Nationwide Population-Based Epidemiologic Study on Childhood Intussusception in South Korea: Emphasis on Treatment and Outcomes

Intussusception is the most common cause of acute bowel obstruction in infants and young children [1]. Intussusception is a medical emergency because it may lead to bowel necrosis and perforation due to reduced arterial blood supply and cause peritonitis and even death, if not promptly diagnosed and treated [2, 3]. Ileocolic intussusception, the most common type in children, requires reduction with ultrasound-guided or fluoroscopic pneumatic or hydrostatic enema, and is successful in most cases [4]. Small-bowel intussusception, which is uncommon in children, can usually be safely monitored and often spontaneously reduces [4]. Regardless of the type of intussusception, surgical intervention is indicated when enema reduction or close observation is unsuccessful [3].

To date, many studies have examined the epidemiology, treatment, and clinical outcomes of childhood intussusception mainly based on hospital data, whereas nationwide population-based studies are limited. In recent years, some nationwide studies from Taiwan and Italy were published [5, 6]; however, they included only inpatients.

The aim of this nationwide population-based study was to investigate the epidemiology, treatment, clinical outcomes, and factors associated with the disease outcomes of childhood intussusception in South Korea through complete enumeration.

This was a nationwide population-based study conducted to elucidate the epidemiology, treatment, disease outcomes, and factors associated with disease outcomes of childhood intussusception in South Korea through complete enumeration.

The overall childhood intussusception incidence from 2007 to 2017 in South Korea was 28.3/10⁵ person-years, which is similar to that in Italy (21/10⁵ children ≤15 years old) but higher than that in Germany (10.4/10⁵ children <15 years old) and Canada (3.0–4.3/10⁵ person-years in children <18 years old) [7, 8]. Geographical and environmental variations in intussusception incidence are known to exist [9, 10]. Furthermore, the incidence differed according to race/ethnicity even within the same country [11, 12]. In our study, the mean incidence in infants <1 year old was 195.2/10⁵ person-years. A literature review showed that the global mean incidence of intussusception was 74/10⁵ (range 9/10⁵–328/10⁵) among infants <1 year old [10]. The mean incidence of intussusception among infants <1 year old was higher in Asia and Australia (185/10⁵ in Japan, 108/10⁵ in Hong Kong, 77/10⁵ in Taiwan, 101/10⁵ in Australia) than in Europe and North America (66/10⁵ in Denmark, 60/10⁵ in Germany, 56/10⁵ in Switzerland, 39/10⁵ in Italy, 24/10⁵ in England, 35/10⁵ in the United States, 34/10⁵ in Canada) [5, 6, 7, 8, 10, 11, 13, 14, 15, 16, 17, 18, 19]. The incidence of intussusception in Korea is higher than that in other countries. There are still gaps in variant incidence rate by region with respect to disease etiology and mechanisms [9].

In the present study, boys showed a higher incidence rate than girls (IRR 1.64). Male predominance in intussusception incidence has been noted in previous studies, with male-to-female ratios ranging from 1.2 to 2.5 [5, 6, 7, 11, 13, 20]. The median age at the first occurrence of intussusception was 18.7 months, similar to studies from other countries (17 months in the United States and Japan, and 21.1 months in Germany) [7, 13, 21]. In our study, boys had a higher median age than girls (19.7 months vs. 16.9 months). Similarly, a previous Taiwanese study showed that age was higher in boys than in girls (27.3 months vs. 24.9 months) [5].

In our study, 3,226/30,444 children (10.6%) had one or more post-discharge recurrences. In the 30,444 cases of first intussusception incidence, 27,475 (90.2%) successfully resolved after enema reduction. Further, after a successful enema reduction, 2,899/27,475 (10.6%) had post-discharge recurrence. A total of 1,842/30,444 (6.1%) had in-hospital recurrences within one admission or one hospital visiting period. The total recurrence rate (children with post-discharge recurrence and/or in-hospital recurrence) was 15.0% (4,580/30,444). A meta-analysis showed that the overall recurrence rates and the recurrence rates within 48 h after enema reduction, except for cases requiring surgery, were 7.5–12.7% and 2.7–6.6%, respectively [22]. A systematic review and meta-analysis showed an overall recurrence rate of 8.8% for the admission group and 10.1% for the emergency department management group [23]. Another systematic review and meta-analysis showed that the overall recurrence rate was 6% for inpatients and 8% for outpatients; however, the pooled estimate of re-admission rate could not be obtained owing to infrequency and inconsistency due to the small number of patients in each study [24]. In a nationwide study based on an inpatient-only database, excluding emergency department or outpatient clinic data, in Taiwan, the overall re-admission rate for intussusception in children <15 years old was 7.9% [5]. This was lower than the post-discharge recurrence rate in the present study. The difference is likely related to the inclusion of not only inpatients but also emergency department and outpatient clinic patients, among children <18 years old, in our study. Although based on data from one institute, recently published long-term retrospective studies showed a somewhat higher recurrence rate than previous studies [25, 26]. The recurrence rate including both early recurrence (within 48 hours) and late recurrence (after 48 hours) was 13.8% (68/491) between January 2007 and January 2019 in a tertiary hospital in South Korea [25]. The total recurrence rate including both short-term recurrence (≤7 days) and long-term recurrence (>7 days) was 16.8% (115/683) between January 2000 and May 2018 in a tertiary hospital in the United States [26]. The median time to the first post-discharge recurrence was 72 days (minimum 0 days, maximum 8.2 years) in the present study. A long-term follow-up study has shown that recurrence of intussusception can occur not only within a short period but also several years after an intussusception episode [27].

In our study, the success rate of enema reduction was approximately 90% in first occurrence cases. In a literature review, the success rate of enema reduction was 67–85%, except in Africa and Central and South America [7, 10]. The success rate of enema reduction in the first event was 79% in the United States [28], 87.7% in Italy [6], and 92.8% in Japan [13].

In our study, 3,296/30,444 patients (10.8%) underwent 3,481 surgeries for intussusception. This was similar to the results in Italy (9.9%) and Japan (7.2%) [6, 13], but relatively lower than the results in other countries. A review article revealed that surgery was performed in 19% (range, 10–68%) of intussusception cases [9]. In another literature review, the overall surgery rate was 33% globally, 16% in Asia, 20% in Europe, 29% in Oceania, and 28% in North America [10].

In the present study, bowel resection was performed in 648/3,481 (18.6%) surgical cases, consistent with a previous review (18%, range 9–54%) [9]. In our study, approximately 2% of 34,688 intussusception cases were treated with bowel resection, consistent with a previous literature review showing that surgical bowel resection was performed in 7% globally, 3% in Asia, 3% in Central and South America, 5% in Europe, 9% in Oceania, and 11% in North America [10]. A recent study in Japan showed that 7.2% of the total cases were treated with surgery and 29.7% of the surgical cases (2.1% of total cases) involved bowel resection [13].

In our study, 728/3,481 surgical cases (20.9%, 2.1% of all intussusception occurrences) had 786 accompanying comorbidity diagnosis codes with the intussusception diagnosis code in 713/3,295 (21.6%) children. Some of them might be potential pathologic leading points. A previous review reported that structural lead points were observed in 3% of patients [9]. A study in Japan also showed that 3.1% of cases had a pathologic lead point [13]. In our study, the common comorbidity diagnoses were appendix problems (46.1%), lymphadenitis or lymph node disorders (13.0%), and Meckel's diverticulum (8.9%). Similarly, in Italy, inflamed appendix was the most common comorbidity [6]. In Europe, enlarged mesenteric lymph nodes were found in 19–50% of pediatric intussusception patients undergoing surgery or investigation by ultrasound [9]. In Japan, the most common pathologic leading point was Henöch-Schönlein purpura followed by Meckel's diverticulum [13]. When surgical cases were divided into children <6 years old and children ≥6 years old, the most common comorbidity in children ≥6 years old was benign neoplasm of the gastrointestinal tract including polyps or Peutz-Jeghers syndrome (22.6%). The second most common comorbidity was appendix problems (20.5%), followed by lymphoma (17.9%). A Taiwanese study comparing child and adulthood intussusception also showed that children aged between 10 and 20 years had a substantially higher incidence of coexisting neoplasms and malignancies than children <10 years of age [29]. Ileal lymphoma, in particular, should be considered in any children with intussusception who are older than 6 years [30, 31, 32].

Our study showed that the initial occurrence of intussusception in summer and autumn was lower than that in spring; however, there was no significant difference in the total number of occurrences. Our results are consistent with a review that showed no seasonal patterns [10]. The seasonality of intussusception occurrence is still controversial in that many studies reported no seasonal variations [1, 10, 12, 17, 33, 34, 35, 36] but several others showed seasonality [5, 18, 37].

Our multiple logistic regression analysis revealed that increasing age, male sex, and tertiary hospitals were associated with post-discharge recurrence of intussusception. The higher OR in tertiary hospitals than in general hospitals may be explained by the fact that pediatric patients might visit tertiary hospitals when intussusception had recurred after discharge. It is reasonable that hospital type is considered an associated factor, not a causal factor, of post-discharge recurrence.

Our multiple logistic regression analysis also revealed that age, sex, seasonality, and hospital type were factors associated with surgery. The higher OR with surgeries in tertiary hospitals than those in general hospitals may be explained by the fact that children might often be transferred to tertiary hospitals when surgical treatment is required. The hospital type can be considered an associated factor, rather than a causal factor, of surgery for intussusception. Furthermore, in cases of post-discharge recurrence, the need for surgery increased compared with that in cases without post-discharge recurrence.

Mortality from intussusception is generally rare (0.03–0.07%), except in Africa [1, 10, 11, 13]. In Italy, the mortality rate of pediatric intussusception was 0.04% [6]. In our study, there were nine mortality cases (four boys and five girls, <1 year old in six cases and ≥3 years old in three cases), showing a mortality rate of 0.03%.

Although recent nationwide studies were performed in Italy, Taiwan, and Japan, they did not cover outpatient settings or emergency departments [5, 6, 13]. According to Cortese et al. [38], the incidence rate of intussusception solely based on inpatient discharge databases, excluding short stay or emergency department data, could underestimate the true incidence of intussusception by >40%. While previous nationwide studies mainly examined incidence rates, our study covered all key issues including incidence, post-discharge recurrence, in-hospital recurrence, treatment, clinical outcomes including mortality, and factors associated with disease outcomes of childhood intussusception in children <18 years old in a nationwide complete enumeration scale.

Our study had some limitations. First, the HIRA database of the Korea NHIS is composed of claim data for medical expenses reimbursement, and not originally collected for academic research per se. Therefore, not all clinical information was available, including types of enema reduction, exact site of intussusception, exact time of starting a reduction procedure, histopathology reports for surgical cases, exact time of recurrence within one admission/hospital visit, or laboratory data. Accompanying diagnosis codes in surgical cases of intussusception were identified to presume possible pathologic leading points. However, an accompanying diagnosis in surgical cases might only be an incidental finding rather than a cause of intussusception. Second, a true intussusception incidence was defined as a case with both the intussusception diagnosis code (K561) and a code for enema reduction or a surgical intervention code. Accordingly, patients without claim data for fluoroscopic pneumatic/barium enema or surgical intervention were excluded from data collection, despite having the intussusception diagnosis ICD-10 code (K561). However, as demonstrated by Kohl et al. [39], the incidence rate of intussusception using a retrospective, solely ICD code-based design may significantly overestimate the incidence rate. Therefore, the combination of the ICD-10 code for intussusception and a procedure code for reduction was applied to provide a more specific and clinically relevant case definition [39]. We might have excluded patients who had spontaneous reduction of intussusception such as small-bowel intussusception. However, spontaneous reduction is relatively rare globally (1%), with a very rare occurrence in North America, 2% in Asia, 3% in Europe, and 4% in Oceania [10]. Third, in the present study, direct medical costs did not include non-insurance medical expenses such as ultrasound cost because the HIRA database included medical items covered by the Korea NHIS. Therefore, the real average medical cost of intussusception treatment may be higher than that reported in our study. Lastly, our results were based on Korea NHIS HIRA data between 2007 and 2017 because complete electronic data sets started to be available in 2007. Therefore, we were not able to compare before and after rotavirus vaccination initiation in South Korea, because rotavirus vaccination was introduced in 2007.

Despite the limitations of the claim data for reimbursement used in this study, the Korea NHIS HIRA database enabled us to investigate exact, useful information on childhood intussusception in South Korea with respect to epidemiology, treatment, clinical outcomes, and factors associated with clinical outcomes through complete enumeration over 11 years on a national scale.