See Figure 1. 
Furthermore, two reference materials, outside the BABITT-study, are chosen as comparators, 
consisting of children, who did not start toilet training during the first year of life (Group C and Group 
D, described below). See Figure 1. 
Group C comprises 110 healthy children in an ongoing longitudinal study in Gothenburg, regarding 
bowel and micturition habits in healthy children (GC, personal communication). Infants were 
recruited from 2014-2019. Children in Group C have not been introduced to toilet training during the 
first year of life and are thus suitable reference material for the BABITT-study. The questionnaires 
used in Group C are congruent with those of the BABITT-study. 
Group D will consist of 4-year-old children in a cross-sectional study called BABIS-4 (Bowel and 
Bladder function In Swedish 4-year olds). The BABIS-4 study is designed and planned by the research 
group (AL, TN, BHS, ALH, US) and will recruit 4 year old children during 2020-2021, at the same CHC 
units as those participating in the BABITT-study in Dalarna, Sweden. In a randomly selected 10% of 
the study participants in Group D, the same specialized staff as in the BABITT-study will perform 
ultrasound measurements of the rectum. See separate study protocol. The questionnaire answered 
by Group D is congruent with the questionnaire at 4 years of age in the BABITT-study.  
 
 
Figure 1. Time schedule for measuring points for questionnaires (web surveys) (X) and rectal 
ultrasound for the BABITT-study (Group A and Group B) and reference groups (Group C and      
Group D).  
 
Age
2 w
1 mo
2 mos
3 mos 6 mos
9 mos
1 yr
1,5 yrs
2 yrs
2,5 yrs
4 yrs
Group A
Group B
rectal 
ultrasound
rectal 
ultrasound
Group C
X
X
X
X
X
X
X
rectal 
ultrasound
rectal 
ultrasound
rectal 
ultrasoun
rectal 
ultrasound
Group D
X
rectal 
ultrasound
B  A  B  I  T  T    reference groups and measuring points
X
X
X
X
X
X
X
X
X

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7. Objectives 
The overall objective is to obtain knowledge on whether assisted infant toilet training, initiated 
during the first year of life, affects the prevalence of functional gastrointestinal or urinary tract 
disorders up to 4 years of age. 
 
Research hypothesis 
Assisted infant toilet training initiated at 0-3 months of age reduces the prevalence of functional 
gastrointestinal disorders (constipation, infant dyschezia and infant colic) up to 9 months of age. 
 
Assisted infant toilet training initiated during the first year of life reduces the prevalence of 
functional gastrointestinal and urinary tract disorders up to 4 years of age.    
 
Primary research questions 
 
Is the prevalence of functional gastrointestinal disorders (constipation, infant dyschezia and 
infant colic) reduced in children introduced to toilet training at 0-3 months of age (Group A), as 
compared to children who are not introduced to infant toilet training (Group B), up to 9 months 
of age? 
 
Secondary research questions 
 
Is the prevalence of functional gastrointestinal disorders (constipation, gastrointestinal 
symptoms and/or stool toileting refusal) reduced in children introduced to toilet training at 
0-3 months of age (Group A), compared to children introduced to toilet training at 9-11 
months of age (Group B), when followed up until 4 years of age? 
 
 
Is the prevalence of urinary tract disorders (bladder dysfunction and/or urinary tract 
infections) reduced in children introduced to toilet training at 0-3 months of age (Group A), 
compared to children introduced to toilet training at 9-11 months of age (Group B), when 
followed up until 4 years of age? 
 
 
Is the prevalence of functional gastrointestinal and urinary tract disorders reduced in 
children introduced to toilet training during the first year of life (Group A and Group B), 
compared to children not introduced to toilet training during the first year of life (reference 
Group C and Group D, described above), when followed up until 4 years of age? 
 
 
Does infant-to-mother attachment differ in families when initiating infant toilet training at 0-
3 months of age (Group A), compared to families not practicing infant toilet training (Group 
B), up to 9 months of age? 
 

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 
Does parental stress differ in families when initiating infant toilet training at 0-3 months of 
age (Group A), compared to families not practicing infant toilet training (Group B), up to 2.5 
years of age? 
 
 
Are there differences regarding the toilet training process in children introduced to toilet 
training at age 0-3 months (Group A), compared to children introduced to toilet training at 
age 9-11 months (Group B), when followed up until 2.5 years of age?  
 
 
What are the overall parental experiences of infant toilet training initiated during the first 
year of life (Group A and Group B), up until 2.5 years of age? 
 
8. Study design 
The BABITT-study is designed as a randomized, controlled, investigator blinded, two-armed 
intervention, multicenter study with follow-up until 4 years of age. Randomization will be performed 
as block randomization with a 1:1 allocation.  
The study protocol is written in the form of the SPIRIT 2013 Statement Explanation and Elaboration 
paper, in order to be able to be published according to the SPIRIT 2013 checklist (28). 
Pilot phase 
The pilot phase started recruitment in April 2019 and was conducted during 12 months at one CHC 
center. The aim was to evaluate study participant eligibility, recruitment rate, withdrawal rate and 
reason for withdrawal, completion of web based questionnaires and intervention adherence and 
acceptablity. Also to gain knowledge of the CHC nurses acceptability of the intervention and 
recruitment, experienced work load and logistics of the study. After evaluation, minor corrections 
were made to ensure data collection and to enhance study logistics. The study participants in the 
pilot phase (n=22) are not included in the full study analysis.  
Recruitment is anticipated to continue throughout 2021. 
Prior to drafting the study design, qualitative work with focus group interviews with CHC nurses and 
parents was performed by AL and TN (unpublished data) in order to better understand the study 
setting(29, 30).  
The questionnaries used in the BABITT-study were validated by a CVI process, further description of 
the process in section 18. 
Report of results from the study will follow the CONSORT statement (31).  
 
9. Study setting 
The BABITT-study is conducted at several CHC centers in an urban-rural setting in central Region 
Dalarna, Sweden. The CHC centers are chosen primarily geographically for operational purposes. The 
full list of CHC centers is available at ClinicalTrials.gov. 
The Swedish CHC is nurse-led, free of charge, available to almost everyone (99%) and focuses on 
preventive care (32).  

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The social insurance system in Sweden provides a parental leave compensation for 480 days. Three 
months are exclusive to each parent; the rest can be divided as the family decides. Day care services 
is available from 1 year of age and is available for all families since the cost is highly subsidized. Of all 
children in Sweden, 80 % are attending day care by 2 years of age (32).   At the time of the start of 
the study, the Swedish day care services do not have any general recommendations on toilet training 
or support in regular toilet habits.  
 
At the Department of Pediatrics in Falun and Mora, specialized staff (MB, LG, PW) will perform the 
ultrasound measurements of rectal diameter. 
 
10. 
Eligibility criteria 
Inclusion Criteria 
 
Full-term infant (born at gestational week 37+0 to 41+6) 
 
Exclusion Criteria 
 
Infants with malformations or disorders that may affect the gastrointestinal or urinary tract in 
any relevant way 
 
Infants born small for gestational age (SGA), <-2 SD 
 
Parents with insufficient understanding of the Swedish language 
 
Infants older than 2 months, 1 week and 6 days at inclusion 
 
11. 
Description of intervention 
The intervention consists of parents practicing infant toilet training with their child.  
 
Preceding the study start, the CHC nurses are given two 60-minute lectures (by AL and TN) on infant 
toilet training techniques and the BABITT-study structure and logistics. They receive a book (“Bebis 
på pottan”) (33) containing more elaborate descriptions of techniques and parental experiences of 
infant toilet training, as well as a brief summary of it produced by the study researchers (AL and TN).  
 
The CHC nurses set up an introductory meeting for children eligible for the study. Due to the corona 
pandemic the introductory meeting was an online video meeting. At this meeting the parents are 
given information on the study by AL or TN. After receiving informed consent from both parents, 
group allocation is determined by randomization.  
 
Parents allocated to Group A are prompted to initiate toilet training as soon as possible, but no later 
than at 3 months of age. After the introductory meeting they receive a potty, oral instructions in how 
to perform infant toilet training, a book on the topic (“Bebis på pottan”) (33) as well as a brief 
summary of the book produced by researchers (AL and TN).  
 

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Parents allocated to Group B are instructed to start toilet training by 9 months of age, but no later 
than at 11 months of age. Group B will receive the information and material described above, at the 
ultrasound appointment at the Pediatric Department at 9 months of age. All parents were offered a 
toilet seat at the ultrasound appointment, or on beforehand, if parents allocated to group A 
contacted the study researchers or CHC nurse. 
 
For further guidance, an educational parental forum was held during 2019. Because of the corona-
pandemic, the educational parental forum was cancelled. Parents were instead encouraged to 
contact their CHC nurse or the study researchers (AL and TN) if further guidance is needed. 
 
In the event of infant colic, a behavioral diary is filled in by the parents (same instructions given to 
both groups at inclusion). General recommendations are given by the CHC nurse, in accordance with 
The Swedish National Guide to Child Health Care (34), to both groups. The general recommendations 
include routine examination by a family physician to rule out organic cause, a test period of milk 
protein free diet (in infant formulas or in mothers’ diet if breast-fed), testing probiotic containing 
Lactobacillus Reuteri and psychosocial support. 
 
To ensure data collection, the study coordinator (EE) will telephone parents who stated in the web 
survey at 2 months of age that their child has periods of prolonged crying, fussing, or irritability 
without obvious cause for more than 60 minutes per day, and encourage them to fill in the 
behavioral diary. The study coordinator (EE) documents the parents’ comments and experiences. 
Parents of infants with colic allocated to Group A will be encouraged to continue and possibly 
intensify infant toilet training, whereas infants allocated to Group B will be given care as usual, but 
no instructions in infant toilet training. 
 
Intervention-adherence 
In each web survey the parents are asked to what extent they perform infant toilet training. Parents 
of children allocated to group B are asked in the web survey at 2, 3, 6 and 9 months of age, if they are 
obeying the group allocation and not undertaking infant toilet training.  
To ensure adherence to the intervention, the study researchers (AL or TN) will contact parents of 
children allocated to group A, if they stated in the web survey at 2 months of age that they conduct 
infant toilet training less than 5 days per week. The parents are asked what obstacles they are facing 
and if they need support or more information. The parents were offered to obtain a toilet seat. If the 
child was recruited to the study less than two weeks before the parents answered the 2-month web 
survey, the study researchers (AL or TN)  waits two weeks (but not beyond the child becoming 3 
months old,  before calling. The same procedure is done with parents of children allocated to group 
B, if they stated that they conduct infant toilet training less than 5 days per week at the 12-month 
web survey. 
Swedish day care services do not have any recommendations on toilet training. The clinical 
experience of parents performing infant toilet training is that day care services seldom offer support 
in regular toilet habits. This can result in relapse in dryness and a need to use diaper at the day care 
services. The study researchers (AL and TN) therefor held a lecture on infant toilet training, the 

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BABITT-study structure and the current guidelines for Swedish CHC centers to principals of affected 
day care services. The lecture was filmed and distributed to staff working at day care services.  
At 9 months of age parents will be encouraged to give a written summary of the BABITT-study 
structure and the current Swedish guidelines for toilet training to the day care service their child will 
attend to.  
At 18 months parents receive an encouraging additional information (sent as an email) prompting 
the parents to plan and start the process of daytime dryness. It contained the information that it is 
best to achieve daytime dryness before the age of 2,5 years, to prevent problems with bowel and 
bladder. 
 
12. 
Outcomes 
Primary outcomes  
 
Prevalence of functional constipation (defined according to ROME IV criteria) up to 9 months of 
age 
 
Prevalence of infant dyschezia (defined according to ROME IV criteria) up to 9 months of age 
 
Prevalence of infant colic (defined according to ROME IV criteria) up to 5 months of age  
 
Secondary outcomes 
 
Prevalence of functional constipation (defined according to ROME IV criteria) up to 4 years of age 
 
Prevalence of gastrointestinal symptoms measured with Pediatric Quality of Life Inventory 
Gastrointestinal Symptoms Module (PedsQLGastro) at 4 years of age 
 
Prevalence of stool toileting refusal up to 4 years of age 
 
Prevalence of bladder dysfunction and/or urinary tract infections up to 4 years of age 
 
Infant-to-mother attachment measured with Maternal Postnatal Attachment Scale (MPAS) up to 
9 months of age 
 
Parental stress measured with Swedish Parenthood Stress Questionnaire (SPSQ) up to 2.5 years 
of age 
 
Experiences of the toilet training process up to 2.5 years of age 
 
Full list of outcome measures 
1. Questionnaire (web survey) at 2, 3, 6, 9, 12, 18 months and at 2, 2.5 and 4 years, validated in 
pilot study by Content Validity index (CVI) (35)  
a. Functional constipation, infant dyschezia and infant colic, defined according to ROME 
IV criteria (16) (also journal review o/d) 
b. Abdominal pain (also journal review o/d) 
c. Stool toileting refusal (7) 
d. Bowel and bladder function defined according to ICCS (18) 
e. Urinary tract infection (also journal review o/d) 
f. Toilet training process 
g. Use of diapers 
h. Use of laxatives  
i. 
Breastfeeding and nutrition 
j. 
Social situation, age and level of education of parents, presence of siblings, family 
history of constipation and attendance at pre-school  
k. Intervention adherence  

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2. Validated rating scale (web survey) 
a. Infant-to-mother attachment, measured with Maternal Postnatal Attachment Scale 
(MPAS) (36) at 3 and 9 months of age 
b. Parental stress, measured with Swedish Parenthood Stress Questionnaire (SPSQ) (37) 
at 3, 9 and 18 months and 2.5 years of age 
c. Gastrointestinal symptoms, measured with Pediatric Quality of Life Inventory 
Gastrointestinal Symptoms Module (PedsQLGastro) (38), at 4 years of age 
 
3. Observational lists (filled in by parents) 
a. Infant behavioral diary (16) (24 hour prospective registration) when infant colic is 
suspected 
 
4. Investigations 
a. Rectal diameter determined by ultrasound measurement (39) at 9 months and 4 
years 
 
13. 
Participant timeline 
Children must be included before reaching 2 months, 1 week and 6 days, but preferably as early as 
possible.  
Web surveys are conducted at 2, 3, 6, 9, 12, 18 months and at 2, 2.5 and 4 years (see Figure 2). A 28-
day window (defined as 14 days before and 14 days after the due date), is allowed for the 2, 3 and 6-
month survey. At 9 months, a 44-day window is allowed (14 days before and 30 days after the due 
date) and at 12, 18 months and at 2 and 2.5 years a 60-day window is allowed (30 days before and 30 
days after the due date). At 4 years of age a 120-day window will be allowed (30 days before and 90 
days after the due date). 
For the rectal ultrasound measurement at 9 months of age, a 60-day window will be desired (14 days 
before and 46 days after the due date). At 4 years of age, a 120-day window will be desired (30 days 
before and 90 days after the due date). 
 
Age
0 mo
1 mo
2 mos
3 mos
6 mos
9 mos
12 mos 18 mos
2 yrs
2,5 yrs
4 yrs
Group A      infant toilet training and parental forum*
Validated 
Questionnaire           
(web survey)
X
X
X
X
X
X
X
X
X
External validated 
instruments                 
(web survey)
MPAS 
SPSQ
MPAS 
SPSQ
SPSQ
SPSQ
PedsQL
Investigation
Rectal 
ultrasound
Rectal 
ultrasound 
Infant toilet training
Group B      infant toilet training and parental forum*
Infant behavioural 
diary (when applicable)
B  A  B  I  T  T    measuring points
( + )
( + )
( + )
( + )
Enrolment in study

Clinical study protocol 
 
 
14 
Protocol version 2.3  
October 29, 2023 
Figure 2. Time schedule for measuring points for questionnaires (web surveys) (X) including Maternal 
Postnatal Attachment Scale (MPAS), Swedish Parenthood Stress Questionnaire (SPSQ), Pediatric 
Quality of Life Inventory Gastrointestinal Symptoms Module (PedsQL), rectal ultrasound and infant 
behavioral diary (+) in the BABITT-study (Group A and Group B).                                                 
*participation in educational parental forum is offered. 
 
14. 
Sample size 
The sample size was calculated on the prevalence of functional gastrointestinal disorders (functional 
constipation, infant dyschezia or infant colic), at age 9 months. In the literature the prevalence of 
functional constipation varies between 0.7-30% (22), unpublished data from an ongoing Swedish 
cohort (Group C) indicate 7% prevalence at 1 year of age (GC, personal communication).  
The prevalence of infant dyschezia varies between 0.9-3.2% (16). Unpublished data from Group C 
indicate a prevalence of 18% at 2 months of age and 4% at 6 months of age (GC, personal 
communication).  
The prevalence of infant colic varies between 17-25% at 6 weeks of age (14).  
We therefore argue that a total prevalence of these disorders could be set to 15% of the general 
population (congruent with Group B) and could be estimated to 4% of children who have been 
introduced to infant toilet training (congruent with Group A).  
In order to find a statistically significant difference (p<0.05) between groups with an 80% power, 121 
children are required in each study group. With an estimated 10% shortfall, 134 children will be 
included in each study group, which gives a total number of 268 children in the BABITT-study.  
 
15. 
Recruitment 
All new-borns registered at the participating CHC centers in Region Dalarna are eligible for the study, 
up to 2 months, 1 week and 6 days of age. Written and oral information about the study is given by 
midwives before childbirth (at the 35 gestational week visit) and at the first visits after childbirth by 
the CHC nurses. For recruitment purposes, posters with written information of the study are 
available at the CHC centers. The family physicians working at the CHC centers are encouraged to 
address the parents regarding the study at the routine medical examination at one month of age. 
 
16. 
Allocation 
Participants are randomly assigned to either Group A or Group B with a 1:1 allocation. The 
randomization is performed by the researchers responsible for inclusion (AL and TN), by using a 
computer program designed by MediCaseAB (40). The randomization is stratified by the gender of 
the child using permuted blocks. The block size will not be disclosed, to ensure concealment. 
Allocation concealment will be ensured since randomization is only possible after the researchers (AL 
and TN) have completed all the baseline data. 
 

Clinical study protocol 
 
 
15 
Protocol version 2.3  
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17. 
Blinding 
Due to the nature of the intervention, parents are informed by the researchers (AL and TN) which 
group they are allocated to. Their CHC nurse is informed when the child enters the study and the 
group allocation.  
The parents and the CHC nurses are informed that the study involves testing two different forms of 
infant toilet training, and that both are considered equal options. Group A reflects how infant toilet 
training is conducted in Vietnam (10) and Group B reflects how we introduced the potty in Sweden in 
the 60´s (2). Group B is also in line with the current recommendations provided by The Swedish 
National Guide to Child Health Care (13).  
The group allocation (Group A or Group B) of the participating children will be masked to the 
specialized staff (MB, LG, PW) performing the ultrasound measurement of rectal diameter at 9 
months and 4 years of age. The parents are asked not to reveal their group allocation to the 
specialized staff (MB, LG, PW) performing the rectal ultrasound measurement.  
When the study is closed, all statistical analyses will be performed with the statistician masked to 
group allocation.  
 
18. 
Data collection methods 
18a. Data collection and description of instruments 
At inclusion the parents are asked who of the two caregivers will be on parental leave for the first 
months with the child. The parent on parental leave first will be asked to fill in all the web surveys in 
the BABITT-study, and therefore the web survey is sent to that parent’s email address. This will 
enable comparisons over time of each parent’s experience regarding parenthood stress (SPSQ) (37), 
and mother-to-infant attachment (MPAS) (36). Using electronic web surveys filled in directly by the 
parent on their own smart phone, tabloid or computer, ensures data accuracy, user acceptability and 
timeliness of data receipt.  
 
All items in the questionnaires (web surveys) were validated in the pilot phase as per the Content 
Validity Index (CVI) (35). In this process, a panel of eight experts have individually scrutinized each 
item in the questionnaires. This panel consisted of two M.D.s with pediatric competence, two 
researchers with relevant scientific competence and four parents with personal experience of infant 
toilet training. The different items receive individual comments and scores on relevance and 
simplicity, from which a total score is calculated. The comments and scores were then analyzed by 
the researchers (AL, TN and BHS) following a revision of the items. After a second round of comments 
and scores from the expert panel, the items got through a final revision by the researchers and the 
total score of the second round can be compared to the score of the first round.  
 
The study coordinator (EE) is easily alerted by the electronic clinical research form (eCRF) when the 
due date to answer the web survey is passed. The study coordinator (EE) then contacts the parent by 
text message or telephone call to remind them to fill in the web survey before the end of the window 
for the survey is passed. If the parent isn´t able to answer the web survey due to technical problems, 
the study coordinator (EE) can read the questions and directly fill in the eCRF accordingly. 

Clinical study protocol 
 
 
16 
Protocol version 2.3  
October 29, 2023 
 
Functional constipation is defined in accordance with ROME IV (16). At least 2 of the following 
criteria are required during a one-month period: 
 
≤2 defecations per week 
 
History of excessive stool retention 
 
History of painful or hard bowel movements  
 
History of large-diameter stools 
 
Presence of a large fecal mass in the rectum 
In toilet-trained children the following additional criteria may be used: 
 
Stool incontinence at least once a week 
 
History of large-diameter stools that may obstruct the toilet  
 
Infant dyschezia is defined in accordance with ROME IV criteria (16): 
 
Healthy infant ≤9 months of age at the onset and cessation of symptoms 
 
At least 10 minutes straining and crying before successful or unsuccessful passage of soft 
stools  
 
Infant colic is defined in accordance with ROME IV (16). All of the following criteria are required: 
 
Healthy infant ≤5 months of age at the onset and cessation of symptoms 
 
Recurrent periods of prolonged crying, fussing, or irritability without obvious cause which 
cannot be prevented or resolved by caregivers 
 
No evidence of infant failure to thrive, fever, or illness 
 
Crying or fussing ≥3 hours during at least 3 days for a period of 7 days  
 
24-hour prospective behavioral diary documenting ≥3 hours crying/fussing. Since there is no 
behavioral diary recommended by the ROME foundation, we have modified the infant 
behavioral diary used in a Swedish infant colic thesis (41).  
 
Gastrointestinal symptoms, are measured with a Pediatric Quality of Life Inventory Gastrointestinal 
Symptoms Module (PedsQLGastro) (38) at 4 years of age. PedsQLGastro contains 58 items. The 
items are reverse-scored and linearly transformed to a 0-100 scale (0=100, 1=75, 2=50, 3=25, 4=0), so 
that lower scores demonstrate more GI symptoms, and hence, lower GI-specific health-related 
quality of life. The scale scores are computed as the sum of the items divided by the number of items 
answered. 
 
Stool toileting refusal (STR) is defined by children who urinate in the potty/toilet but refuse to have 
a bowel evacuation there, for more than one month (7). 
 
Rectal diameter will be measured with ultrasound (39) according to a method manual from the 
University of Gothenburg (GC, personal communication). An inter-rater agreement analysis will be 
performed on measurement results from the specialized staff (MB, LG, PW) of the BABITT-study.  
 
Bladder dysfunction is defined according to ICCS terminology (18): 
 
Urinary incontinence  
 
Enuresis  
 
Nocturia  
 
Voiding frequency ≤3 or ≥8 per day  
 
Urgency 
 
Urinary tract infection is defined by the diagnoses N.30.0 (acute cystitis) and N30.9 (cystitis UNS) 
also N10.9 (acute tubulointerstitial nephritis).  

Clinical study protocol 
 
 
17 
Protocol version 2.3  
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Infant-to-mother attachment, is measured with Maternal Postnatal Attachment Scale (MPAS) (36) at 
3 and 9 months of age. MPAS is measured by 19 issues. Questions are scored 1-5. Total score is 
calculated by adding scores on all issues. Scale range for total score is 19-95. A high score indicates 
higher mother-to-infant attachment. 
 
Parental stress, is measured with Swedish Parenthood Stress Questionnaire (SPSQ) (37) at 3, 9 and 
18 months and 2.5 years of age. SPSQ contains 34 issues each scoring 1-5. Total score is calculated as 
an average on answers (1-5) on all issues. Scale range for total score is 34-170. A high score indicates 
higher parental stress. 
 
To obtain the complete questionnaires of the BABITT-study, please contact study researchers (BHS, 
AL or TN). 
 
18b. Retention of participants 
Regardless of adherence, all participants will be included in an intention to treat analysis. Parents are 
encouraged to leave comments in a free text section in the web survey, in case of non-adherence to 
the intervention. 
To ensure complete follow up, symbolic gifts will be given after the appointment for the rectal 
diameter measurements at the Pediatric Department. If the parents cannot attend, they are still 
encouraged to continue to fill in the web surveys.  
 
Participants may withdraw from the study for any reason at any time. They are asked (but not 
obliged) to state the reason for withdrawing (according to GCP standards) in a form. It is clearly 
stated that withdrawal will not affect the future care given by the CHC centers. Participants may also 
be withdrawn if the study sponsor or government or regulatory authorities terminate the study prior 
to its planned end date. 
 
19. 
Data management 
All information collected in the BABITT-study will be electronically entered into the eCRF provided by 
MediCaseAB (40) and then securely stored in a database located in Sweden. Only the study 
researchers (AL, TN and BHS) and the study coordinator (EE) have a personal login to assess the eCRF. 
The personal information and contact information of the participants is not accessible assessable to 
MediCaseAB. Demographic data at inclusion in the study is entered electronically into the eCRF by 
the study researchers (AL and TN) and the parents fill in the web surveys electronically. The clinical 
research form (CRF) used during the measurement of the rectal diameter is entered in the eCRF by 
the study researchers (AL and TN) consecutively. At inclusion, study participants are given a specific 
study ID that is used on the paper CRF and in the behavioral diaries. Behavioral diaries are given to 
the CHC nurse who collects them in the clinic folder, and they are then consecutively entered in the 
eCRF by study researchers (AL and TN). Participant coded files will be stored in a secure manner at 
CHC centers, at the Department of Pediatrics at Falun Hospital and eventually all coded data will be 
stored at the Clinical Research Center Dalarna, Region Dalarna, Falun. Original data will be kept 10 
years after the last publication. 
 

Clinical study protocol 
 
 
18 
Protocol version 2.3  
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In the eCRF there are range checks for data values when appropriate. Written documentation of all 
changes in the eCRF is available via electronic logs and audit trails. 
 
All data will be coded under data processing and publication of results. The code key will be 
destroyed when no longer needed or 10 years after the last publication. 
 
20. 
Statistical methods 
The results will be analyzed in accordance with intention-to-treat. Group A will be compared with the 
control (Group B) for all primary analysis. For comparison of dichotomous variables between the 
groups, the Chi-2 or Fisher’s extract test will be used. For continuous variables the Mann-Whitney U-
test will be used for comparison between groups. For correlation and agreement between scales, 
Pearson’s correlation test or Cohen’s kappa will be used when appropriate. Subsequently logistic 
regression analysis will be used to evaluate outcome measures in relation to baseline data. For all 
tests, we will use 2-sided p-values with alpha ≤0.05 level of significance.  
Further calculations will be made in accordance with statistical consultants in order to correctly 
compare Group A, Group B and reference materials Group C and Group D. 
Quantitative longitudinal data will be analyzed statistically in conjunction with qualitative data 
(mixed method) from the questionnaires. Data will be analyzed according to the method described 
by Malterud (42). By this procedure, transcribed text from the comment sections is read in order to 
find overarching themes. Thereafter, meaningful elements are identified and extracted (de-
contextualization), out of which condensed meaningful elements are created and grouped. The 
proceeding step is to re-formulate the content in summarized descriptions (re-contextualization). To 
assure preserved congruence, the text is compared to raw data. Finally, the result is validated by 
separate analysis by the other researcher (AL or TN).  
 
A professional academic statistician will be blinded to study groups when conducting all statistical 
analyses. 
 
21. 
Data monitoring 
Since the BABITT-study is not a pharmacological trial, monitoring is not considered applicable. This is 
furthered supported by the fact that the group allocation is not blinded to the parents and the web 
surveys are filled in by the parents. The intervention is easy to perform and is not expected to do 
harm. No interim analysis will be performed.  
 
22. 
Harms 
Infant toilet training is widely spread over the world. In some cultures, it is part of the cultural 
heritage. In the western world, information is easily assessable on the internet. Reporting adverse 
effects by the CHC nurses over the long follow-up period was not needed for medical reasons, not 
possible due to the workload of CHC nurses and not suggested by the Ethical Review Board in 

Clinical study protocol 
 
 
19 
Protocol version 2.3  
October 29, 2023 
Uppsala. In the web surveys there are free text areas were the parents can report positive and 
negative experiences regarding infant toilet training.  
 
23. 
Auditing 
Not applicable. 
 
24. 
Research ethics approval 
The Ethical Review Board in Uppsala, Sweden, has reviewed and approved the study protocol, the 
scientific content and compliance with applicable research and human subject regulations. The 
application was approved 2018-11-14 (Dnr 2018 / 388) with a minor revision 2019-04-03 (Dnr 2019-
01668).  
 
25. 
Protocol amendments 
Modifications to the study protocol that may impact on the conduct of the study, including changes 
of study objectives, study design, patient population, sample sizes or significant administrative 
aspects, will be added as a formal amendment to the protocol. Amendments will be agreed by the 
research group and approved by the Swedish Ethical Review Board in Sweden prior to 
implementation. Administrative changes of the protocol with minor corrections and/or clarifications 
that have no effect on the way the study is to be conducted will be agreed upon by the research 
group, and will be documented in a memorandum.  
 
26. 
Consent 
The CHC nurses give verbal information on the study and provide written information about the 
study. The written information is designed and approved according to the Swedish Ethical Review 
Board. If the parents are interested, an introductory meeting regarding the study is set between the 
parents and the study researchers (AL or TN). At the meeting, the parents get verbal informed about 
the study in a standardized manner and they are encouraged to ask questions. At the meeting, they 
are informed that participation is voluntary. If the parents agree to participate, AL or TN will obtain 
written informed consent from both parents. 
 
27. 
Confidentiality 
If parents are interested in the study the CHC nurses book a meeting in the electronic patient journal 
system used at the CHC centers. AL and TN have access to the journal system through personal login 
and can then contact the parents. 
 
All information collected in the BABITT-study will be electronically entered into the eCRF provided by 
MediCaseAB (40), and then securely stored in a database located in Sweden. Only the study 
researchers (AL, TN and BHS) and the study coordinator (EE) have a personal login to assess the eCRF. 

Clinical study protocol 
 
 
20 
Protocol version 2.3  
October 29, 2023 
The personal information and contact information of the participants is not accessible to 
MediCaseAB.  
 
At inclusion, study participants are given a specific study ID that is used on study forms to maintain 
confidentiality.  
 
Participant coded forms will be stored in a secure manner at CHC centers, at the Department of 
Pediatrics at Falun Hospital and eventually all coded data will be stored at the Clinical Research 
Center Dalarna in Falun. Original data will be kept 10 years after the last publication from the study. 
 
All data will be coded under data processing and publication of results. The code key will be 
destroyed when no longer needed or 10 years after the last publication. 
 
28. 
Declaration of interests 
The authors declare no competing interests. 
 
29. 
Access to data 
Only study researchers (BHS, AL and TN) will have full access to data. To ensure confidentiality only 
coded data will be accessible to the rest of the research group or the statistical co-worker. According 
to Swedish law and GDPR restrictions, a contract will be signed before access to any coded data is 
permitted. 
 
30. 
Ancillary and post-trial care 
All participants are insured according to national assurance of patients. Economical compensation for 
participation is not offered. Symbolic gifts will be offered during the study to enhance study 
participation. Public transportation is free of charge when going to the appointment at hospital, 
according to national standards. All medical care is free of charge up to 18 years of age in Sweden 
(32). 
 
31. 
Dissemination policy  
The BABITT-study and the cross-sectional study of 4 year-olds in Dalarna, BABIS-4 (Group D) will 
form the basis for two PhD theses (by AL and TN). The results of the study are planned to be reported 
in appropriate international medical journals regardless of the magnitude or direction of effect. Every 
attempt will be made to reduce the time interval between the completion of data collection and the 
release of the study results. The study results will also be released to participating CHC centers and 
the general medical community. 
Professional medical writers will not be used. 

Clinical study protocol 
 
 
21 
Protocol version 2.3  
October 29, 2023 
The full study protocol of the BABITT-study is published at ClinicalTrials.gov. 
 
32. 
Informed consent materials 
Consent and participant information forms are approved by the Swedish Ethical Review Board. See 
Appendix 1 (in Swedish). 
 
33. 
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