Post-Operative Anorectal Manometry in Children following Anorectal Malformation Repair: A Systematic Review

Despite surgical correction, children with anorectal malformations may experience long-term bowel dysfunction, including fecal incontinence and/or disorders of evacuation. Anorectal manometry is the most widely used test of anorectal function. Although considerable attention has been devoted to its application in the anorectal malformation cohort, there have been few attempts to consolidate the findings obtained. This systematic review aimed to (1) synthesize and evaluate the existing data regarding anorectal manometry results in children following anorectal malformation repair, and (2) evaluate the manometry protocols utilized, including equipment, assessment approach, and interpretation. We reviewed four databases (Embase, MEDLINE, the Cochrane Library, and PubMed) for relevant articles published between 1 January 1985 and 10 March 2022. Studies reporting post-operative anorectal manometry in children (<18 years) following anorectal malformation repair were evaluated for eligibility. Sixty-three studies were eligible for inclusion. Of the combined total cohort of 2155 patients, anorectal manometry results were reported for 1755 children following repair of anorectal malformations. Reduced resting pressure was consistently identified in children with anorectal malformations, particularly in those with more complex malformation types and/or fecal incontinence. Significant variability was identified in relation to manometry equipment, protocols, and interpretation. Few studies provided adequate cohort medical characteristics to facilitate interpretation of anorectal manometry findings within the context of the broader continence mechanism. This review highlights a widespread lack of standardization in the anorectal manometry procedure used to assess anorectal function in children following anorectal malformation repair. Consequently, interpretation and comparison of findings, both within and between institutions, is exceedingly challenging, if not impossible. Standardized manometry protocols, accompanied by a consistent approach to analysis, including definitions of normality and abnormality, are essential to enhance the comparability and clinical relevance of results.


Introduction
Anorectal malformations represent a spectrum of anomalies affecting the anus, rectum, urinary, and/or genital tracts [1]. The fundamental aims of surgical correction remain consistent today with those described by Rudolph Matas in 1897: "the ideal result of this kind of operation is the restoration of the passage of stool, creating an anus in a normal position with bowel control" [2]. Outcomes with respect to bowel function have greatly improved alongside the evolution of operative repair techniques, most notably, following the advent of the posterior sagittal anorectoplasty [PSARP]) [3]. However, persistent bowel dysfunction, including constipation and fecal incontinence, continues to impact upon a significant proportion of patients long-term [4,5].
As the anal sphincter plays a critical role in both fecal continence and defecation, its function in children with persistent bowel problems after surgical procedures becomes a focal point for investigation. Anorectal manometry is the most widely used investigation to identify abnormalities of anorectal coordination and/or anal sphincter complex dysfunction [6]. The assessment typically comprises a combination of pressure measurements, including evaluation of involuntary function of the anal canal (at rest); voluntary function (squeeze); rectal balloon distension to determine the existence of the rectoanal inhibitory reflex (RAIR); rectoanal coordination during simulated defecation (push maneuver); and rectal sensation [6][7][8][9].
Despite extensive testing with anorectal manometry, the relationships between manometry results and patient symptoms remain poorly defined. In this review, we sought to summarize the methodology and outcomes of anorectal manometry performed in children following repair of anorectal malformations, to appraise current understanding of anorectal function, and guide future work in this cohort.

Methods
This systematic review was conducted in compliance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) [10]. A primary search was conducted in Embase, MEDLINE, PubMed, and the Cochrane Library in March 2020, and subsequently repeated in March 2022. The search was restricted to human studies published since 1st January 1985. The methodology was published prospectively on PROS-PERO (PROSPERO registration: CRD42020177344). The search strategy is summarized in Appendix A.

Study Selection
After removal of duplicate articles, title and abstract were assessed for eligibility independently by two authors (H.E.B. and M.Y.T.). Cohort studies, case studies, longitudinal studies, and clinical trials were included for review. Conference abstracts, meta-analyses, systematic reviews, animal studies, and in vitro studies were excluded.
The following inclusion criteria were utilized for abstract screening: anorectal manometry performed in children following surgical repair of an anorectal malformation, published in the English language. Studies reporting manometry outcomes in mixed populations (anorectal malformations and other conditions, mixed pediatric and adult cohorts) were included, provided results from children (aged 18 years or less) with anorectal malformations were reported separately in the final analysis. Studies reporting only the pre-operative use of anorectal manometry were excluded.

Data Extraction
Data were independently extracted by two authors (H.E.B. and M.Y.T.). Extracted cohort characteristics included patient sex; age at assessment; anorectal malformation type; associated anomalies; and post-operative bowel function, including assessment instruments and outcomes. With respect to manometry characteristics, extracted data points included manometry type, including catheter specifications; assessment protocol, including parameters assessed; and motility outcomes, including bowel function correlates. From the combined total cohort of 2155 patients, anorectal manometry results were reported for 1755 children (age range 2 months-18 years) with repaired anorectal malformations. The remainder were either part of a study with a mixed diagnostic cohort (and had a condition other than an anorectal malformation), and/or only a proportion of the cohort underwent anorectal manometry. The median manometry cohort size was 22 children (range . Insufficient data were provided to calculate the median age or sex ratio. Study characteristics are summarized in Table 1. Anorectal malformation type was specified for the majority of the cohort (1523/1755 children, 86.8%). The Krickenbeck and Wingspread anorectal malformation classification systems were the most frequently utilized [12,13]. The most frequently reported malformation types were, "high" (267 children); "rectoprostatic fistula" (198 children); and "intermediate" (169 children). The approach to operative repair type was reported for 1250/1755 (71.2%) children in the manometry cohort. Of these, the posterior sagittal anorectoplasty (PSARP) and its variants were the most commonly utilized procedures (868/1250, 69.4%), followed by laparoscopically assisted anorectoplasty (LAARP) (73/1250, 5.8%). Details regarding associated malformations (including sacrospinal anomalies) were provided by less than half of the studies identified for review (28/63, 44.4%). Cohort clinical characteristics are summarized in Table 1.

Quality Assessment
Only 12 included studies adequately addressed the criteria outlined in the Newcastle Ottawa Scale and were classified as "good quality". The majority were classified as "poor quality", predominately due to limitations identified in the "comparability" category. Quality evaluations are presented in Table S1.

Parameters
Assessment of a variety of anorectal manometry parameters was reported. The most commonly reported were resting pressure (anal, rectal or both) (55/63, 87%), rectoanal inhibitory reflex (RAIR) (52/63, 83%), and anal squeeze pressure (29/63, 46%). Reported parameters are summarized in Table 3. Criteria used to define assessed parameters were inconsistent; study definitions are summarized in Table S2.  [47]; not further specified.  1 Anorectal malformation type, as reported in original article. 2 Total cohort with anorectal malformation. 3 Refers to cohort of children undergoing post-operative anorectal manometry following anorectal malformation repair. 4 Good prognosis: specific malformation types (rectoperineal fistula, rectovestibular fistula, imperforate anus without fistula, rectal atresia, cloaca with common channel < 3 cm); associated with a prominent midline groove, suggestive of good perineal muscle, and a normal sacrum. 5 Six of 14 patients with megarectum underwent post-operative anorectal manometry. 6 Subgroup of children operated on at another hospital with normal bowel function excluded due to age >18 years. Other analyses included in the narrative synthesis. 7 Findings of the "high" malformation group excluded from synthesis due to inclusion of participants >18 years of age. 8 Table 1 listed a total of 29 patients, including eight patients following repair of rectovestibular fistula, which is greater than the total study number reported (n = 23). Table 2 (n = 23) reported two patients with rectovestibular fistulae: data taken from Table 2. 9 The number of patients reported to have undergone repair of rectovaginal fistulae differed in the article; data included as presented in Tables 1 and 2

Anorectal Manometry Outcomes
Studies demonstrated significant variation with respect to the equipment, assessment protocols, and parameter definitions utilized. As such, absolute values for manometry outcomes were not combined. Key findings and study limitations are summarized in Table 4; absolute values of consistently reported parameters are summarized in Table S2.
Reported absolute values of resting pressure varied between studies. Resting pressure ranged from 6.57 mmHg (measure of central tendency not described) in the incontinent group assessed by Martins et al. [50], to 75.75 ± 16.8 mmHg identified, using computerized vector manometry, by Schuster et al. [19]. Outcomes of anorectal manometry, including absolute values, are summarized in Table S2.
Resting pressure was consistently reduced in children with anorectal malformations, compared with either normative values obtained from healthy children [42,46,57,64] or other diagnostic groups [72]. More complex malformations were typically associated with lower resting pressures than less complex malformations [23,33,43,45,48,49,51,62,76], although this was not uniform [63]. Reduced resting pressure was frequently identified in the setting of fecal incontinence [25,37,39,40,45,46,[48][49][50][51]53,58,65,73,74,76]. With respect to obstructive symptoms, two studies identified significantly higher resting pressures in constipated than non-constipated patients [43,63], whilst another did not [58].      16 Resting and squeeze pressures of the puborectalis muscle: recorded in segments covering its anatomical location. 17 Sphincterial asymmetry: difference of resting and squeeze pressure >20% between four cardinal anal segments on 3D analysis. 18 Volume (mL) of rectal balloon inflation which elicited defecatory urge. 19 Resting anal pressure, resting rectal pressure, and anorectal pressure gradient. 20 Voluntary contraction pressure. 21 Resting rectal pressure. 22 It is unclear how anorectal manometry was used to facilitate assessment of active systolic blood pressure; calculation of rectal compliance was not defined. 23 Maximum anal canal static pressure. 24 LFS: length of internal functional sphincter. 25 Anorectal pressure difference: difference between maximum anal pressure (at anal verge) and resting rectal pressure. 26 Rectal pressure and maximum anal canal pressure. 27 Anorectal reflex: not further defined. 28 Resting rectoanal pressure gradient: the difference between the resting rectal pressure and the resting anal pressure. 29 Maximal mean segmental pressure at rest. 30 Vector volume: all sampled pressure values (as vectors) and anal canal length were combined, and the volume of the imaginary pressure cylinder was calculated. 31 Maximal mean segmental pressure at rest. 32 Maximal mean segmental pressure during squeeze. 33 Functional anal canal length: the distance between the anal verge and the proximal functional border of the anal canal, represented by the increased pressure of the muscular tube, compared to the baseline pressure in the rectum. 34 Vector volume: calculated volume of the imaginary pressure cylinder. 35 Inter-quadrant pressure asymmetry index (∆p): inter-quadrant pressure difference divided by the maximal quadrant pressure, expressed as a percentage. 36 Vector volume: direct representation of individual force of the anorectal contractile units; integration of pressure and length. 37 Voluntary contraction pressure. IAS: internal anal sphincter; LFS: length of internal functional sphincter; RAIR: rectoanal inhibitory reflex. Table 4. Summary of key anorectal manometry findings.

First Author Manometry Population Summary Summary of Key Anorectal Manometry Findings Key Limitations
Arnoldi [14] Toilet-trained children with anorectal malformations with a good predicted prognosis 38 • Significantly lower resting pressure (RP) in children with neurospinal dysraphism (ND) and/or children with a neonatal colostomy, than children without; RP in patients without ND or neonatal colostomy comparable to control children.

•
In patients with a pathologic Rintala score, RP was significantly lower and RAIR was identified in less than half; the reflex was identified in 100% of children with a normal Rintala score.
Exclusion based on toilet training status introduces potential selection bias (excluding children who may never attain continence); although the homogenous population is a strength, findings not generalizable to the wider anorectal malformation cohort.
Banasiuk [64] Children who had undergone surgery for anorectal disorders, including anal atresia • Lowest RP, squeeze pressure (SP), and pressure of the puborectalis muscle were observed in the anal atresia group; these parameters were significantly lower than healthy controls.

•
Patients with non-retentive fecal incontinence demonstrated significantly decreased RP compared to healthy controls.
Clinical characteristics, such as gender of diagnostic subgroups and operative repair type unknown; small, heterogenous anorectal malformation cohort: wide age range with diverse malformation types.
Becmeur [23] Children following three-flap anoplasty for primary or re-do repair Small, heterogeneous cohort; significant proportion of cohort with comorbidities likely to impact continence; very limited description of manometry methods/results.
Bhat [56] High or intermediate anorectal malformation, following sigmoid colostomy formation but prior to PSARP • Pre-PSARP mean rectal pouch pressure reported to be similar to the mean post-PSARP and post-colostomy closure anal canal pressures. Kelly's score (functional assessment) reported to be related to anal canal pressure.

•
The authors reported that these associations demonstrated the ability to predict post-operative continence pre-operatively.
Small cohort; associated anomalies not reported; limited description of statistical methods to support findings (e.g., correlation between anal canal pressures and Kelly score); short follow up period to support conclusion that post-operative continence may be predicted pre-operatively (median age 29 months (range 19-60) at assessment).

First Author Manometry Population Summary Summary of Key Anorectal Manometry Findings Key Limitations
Burjonrappa [61] Patients with megarectum following surgery for anorectal malformation • All children who underwent anorectal manometry prior to excision of megarectum (n = 5) had an intact RAIR. • Two children underwent colonic manometry which demonstrated "hyperperistalsis" and "a neorectum very sensitive to distension".
Small, heterogeneous manometry cohort (six children); select population (children with megarectum); limited manometric assessment with variable reporting of findings.
Cahill [24] Patients with anorectal malformation following PSARP • Four of five patients had "normal" rectal sensation and mean anal canal pressures following PSARP, suggesting the procedure is applicable to young infants with high imperforate anus.
Small cohort; limited description of manometry techniques, findings, and interpretation; too young at follow up to adequately assess bowel function to support the interpretation of findings.
Caldaro [43] Neurologically healthy children, >4 years, with constipation/FI, following anorectal malformation repair • Average anal resting pressure (aARP) significantly higher in the low malformation group, than intermediate or high malformation groups.

•
Fecal incontinence in the setting of IAS disruption (identified using 3D endoanal ultrasound) responded to biofeedback +/− laxatives if aARP > 20 mHg, whereas daily enemas were necessary if aARP < 20 mmHg. • Statistical correlation identified between manometric, endosonographic, and clinical findings; useful to define most appropriate treatments based on anal sphincter assessment and understanding of continence "potential".
Small malformation subgroups limit strength of findings with respect to malformation types.
Caruso [67] Neurologically heathy children >4 years with "true" FI following anorectal malformation repair • Anorectal manometry can evaluate potential sphincteric recovery after biofeedback for the treatment of FI; further prognostic benefit if correlated to morphologic evaluation with MRI. Alternative treatment should be considered in patients with unfavorable pre-treatment assessment. • Improvement in manometric values associated with improved clinical score after biofeedback therapy.
Manometry/MRI assessment would benefit from clarification of scoring; relatively small subgroups (determined by pre-operative assessment). Sphincter anomalies, identified using 3D HRAM, were the most important prognostic factor for TAI efficacy: associated with worse scores of function, and slower improvement following TAI initiation.
Small anorectal malformation cohort; surgical repair type not reported.
Chen [73] All children with anorectal malformation repaired by a single surgeon • Resting rectal pressure (RrP) lower and anorectal pressure gradient (ARPG) higher in the constipated than the non-constipated children.

•
The RrP was higher and the resting anal pressure and ARPG lower in the patients with soiling.
Limited cohort data provided for manometry cohort; limited by technology available; idiosyncratic symptom assessments may limit comparability.

•
The majority of patients demonstrated normal sphincteric resting pressure following LAARP. • Patients demonstrated higher sphincteric resting pressure and bowel function scores following LAARP (compared with PSARP).
Small operative/malformation subgroups; difference in time period between operative subgroups-results may be confounded by evolution of pre-and post-operative care; PSARP subgroup older than LAARP cohort and includes subjects >18 years, limiting comparability.
Doolin [44] Children following repair of anal atresia • Manometry findings were not significantly correlated with functional outcomes. No objective criteria were identified that could evaluate the patient's clinical result or guide therapy.
Malformation classification not known for all patients; limited by technology available.

First Author Manometry Population Summary Summary of Key Anorectal Manometry Findings Key Limitations
El-Debeiky [25] Males with high anorectal malformation treated with laparoscopic-assisted pull-through • "High" resting pressure that decreased on straining in patients without soiling (n = 7) and "low" in two patients with soiling.
Small cohort; unclear age at assessment limited, qualitative reporting of manometry findings, without clarification of interpretation (e.g., "high" versus "low" resting pressure); assessment of correlation between manometry findings and function not reported.
Emblem [40] Adolescents with low anorectal malformations following repair

First Author Manometry Population Summary Summary of Key Anorectal Manometry Findings Key Limitations
Hedlund [46] Patients with anorectal malformations following PSARP, without major sacral malformation • Anal resting tone (ART) and anal squeezing pressure (ASP) subnormal in most patients, with soiling more common in patients with very low ART (<40 cm H 2 O) and a low ASP (<100 cm H 2 O). • Constipation more common in patients with a large rectal volume.

•
Presence of a rectoanal inhibitory reflex correlated to both a comparatively high ART and low incidence of soiling.
Statistical assessment of correlation between manometry findings and clinical outcomes not reported; limited reporting of patient cohort data; limited reporting of manometry outcomes.
Heikenen [74] Children with FI refractory to standard medical therapy following repair of anorectal malformation • Anal RP was reduced in 60% of children, all with refractory fecal incontinence; average resting pressure 19.5 mmHg.
Limited reporting of anorectal manometry technique and outcomes; small cohort; anorectal manometry not performed in all children.
Hettiarachchi [47] Children with chronic constipation and/or FI following anorectal malformation repair • Manometric IAS scores correlated with functional scores (assessed using the modified Wingfield score (MWS)), as did overall manometric scores (IAS + rectal score).

•
Combined manometric and MRI scores showed a correlation with MWS; however, MRI scores alone did not.
Small, heterogenous cohort, particularly with respect to age, repair, malformation type, associated anomalies, and functional outcomes; idiosyncratic scoring system limits comparability; limited objective reporting of manometry findings.
Huang [20] Female patients with rectovestibular fistula • No significant difference in resting rectal pressure between surgical groups, despite lower rates of FI and constipation in the modified-PSARP cohort; however, assessment of manometry findings and correlation with symptom subtypes does not appear to have been performed.
Manometric assessment of "active systolic blood pressure" and measurement of rectal compliance unclear; assessment of correlation between symptom groups and manometry findings not performed.
Husberg [    The IAS-like structure not essential for continence or RAR: in the presence of a damaged IAS-like structure, or its complete absence, adaptation of the neoanus through reinnervation of the bowel end was speculated to cause it to behave like an IAS, accounting for the appearance of RAR in patients without IAS-saving procedures.
Small cohort in the context of multiple operative subgroups; study-specific assessment of bowel function may limit comparability of findings. Small operative sub-groups; assessment of bowel function based on stool frequency, without report of associated symptoms (e.g., constipation, FI).
Liu [32] Patients with intermediate or high malformations following PSARP • Mean anal resting pressure (MARP) did not differ significantly between operative groups: no significant difference in MARP between patients showing "excellent and good" outcome versus "fair and poor" outcome. • Findings reported to reflect comparable long-term outcomes between traditional staged PSARP, and 1-stage neonatal PSARP.
Martins [50] Patients with intermediate or high malformations following PSARP • Initial pressure, pressure after coughing, pressure after voluntary contraction, pressure after perianal stimulation, and pressure after crying were significantly higher in continent patients.

•
Manometry findings reported to correlate with continence. • Lower percentage of "normal" pressure curves in incontinent group.
Limited by technology available; study-specific continence assessment may limit comparability of findings; limited reporting of manometry findings. Nagashima [62] Children following repair of anorectal malformations • Maximum anal pressure and anorectal pressure difference were significantly lower in high type, compared with low type, malformations. • Threshold sensation pressure and maximum tolerable pressure were significantly higher in high type than low type malformations. • Inadequate anal resting pressure and loss of optimal rectal sensation/reservoir function may contribute to fecal incontinence in high type malformations.
Small cohort given heterogenous nature of malformation types and patient ages; limited by technology available; study-specific scoring system lacks specificity, may limit comparability.
Niedzielski [33] Children following PSARP • Mean values of all assessed anorectal manometry parameters were significantly lower in high versus low defect and reference groups.

•
Mean values of all assessed parameters, except for resting anal pressure, were significantly lower in the low defect group versus the reference group.
Wide age range/time elapsed post-operatively at manometric assessment; limited description of manometric technique; statistical assessment of correlation of manometric outcomes with bowel function not reported/performed. Okada [21] Patients following ASARP for re-operation due to FI following anorectal malformation repair • Significant increase in anal resting pressure post-operatively, with a concurrent significant increase in clinical assessment (Kelly score). • Total, accident, and staining components of the Kelly score were significantly increased.
Small manometry cohort (n = 6); limited by available technology; assessment of correlation between manometry findings and symptoms not performed; cohort characteristics and bowel function scores provided for total cohort only.
Penninckx [16] Infants with anorectal malformation treated at a single center  Positive RAIR, considered indicative of functioning internal anal sphincter, was identified in 83%. Anal resting pressure was significantly higher in this group and a lesser proportion experienced fecal soiling (12% versus 71%).
Limited by technology available; limited description of cohort characteristics, including age at assessment; study-specific rating of bowel function may limit comparability. Ruttenstock [18] Patients with an externally accessible fistula • Normal presence of the RAIR identified in all pre-and post-operative rectal manometry studies.

•
No differences between pre-and post-operative assessment with respect to RP or length of high-pressure zone.
Small cohort; limited by technology available.
Sangkhathat [63] Infants less than three years of age, post-anoplasty for treatment of anorectal malformation • Anal resting pressure significantly higher (p < 0.05) and RAIR present in significantly fewer (12.5% versus 93.8%; p < 0.01) children with post-operative constipation than those without.

•
No difference in RrP, ArP, RAIR, or peak squeeze pressure (PSP) between low and non-low malformation groups.
Limited characterization of bowel function; limited description of associated anomalies, including spinal anomalies.

First Author Manometry Population Summary Summary of Key Anorectal Manometry Findings Key Limitations
Schuster [19] Patients managed for perineal fistula using anal transposition technique • Maximal mean segmental pressure at rest did not differ significantly from standard results, nor did total asymmetry index; however, it was unclear whether these findings related to pre-or post-operative assessment, or a combination.
Small cohort; unclear whether post-operative manometry results were provided (assessed pre-and post-operatively).
Schuster [42] Children with anorectal malformations following PSARP • Maximal mean segmental pressure at rest and during squeeze were reduced. Values at rest were described as pathologically low (range 6-65 mmHg), being two standard deviations below findings in healthy children (range 84-117 mmHg).

•
No correlation between quantitative manometry outcomes and clinical score. Qualitative manometry and MRI findings were correlated; however, only a limited correlation with clinical score was identified (R = 0.425).
Small cohort; range of anorectal malformation types further restricts subgroup size.
Senel [51] Children with anorectal malformations following repair • Significantly lower aARP in high versus intermediate anorectal malformation groups.

•
Significantly lower aARP in good versus fair or bad continence groups.
Small, heterogenous cohort; limited description of associated anomalies (including spinal); function reported as summative scores of assessment instruments, which may limit comparability.
Sonnino [37] Children with FI treated with gracilis muscle transposition • Continence improved post-operatively (following gracilis transposition), accompanied by an apparent trend toward great maximal pressures; however, assessment of significance not reported.
Small, heterogenous cohort; limited description of manometry outcomes; limited statistical analysis reported to aid interpretation of the significance of findings.

First Author Manometry Population Summary Summary of Key Anorectal Manometry Findings Key Limitations
Tong [38] Infants with high anorectal malformation treated with LAARP vs. PSARP • Patients following LAARPT demonstrated significantly lower asymmetric index, larger vector volume, and higher anal canal pressure at rest than the PSARP group. • No significant differences in length of HPZ or presence of rectoanal relaxation reflex.
Choice of intervention based on surgeon and/or parent preference (non-randomized); statistical assessment of correlation between clinical score and manometry findings not reported.
Vital Junior [53] Children with anorectal malformation following PSARP • Overall low RP; however, RP was significantly higher in continent vs. partially continent and incontinent groups.

•
The VCP was significantly higher in continent vs. incontinent groups. Partially continent group demonstrated VCP approaching that of the continent group, with potential positive implications for prognosis. • Presence of RSR varied by group: continent: 35.5%; partially continent: 4.8%; incontinent: 6.7%.
Limited description of malformation type; idiosyncratic aspects of continence assessment may impact upon the comparability of findings.
Wang [54] Children treated at a single center without congenital megarectum, sacral or spinal deformities • Significantly higher balloon volumes to elicit an RAIR in the anorectal malformation (vs. control) group and the low (vs. intermediate-high) defect group. • An RAIR was identified in 95.7% of patients; 61.7% had "good" function. • Minimum balloon volume to elicit an RAIR was negatively correlated with anal function scores.
Limited reporting of manometry findings; limited description of manometry parameters/interpretation utilized; heterogenous cohort.

First Author Manometry Population Summary Summary of Key Anorectal Manometry Findings Key Limitations
Yang [39] Children with high anorectal malformation following PSARP or LAARP • Anal canal resting pressure (ACRP) significantly higher in LAARPT group, compared with the PSARP group. • No significant difference with respect to RAIR between cohorts. • Absent RAIR and "lowest" ACRP reportedly observed in patients with FI.
Small sub-cohorts; association between functional outcomes and manometry findings reported without assessment of statistical correlation; relatively short follow up period and young cohort age given reported associations between anorectal manometry findings and functional outcomes. 38 Good prognosis: specific malformation types (rectoperineal fistula, rectovestibular fistula, imperforate anus without fistula, rectal atresia, cloaca with common channel < 3 cm); associated with a prominent midline groove, suggestive of good perineal muscle, and a normal sacrum.

Normal Findings
In order to define abnormalities of anorectal function, an understanding of "normal" pediatric physiology is needed. However, the definitions of what was considered normal were either not reported or incompletely described by most studies included in this review. For example, there was variability with respect to both anorectal manometry parameters considered to be significant, and the absolute pressure values within parameters that were considered within normal range. Consequently, the understanding of "normal" varied markedly between studies (Table S2).

First Author
Year Assessment

Discussion
A significant proportion of children with anorectal malformations experience disorders of evacuation and/or fecal incontinence following operative repair. Continence may be affected by a variety of factors, including malformation type, associated sacro-/spinal anomalies, and operative repair type, including intra-and/or post-operative complications. Due to the variable etiology of fecal incontinence and evacuation disorders, symptoms alone are often insufficient to direct treatment in cases refractory to conservative management [6]. Anorectal manometry may be used to investigate the pathophysiology underlying anorectal dysfunction. To our knowledge, this review is the first to systematically evaluate postoperative anorectal manometry performed in children with anorectal malformations.
In assessing 63 studies, our overall finding was a complete lack of consistency between manometry protocols, analysis of data, and interpretation of findings. This echoes the conclusion of a similar review of anorectal manometry performed in adult populations [7]. Despite studies identifying abnormalities in anorectal function, definitions of normal were rarely provided or vaguely described. Collectively, this makes interpretation of the findings difficult, whilst comparison of data between studies is impossible.

Manometry Outcomes
In 1834, Roux de Brignoles described the importance of preserving the fibers of the sphincter mechanism during anorectal malformation repair, demonstrating the longstanding recognition of their importance [2]. In contemporary practice, anorectal manometry may be used to assess post-operative function of the sphincter complex: activity of the internal anal sphincter (IAS) is understood to provide the majority of resting anal pressure, whilst the external anal sphincter (EAS) is largely responsible for voluntary contraction (squeeze pressure). Hypotonia may, therefore, be associated with presentations of fecal incontinence, whilst increased resting pressure may underlie some rectal evacuation disorders.
These findings are not unexpected, considering the underlying developmental abnormalities and the subsequent impacts of operative intervention on an underdeveloped continence apparatus in these children. From a clinical perspective, the thresholds at which fecal incontinence may be attributed to sphincter dysfunction are more difficult to determine. Despite reduced resting pressure, not all children with anorectal malformations experience incontinence. Poor concordance between severity of fecal incontinence and tests of anorectal function have been similarly demonstrated in adult populations [77,78]. Whilst these findings may appear to limit the utility of anorectal manometry, several factors may contribute to this apparent discrepancy. Firstly, given the wide range of resting pressures reported by studies included in this review, and a lack of "normal" values, identifying a precise threshold at which incontinence may be expected is challenging. The need to establish optimal manometric measurements for the diagnosis of anorectal dysfunction has been emphasized for this technique globally [6], and the additional challenges inherent to the pediatric setting are well-recognized [9].
Secondly, continence may be impacted upon by factors extrinsic to the anorectum and thus not evaluated by anorectal manometry. The regulation of defecation and its control (continence) is multifactorial; it is reliant on the interplay between key anatomical structures (principally the colon, anorectum, and pelvic floor musculature) and physiological systems (principally nervous, muscular, hormonal, and cognitive) [79]. As colonic motor activity propels luminal contents distally, progressive rectal distension produces the defecatory urge. If the timing is unsuitable, voluntary contraction of the EAS results in deferral of defecation, and retrograde colonic motor patterns return luminal contents to the sigmoid colon [79]. Alternatively, the expulsive phase sees reversal of the rectoanal pressure gradient through (1) voluntary relaxation of the EAS; (2) reflex relaxation of the IAS and pelvic floor musculature; and (3) reduction of the anorectal angle. Following evacuation, the basal rectoanal pressure gradient is restored and continence is re-established [79].
Given the complexity of interactions required for successful control of defecation, it is perhaps unsurprising that a significant proportion of children with anorectal malformations experience disorders of defecation, despite careful anatomic reconstruction [5,80,81]. Characteristic congenital defects of the anus and rectum may be intuitively associated with impaired continence. In addition, under-developed pelvic musculature, surgical interventions (particularly in the setting of revision procedures), and associated sacro-/spinal anomalies may impact upon the neuromuscular integrity of the continence system [1,82,83].
In this review, the array of approaches used to define and assess the RAIR made it challenging to understand the contribution of the reflex to the continence outcomes. It is likely that, alongside any true differences in prevalence, the variability observed was significantly influenced by the inconsistent criteria used. Despite these limitations, there is some evidence that presence of the RAIR impacts positively upon bowel function in this cohort, and, in concert with other parameters, may aid efforts to prognosticate continence outcomes.
As emphasized by Kumar et al., in the setting of anorectal malformations, RAIR absence is often described in relation to IAS dysfunction (resulting from congenital abnormalities and/or surgical disruption) [57]. However, the higher rectal balloon volumes required to elicit the RAIR in their studied cohort, and reflex absence in children with severe sacral anomalies, led the authors to emphasize the other arm of the reflex arc: the impact of disrupted sensory perception (rather than solely IAS dysfunction) in these patients [57]. Future work should seek to carefully characterize the relationship between presence of an RAIR, key medical characteristics (including malformation type, operative repair approach, and sacrospinal anomalies), bowel function, and response to interventions. This may facilitate understanding of the contribution of the RAIR, and utility in relation to prognostication, within the broader continence apparatus.
Proximal to the anal canal, there is increasing recognition of role of the colon in maintaining fecal continence, particularly through the regulation of rectal filling [86][87][88][89]. Included in this review, Heikenen et al. evaluated both colonic and anorectal motility in children with fecal incontinence following anorectal malformation repair [74]. Whilst a considerable proportion of the children demonstrated reduced resting pressure (60%), propagation of an "excessive" number of colonic motor complexes into the neorectum was demonstrated [74]. Although subject to significant limitations, the findings suggest the refractory fecal incontinence demonstrated by their cohort resulted from multiple factors, including those arising beyond the limits of the anorectum [74]. Our current understanding of colonic motility in this cohort remains poor; however, such studies may be of value in helping to understand the ongoing symptoms in children after repair of anorectal malformations.
While not assessed in this paper, several included studies used other modalities, in addition to anorectal manometry, to help define anorectal abnormalities [41,43,47,49,69]. For example, correlation between findings of manometry and anal endosonography were demonstrated in two studies [49,69]. However, these findings have been questioned, given the limited size and composition of the cohort and the probable technical limitations introduced by the use of a Foley catheter for anorectal manometry [41]. Caldaro et al. similarly utilized manometry and anal endosonography in combination to prognosticate response to treatment [43]. Symptoms in the setting of IAS disruption (identified using anal endosonography) were found to be responsive to biofeedback and laxatives if anal resting pressure (identified using manometry) was greater than 20 mmHg [43]. Utilization of a combination of select investigations is recommended to understand structure and function of the anorectum [6]. The need to establish classification systems encompassing outcomes of multiple tests of anorectal structure and function has been highlighted previously, and would similarly be of benefit to this patient cohort [6].

Manometry Outcomes and Clinical Correlates
The approach to bowel function assessment was highly variable between studies. Few studies provided symptom definitions, designating groups with constipation or fecal incontinence without specifying the diagnostic criteria. Those that did provide an explanation of their diagnostic terminology demonstrated inconsistencies. For example, constipation was defined as "less than three bowel actions per week", "less than one bowel action per day", and "enema required daily to achieve bowel action" [32,62,63]. Similarly, criteria used to report severity often lacked specificity. Studies often assigned grades or terminology (such as minor or infrequent), without specifying the features of each category. This discordant approach to outcome assessment limits meaningful comparison of findings between studies, identification of manometry-symptom correlates, and response to manometry-guided management strategies.

Practice Variability
Variability has been a common theme throughout this review. We have identified variability in cohort reporting, bowel function assessment, and symptom profiles. Variability in practice has been highlighted, with notable differences in the equipment, protocols, motility criteria, and interpretation used by included studies. Despite the impact of the manometry catheter and assessment protocol on absolute values achieved, notably few studies adequately described the catheter and approach utilized, whilst seven studies provided no description of their approach [20,23,28,33,39,70,71]. This presented a significant challenge when attempting to compare outcomes.
Fundamental to improving the consistency of this work is a coordinated effort to standardize anorectal manometry assessment, its interpretation, and reporting of findings, as has recently been developed for adult anorectal manometry studies [6,7]. Future studies should utilize a recognized manometry protocol and reporting framework; consensus statements have been developed for this purpose [8,9]. Similarly, this must be accompanied by robust reporting of relevant cohort medical characteristics (particularly malformation type, approach to operative repair, and associated anomalies affecting the spine and sacrum); evaluation of bowel function; and assessment of their relationship to manometry findings ( Figure 2). Development of minimum standards should be considered, to guide reporting of key cohort characteristics in this population.

Figure 2.
Suggested key cohort medical characteristics for reporting anorectal manometry studies performed in children with a repaired anorectal malformation.

Limitations and Conclusions
This review was limited to children following anorectal malformation repair. Studies including manometry outcomes in this cohort may have been excluded if the findings were not separated by age and/or diagnostic group. Consequently, the included studies may not reflect all anorectal manometry findings in this cohort. Similarly, our review was restricted to studies published in English and may be subject to a language bias.
Whilst altered anorectal function may be intuitively presumed to impact upon continence, regulation of defecation is multifactorial. The prevailing limitation of our current understanding of bowel dysfunction following anorectal malformation repair is the failure to place manometry findings into this wider context. Along with standardization of the approach used to perform anorectal manometry, this should be the focus of future work assessing anorectal function in this cohort. To support this process, the development of reporting guidelines for cohort characteristics and clinical outcomes should be considered, specific to children with anorectal malformations undergoing motility assessment. Whilst high-resolution techniques may provide greater insight into anorectal structure and function, interpreting manometry findings within the context of the broader continence mechanism is essential to enhancing our understanding of the long-term bowel dysfunction experienced by this cohort.
Supplementary Materials: The following supporting information can be downloaded at: www.mdpi.com/xxx/s1, Table S1: The Newcastle-Ottawa Scale: study quality assessment [11]; Table S2: Summary of consistently reported anorectal manometry parameters: parameter definitions, resting pressure, squeeze pressure, and rectoanal inhibitory reflex. Units of pressure standardized to mmHg; Table S3: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Checklist [10].

Limitations and Conclusions
This review was limited to children following anorectal malformation repair. Studies including manometry outcomes in this cohort may have been excluded if the findings were not separated by age and/or diagnostic group. Consequently, the included studies may not reflect all anorectal manometry findings in this cohort. Similarly, our review was restricted to studies published in English and may be subject to a language bias.
Whilst altered anorectal function may be intuitively presumed to impact upon continence, regulation of defecation is multifactorial. The prevailing limitation of our current understanding of bowel dysfunction following anorectal malformation repair is the failure to place manometry findings into this wider context. Along with standardization of the approach used to perform anorectal manometry, this should be the focus of future work assessing anorectal function in this cohort. To support this process, the development of reporting guidelines for cohort characteristics and clinical outcomes should be considered, specific to children with anorectal malformations undergoing motility assessment. Whilst high-resolution techniques may provide greater insight into anorectal structure and function, interpreting manometry findings within the context of the broader continence mechanism is essential to enhancing our understanding of the long-term bowel dysfunction experienced by this cohort.
Supplementary Materials: The following supporting information can be downloaded at: https: //www.mdpi.com/article/10.3390/jcm12072543/s1, Table S1: The Newcastle-Ottawa Scale: study quality assessment [11]; Table S2: Summary of consistently reported anorectal manometry parameters: parameter definitions, resting pressure, squeeze pressure, and rectoanal inhibitory reflex. Units of pressure standardized to mmHg; Table S3: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Checklist [10]. Funding: There was no funding for this systematic review. King is generously supported in his role as an Academic Paediatric Surgeon by The Royal Children's Hospital Foundation. Evans-Barns is supported by an Australian Government Research Training Program (RTP) Scholarship, the Murdoch Children's Research Institute Professor David Danks Scholarship, and a One in 5000 Foundation Research Award. None of the authors have any financial relationships relevant to this article to disclose.

Data Availability Statement:
No new data were created or analyzed in this study. Data sharing is not applicable to this article.

Conflicts of Interest:
The authors declare no conflict of interest.