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Received: 10 December 2019    Revised: 6 May 2020    Accepted: 11 May 2020

DOI: 10.1111/nmo.13912

ORIGINAL ARTICLE

The impact of incorporating toilet-training status in the

pediatric Rome IV criteria for functional constipation in infant
and toddlers

Miguel Saps1 | Carlos Alberto Velasco-Benitez2,3 | Lilibet Fernandez Valdes4 |

Jorge Mejia2 | Eder Villamarin2 | Jairo Moreno5 | Carmen Ramirez6 |
María José González7 | Isabella Vallenilla8 | Ana Corina Falcon1 | Cara Axelrod1

1
University of Miami Miller School of
Medicine, Miami, FL, USA Abstract
2
Department of Pediatrics, Universidad del Background: The diagnosis of functional constipation (FC) is based on the Rome
Valle, Cali, Colombia
criteria. The last edition of the criteria (Rome IV) for infants and toddlers modified
3
Program in Clinical Medicine and Public
Health, University of Granada, Granada,
the criteria to differentiate toilet-trained (TT) and non-toilet-trained (NTT) children.
Spain These changes have not been validated. We aimed to understand the impact of add-
4
Jackson Memorial Hospital, University of ing toilet training to the diagnostic criteria and to assess the prevalence of FC.
Miami, Miami, FL, USA
5 Methods: Parents of infants and toddlers from six outpatient clinics (four public, two
Clinica Pediatrica Colsanitas, Bogota,
Colombia private) located in three geographically dispersed cities in Colombia completed vali-
6
Hospital Regional Maria Inmaculada, dated questionnaires to diagnose functional gastrointestinal disorders according to
Florencia, Colombia
7 Spanish version of Rome IV criteria (QPGS-IV).
Central University of Venezuela, Caracas,
Venezuela Results: A total of 1334 children (24.4 months ±15.0) participated: 482 (36%) TT and
8
Lisandro Alvarado Western University, 852 (64%) NTT. The prevalence of FC was 21.1%. The prevalence increased with age,
Barquisimeto, Venezuela
0-1 years 7.7%; 2 years 18.2%; 3 years 23.7%; and 4 years 37.2%. TT vs NTT for FC
Correspondence 41.9% vs 9.3%, respectively (OR 7.06, 95% CI 5.26-9.47, P < .0001). TT more likely to
Miguel Saps, Division of Pediatric
Gastroenterology, Hepatology and
report ≥ 3 criteria (OR = 2.43, 95% CI 1.41-4.21, P = .0015). 18.3% of TT had episodes
Nutrition, Mailman Center, University of of fecal incontinence that met the frequency required by Rome for FC (≤1 episode/
Miami Miller School of Medicine, 1601 NW
12 AVE, Suite 3005A, Miami, FL 33136,
week). However, 87.1% had fecal incontinence less often. 7.4% of them characterized
USA. as large quantity.
Email: msaps@med.miami.edu
Conclusion: We found no changes in the prevalence of FC using the Rome IV criteria
vs Rome III. TT children are more likely to have FC. Study suggests that changes in
Rome IV criteria were potentially clinically relevant and to have adequate face valid-
ity. Future studies should confirm our findings.

KEYWORDS

functional constipation, functional gastrointestinal disorders, non-toilet trained, Rome

criteria, toilet trained

1 |  I NTRO D U C TI O N The treatment of FC remains a challenge. Approximately 25% of

children treated for FC continue to have symptoms into adulthood. 2
Functional constipation (FC) is common in childhood and accounts Medications approved for the treatment of chronic constipation in
for approximately one in four pediatric gastroenterology consults.1 adults (linaclotide, lubiprostone, and prucalopride) have not proven

Neurogastroenterology & Motility. 2020;00:e13912. wileyonlinelibrary.com/journal/nmo |

© 2020 John Wiley & Sons Ltd     1 of 6
https://doi.org/10.1111/nmo.13912
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2 of 6       SAPS et al.
to be efficacious in childhood.3,4 Studies have shown that delayed
5
treatment worsens the outcome. Most children develop constipa-
tion as infant or toddlers.6 Still, none of the latest pediatric pharma-
ceutical clinical trials were conducted in young children.
The importance of early treatment underscores the need for an
accurate and early diagnosis. The diagnosis of FC is clinical and based
on the Rome criteria. In children, the Rome criteria are divided into
two age groups. The youngest age group includes infants, toddlers,
and children up to 4 years of age. 5 In the latest edition of the Rome
criteria (Rome IV), the diagnosis of FC for this age group was slightly
modified. Because of the fact that most children less than 2 years of
age are non-toilet-trained and fecal incontinence in a child wearing
diaper is impossible to assess, the Rome criteria established different
criteria for toilet-trained and non-toilet-trained children. No other
changes were made.
Although the conceptual framework of refining the criteria to
include toilet training seems logical, the impact of distinguishing
children who are toilet-trained from those who are not has not
been studied. It is unclear whether the differentiation of children
according to toilet training provides useful information that merits
its continued use, and if the modifications in the diagnostic criteria
from Rome III to Rome IV resulted in changes in the prevalence of FC
in this age group. The clarification of these aspects would provide
important information for the Rome committee prior to considering
issuing newer diagnostic criteria.
We conducted a study to better understand the effect of the
changes to the Rome criteria in the diagnosis of FC. Our primary aim
was to evaluate the impact of adding toilet training to the diagnostic
criteria in infants and children up to 4 years of age. Our secondary
aim was to assess the prevalence of FC in this age group. We hy-
pothesized that we would find significant differences in diagnostic
criteria comparing children that are toilet-trained versus non-toilet-
trained, but that there would be no changes in the overall prevalence
of FC using the Rome IV criteria compared to the Rome III criteria.
2 |  M E TH O DS
This cross-sectional study was conducted from June 2018 to April
2019 in six urban outpatient clinics (four public, two private) of three
geographically dispersed cities in Colombia (Bogota 10 779 000, Cali
2 319 655, and Florencia, 163 323 inhabitants).
2.1 | Selection of cases and controls
Parents of children between 1 month and 4 years old who attended
well-child visit were invited to participate in the study. The well-child
regular visits were with their primary care doctors in Cali (Valle),
Bogota (Distrito Capital), and Florencia (Caqueta), Colombia. Those
accepting to participate signed a consent form and were enrolled
in the study. Children with a history of organic diseases and those
above 48 months of age were excluded.
2.2 | Study protocol
Parents completed age appropriate validated questionnaires to diag-
nose functional gastrointestinal disorders according to the Spanish
version of Rome IV criteria (QPGS-IV) (Adaptation from the QPGS
Infant Toddler version, 2015).7 Screening questions were included at
the time of survey, such as the patient's medical history, use of medi-
cations, and previous hospitalizations. Members of the research
team administered the questionnaires in clinic.
2.3 | Diagnosis of FC
Children were diagnosed with FC if they met Rome IV criteria8: at
least 1 month of two or more of the following criteria: two or fewer
defecations per week, history of pain/hard bowel movements, his-
tory of large-diameter stools, presence of a large fecal mass in the
rectum, and history of excessive stool retention. In toilet-trained
children, additional criteria include at least 1 episode/week of fecal
incontinence and history of large-diameter stools that may obstruct
the toilet.
2.4 | Statistical analysis
Age, sex, race, toilet-training status, and the frequency of FC symp-
toms were assessed for all participants. Age was calculated as mean
and SD. The presence of each criterion in Rome was independently
analyzed: ≤2 time's evacuations per week, hard or very hard stools,
pain during defecation, large stools, fecalomas, and stool retention
and compared between children that were and were non-toilet-
trained. Data were calculated as separate odds ratios (OR) and 95%
confidence intervals (95% CI) for each criterion and to compare the
likelihood of FC between children who were toilet-trained from those
who were non-toilet-trained. Fisher's exact test was used for categori-
cal variables and Student's t test to establish significance when com-
paring means. P value of <.05 was considered statistically significant.
The study was approved by the Institutional Review Board and Human
Subjects Committee of the Hospital Universitario del Valle, Colombia.
3 | R E S U LT S
Between June 1, 2018, and April 1, 2019, a total of 1390 families
were invited to participate in the study. Of these, 33 children de-
clined to participate and 23 were excluded due to the presence of
organic diseases. A total of 1334 children (mean age of 24.4 months
±15.0) were included in the study (Figure 1). Out of the 1334 par-
ticipants, 389 were infants and 945 were 13-48 months. There were
482 (36%) toilet-trained participants and 852 (64%) that were not.
There was a similar distribution of females (680) and males (654).
Most children were of mixed race (683, 51.2%; Table  1). To note,
there was a variation in rates of FC observed between racial groups.
SAPS et al. |
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White children had significantly higher rates of FC compared with we were interested in comparing the likelihood of meeting 3 or more
non-white children (P < .0001). criteria in different age groups. We compared the subgroup of par-
ticipants 0-2 years of age with those 3 and 4 years at age (an age
group with a larger number of children that are already toilet-trained)
3.1 | Prevalence of FC (OR 1.29, 95% CI 0.80-2.09, P = .29).

The prevalence of FC was 21.1%. To better understand some items

of interest, we analyzed the prevalence of FC by age and toilet-train-
ing status (Table 2).
3.2 | Functional constipation and age
The prevalence of FC consistently increased with age, first year of life
7.7%; 2 years 18.2%; 3 years 23.7%; and 4 years 37.2% (P = .0053)
(Figure 2). As the diagnosis of FC requires to meet at least 2 criteria,
Identification
3.3 | Functional constipation and toilet training
Toilet-trained children were significantly more likely to meet diag-
nostic criteria for FC than non-toilet-trained children, 41.9% vs 9.3%,
respectively (OR 7.06, 95% CI 5.26-9.47, P  <  .0001). Children that
were toilet-trained were also more likely to report 3 or more criteria,
(OR = 2.43, 95% CI 1.41-4.21, P = .0015). There was no significant
difference in frequency of any individual criterion between children
that were toilet-trained and children that were non-toilet-trained.

Families invited to participate in

the study
(n = 1390) Excluded
(n = 56)
(33) Declined participation
(13) Cow's milk protein allergy
(4) Gastroesophageal reflux disease
Screening

Participated
(3) Anorectal abnormalities
(n = 1334)
(1) Congenital heart disease
(1) Seizure disorder
(1) Urinary tract infection
FGIDs* No FGIDs*
(n = 408) (n = 926)
Eligibility

Functional Other FGIDs*

Constipation
(n = 127)
(n = 281)
Included

Toilet trained Non-toilet-trained

(n = 202) (n = 79)

F I G U R E 1   Flow diagram of participants' enrollment. *=Functional gastrointestinal disorders (FGIDs)

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4 of 6       SAPS et al.

TA B L E 1   Demographic information
Colombia
among all participants (N = 1334)
Total (%) Cali (%) Florencia (%) Bogotá (%)

1334 771 463 100

Age 24.4 ± 15.0 24.2 ± 14.9 25.4 ± 15.5 20.6 ± 12.6

Age groups
1-12 mo 389 (29.2) 227 (29.4) 131 (28.3) 31 (31.0)
13-48 mo 945 (70.8) 544 (70.6) 332 (71.7) 69 (69.0)
Sex
Female 680 (51.0) 391 (50.7) 237 (51.2) 52 (52.0)
Male 654 (49.0) 380 (49.3) 226 (48.8) 48 (48.0)
Race
Mixed race 683 (51.2) 420 (54.5) 231 (49.9) 32 (32.0)
African descent 103 (7.7) 69 (9.0) 34 (7.3) 0 (0.0)
White 393 (29.5) 145 (18.8) 180 (38.9) 68 (68.0)
Native 155 (11.6) 137 (17.8) 18 (3.9) 0 (0.0)
Toilet trained
No 852 (63.9) 545 (70.7) 251 (54.2) 56 (56.0)
Yes 482 (36.1) 226 (29.3) 212 (45.8) 44 (44.0)

TA B L E 2   Functional constipation (FC) by age group and toilet- ROME IV criteria. Moreover, this is also the first study to evaluate
training status the impact of adding toilet training to the diagnostic criteria.
The Rome IV criteria for FC made little changes from the pre-
Function constipation
vious iteration; however, it was refined by distinguishing between
Non-toilet children that were and were non-toilet-trained. This led to our hy-
Toilet trained trained
pothesis that the changes made in the last edition of the Rome IV cri-
n 202 (71.9%) 79 (28.1%) P teria were unlikely to result in a change in prevalence. We found that

0-6 mo 3 0 (0.0%) 3 (100.0%) .022 21.1% of the participants met criteria for FC. A previous study by
our group is a similarly large sample of Colombian children (n = 1231)
6-12 mo 27 5 (18.5%) 22 (81.5%) .000
from the same cities and under same methodology, but using the
12-18 mo 28 11 (39.3%) 17 (60.7%) .000
Rome III criteria showed comparable prevalence (22.1%; P  =  .96).9
18-24 mo 37 21 (56.8%) 16 (43.2%) .025
Our findings contrast with studies from other countries that also
24-36 mo 56 46 (82.1%) 10 (17.9%) .038
used the Rome IV criteria and reported a lower prevalence of FC
36-48 mo 129 118 (91.5%) 11 (8.5%) .000
(12% United States; 13.6% Italy).10,11 This suggests that changes in
the Rome IV criteria (compared to the Rome III criteria) in this age
Parents of children who were non-toilet-trained were more likely to group did not modify the overall prevalence of FC and that the prev-
answer positively to the question on whether they have been told by alence of FC seems to vary among regions.
a doctor or a nurse that the child had a large amount of stools, 40.5% The main change in Rome IV criteria in children younger than
vs 26.7% (P = .018). 4 years was the differentiation between toilet-trained and non-toi-
Out of all the children who were toilet-trained (202), 18.3% re- let-trained children.12 Our study showed that as emphasized by the
ported episodes of fecal incontinence that met the frequency crite- Rome IV committee, toilet training is an important milestone in the
rion required by Rome IV for diagnosis of FC (at least 1 episode/week). history of FC in young children. We found that children that were
However, most children had episodes of fecal incontinence less than toilet-trained were significantly more likely to meet Rome IV crite-
once a week (87.1%). Among all children that had episodes of fecal ria for FC. Interestingly, although children that were toilet-trained
incontinence, 7.4% of them were characterized as large quantity. did not have a higher frequency in any individual criterion of Rome,
they met a higher number of criteria. We also found that children
who were toilet-trained had episodes of fecal incontinence occurring
4 |  D I S CU S S I O N at least once weekly in 18.3% but that a large proportion of them
(87.1%) had some episodes of incontinence. As the frequency of
This is the first study to establish the prevalence of FC in children fecal incontinence episodes (at least once a week) required to meet
between the ages of 1 month to 4 years in Latin America using the Rome criteria is arbitrary, it would be important to know the number
SAPS et al.
F I G U R E 2   Functional constipation and 100%
age in all participants
90%
80%
70%
60%
359
50%
40%
30%
20%
10%
30
0%
0-12 m
of episodes of incontinence that causes distress to the family or pre-
cludes children from attending regular day care. The knowledge of
this information could help establishing a meaningful number that
allows normal functioning for children and families what could be-
come an important endpoint for pediatric clinical trials.
Together, the results of our study suggest that the contribu-
tion of the Rome IV criteria in terms of adding a key aspect of the
child's development was important and pertinent. Classification of
children according to toilet training will facilitate conducting highly
needed clinical trials in this age group. The fact that the overall
prevalence of FC was not affected by modifications in the Rome
criteria (that were not expected to result in changes of prevalence)
speaks of the reliability of the criteria. Differences in frequency of
criteria associated with toilet training suggest that the criteria have
adequate face validity. Knowing that the toilet training addition to
the previous criteria measures what is supposed to measure is reas-
suring and an important first step in the validation of the pediatric
criteria.
We also found that the prevalence of FC increased with age.
Among participants aged 1-12  months, 7.7% had FC compared to
26.6% of those 37-48 months. This was also observed in a previous
study by our group that was also conducted in Colombian children9
and by Van Tilburg et al in North American children.13 Although the
reason for this finding is unclear, it could be explained by the effect
of maturational mechanisms on the disorder's pathophysiology and
partially by the effect of toilet training. It is possible that as children
advance in age and become toilet trained, parents pay more atten-
tion to the children's stool patterns what may result in attention bias.
Explaining the increase in prevalence with age, solely by the increas-
ing number of children being toilet trained as they grow older, would
be unlikely as this phenomenon is even seen in children prior to the
age of toilet training.
There are several strengths to our study. Prevalence data were
assessed in a very large and diverse sample from well-child clinics in
multiple sites in three urban cities. We believe the high recruitment
|
      5 of 6
218
180
296
129
56
66
12-24 m 24-36 m 36-48 m
Absence of Functional Constipation
Presence of Functional Constipation
rate may have been due to the following: (a) at the beginning of the
visit, the pediatricians explained the study to the parents, and (b) all
the questions included in the questionnaires were answered by the
parents during a regular pediatric clinic visit. Some of the additional
strengths of our study include the use of validated questionnaires
that were translated by our group with reverse translation and focus
groups to assure understanding.
Our study is not without limitations. The selection sample of
children from a well-child consultation may not represent the entire
population of the country studied, and the possibility of caregiv-
ers of sick children visiting well-child consultation more often than
healthy children could represent a selection bias. In addition, parents
with gastrointestinal issues themselves may likely pay more atten-
tion to the children's stool patterns what may also result in atten-
tion bias. In retrospect, this question would have strengthened our
study. The use of a questionnaire as the only tool for data collection
also has some intrinsic limitations, including the complete reliance
on parents’ subjective perception of symptoms and understanding
of questions. Adding the information derived from the physical ex-
amination including digital rectal examination could have led to an
increased prevalence of FC by the detection of additional objective
criteria; however, it would not be possible or ethical to conduct this
examination in every infant and child. Finally, data on social depriva-
tion were not collected. Although we acknowledge that interactions
with siblings, peers, and adults can influence bathroom behavior,
this question was not included in our study. Including this question
would have strengthened our study.
In conclusion, our study demonstrated that there were no
changes in the prevalence of FC in infants and toddlers using the
Rome IV criteria compared to the previous edition and that children
that are toilet-trained are more likely to have FC. Our study suggests
that changes in the Rome IV criteria were potentially clinically rel-
evant. Future studies should be conducted to confirm our findings
and to establish the number of episodes of fecal incontinence that is
distressful for the family and limits the child's daily function.
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6 of 6       SAPS et al.
AC K N OW L E D G M E N T
The study was conducted by the Functional International Digestive
Epidemiological Research Survey (FINDERS) group.
C O N FL I C T S O F I N T E R E S T
None declared.
AU T H O R C O N T R I B U T I O N S
CVB, JM, EV, JM, and CRH conceptualized and designed the study;
collected, analyzed, and interpreted data; drafted the initial manu-
script; and reviewed and revised the manuscript; MS, LFV, MCJG, IV,
AF, and CA reviewed and revised the manuscript critically for impor-
tant intellectual content; all authors approved the final manuscript
as submitted and agree to be accountable for all aspects of the work.
ORCID
Cara Axelrod  https://orcid.org/0000-0002-0812-1355
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How to cite this article: Saps M, Velasco-Benitez CA,
Fernandez Valdes L, et al. The impact of incorporating
toilet-training status in the pediatric Rome IV criteria for
functional constipation in infant and toddlers.
Neurogastroenterology & Motility. 2020;00:e13912.
https://doi.org/10.1111/nmo.13912