Consequences of transanal pull-through surgery for Hirschsprung's disease are not always as favorable as the surgeon imagines. Incomplete continence, constipation and postoperative enterocolitis should not be ignored [33–36]. Previous studies have attempted to investigate the relationship between preoperative characteristics and surgical outcomes in patients with Hirschsprung's such as age, gender, length of aganglionosis, age at surgery, preoperative enterocolitis, comorbidities, and genetic background [37–40]. Despite the fact, there is always a challenge for the best age of operation. Therefore, here we mainly tried to categorize studies that prefer the neonatal period as the best age against those who believe to postpone it. We mostly focused on 16 studies according to our inclusion and exclusion criteria. in summary 11 investigations were in favor of postponing the operation above one month, 2 studies found no difference and 3 reported better outcomes in the neonatal period.
One important issue here is the accuracy of diagnostic modalities to detect patients. A recent study by Chen et al. showed a 88.5% correlation between radiological and pathological TZ in rectosigmoid Hirschsprung. This was depended on the patient's age. They showed 69% correlation for children below 3 months versus 85.3% (strong severity) for older ones [41]. Overall, different studies mentioned above indicated that longer periods of disease may lead to better development of radiological TZ. Therefore, determining the transition zone with a high accuracy is necessary. Most children with Hirschsprung's disease present during the neonatal period with delayed passage of meconium beyond the first 24 hours, abdominal distention, bilious vomiting and feeding intolerance and are diagnosed by a rectal biopsy in the first month of life. However, a definite diagnosis before surgery is mandatory.
The extent of colon caliber changes depend on the duration of distal bowel obstruction, which is limited in newborns. Therefore, contrast enema is not appropriate in newborns. This is the reason why some surgeons prefer to wait for 1–2 months. A colon enema performed before the age of 30 days had a sevenfold higher probability of false-negative results [42].
Despite the fact, the main risk of postponing surgery is the possibility of enterocolitis during the waiting period. This risk can be lessened by ensuring rectal pressure relief with adequate irrigation (usually 10–20 ml/kg, several times daily), administration of prophylactic metronidazole or probiotics. Due to the risk of enterocolitis, many pediatric surgeons believe that once a diagnosis is made, even in small infants, a laparoscopic or transanal operation can be performed successfully and safely [43]. A survey by the European Society of Pediatric Surgeons found that 33% of pediatric surgeons prefer to perform endorectal pull-through surgery at diagnosis and 67% prefer a delayed approach (4 months or > 5 kg) [44].
In addition, anorectal manometry is an effective and safe method that complements the diagnosis of HD in newborns. Anorectal sphincter pressure progressively matures with incremental increase during the first months of life [45–47].
Kaiser Decker et al. reported that the sensitivity of a rectal suction biopsy (RSB) was 81% and its specificity 97%. Therefore, a repeated sampling may be necessary. They found that RSB can also be reliable and safely performed in preterm born infants [48]. However, repeated biopsies in neonates may lead to intestinal perforation. In the study of Putnam, L.R., et al, in clinically suspicious neonates for HD, contrast enema studies showed inconclusive results in 32% of cases [49].
Kumar et al., concluded that delaying surgery is not logical and neonates and infants might benefit most than other age groups. As their study design was retrospective with few number of patients in each sub group, they could not provide a detailed comparison between neonates and those between 1–12 months. However, the risk of reported complications was more in neonates [21].
Besides, Kastenberg et al., compared delayed primary endorectal pull-through (≥ 31 days) [The median age at operation 98 days (IQR 61–188 days)] with neonates. They assess 82 patients, 49 neonates and 33 non-neonates. Fifteen of neonates compared to five non-neonates developed fecal incontinence (P value = 0.13). Besides, enterocolitis and other complications were not different between the two groups. As fecal incontinence was more reported in neonates, but without a statistically significant difference, the authors tend to conclude that operation in neonates is as safe as those above one month, which is not logical in our opinion. This study had good mythological design but with a small sample size. Therefore, we might not rely completely on this analysis to advocate surgery in neonates [22].
In another investigation, Remi Andre Karlsen compared the outcomes of laparoscopic and trans-anal pull-through and reported poorer outcomes In the neonatal period. This study did not fulfill our inclusion and exclusion criteria but higher complications were reported in neonates [50].
In another study by Ivana et al. [32]. no association was found between age at surgery and functional outcomes in Hirschsprung patients. In our idea this study lacks a large sample size. Also they categorized their patients into two groups of below 4 years and above it, which ignores any classification regarding neonates, therefore, the results might not be very helpful in our data interpretation. Despite the fact, soiling was more reported in patients older than 4 years which is consistent with some other reports. Accordingly, delaying surgery above 2–4 years is completely erroneous.
On the other hand, Miyano study showed that age at surgery was not correlated with postoperative bowel function in Hirschsprung's disease. However, they emphasized to validate and highlight their modified laparoscopic technique for HD and their main goal was no comparison between neonates and non-neonates regarding outcomes [24].
In addition, Hoff et al., reported no risk factor for short-term complication using the Clavien-Dindo-grading system, including age at surgery [25]. They only evaluated outcomes during the first months after surgery, as early post-operation complications, and long-term outcomes were not assessed.
On the other hand, in a multicenter study in Scandinavia to evaluate the predictors of functional outcomes, age at surgery did not have a significant effect on poor outcomes using a multivariate model [27]. This study was a retrospective investigation mainly to identify long-term complications of children with HDs after operation. Age classification in this study is only given in a table categorized as 0.4 to 1, 1-2.9, 3-7.5 and 7.9–133 months. No detailed information regarding the number of patients in each quartile was found. Despite the fact, their main goal was to assess long-term bowel function and not to compare complications at different age groups. Therefore, we cannot conclude that the results are against our recommendation.
The most reliable study against postponing the operation to above one month was belonged to Yanan Zhang et al. on 229 neonates [28]. They reported that operation in the neonatal period was quite safe with few complications (age of 6–28 days). This is approximately the only well-organized study to defend the operation in neonatal period with a quite large sample size. We admire the authors to have such a settings. Despite the fact, We believe that these outcomes are due to high expertise of staff in this center as they could record 229 patients in 13 years. As most studies reported smaller number of patients, we think delaying the operation to above one month is logical in smaller centers. However, in very few tertiary centers with highly organized settings and experienced pediatric surgeons, we might recommend surgery in neonates.
In terms of postoperative complications, infants who undergo transanal pull-through surgery are exposed to undesirable short-term consequences. Huang et al. [51] reported that neonates have a longer recovery period after surgery than non-neonates. Furthermore, active immunodeficiency and inactive immunity of maternal antibodies result in low resistance to infection in neonates. In a retrospective study evaluating the results of a single-stage transanal pull-through on 650 children, the authors concluded that the operation might be more appropriate in non-neonatal period than the neonatal period. Because there was a higher rate of perianal excoriation, anastomotic stenosis and leakage, postoperative enterocolitis and incomplete postoperative continence in neonates than non-neonates [13]. In addition, Stensrud [31] compared two groups of patients who underwent trans-anal and trans-abdominal surgery regarding anal sphincter damage using ultrasonography. They showed that children who underwent trans-anal pull-through had higher rates of injury. The median age of patients in trans-anal and trans-abdominal surgery were 1.8 (0.4–133) and 13 (1.2–100) months. We might conclude that operation at lower ages and using tans-anal approach would increase the likelihood of sphincter injury.
A meta-analysis by Maggie et al. [52] published in 2021 included 4 studies in addition to their own center data to assess the best time to perform the operation for children with Hirschsprung disease. They included Miyano et al., Zhu et al, Lu et al and Chung et al. investigations in their pool analysis. The first three were discussed above, but the Chung et al. [53] study could not be entered because they did not include a clear age classification to separate neonates versus non-neonates. However, as they provided their data sheet, Maggie could include it. Overall, Maggie et al. claimed that children below 2.5 months old at surgery would have poorer outcomes, which is somehow in line with the results of our systematic review.
This study had some limitations. As all systematic reviews, we had to rely on other studies information. A recall bias is inevitable when compiling information from other investigations. Some studies did not include necessary information needed for our review. Therefore, some high-quality studies might have been excluded due to a high bias score using the checklist. Besides, some studies included patients with concurrent syndromes which were not assessed in our review. We do not know whether Down syndrome might affect the decision for age selection. It is suggested to perform large multicentric studies to collect data on different ethnicities.