REVIEW ARTICLE PEDIATRICS Volume 138, number 3, September 2016:e20161417 Functional Defecation Disorders and Excessive Body Weight: A Systematic Review Ilan J.N. Koppen, MD, a,b Sophie Kuizenga-Wessel, MD, a Miguel Saps, MD, b Carlo Di Lorenzo, MD, b Marc A. Benninga, MD, PhD, a Faridi S. van Etten–Jamaludin, B, c Merit M. Tabbers, MD, PhD a abstract CONTEXT: Several studies have suggested an association between functional defecation disorders (FDDs) and overweight/obesity in children. OBJECTIVE: To synthesize current evidence evaluating the association between FDDs and overweight/obesity in children. DATA SOURCES: PubMed, Medline, and Embase were searched from inception until January 25, 2016. STUDY SELECTION: Prospective and cross-sectional studies investigating the association between FDDs and overweight/obesity in children 0 to 18 years were included. DATA EXTRACTION: Data generation was performed independently by 2 authors and quality was assessed by using quality assessment tools from the National Heart, Lung, and Blood Institute. RESULTS: Eight studies were included: 2 studies evaluating the prevalence of FDDs in obese children, 3 studies evaluating the prevalence of overweight/obesity in children with FDDs, and 3 population-based studies. Both studies in obesity clinics revealed a higher prevalence of functional constipation (21%–23%) compared with the general population (3%–16%). In 3 case-control studies, the prevalence of overweight (12%–33%) and obesity (17%–20%) was found to be higher in FDD patients compared with controls (13%–23% and 0%–12%, respectively), this difference was significant in 2/3 studies. One of 3 population-based studies revealed evidence for an association between FDDs and overweight/obesity. Quality of 7/8 studies was rated fair or poor. LIMITATIONS: Due to heterogeneity of the study designs, we refrained from statistically pooling. CONCLUSIONS: Although several studies have revealed the potential association between FDDs and excessive bodyweight in children, results across included studies in this review differ strongly and are conflicting. Therefore, this systematic review could not confirm or refute this association. a Department of Pediatric Gastroenterology and Nutrition, Emma Children’s Hospital/Academic Medical Center, Amsterdam, Netherlands; c Medical Library, Academic Medical Center, Amsterdam, Netherlands; and b Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Nationwide Children’s Hospital, Columbus, Ohio Dr Koppen conceptualized and designed the study, screened citations, and assessed studies for eligibility, extracted data, performed quality assessments, and drafted the initial manuscript; Dr Kuizenga-Wessel screened citations and assessed studies for eligibility, extracted data, performed quality assessments, and reviewed and revised the manuscript; Drs Benninga, Saps, and Di Lorenzo interpreted data, and reviewed and revised the manuscript; Mrs van Etten–Jamaludin designed the search strategy, coordinated data collection, and reviewed the manuscript; Dr Tabbers designed the study, supervised data collection and interpretation, and reviewed and revised the manuscript; and all authors approved the final manuscript as submitted. To cite: Koppen IJ, Kuizenga-Wessel S, Saps M, et al. Functional Defecation Disorders and Excessive Body Weight: A Systematic Review. Pediatrics. 2016;138(3):e20161417 by guest on August 15, 2020 www.aappublications.org/news Downloaded from
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REVIEW ARTICLEPEDIATRICS Volume 138 , number 3 , September 2016 :e 20161417
Functional Defecation Disorders and Excessive Body Weight: A Systematic ReviewIlan J.N. Koppen, MD, a, b Sophie Kuizenga-Wessel, MD, a Miguel Saps, MD, b Carlo Di Lorenzo, MD, b Marc A. Benninga, MD, PhD, a Faridi S. van Etten–Jamaludin, B, c Merit M. Tabbers, MD, PhDa
abstractCONTEXT: Several studies have suggested an association between functional defecation disorders (FDDs) and overweight/obesity in children.
OBJECTIVE: To synthesize current evidence evaluating the association between FDDs and overweight/obesity in children.
DATA SOURCES: PubMed, Medline, and Embase were searched from inception until January 25, 2016.
STUDY SELECTION: Prospective and cross-sectional studies investigating the association between FDDs and overweight/obesity in children 0 to 18 years were included.
DATA EXTRACTION: Data generation was performed independently by 2 authors and quality was assessed by using quality assessment tools from the National Heart, Lung, and Blood Institute.
RESULTS: Eight studies were included: 2 studies evaluating the prevalence of FDDs in obese children, 3 studies evaluating the prevalence of overweight/obesity in children with FDDs, and 3 population-based studies. Both studies in obesity clinics revealed a higher prevalence of functional constipation (21%–23%) compared with the general population (3%–16%). In 3 case-control studies, the prevalence of overweight (12%–33%) and obesity (17%–20%) was found to be higher in FDD patients compared with controls (13%–23% and 0%–12%, respectively), this difference was significant in 2/3 studies. One of 3 population-based studies revealed evidence for an association between FDDs and overweight/obesity. Quality of 7/8 studies was rated fair or poor.
LIMITATIONS: Due to heterogeneity of the study designs, we refrained from statistically pooling.
CONCLUSIONS: Although several studies have revealed the potential association between FDDs and excessive bodyweight in children, results across included studies in this review differ strongly and are conflicting. Therefore, this systematic review could not confirm or refute this association.
aDepartment of Pediatric Gastroenterology and Nutrition, Emma Children’s Hospital/Academic Medical Center, Amsterdam, Netherlands; cMedical Library, Academic Medical Center,
Amsterdam, Netherlands; and bDepartment of Pediatric Gastroenterology, Hepatology, and Nutrition, Nationwide Children’s Hospital, Columbus, Ohio
Dr Koppen conceptualized and designed the study, screened citations, and assessed studies for eligibility, extracted data, performed quality assessments, and
drafted the initial manuscript; Dr Kuizenga-Wessel screened citations and assessed studies for eligibility, extracted data, performed quality assessments, and
reviewed and revised the manuscript; Drs Benninga, Saps, and Di Lorenzo interpreted data, and reviewed and revised the manuscript; Mrs van Etten–Jamaludin
designed the search strategy, coordinated data collection, and reviewed the manuscript; Dr Tabbers designed the study, supervised data collection and
interpretation, and reviewed and revised the manuscript; and all authors approved the fi nal manuscript as submitted.
To cite: Koppen IJ, Kuizenga-Wessel S, Saps M, et al. Functional Defecation Disorders and Excessive Body Weight: A Systematic Review. Pediatrics. 2016;138(3):e20161417
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KOPPEN et al
Functional defecation disorders (FDDs) are commonly encountered in pediatric health care and comprise functional constipation (FC) and functional nonretentive fecal incontinence (FNRFI). 1, 2 FC has a reported prevalence ranging from 0.7% to 29.6%. 3 FNRFI is less prevalent and estimated to occur in <1% of children in the general population. 2 FDDs are diagnosed according to the internationally accepted Rome III criteria (Table 1). 4 These disorders are known to have a significant impact on the quality of life. 5 – 7 The pathophysiology of FDDs is still incompletely understood, although genetic, biochemical, microbial, behavioral, and psychosocial factors have been suggested to potentially play a role.1, 2, 8 More recently, several studies have suggested that there is an association between FDDs and overweight and/or obesity in children. 9 – 13
Pediatric overweight and obesity have emerged as a serious public health concern in the 21st century. The global prevalence of childhood overweight and obesity has increased dramatically over the past decades; rising by 47% between 1980 and 2013: from 10% to 15%. 14 Obesity is known to cause various comorbidities, such
as hypertension, dyslipidemia, and fatty liver disease. 15 Factors that may be involved in the pathophysiology of both FDDs and overweight in children include diet (eg, a lack of fiber or a high-fat diet), a lack of physical activity, gut microbiota dysbiosis, psychological factors, and socioeconomic status. 1, 2, 8, 9, 13, 16 – 21 Since these factors are associated with both FDDs and excessive bodyweight in children, they could account for the commonly reported cooccurrence between these disorders.
To date, no comprehensive systematic review has been published to evaluate the potential association between FDDs and overweight/obesity in children. If an association exists, this could have important implications regarding early detection of FDDs in children with overweight and of overweight in children with FDDs in the clinical care setting. For both FDDs and overweight, early detection and intervention are of key importance since a delay in treatment increases the likelihood of poor long-term outcome. 22, 23 Therefore, our aim was to systematically review currently available literature regarding the association between FDDs and overweight/obesity in children.
METHODS
PubMed, Medline, and Embase were searched from inception until January 2016. Publication language was restricted to English. Prospective and cross-sectional studies describing the association between FDDs and overweight/obesity in children (0–18 years) were included. Studies including a combination of children and adolescents (<21 years) were eligible for inclusion as long as the majority of subjects was <18 years of age. As a prerequisite for eligibility for inclusion, a clear definition for overweight/obesity and FDDs needed to be provided. For FC, this definition had to at least include defecation frequency (<3 times per week), FNRFI had to be described as fecal incontinence in the absence of FC and for overweight/obesity, the definition had to include the BMI. The primary outcomes of interest were the prevalence of FDDs and of overweight/obesity (in %). Exclusion criteria were organic causes of defecation disorders or of excessive body weight and insufficient data on the outcomes of interest. Search strategies included controlled vocabulary terms: Medical Subject Headings (MeSH) for PubMed and Medline and Emtree terms for Embase. Search terms
2
TABLE 1 Rome III Criteria for FDDs in Children
Rome III Criteria Children <4 y Children With a Developmental Age of ≥4 y
FC 1. <3 defecations per week 1. <3 defecations in the toilet per week
2. ≥1 episode of fecal incontinence per week after the
acquisition of toileting skills
2. ≥1 episode of fecal incontinence per week
3. History of excessive stool retention 3. History of retentive posturing or excessive volitional stool
retention
4. History of painful or hard bowel movements 4. History of painful or hard bowel movements
5. Presence of a large fecal mass in the rectum 5. Presence of a large fecal mass in the rectum
6. History of large diameter stools that may obstruct the
toilet
6. History of large diameter stools that may obstruct the toilet
Must fulfi ll ≥2 criteria for ≥1 mo before diagnosis. Must fulfi ll ≥2 criteria at least once per week for ≥2 mo before
diagnosis with insuffi cient criteria for the diagnosis of irritable
bowel syndrome.
FNRFI Not applicable 1. Defecation into places inappropriate to the social context at least
once per month
2. No evidence of an infl ammatory, anatomic, metabolic, or
neoplastic process that explains the subject’s symptoms
3. No evidence of fecal retention
Must fulfi ll all criteria for ≥2 mo
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PEDIATRICS Volume 138 , number 3 , September 2016
included the following: constipation, fecal impaction, fecal incontinence, defecation, gastrointestinal motility; children, infants, adolescents, pediatrics; obesity, overweight, body size, BMI. The electronic search strategy, including the limits used, is provided in the Supplemental Information.
Data generation was performed independently by 2 authors (Drs Koppen and Kuizenga-Wessel). This process involved searching literature, data selection, and data extraction. In case of disagreement between these authors, consensus was reached by discussion or by consulting a third author (Dr Tabbers). To identify additional studies, reference lists of reviews and included studies were searched.
Quality Assessment
Quality of the studies was assessed by using quality assessment tools from the National Heart, Lung, and Blood Institute (NHLBI); the choice for the applied tool was based on the study designs. We used 1 tool for observational cohort and cross-sectional studies and another tool for case-control studies. Both tools assessed the internal validity and risk of bias in a similar manner. 24 Two authors (Drs Koppen and Kuizenga-Wessel) applied these tools; they independently evaluated the items of the tools as “yes, ” “no, ” “not applicable, ” “cannot determine, ” or “not reported.” This was used to guide the overall rating for the quality of each study as “good, ” “fair, ” or “poor.” In case of disagreement, consensus was reached through discussion or by consulting a third author (Dr Tabbers).
RESULTS
A flowchart of the selection process is depicted in Fig 1. Eight studies were included, which were categorized into 3 groups: (1) studies that evaluated the prevalence of FDDs in
obese children (n = 2; Table 2); (2) studies that evaluated the prevalence of overweight/obesity in children with FDDs (n = 3; Table 3); (3) population-based studies assessing the association between FDDs and overweight/obesity (n = 3; Table 4). Studies were conducted in 6 different countries across 4 continents. Five studies were conducted in tertiary care centers, 2 studies were conducted in schools, and 1 study was conducted in primary care centers. In total, 5442 children were described (1–20 years, 49.5% boys), this number reflects all study group children in the different studies and not only those with conditions of interest. Only 3 studies had a case-control design, and the total number of children in the control groups was 1870 (2–20 years, 49.3% boys). The quality assessment for all included studies is presented in Tables 5 and 6.
Group 1: Prevalence of FDDs in Obese Children
Fishman et al 13 administered a self-developed bowel questionnaire to 80 consecutive pediatric patients presenting at an obesity clinic. They found a prevalence of FC of 23%, which was higher than the previously reported prevalence of 8.9% in the general population. They also observed that 12 (15%) obese children suffered from fecal incontinence; in 6 of them this was associated with FC. However, in the other 6 children (7.5% of the total obese population), it was not associated with FC and they were diagnosed as having nonretentive soiling, a disorder now referred to as FNRFI.
Van der Baan-Slootweg et al 12 evaluated the bowel habits of 91 morbidly obese children included in an obesity treatment trial, using questionnaires and a 2-week bowel diary. A physical examination was performed in all children, and a rectal examination was performed
in 69 (76%) children. Nineteen of 91 (21%) morbidly obese children were found to have FC according to the Rome III criteria. In addition, colonic transit time (CTT) was determined in all study subjects by using a radiopaque marker test using the method described by Bouchoucha et al. 27 A prolonged CTT (>62 hours) was found in 2 (11%) children with constipation and in 6 (8%) children who did not have FC according the Rome III criteria. FNRFI was found in 1 patient and, as expected, CTT was normal in this child. Furthermore, food intake was measured by using a 7-day diary record kept by the children after instructions from a dietitian; no difference was found between the diet of children with or without constipation, including regarding fiber and fat intake.
Group 2: Prevalence of Overweight and Obesity in Children With FDDs
In a prospective case control study, Kavehmanesh et al 28 compared 124 children with FC with 135 controls (patients admitted for other diseases). Obesity (18% vs 12%) and overweight (33% vs 23%) were more prevalent in the FC group compared with the controls, but these differences were not statistically significant. The authors mentioned that the prevalence of both overweight and constipation found in this study (both in constipated children and controls) was much higher than found in a nationwide study (4% and 9%, respectively). 29
Teitelbaum et al 30 performed a prospective case-control study to investigate the association between functional gastrointestinal disorders and overweight. They compared 757 children who presented to their pediatric gastroenterologist for upper and lower functional gastrointestinal disorders with 2 healthy control groups from a local pediatric practice (control group 1) and a high school (control group 2),
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KOPPEN et al
comprising 1691 controls. 30 Out of all children with FC (n = 196), 37 (19%) were considered to be overweight and 45 (23%) were obese; the obesity rate in the FC group was significantly higher compared with the healthy controls (8% in control group 1 and 11% in control group 2, P < .001 for both comparisons). For
fecal incontinence (with or without FC), overweight and obesity were both significantly more prevalent in the patient group (25% and 25%, respectively) compared with both healthy control groups (overweight control group 1: 13%; overweight control group 2: 15%; obesity control group 1: 8%; overweight control
group 2: 11%; comparisons are further specified in Table 3).
Wagner et al 31 recently published a prospective case-control study describing 43 children who presented with fecal and/or urinary incontinence problems, including 17 children (40%) with fecal
4
FIGURE 1Flowchart of study screening and selection process. aTwo studies were excluded due to insuffi cient details on the outcomes of interest: Kiefte et al 25 was excluded due to insuffi cient information. The authors performed a large prospective birth cohort study and reported outcomes at 24, 36, and 48 months of age. However, follow-up response rate differed per time point, and the exact total number of children with FC and/or overweight/obesity at each of these ages was not provided. The authors reported that prevalence of overweight was almost similar in children with and without constipation (8% vs 11%; P = .46, 13% vs 10%; P = .10 and 8% vs 9%; P = .60 at the age of 24, 36, and 48 months, respectively). More information is not available. Chien et al 26 was excluded because recalculation of the data provided in the tables resulted in different results than those provided by the authors, indicating that the authors performed an analysis that was not described clearly and could not be repeated by us. Furthermore, in this study an odds ratio was reported without a confi dence interval, thereby making it impossible to interpret. This study had other methodological weaknesses; obesity was based on self-reported height and weight via a questionnaire and low defecation frequency (assessed by a questionnaire) was used as an indicator of constipation.
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PEDIATRICS Volume 138 , number 3 , September 2016 5
TABL
E 2
Pre
vale
nce
of
FDD
s in
Ob
ese
Ch
ildre
n
Stu
dy
Cou
ntr
y, s
etti
ng
Pop
ula
tion
Con
trol
sD
efi n
itio
n O
W/
OB
an
d it
s
Mea
sure
men
t
Defi
nit
ion
FC
an
d it
s M
easu
rem
ent
n (
%)
FCn
(%
) FI
Con
clu
sion
Com
men
ts
Fish
man
et
al
2004
US
A, p
rosp
ecti
ve
obse
rvat
ion
al
stu
dy
at
obes
ity
clin
ic;
Tert
iary
car
e
cen
ter
n =
80;
1–18
y;
♂: 3
9%
NA
OW
: NA;
OB
: BM
I >
95th
per
cen
tile
;
Wei
ght
and
hei
ght
mea
sure
men
ts;
Not
rep
orte
d
wh
ich
refe
ren
ce
valu
es w
ere
use
d
2 or
mor
e of
th
e fo
llow
ing,
≥25
% o
f th
e
tim
e, ≥
3 m
o: h
ard
or
pel
let-
like
stoo
ls,
infr
equ
ent
stoo
ls (
<3
per
wk)
, str
ain
ing,
pai
nfu
l def
ecat
ion
, or
sen
se o
f in
com
ple
te
evac
uat
ion
. Soi
ling
was
defi
ned
as
pre
sen
ce o
f fe
cal m
ater
ial i
n u
nd
erw
ear
or p
ajam
as in
a c
hild
old
er t
han
48
mo
of a
ge f
or a
t le
ast
3 m
o; A
sses
sed
wit
h
stan
dar
diz
ed q
ues
tion
nai
re
18/8
0 (2
3)To
tal:
12/8
0 (1
5);
FNR
FIa :
6/8
0 (8
);
FC: 6
/18
(33)
Pre
vale
nce
of
FC
in O
B c
hild
ren
(23%
) h
igh
er
than
pre
viou
s
rep
orts
(3%
–16
%)
BM
I ad
just
ed f
or a
ge a
nd
gen
der
, not
rep
orte
d
wh
ich
ref
eren
ce
valu
es w
ere
use
d;
Dis
crep
ancy
nu
mb
er
of b
oys:
30
acco
rdin
g
to t
ext
and
31
acco
rdin
g to
tab
le)
Van
der
Baa
n–
Slo
otw
eg
et a
l 201
1
The
Net
her
lan
ds,
pro
spec
tive
obse
rvat
ion
al
stu
dy
at
obes
ity
clin
ic;
Tert
iary
car
e
cen
ter
n =
91;
8–18
y;
♂: 3
4%
NA
OW
: NA;
OB
: BM
I
≥35,
or
BM
I
≥30
in t
he
pre
sen
ce o
f
obes
ity-
rela
ted
mor
bid
ity;
Met
hod
s of
anth
rop
omet
ric
dat
a co
llect
ion
not
rep
orte
d;
Ref
eren
ce
valu
es
bas
ed o
n t
he
Inte
rnat
ion
al
Ob
esit
y Ta
sk
Forc
e: t
o ob
tain
the
curv
e
corr
esp
ond
ing
to a
n a
du
lt
BM
I of
35, t
he
dif
fere
nce
of
the
dis
tan
ce
bet
wee
n t
he
25
and
30
curv
es
was
ad
ded
to
the
30 c
urv
e
Rom
e III
cri
teri
a; A
sses
sed
wit
h s
tan
dar
diz
ed
qu
esti
onn
aire
19/9
1 (2
1)To
tal:
5/91
(5)
;
FNR
FIa :
1/9
1 (1
);
FC: 4
/19
(21)
Hig
her
freq
uen
cy
of F
C in
child
ren
wit
h
obes
ity
(21%
)
com
par
ed
wit
h
wor
ldw
ide
pre
vale
nce
(8.9
%)
—
C, c
ontr
ol g
rou
p; F
I, fe
cal i
nco
nti
nen
ce; N
A, n
ot a
pp
licab
le; O
B, o
bes
ity;
OW
, ove
rwei
ght.
a FI
in c
hild
ren
wh
o d
id n
ot f
ulfi
ll th
e cr
iter
ia f
or F
C w
as c
onsi
der
ed F
NR
FI.
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KOPPEN et al 6
TABL
E 3
Pre
vale
nce
of
Ove
rwei
ght
and
Ob
esit
y in
Ch
ildre
n W
ith
FD
Ds
Stu
dy
Cou
ntr
y, s
etti
ng
Pop
ula
tion
(P
)C
ontr
ols
(C)
Defi
nit
ion
FC
an
d
Mea
sure
men
t
n (
%)
FCn
(%
) FI
Defi
nit
ion
OW
/OB
and
Mea
sure
men
t
n (
%)
OW
n (
%)
OB
Con
clu
sion
Com
men
ts
Kave
h-
man
esh
et a
l
2013
Iran
, pro
spec
tive
case
con
trol
stu
dy
in c
hild
ren
adm
itte
d t
o th
e
hos
pit
al; T
erti
ary
care
cen
ter
n =
124
; 2–
14 y
; ♂:
52%
; Pat
ien
ts
adm
itte
d w
ith
FC
sym
pto
ms
n =
135
;
♂: 5
2%;
Pat
ien
ts in
the
sam
e
age
grou
p,
wit
hou
t FC
or w
eigh
t/
hei
ght
affe
ctin
g
dis
ease
Rom
e II
crit
eria
;
Asse
ssed
usi
ng
self
-
dev
elop
ed
qu
esti
onn
aire
P: 1
24/1
24
(100
);
C: N
A
P: 3
1/12
4
(25)
; C:
NA
OW
: BM
I >85
th
per
cen
tile
; OB
:
BM
I > 9
5th
per
cen
tile
;
Met
hod
s of
anth
rop
omet
ric
dat
a co
llect
ion
not
rep
orte
d; N
ot
rep
orte
d w
hic
h
refe
ren
ce v
alu
es
wer
e u
sed
P: 4
1/12
4
(33)
; C:
31/1
35
(23)
P: 2
2/12
4
(18)
; C:
16/1
35
(12)
No
sign
ifi ca
nt
dif
fere
nce
in
pre
vale
nce
of
OW
/OB
bet
wee
n
child
ren
wit
h/
wit
hou
t FC
.
Ther
efor
e, n
o
clea
r as
soci
atio
n
bet
wee
n O
W/O
B
and
FC
.
Teit
elb
aum
et a
l
2009
US
A, p
rosp
ecti
ve
case
con
trol
stu
dy
at p
edia
tric
gast
roen
tero
logy
clin
ic (
GI g
rou
p);
Tert
iary
car
e
cen
ter
n =
757
; 2–
20 y
; ♂:
51%
; Pat
ien
ts
refe
rred
to
ped
iatr
ic
gast
roen
tero
logi
st
(GI g
rou
p)
Con
trol
gro
up
1: n
= 2
55,
♂: 5
1%;
Hea
lth
y
child
ren
wit
hou
t
un
der
lyin
g
chro
nic
dis
ease
;
Con
trol
grou
p 2
: n
= 1
436;
♂:
49%
; Hig
h
sch
ool
stu
den
ts
Rom
e III
cri
teri
a;
Met
hod
s of
dat
a co
llect
ion
not
rep
orte
d
P: 1
96/7
57
(26)
; C:
NA
P: 1
26/7
57
(17)
;
FNR
FI:
71/7
57
(9);
FC
:
55/1
96
(28)
;
C1:
NA;
C2:
NA
OW
: BM
I 85t
h–
95th
per
cen
tile
;
OB
: BM
I ≥95
th
per
cen
tile
; For
the
GI g
rou
p a
nd
con
trol
gro
up
1
wei
ght
and
hei
ght
wer
e m
easu
red
.
For
con
trol
grou
p 2
, wei
ght
and
hei
ght
wer
e
self
-rep
orte
d; N
ot
rep
orte
d w
hic
h
refe
ren
ce v
alu
es
wer
e u
sed
P: 1
22/7
57
(16)
; FC
:
37/1
96
(19)
; FI:
18/7
1
(25)
;
FC+
FI:
14/5
5
(25)
; C1:
32/2
55
(13)
; C2:
221/
1436
(15)
P: 1
52/7
57
(20)
; FC
:
45/1
96
(23)
; FI:
18/7
1
(25)
;
FC+
FI:
15/5
5
(27)
; C1:
21/2
55
(8);
C2:
163/
1436
(11)
Hig
h p
reva
len
ce o
f O
W
and
OB
in p
atie
nts
wit
h F
DD
; OW
in
FC (
19%
) vs
C1/
C2
13%
/15%
): P
val
ue
.065
/.21
0 (N
S/N
S);
OB
in F
C (
23%
) vs
C1/
C2
8%/1
1%):
P
valu
e <
.001
* /<
.001
* ;
OW
in F
I (25
%)
vs
C1/
C2
13%
/15%
): P
valu
e .0
08* /
.025
* ; O
B
(25%
) in
FI v
ersu
s
C1/
C2
8%/1
1%):
P
valu
e: <
.001
* /<
.001
* ;
OW
in F
C+
FI (
25%
)
vs C
1/C
2 13
%/1
5%):
P v
alu
e .0
15* /
.045
* ;
OB
in F
C+
FI
(27%
) vs
C1/
C2
8%/1
1%):
P v
alu
e
<.0
01* /
<.0
01*
Con
trol
s
wer
e
mat
ched
for
age
and
sex
,
actu
al
age
ran
ge n
ot
pro
vid
ed.
This
stu
dy
incl
ud
ed
sub
ject
s
>18
y o
f
age
bu
t
<21
y o
f
age.
Th
e
mea
n a
ge
was
9.6
±
4.6
y.
Wag
ner
et a
l
2015
Ger
man
y,
pro
spec
tive
cas
e
con
trol
stu
dy
at p
edia
tric
gast
roen
tero
logy
clin
ic; T
erti
ary
care
cen
ter
n =
43;
5–
12 y
, ; ♂:
58%
; Pat
ien
ts
refe
rred
for
FI
or U
I
n =
44;
5–
12
y; ♂
: 55%
;
Ch
ildre
n
from
loca
l
sch
ools
Rom
e III
cri
teri
a;
All c
hild
ren
rece
ived
a p
hys
ical
exam
inat
ion
and
rec
tal
ult
raso
un
d
P: 2
0/43
(47)
; C:
NA
P: 1
7/43
(40)
FNR
FI:
3/43
(7);
FC
:
14/2
0
(70)
; C:
NA
OW
: BM
I 85t
h–
95th
per
cen
tile
OB
: BM
I
≥95t
h p
erce
nti
le;
Wei
ght
and
hei
ght
mea
sure
men
ts;
Sta
nd
ard
dat
a
from
th
e C
ente
r
for
Dis
ease
con
trol
an
d
Pre
ven
tion
wer
e
use
d a
s re
fere
nce
P: 5
/43
(12)
;
FC: N
A; F
I:
1/17
(6)
;
C: 6
/44
(14)
P: 7
/43
(17)
;
FC: N
A; F
I:
4/17
(24
);
C: 0
/44
(0)
Incr
ease
d r
ate
of O
B
(24%
) in
ch
ildre
n
wit
h F
I, ve
rsu
s
con
trol
s (0
%)
C, c
ontr
ol g
rou
p; F
I, fe
cal i
nco
nti
nen
ce; N
A, n
ot a
pp
licab
le; N
S, n
ot s
ign
ifi ca
nt;
OB
, ob
esit
y; O
W, o
verw
eigh
t; U
I, u
rin
ary
inco
nti
nen
ce.
* Sig
nifi
can
t d
iffe
ren
ce.
by guest on August 15, 2020www.aappublications.org/newsDownloaded from
PEDIATRICS Volume 138 , number 3 , September 2016 7
TABL
E 4
Pre
vale
nce
of
Ove
rwei
ght,
Ob
esit
y, a
nd
FD
Ds
in P
edia
tric
Pop
ula
tion
-Bas
ed S
tud
ies
Stu
dy
Cou
ntr
yP
opu
lati
on
(P)
Defi
nit
ion
FC
an
d M
easu
rem
ent
n (
%)
FCn
(%
) FI
Defi
nit
ion
OW
/OB
and
Mea
sure
men
t
n (
%)
OW
n (
%)
OB
Con
clu
sion
Com
men
ts
Ph
atak
et
al
2014
US
A, p
edia
tric
an
d
adol
esce
nt
clin
ic
and
pri
vate
ped
iatr
ic p
ract
ice;
Pri
mar
y ca
re
cen
ters
n =
450
;
4–18
y;
♂:45
%
Rom
e III
cri
teri
a; A
sses
sed
usi
ng
qu
esti
onn
aire
(in
terv
iew
)
P: 8
0/45
0 (1
8);
NW
: 36/
259
(14)
; OW
/OB
:
44/1
91 (
23)
NA
OW
: BM
I 85t
h–
95th
per
cen
tile
OB
: BM
I>95
th
per
cen
tile
;
Wei
ght
and
hei
ght
wer
e
mea
sure
d;
Sta
nd
ard
dat
a fr
om t
he
Cen
ters
for
Dis
ease
con
trol
and
Pre
ven
tion
wer
e u
sed
as
refe
ren
ce
P: 6
8/45
0
(15)
;
FC: N
A;
non
-FC
:
NA
P: 1
23/4
50
(27)
; FC
:
NA;
non
-
FC: N
A
Pro
bab
ility
of
hav
ing
FC
in O
W/O
B
pop
ula
tion
23%
vs
14%
in N
W
pop
ula
tion
(OR
=1.
83,
P =
.01)
In t
he
text
of
the
arti
cle
by
Ph
atak
et
al,
13%
of
NW
child
ren
are
men
tion
ed t
o
hav
e FC
, in
th
e
tab
le o
f th
is
sam
e ar
ticl
e
this
nu
mb
er
is r
epor
ted
to
be
13.9
% (
the
latt
er n
um
ber
is a
dop
ted
in t
his
syst
emat
ic
revi
ew).
Cos
ta e
t al
2011
Bra
zil,
cros
s-
sect
ion
al s
urv
ey
con
du
cted
at
sch
ools
n =
107
7;
10–
18 y
;
♂: 4
6%
Mod
ifi ed
Rom
e III
cri
teri
a,
com
bin
atio
n o
f p
edia
tric
and
ad
ult
cri
teri
a: ≥
2 of
the
follo
win
g: 2
or
few
er
def
ecat
ion
s in
th
e to
ilet
per
wee
k, a
his
tory
of
pai
nfu
l
or h
ard
bow
el m
ovem
ents
,
har
d s
tool
s th
at r
esem
ble
d
a sa
usa
ge b
ut
hav
e cr
acks
on t
hei
r su
rfac
e or
sep
arat
e
har
d lu
mp
s, a
sen
sati
on o
f
inco
mp
lete
eva
cuat
ion
, a
his
tory
of
larg
e d
iam
eter
stoo
ls t
hat
may
ob
stru
ct t
he
toile
t, a
nd
a h
isto
ry o
f fe
cal
inco
nti
nen
ce.;
Asse
ssed
usi
ng
valid
ated
qu
esti
onn
aire
P: 1
96/1
077
(18)
;
NW
: 168
/933
(18)
; OW
:
28/1
44 (
19)
P: 2
5/10
77
(2);
FN
RFI
:
3/10
77 (
0);
FC: 2
2/19
6
(11)
; FC
+
FI: O
W: 8
/28
(29)
; non
-
OW
: 14/
168
(8);
FN
RFI
:
OW
: NA;
non
-
OW
: NA
OW
: BM
I ≥85
th
per
cen
tile
;
OB
: NA;
Wei
ght
and
hei
ght
asse
ssed
usi
ng
qu
esti
onn
aire
;
Sta
nd
ard
dat
a fr
om t
he
Cen
ters
for
Dis
ease
Con
trol
and
Pre
ven
tion
wer
e u
sed
as
refe
ren
ce
P: 1
44/1
077
(14%
); F
C:
28/1
96
(14)
;
non
-FC
:
116/
881
(13)
; FI:
NA;
non
-FI:
NA
NA
No
sign
ifi ca
nt
dif
fere
nce
bet
wee
n
BM
I of
adol
esce
nts
wit
h/w
ith
out
FC (
med
ian
s:
19.4
vs
19.3
kg/m
2 ,
P =
.941
).
Ther
e w
as a
sign
ifi ca
nt
asso
ciat
ion
bet
wee
n F
C-
asso
ciat
ed
FI a
nd
OW
(OR
4.4
0, P
=
.005
).
Acco
rdin
g to
the
tab
le,
the
nu
mb
er
of c
hild
ren
wit
h O
W in
the
stu
dy
pop
ula
tion
is 1
44 (
and
not
145
as
men
tion
ed in
the
arti
cle)
.
8/28
ch
ildre
n
wit
h F
C a
nd
FI w
ere
OW
,
the
auth
ors
rep
orte
d t
hat
this
was
37%
,
bu
t ac
cord
ing
to o
ur
calc
ula
tion
s
this
sh
ould
be
29%
. Au
thor
s
stat
e th
at t
he
qu
esti
onn
aire
is v
alid
ated
,
bu
t d
o n
ot
pro
vid
e a
refe
ren
ce.
by guest on August 15, 2020www.aappublications.org/newsDownloaded from
KOPPEN et al
incontinence. Of these 17 children with fecal incontinence, 14 (82%) were found to have FC based on the Rome III criteria. The authors compared children with incontinence (both urinary incontinence and fecal incontinence) to 44 matched healthy controls. There was no statistically significant difference in FC prevalence between BMI groups. In children with fecal incontinence (both FNRFI and FC-associated fecal incontinence), the rate of obesity was high (24%) compared with controls (0% obese, 14% overweight; no statistical analysis reported).
Group 3: Prevalence of Overweight, Obesity, and FDDs in Pediatric Population-Based Studies
In a survey study among 450 healthy children in the United States, Phatak et al 9 found that FC was significantly more prevalent in overweight and obese children (44/191, 23%) than in normal-weight children (36/259, 14%). 9 The odds ratio for having FC in the combined overweight and obese population was 1.83 (P = .01). An important feature of this study was that a logistic regression analysis was performed after including factors such as age, gender, ethnicity, and recruitment site.
Costa et al 32 performed a study in 1077 adolescents (10–18 years) in Brazil. They defined constipation according to a combination of pediatric and adult Rome III criteria ( Table 4). Overweight was defined as a BMI >85th percentile, and this study did not differentiate further between obesity and overweight. They found no association between overweight and constipation in adolescents. However, in a subanalysis in constipated adolescents, an association between overweight and fecal incontinence was confirmed; fecal incontinence occurred in 8/28 (29%) of overweight patients versus 14/168 (8%) in nonoverweight patients.
In the most recent study on this topic, our research group investigated
2820 Colombian school children by using a Spanish translation of the Questionnaire on Pediatric Gastrointestinal Symptoms-Rome III Version and anthropometric measurements. 21 In this sample, FC was not significantly more prevalent in children who were obese (28/188, 15%) or overweight (71/542, 13%) compared with children with normal weight (269/2090, 13%).
Quality Assessment
Quality assessment tools from the NHLBI were used to assess the methodological quality of the included studies ( Tables 5 and 6). Outcomes were used to assess the internal validity and risk of bias for each study and the overall quality was rated as good, fair, or poor. Only 1 study had an overall rating of good. 9 Four studies were rated fair, 12, 13, 21, 31 and the remaining 3 articles were rated poor. 28, 30, 32 In general, studies lacked sample size justification, some studies did not differentiate between overweight and obesity and all but 1 study did not adjust for key potential confounding variables. In addition, some items of the quality assessment tools were not reported across studies ( Tables 5 and 6).
DISCUSSION
This systematic review could not confirm or refute the association between FDDs and overweight/obesity because results are conflicting across the studies.
Both studies in obesity clinics revealed a high prevalence (21%–23%) of FC compared with the general population (3%–16%), and 2 out of 3 case-control studies in children with defecation disorders revealed a higher prevalence of overweight and obesity in patients with FDD (12%–33% and 17%–20%, respectively) compared with controls (13%–23% and 0%–12%, respectively). On the other hand,
8
Stu
dy
Cou
ntr
yP
opu
lati
on
(P)
Defi
nit
ion
FC
an
d M
easu
rem
ent
n (
%)
FCn
(%
) FI
Defi
nit
ion
OW
/OB
and
Mea
sure
men
t
n (
%)
OW
n (
%)
OB
Con
clu
sion
Com
men
ts
Kop
pen
et
al
2016
Col
omb
ia, c
ross
-
sect
ion
al s
tud
y
con
du
cted
at
sch
ools
n =
282
0;
8–18
y;
♂: 5
2%
Rom
e III
cri
teri
a; A
sses
sed
usi
ng
a S
pan
ish
tra
nsl
atio
n o
f th
e
Qu
esti
onn
aire
on
Ped
iatr
ic
Gas
troi
nte
stin
al S
ymp
tom
s-
Rom
e III
Ver
sion
(Q
PG
S-R
III)
P: 3
68/2
820
(13)
;
NW
: 269
/209
0
(13)
; OW
:
71/5
42 (
13);
OB
: 28/
188
(15)
NA
OW
: BM
I z s
core
bet
wee
n +
1
and
+2;
OB
: BM
I
z sc
ore
> +
2;
Wei
ght
and
hei
ght
wer
e
mea
sure
d;
WH
O r
efer
ence
valu
es w
ere
use
d
P: 5
42/2
820
(19)
; FC
:
71/3
68
(19)
;
non
-FC
:
471/
2452
(19)
P: 1
88/2
820
(7);
FC
:
28/3
68
(8);
non
-FC
:
160/
2452
(7)
No
asso
ciat
ion
bet
wee
n F
C
and
OW
/OB
was
fou
nd
C, c
ontr
ol g
rou
p; F
I, fe
cal i
nco
nti
nen
ce; N
A, n
ot a
pp
licab
le; N
W, n
orm
al w
eigh
t; O
B, o
bes
ity;
OW
, ove
rwei
ght.
TABL
E 4
Con
tin
ued
by guest on August 15, 2020www.aappublications.org/newsDownloaded from
PEDIATRICS Volume 138 , number 3 , September 2016 9
TABLE 5 NHLBI Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies
Fishman et al Van der Baan-
Slootweg et al
Phatak et al Costa et al Koppen et al
1. Was the research question or objective in this paper clearly stated? Yes Yes Yes Yes Yes
2. Was the study population clearly specifi ed and defi ned? Yes Yes Yes Yes Yes
3. Was the participation rate of eligible persons at least 50%? Yes Yes CD CD Yes
4. Were all the subjects selected or recruited from the same or similar
populations (including the same time period)? Were inclusion and
exclusion criteria for being in the study prespecifi ed and applied
uniformly to all participants?
Yes Yes Yes Yes Yes
5. Was a sample size justifi cation, power description, or variance and effect
estimates provided?
No No No No No
6. For the analyses in this paper, were the exposure(s) of interest measured
prior to the outcome(s) being measured?
Yes Yes No No No
7. Was the time frame suffi cient so that one could reasonably expect to see
an association between exposure and outcome if it existed?
No No No No No
8. For exposures that can vary in amount or level, did the study examine
different levels of the exposure as related to the outcome (eg, categories
of exposure, or exposure measured as continuous variable)?
No No Yes No Yes
9. Were the exposure measures (independent variables) clearly defi ned,
valid, reliable, and implemented consistently across all study participants?
CD CD Yes No Yes
10. Was the exposure(s) assessed more than once over time? No No No No No
11. Were the outcome measures (dependent variables) clearly defi ned, valid,
reliable, and implemented consistently across all study participants?
Yes Yes Yes Yes Yes
12. Were the outcome assessors blinded to the exposure status of
participants?
NR NR NR NR NR
13. Was loss to follow-up after baseline 20% or less? NA NA NA NA NA
14. Were key potential confounding variables measured and adjusted
statistically for their impact on the relationship between exposure(s) and
outcome(s)?
No No Yes No No
Rating Fair Fair Good Poor Fair
Available at: http:// www. nhlbi. nih. gov/ health- pro/ guidelines/ in- develop/ cardiovascular- risk- reduction/ tools/ cohort). CD, cannot determine; NA, not applicable; NR, not reported.
TABLE 6 NHLBI Quality Assessment of Case-Control Studies
Kavehmanesh et al Teitelbaum et al Wagner et al
1. Was the research question or objective in this paper clearly stated and
appropriate?
Yes Yes Yes
2. Was the study population clearly specifi ed and defi ned? Yes Yes Yes
3. Did the authors include a sample size justifi cation? No No No
4. Were controls selected or recruited from the same or similar population that gave
rise to the cases (including the same time frame)?
Yes CD CD
5. Were the defi nitions, inclusion and exclusion criteria, algorithms, or processes
used to identify or select cases and controls valid, reliable, and implemented
consistently across all study participants?
No Yes Yes
6. Were the cases clearly defi ned and differentiated from controls? No Yes Yes
7. If less than 100% of eligible cases and/or controls were selected for the study, were
the cases and/or controls randomly selected from those eligible?
NR NR NR
8. Was there use of concurrent controls? CD CD CD
9. Were the investigators able to confi rm that the exposure/risk occurred prior to the
development of the condition or event that defi ned a participant as a case?
CD CD CD
10. Were the measures of exposure/risk clearly defi ned, valid, reliable, and
implemented consistently (including the same time period) across all study
participants?
CD No Yes
11. Were the assessors of exposure/risk blinded to the case or control status of
participants?
NR NR NR
12. Were key potential confounding variables measured and adjusted statistically in
the analyses? If matching was used, did the investigators account for matching
during study analysis?
No No No
Rating Poor Poor Fair
Available at: http:// www. nhlbi. nih. gov/ health- pro/ guidelines/ in- develop/ cardiovascular- risk- reduction/ tools/ case- control. CD, cannot determine; NA, not applicable; NR, not reported.
by guest on August 15, 2020www.aappublications.org/newsDownloaded from
KOPPEN et al
only 1 of 3 population-based studies revealed evidence for an association.
There are multiple factors that may partially explain these different and conflicting results. As is shown in Tables 2, 3, and 4, the definitions of overweight and obesity differed among studies. Some studies have used the 85th and 95th percentiles of BMI for age and sex published in a study from the United States as cutoff points to identify overweight and obesity. 33 Other studies have used centile curves on the basis of data from multiple countries (the International Obesity Task Force cutoff values)34 or the Centers for Disease Control and Prevention growth charts. One study used the cutoff values provided by the World Health Organization (WHO), these gender-specific BMI-for-age percentile curves use z scores. 35 The WHO Child Growth Standards are now widely implemented worldwide in clinical care. 36, 37 It has been shown that using different definitions of overweight and obesity may lead to different results in epidemiologic studies. 38, 39 This could partially explain the different findings among the studies included in this systematic review. In addition, studies used different definitions for FDDs. Although in all studies, the diagnosis of FDDs was based on the Rome criteria, some used the Rome II criteria, others used the Rome III criteria, and some studies had modified the criteria. It has been shown that using different criteria can lead to major differences in the evaluation of the prevalence of FDDs. 40 Furthermore, only 1 study was rated to be of good quality on the basis of an assessment of the internal validity and risk of bias, whereas most studies were rated to be of fair or poor quality. Thus, most of these studies are at some risk of bias and should be interpreted with caution. Future high-quality studies are needed to shed more light on this issue.
Although evidence from studies performed in tertiary hospital settings seems indicative for an association between FC and overweight, evidence from population-based studies is much less convincing. Potentially, patients in tertiary care centers may not be representative of the population as a whole. These patients may represent a subset of patients with risk factors for FDDs and overweight/obesity that were not accounted for in the studies.
Lifestyle factors such as diet and a physical activity are assumed to play an important role in the pathophysiology of both FC and overweight, 20, 26, 41 – 44 which may explain why some studies have revealed an association between these disorders. For overweight and obesity, the pathophysiological importance of dietary factors (eg, high-caloric diet and low fiber intake) and a sedentary lifestyle is well recognized. 20, 45 – 49 Therefore, treatment of childhood obesity mainly consists of dietary and physical activity modifications, often utilizing behavioral interventions. 50, 51 The suggested role of dietary factors, especially the role of fiber, in the pathogenesis of FC is generally well-accepted, although pediatric data are scarce.20, 25, 41, 42, 52 The pathophysiological role of physical exercise is less well described and may be disputable.25, 26, 43, 44 Studies on fiber supplementation in the treatment of FC in children have resulted in conflicting results 53 and no randomized controlled trials on the effect of increased physical activity on FC in children have been performed.54 Interestingly, studies conducted in developed countries (Germany, the Netherlands, and the United States) seem to demonstrate an association between FDDs and excessive bodyweight, whereas studies in developing countries (Brazil, Colombia, and Iran) were unable to confirm this finding. This
raises the question whether there are pathophysiological differences between developing countries and more economically developed countries regarding the association between FDDs and excessive body weight. Possible shared etiological factors involved in the pathogenesis of overweight/obesity and FDDs are eating behavior, low fiber intake, physical exercise, hormonal dysfunction, gut microbiota, genetic predisposition, psychological factors, and socioeconomic status. 1, 9, 13, 16, 21 Many of these factors likely differ between developed and developing countries. Potentially, a high-calorie, high-fat, low-fiber diet and a sedentary lifestyle, which are common in developed countries, impact body weight and FDDs differently compared with lifestyle habits in developing countries.
One other potential pathophysiological factor that has been under increased attention over the past decades is the gut microbiota. It has been well established that obesity is associated with changes in the composition of the gut microbiota. 55 – 62 Studies in mice and humans strongly suggest that the gut microbiota plays an important role in energy metabolism and that there is a causative role for the microbiota in the development of obesity. 55, 56, 61 Gut microbiota involvement in children with constipation has also been suggested. 63 Although it is yet unclear whether the gut microbiota plays a causative role, it has been suggested that biochemical substances related to the gut microbiota may influence motility. 8, 63 – 66 It is highly likely that dietary factors also play an important role in these microbiota-associated biochemical processes. 67 –69 However, further studies in this field are needed to further elucidate the association between the gut microbiota, FDDs, and excessive body weight.
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Several studies specifically revealed that fecal incontinence (FNRFI, FC-associated fecal incontinence, and fecal incontinence not otherwise specified) was more common in children with excessive body weight. 13, 30 – 32 However, not all included studies reported on fecal incontinence; therefore, it is difficult to draw firm conclusions from these pediatric data. A high prevalence of fecal incontinence has been previously described in obese adults, and in the adult population fecal incontinence may improve after weight loss due to bariatric surgery.70, 71 The underlying pathophysiological mechanism behind this association is incompletely understood, but it has been hypothesized that this is due to pelvic floor dysfunction. 72, 73 Most likely, the excessive weight on the pelvic floor causes direct mechanical and neurologic dysfunction together with indirect effects of obesity such as diabetes, nerve conduction abnormalities, and intervertebral disc herniation. 71, 72 Whether the same mechanisms apply in children is yet to be sought out. These findings warrant further studies, especially because fecal incontinence is known to have a major negative impact on quality of life. 5, 6
This is the first systematic review evaluating the association between FDDs and overweight/obesity in children. Because both FDDs and overweight/obesity are such significant pediatric health care
problems, it is of key importance to investigate a potential association between them to improve pediatric health care worldwide. However, there are some limitations to this systematic review. First of all, the included studies have adopted a variance of definitions for FDDs and overweight/obesity and are conducted in different settings using different study designs; therefore, it is difficult to draw firm conclusions. Moreover, we were unable to perform a quantitative analysis due to the heterogeneity of the data. By including only articles written in English, this systematic review is at risk for some level of selection bias. However, we consider this risk to be very low, because most relevant literature is likely published in English. Finally, there is a potential risk of publication bias, although negative studies were identified and included in this systematic review, we may potentially have been unable to identify unpublished negative data.
CONCLUSIONS
Although several studies have reported on the potential association between FDDs and excessive body weight in children, the results from studies included in this systematic review are conflicting. Moreover, only 1 study was rated to be of good quality on the basis of an assessment of the internal validity and risk of bias, whereas most studies were rated to be of fair or poor quality.
Therefore, we cannot draw firm conclusions. There is a need for high quality prospective cohort studies using uniform definitions and well-defined inclusion and exclusion criteria according to accepted guidelines.
Future studies assessing the association between FDDs and overweight in children should aim to further investigate the role of factors such as dietary factors, physical exercise, and psychological factors. Furthermore, the differences in study results between developed and developing countries warrants further investigation into the role of social economic status and the indirect consequences thereof. In addition, the potential risk of pelvic floor dysfunction in obese children needs to be sought out further. Finally, the field of microbiome studies is relatively young, but very promising and future studies investigating the potential role of the gut microbiota would seem to be of much interest.
FINANCIAL DISCLOSURE: The authors have indicated they have no fi nancial relationships relevant to this article to disclose.
FUNDING: Dr Koppen received fi nancial support from The Royal Netherlands Academy of Arts and Sciences (Academy Ter Meulen Grant) and the European Society
for Pediatric Gastroenterology, Hepatology, and Nutrition (Charlotte Anderson Travel Award) to conduct this research.
POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential confl icts of interest to disclose.
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DOI: 10.1542/peds.2016-1417 originally published online August 16, 2016; 2016;138;Pediatrics
Benninga, Faridi S. van Etten-Jamaludin and Merit M. TabbersIlan J.N. Koppen, Sophie Kuizenga-Wessel, Miguel Saps, Carlo Di Lorenzo, Marc A.
ReviewFunctional Defecation Disorders and Excessive Body Weight: A Systematic
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