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Functional defecation disorders in children
Associated comorbidity and advances in management Kuizenga-Wessel, S. Publication date 2017 Document Version Other version License Other Link to publicationCitation for published version (APA):
Kuizenga-Wessel, S. (2017). Functional defecation disorders in children: Associated comorbidity and advances in management.
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FUNCTIONAL
DEFECATION DISORDERS
AND EXCESSIVE
BODY WEIGHT
A systematic review
I.J.N. Koppen, S. Kuizenga-Wessel, M. Saps, C. Di Lorenzo, M.A. Benninga,
F.S. van Etten–Jamaludin, M.M. Tabbers
Pediatrics. 2016,138(3):e20161417
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.
Study selection
PubMed, Medline, and Embase were searched from inception until January 25, 2016. 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%, respec-tively), 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. 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.
Ob es ity a nd F D D s 3
INTRODUCTION
Functional defecation disorders (FDDs) are commonly encountered in pediatric health care and comprise functional constipation (FC) and functional nonre-tentive 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 chil-dren in the general population.2 FDDs are diagnosed according to the
interna-tionally 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, behav-ioral, 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 over-weight 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 socio-economic 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 co-occurrence 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 Head-ings (MeSH) for PubMed and Medline and Emtree terms for Embase. Search terms 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.
Table 1 Rome III criteria for pediatric functional constipation
Diagnostic criteria must include must include:
- Two or more criteria for at least 1 months in infants up to 4 years
- Two or more symptoms for at least once per week for at least 2 months in children of at least 4 years
1 Two or fewer defecations per week
2 At least one episode of fecal incontinence per week
3 History of retentive posturing or excessive stool retention
4 History of painful or hard bowel movements
5 Presence of a large fecal mass in the rectum
6 History of large diameter stool that may obstruct the toilet
Ob es ity a nd F D D s 3
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 crosssectional 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 inde-pendently 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 disagree-ment, 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 inobese 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 over-weight/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 FDDS IN OBESE CHILDREN
Fishman et al13 administered a self-developed bowel questionnaire to 80
consec-utive pediatric patients presenting at an obesity clinic. They found a preva-lence of FC of 23%, which was higher than the previously reported prevapreva-lence of 8.9% in the general population. They also observed that 12 (15%) obese chil-dren 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.
* Two studies were excluded due to insufficient details on the outcomes of interest: Kiefte et al.52
was excluded due to insufficient 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 over-weight was almost similar in children with and without constipation (8% vs. 11%; p=0.46, 13% vs. 10%; P=0.10 and 8% vs. 9%; P=0.60 at the age of 24, 36 and 48 months, respectively). More information
is not available. Chien et al.53 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. Further-more, in this study an odds ratio was reported without a confidence 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.
Records identified through database searching
(n = 2284)
Additional records identified through other sources
(n = 0)
Records after duplicates removed (n = 1496)
Records screened (n = 1496)
Full-text articles assessed for eligibility
(n = 34)
Studies included in qualitative synthesis
(n = 8)
Full-text articles excluded, with reasons
(n = 26)
no cross-sectional or prospective study design: n=7 no clear criteria FDDs oroverweight/obesity: n=5 no data reported concerning association between FDDs and overweight/obesity: n=2 adult population: n=1
underlying disease/disorder: n=2 (studies in children with eating disorders) no full text in English available: n=2 conference abstracts: n=5
excluded based on insufficient information on primary outcome measures: n=2*
Records excluded (n = 1462) Studies included in quantitative synthesis (meta-analysis) (n = 0) Scr een in g In cl ud ed El igibi lity Id en tif ic ati on
Ob es ity a nd F D D s 3
Van der Baan-Slootweg et al12 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%)
chil-dren with constipation and in 6 (8%) chilchil-dren 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 differ-ence was found between the diet of children with or without constipation, including regarding fiber and fat intake.
GROUP 2 OVERWEIGHT AND OBESITY IN CHILDREN WITH FDDS
In a prospective case control study, Kavehmanesh et al 28 compared 124 chil-dren 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 signif-icant. 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 al30 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), 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 compari-sons). 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).
Table 2 Prevalence of functional defecation disorders in obese children Au th or , ye ar Co un tr y, se tt in g Po pu la tio n (P ) Co nt ro ls (C ) D ef in iti on O W /O B an d m ea su re m en t D ef in iti on F C an d m ea su re m en t n ( % ) F C n ( % ) F I Co nc lu si on Co m m en ts Fi sh m an et a l. 20 04 U SA , pr os pe ct iv e ob se rva -tio na l s tu dy at o be sit y cl in ic Te rt ia ry ca re c en te r n= 80 1-18 y ea rs ♂ : 3 9% n/ a O W : n /a OB : B M I > 9 5 th p er ce nt ile W ei gh t a nd h ei gh t m ea su re m en ts N ot r ep or te d w hi ch re fe re nc e va lu es w er e used 2 o r m or e o f t he f ol lo w in g, ≥2 5% o f t he t im e, ≥3 m on th s: ha rd o r p el le t-like s to ol s, in fre qu en t s to ol s ( le ss t ha n 3 p er w ee k) , s tr ai ni ng , pa in fu l d ef ec at io n, o r s en se of i nc om pl et e e va cu at io n. So ili ng w as d ef in ed a s p re s-en ce o f f ec al m at er ia l i n un de rw ea r o r p a ja m as i n a ch ild o ld er t ha n 48 m on th s of a ge f or a t l ea st 3 m on th s A ss es se d w ith s ta nd ar di ze d qu es tio nn ai re 18 /8 0 ( 23 % ) To ta l: 12 /8 0 ( 15 % ) -F N RF I 1: 6 /8 0 ( 8% ) FC : 6 /1 8 ( 33 % ) Pr eva le nc e o f F C i n O B c hi l-dr en ( 23 % ) h ig he r t ha n p re vi ou s re po rt s ( 3-16 % ) BM I a d ju st ed f or a ge a nd ge nd er , n ot r ep or te d w hi ch re fe re nc e va lu es w er e u se d D isc re pa nc y n um be r o f m al es : 3 0 a cc or di ng t o t ex t an d 31 a cc or di ng t o t ab le ) Va n d er Ba an – Sl oo tw eg et a l. 20 11 Th e N et h-er la nd s, pr os pe ct iv e ob se rva -tio na l s tu dy at o be sit y cl in ic Te rt ia ry ca re c en te r n= 91 8-18 y ea rs ♂ : 3 4% n/ a O W : n /a O B: B M I ≥3 5, o r B M I ≥3 0 i n t he p re se nc e of o be sit y-re la te d mo rb id ity M et ho ds o f a nt hr op o-m et ric d at a c ol le ct io n no t r ep or te d Re fe re nc e va lu es ba se d o n t he I nt er -na tio na l O be sit y T as k Fo rc e: t o o bt ai n t he cu rv e c or re sp on di ng to a n a du lt B M I o f 35 , th e d iff er en ce o f t he di st an ce o f t he 25 a nd 30 c ur ve s w as a dd ed to t he 30 c ur ve Ro m e I II c rit er ia A ss es se d w ith s ta nd ar di ze d qu es tio nn ai re 19 /9 1 ( 21 % ) To ta l: 5/ 91 ( 5% ) -F N RF I 1: 1 /9 1 ( 1% ) FC : 4 /1 9 ( 21 % ) H ig he r f re qu en cy o f F C i n ch ild re n w ith o be sit y ( 21 % ) co m pa re d t o w or ld w id e p re va -le nc e ( 8. 9% )
Ob es ity a nd F D D s 3 Table 3 Prevalence of overweight and obesity in children with functional
defecation disorders St ud y C ou nt ry , se tt in g Po pu la -tio n ( P) C on tr ol s (C ) D ef in iti on F C an d m ea su re m en t D ef in iti on O W /O B an d m ea su re m en t n ( % ) FC n ( % ) FI n ( % ) OW n ( % ) OB Co nc lu si on Co m m en ts Ka ve h-m an es h et a l. 20 13 Ira n, pr os pe ct iv e ca se c on tr ol st ud y i n c hi l-dr en a dm itt ed to t he h os pi ta l Te rt ia ry c ar e ce nt er n= 12 4 2-14 y ea rs ♂ : 5 2% Pa tie nt s ad m itt ed w ith F C sy m pt om s n= 13 5 ♂ : 5 2% Pa tie nt s in th e sa m e ag e gr ou p, wi th ou t FC o r we ig ht /h ei gh t aff ec tin g di se as e Ro m e I I c rit er ia A ss es se d u sin g se lf-de ve lo pe d qu es tio nn ai re O W : B M I > 85 th p er ce nt ile O B: B M I > 95 th p er ce nt ile M et ho ds o f a nt hr op o-m et ric d at a c ol le ct io n no t r ep or te d N ot r ep or te d w hi ch re fe re nc e va lu es w er e used P: 1 24 /1 24 (1 00 % ) C: n /a P: 3 1/ 12 4 (2 5% ) C: n /a P: 4 1/ 12 4 (3 3% ) C : 3 1/ 13 5 (2 3% ) P: 2 2/ 12 4 (1 8% ) C: 1 6/ 13 5 (1 2% ) No s ig ni fic an t di ffe re nc e in pr ev al en ce o f O W /O B be twe en ch ild re n w ith /w ith ou t FC . Th er ef or e, n o cl ear as so ci at io n be tw een O W /OB a nd F C . Te ite l-ba um et a l. 20 09 U SA , pr os pe ct iv e ca se c on tr ol st ud y a t p ed i-at ric g as tr oe n-te ro lo gy c lin ic (G I g ro up ) Te rt ia ry c ar e ce nt er n= 75 7 2-20 y ea rs ♂ : 5 1% Pa tie nt s re fe rr ed t o pe di at ric ga st ro en te r-ol og ist ( G I gr ou p) C O N TR O L GR O U P 1 n= 25 5, ♂ : 5 1% He al th y ch ild re n wi th ou t un de r-ly in g ch ro ni c di se as e C O N TR O L G RO U P 2 n= 1, 43 6 ♂ : 4 9% , H ig h sc ho ol st ud en ts Ro m e I II c rit er ia M et ho ds o f d at a co lle ct io n n ot re po rt ed OW : B M I 8 5-95 th p er ce nt ile O B: B M I ≥9 5 th p er ce nt ile Fo r t he G I g ro up a nd co nt ro l g ro up 1 w ei gh t an d h ei gh t w er e m ea su re d . Fo r c on tr ol g ro up 2, w ei gh t a nd he ig ht w er e s el f-re po rt ed . N ot r ep or te d w hi ch re fe re nc e v al ue s w er e used P: 1 96 /7 57 (2 6% ) C: n /a P: 1 26 /7 57 (1 7% ) -F NR FI : 71 /7 57 (9 % ) FC : 5 5/ 19 6 (2 8% ) C 1: n/ a C 2: n /a P: 1 22 /7 57 (1 6% ) FC : 37 /1 96 (1 9% ) FI : 1 8/ 71 (2 5% ) FC +F I: 14 /5 5 (2 5% ) C 1: 32 /2 55 (1 3% ) C 2: 221/1, 43 6 (1 5% ) P: 1 52 /7 57 (2 0% ) FC : 4 5/ 19 6 (2 3% ) FI : 1 8/ 71 (2 5% ) FC +F I: 15 /5 5 (2 7% ) C 1: 21 /2 55 (8 % ) C 2: 163/1, 43 6 (1 1% ) Hi gh p re va le nc e of O W a nd O B in p at ie nt s w ith F D D O W in F C (1 9% ) v s C 1/ C 2 (1 3% /1 5% ): p-va lu e 0. 06 5/ 0. 21 0 (n s/ ns ) O B in F C ( 23 % ) vs C 1/ C 2 (8 % /1 1% ): p-va lu e <0 .0 01 */ <0 .0 01 * O W in F I ( 25 % ) vs C 1/ C 2 (1 3% /1 5% ): p-va lu e 0. 00 8* /0 .0 25 * O B (2 5% ) in F I v s C 1/ C 2 (8 % /1 1% ): p-va lu e: < 0. 00 1* /< 0. 00 1* O W in F C +F I ( 25 % ) vs C 1/ C 2 (1 3% /1 5% ): p-va lu e 0. 01 5* /0 .0 45 * O B in F C +F I ( 27 % ) vs C 1/ C 2 (8 % /1 1% ): p-va lu e <0 .0 01 */ <0 .0 01 * C on tr ol s w er e m at ch ed f or ag e a nd s ex , ac tu al a ge ra ng e n ot pr ov id ed . Th is s tu dy in cl ud ed c hi l-dr en > 18 y ea rs of a ge b ut < 21 ye ar s o f a ge . H ow ev er , t he m ea n a ge w as 9.6 ± 4. 6 y ea rs . W ag ne r et a l. 20 15 G er m an y, pr os pe ct iv e ca se c on tr ol st ud y a t p ed i-at ric g as tr oe n-te ro lo gy c lin ic Te rt ia ry c ar e ce nt er n= 43 5-12 y ea rs , ♂ : 5 8% Pat ie nt s re fe rr ed fo r F I o r UI n= 44 5-12 y ea rs ♂ : 5 5% C hi ld re n fro m l oc al sc ho ol s Ro m e III c rit er ia A ll ch ild re n re ce iv ed a ph ys ic al e xa m in a-tio n an d re ct al ul tra so un d OW : B M I 8 5-95 th p er ce nt ile O B: B M I ≥9 5 th p er ce nt ile W ei gh t a nd h ei gh t me as ur eme nt s St an da rd d at a f ro m th e C en te r f or D ise as e co nt ro l a nd P re ve nt io n w er e u se d a s r ef er en ce P: 2 0/ 43 (4 7% ) C: n /a P: 1 7/ 43 (4 0% ) -F NR FI : 3/ 43 ( 7% ) FC : 1 4/ 20 (7 0% ) C: n /a P: 5 /4 3 (1 2% ) FC : n /a FI : 1 /1 7 (6 % ) C : 6 /4 4 (1 4% ) P: 7 /4 3 (1 7% ) FC : n /a FI : 4 /1 7 (2 4% ) C : 0 /4 4 (0 % ) In cr ea se d ra te o f O B (2 4% ) in ch ild re n w ith F I, ve rs us c on tro ls ( 0% )
Wagner et al31 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 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 incon-tinence and fecal inconincon-tinence) 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 inconti-nence), the rate of obesity was high (24%) compared with controls (0% obese, 14% overweight; no statistical analysis reported).
GROUP 3 OVERWEIGHT, OBESITY, AND FDDS IN PEDIATRIC POPULATION- BASED STUDIES
In a survey study among 450 healthy children in the United States, Phatak et al9 found that FC was significantly more prevalent in overweight and obese
children (44/91, 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 al32 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 sub-analysis in constipated adolescents, an association between over-weight and fecal incontinence was confirmed; fecal incontinence occurred in 8/28 (29%) of overweight patients versus 14/168 (8%) in non-overweight 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 chil-dren 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 method-ological 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
Ob es ity a nd F D D s 3
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).
Table 4 Prevalence of overweight, obesity and functional defecation
disorders in pediatric population-based studies
St ud y C ou nt ry , se tt in g Po pu la -tio n ( P) D ef in iti on F C an d m ea su re m en t D ef in iti on O W /O B an d m ea sur em en t n ( % ) FC n ( % ) FI n ( % ) OW n ( % ) OB Co nc lu si on Co m m en ts Ph at a k et a l. 20 14 U SA , pe di at ric an d a do le s-ce nt c lin ic an d p riva te pe di at ric pr ac tic e Pr im ar y ca re c en te rs n= 45 0 4-18 y ea rs ♂ :4 5% Ro m e I II c rit er ia A ss es se d u sin g q ue st io nn ai re (in te rv ie w ) OW : B M I 8 5-95 th p er ce nt ile OB : B M I> 95 th p er ce nt ile W ei gh t an d he ig ht we re me as ur ed St an da rd d at a fro m t he C en te r fo r D ise as e co nt ro l an d Pr ev en tio n we re u se d as r ef er en ce P: 80 /4 50 (1 8% ) N W : 3 6/ 25 9 (1 4% ) O W /O B: 44 /1 91 (2 3% ) n/ a P: 68 /4 50 (1 5% ) FC : n /a no n-FC : n/ a P: 12 3/ 45 0 (2 7% ) FC : n /a no n-FC : n/ a Pr ob ab ili ty o f ha vi ng F C i n O W / O B p op ul at io n 23 % vs 14 % i n n or m al w ei gh t p op ul at io n (O R= 1. 83 , p =0 .0 1) In t he t ex t o f t he a rt ic le b y Ph at ak e t a l., 13 % o f N W ch ild re n a re m en tio ne d to h av e F C , i n t he t ab le of t hi s s am e a rt ic le t hi s nu m be r i s r ep or te d t o b e 13 .9 % ( th e l at te r n um be r is a do pt ed i n t hi s s ys te m -at ic r ev ie w ). C os ta et a l. 20 11 Br a zi l, cr os s-se ct io na l su rv ey co nd uc te d at s ch oo ls n= 1, 07 7 10 -1 8 ye ar s ♂ : 4 6% M od ifi ed R om e I II c rit er ia , co m bi na tio n o f p ed ia tr ic an d a du lt c rit er ia : ≥ 2 o f t he fo llo w in g: 2 o r f ew er d ef ec a-tio ns i n t he t oi le t p er w ee k, a hi st or y o f p ai nf ul o r h ar d b ow el m ov em en ts , h ar d s to ol s t ha t re se m bl ed a s au sa ge b ut h av e cr ac ks o n t he ir s ur fa ce o r s ep a-ra te h ar d l um ps , a s en sa tio n of i nc om pl et e e va cu at io n, a hi st or y o f l ar ge d ia m et er s to ol s th at m ay o bs tr uc t t he t oi le t a nd a h ist or y o f f ec al i nc on tin en ce . A ss es se d u sin g v al id at ed q ue s-tio nn ai re OW : B M I ≥ 85 th p er ce nt ile OB : n /a W ei gh t an d he ig ht a ss es se d usi ng q ue st io nn ai re St an da rd d at a fro m t he C en te r fo r D ise as e co nt ro l an d Pr ev en tio n we re u se d as r ef er en ce P: 19 6/ 1, 07 7 (1 8% ) N W : 16 8/ 93 3 (1 8% ) O W : 2 8/ 14 4 (1 9% ) P: 25 /1 ,0 77 (2 % ) -F N RF I: 3/ 1, 07 7 (0 % ) FC : 2 2/ 19 6 (1 1% ) FC + F I: -O W : 8 /2 8 (2 9% ) -n on -O W : 14 /1 68 ( 8% ) FN RF I: -O W : n /a -n on -O W : n/ a P: 14 4/ 1, 07 7 (1 4% ) FC : 2 8/ 19 6 (1 4% ) no n-FC : 11 6/ 88 1 (1 3% ) FI : n /a no n-FI : n /a n/ a N o s ig ni fic an t d iff er -en ce b et w ee n B M I of a do le sc en ts w ith /w ith ou t F C (m ed ia ns : 1 9. 4 v s 19 .3 k g/ m 2, p =0 .94 1) . Th er e w as a s ig ni f-ic an t a ss oc ia tio n be tw ee n F C -a ss o-ci at ed F I a nd O W (O R 4. 40 , p =0 .0 05 ). A cc or di ng t o t he t ab le , t he nu m be r o f c hi ld re n w ith O W i n t he s tu dy p op ul a-tio n i s 14 4 ( an d n ot 14 5 a s m en tio ne d i n t he a rt ic le ). 8/ 28 c hi ld re n w ith F C a nd FI w er e O W , t he a ut ho rs re po rt ed t ha t t hi s w as 37 % , b ut a cc or di ng t o o ur ca lc ul at io ns t hi s s ho ul d be 29 % . A ut ho rs s ta te t ha t t he qu es tio nn ai re i s va lid at ed , bu t d o n ot p rov id e a re fe re nc e. Ko pp en et a l. 20 16 C ol om bi a , cr os s-se c-tio na l s tu dy co nd uc te d at s ch oo ls n= 2, 82 0 8 -18 ye ar s ♂ : 5 2% Ro m e I II c rit er ia A ss es se d u sin g a S pa ni sh t ra ns -la tio n o f t he Q ue st io nn ai re on P ed ia tr ic G as tr oi nt es tio na l Sy m pt om s-Ro m e I II V er sio n (Q PG S-RI II) O W : B M I z s co re b et w ee n +1 a nd + 2 OB : B M I z s co re > + 2 W ei gh t an d he ig ht we re me as ur ed W H O r ef er en ce v al ue s we re u se d P: 36 8 ( 13 % ) N W : 26 9/ 2, 09 0 (1 3% ) O W : 7 1/ 54 2 (1 3% ) O B: 28 /1 88 (1 5% ) n/ a P: 54 2 (1 9% ) FC : 7 1/ 36 8 (1 9% ) no n-FC : 47 1/ 2, 45 2 (1 9% ) P: 18 8 (7 % ) FC : 2 8/ 36 8 (8 % ) no n-FC : 16 0/ 2, 45 2 (7 % ) N o a ss oc ia tio n be tw ee n F C a nd O W / O B w as f ou nd
Ob es ity a nd F D D s 3 Table 5 NHLBI Quality Assessment Tool for Observational Cohort
and Cross-Sectional Studies
v/ d B aa n-Sl oo tw eg e t a l. Fi sh m an et a l. Co st a et a l. Ph at ak et a l. Ko pp en et a l.
1 Was the research question or objective in this paper clearly stated? Yes Yes Yes Yes Yes 2 Was the study population clearly specified and defined? 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 prespecified and applied uniformly to all participants?
Yes Yes Yes Yes Yes
5 Was a sample size justification, 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 timeframe sufficient 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 (e.g., categories of exposure, or exposure measured
as continuous variable)?
No No No Yes Yes
9 Were the exposure measures (independent variables) clearly defined, valid, reliable, and implemented consistently across all study participants?
CD CD No Yes 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
defined, 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 No Yes No
Rating Fair Fair Poor Good 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 Ka ve hm an es h et a l. Te ite lb au m et a l. Wa gn er e t a l.
1 Was the research question or objective in this paper clearly stated and appropriate?
Yes Yes Yes 2 Was the study population clearly specified and defined? Yes Yes Yes 3 Did the authors include a sample size justification? No No No 4 Were controls selected or recruited from the same or similar population
that gave rise to the cases (including the same timeframe)?
Yes CD CD 5 Were the definitions, 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 defined and differentiated from controls? No Yes Yes 7 If less than 100 percent 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 confirm that the exposure/risk occurred
prior to the development of the condition or event that defined a participant as a case?
CD CD CD
10 Were the measures of exposure/risk clearly defined, valid, reliable, and implemented consistently (includingthe 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-reduc-tion/tools/case-control. CD, cannot determine; NA, not applicable; NR, not reported
Ob es ity a nd F D D s 3
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%, respec-tively) compared with controls (13%–23% and 0%–12%, respecrespec-tively). On the other hand, 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 over-weight 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 Inter-national 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 differ-ences 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 over-weight/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
phys-ical 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 predis-position, psychological factors, and socioeconomic status.1, 9, 13, 16, 21
Many of these factors likely differ between developed and developing coun-tries. 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 estab-lished 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
Ob es ity a nd F D D s 3
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 micro-biota 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 associ-ation between the gut microbiota, FDDs, and excessive body weight.
Several studies specifically revealed that fecal incontinence (FNRFI, FC-associ-ated 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 inconti-nence has been previously described in obese adults, and in the adult popula-tion fecal incontinence may improve after weight loss due to bariatric surgery.70, 71
The underlying pathophysiological mechanism behind this association is incom-pletely 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 herni-ation. 71, 72 Whether the same mechanisms apply in children is yet to be sought
out. These findings warrant further studies, especially because fecal inconti-nence 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 inves-tigate 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 exclu-sion 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 differ-ences 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 micro-biome studies is relatively young, but very promising and future studies inves-tigating the potential role of the gut microbiota would seem to be of much interest.
Ob es ity a nd F D D s 3
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