Prevalence of Gastrointestinal Symptoms and Impact on Quality of Life at 1-Year Follow-Up of Initial Attack of Acute Pancreatitis

Abstract

Objectives:

This study aims to describe the prevalence of gastrointestinal symptoms following the first time occurrence of acute pancreatitis (AP) and to measure the impact of the episode on patient health-related quality of life (HRQOL) from the perspectives of patients and parents.

Methods:

Questionnaires regarding gastrointestinal symptoms 1 year following the initial occurrence of AP were obtained from 74 pediatric patients. Thirty of these patients completed both the Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales and the PedsQL Gastrointestinal Symptoms and Worry Scales. These data were compared to legacy matched healthy controls.

Results:

Children with a standalone occurrence of AP experienced a similar rate of gastrointestinal symptoms compared to those who progressed to acute recurrent pancreatitis (ARP) within one year. PedsQL 4.0 Generic Core Scales scores were significantly lower for children self-report and parent proxy-report for patients that experienced AP compared to healthy controls. AP patients also demonstrated significantly more symptoms than healthy controls in the Gastrointestinal Symptoms and Worry Scales across multiple domains.

Conclusions:

Gastrointestinal symptoms affect many children who experience a single AP event even without recurrent attacks. The burden of symptoms is not significantly different from those who develop ARP. This is a novel study that evaluates patient-reported outcomes in children following an AP attack and demonstrates there is a significant impact on HRQOL in children and family experiences post-AP. More data are needed to study the progression of disease and the extended impact of AP following an initial AP attack in pediatric patients.

Introduction

Acute pancreatitis is a debilitating illness that requires hospitalization which causes a significant health economic burden(1, 2). Additionally, exocrine and endocrine insufficiency have been seen following a one time occurrence of AP (7, 8). In adults, abdominal pain and disability have been shown to be significant morbidities in the year following an AP attack(3). This is of particular importance for pediatric patients as there is a wider variation in etiologies of AP in children (2). Whether similar or different morbidities exist in children following a single occurrence of AP remains unknown.

It is unknown what the progression of symptoms is following a single AP episode in children. Additionally, there is little data how patients fare at home with a lack of long-term follow up. Some of these patients with their first AP attack later develop acute recurrent pancreatitis (ARP) with the majority of these patients (70%) progressing within five months from the initial attack(4).

It is essential to study the gastrointestinal (GI) symptoms and overall health-related quality of life (HRQOL) following a single occurrence of AP in children. Patient reported outcomes (PRO) need to be benchmarked to matched healthy controls in order to determine the severity of symptoms relative to healthy populations to facilitate treatment goals(5, 6).

Previous research has shown that specific GI symptoms as measured by the PedsQL^™ Gastrointestinal Symptoms Scales predicted decreased overall generic HRQOL across numerous pediatric functional and organic GI diseases, however this has not been investigated in pediatric AP(7, 8). We designed our study to investigate the impact of AP on generic HRQOL and GI symptoms from the patient and caregiver’s perspective at the one year follow up post first attack.

Based on the available literature(6, 9), we hypothesized that pediatric patients with AP would report more severe GI symptoms and lower generic HRQOL compared to the matched healthy controls. The aim of this study is to evaluate the progression of symptoms and impact on HRQOL baesd on PRO following a single episode of AP in children.

Methods

Patients were prospectively enrolled between February 2013 and October 2019 in our AP registry. This AP registry is an institutional review board approved observational cohort study of pediatric patients (<21-years-old) presenting to Cincinnati Children’s Hospital Medical Center (CCHMC, Cincinnati, Ohio, USA) with their first documented attack of AP. The diagnosis of AP was based on meeting 2 out of 3 diagnostic criteria per the INSPPIRE definition(10). The attack was also determined as mild, moderately severe or severe based on the most recent NASPGHAN classification(11). Enrolled patients within the registry are followed longitudinally up to 3 years post index AP.

The database includes data from a patient’s first documented occurrence of AP including clinical course and mangement, laboratory and demographic information that is recorded via REDCap (Research Electronic Data Capture, Nashville, Tennessee, USA). There have been prior publications from the AP registry including a subset of study subjects with different goals and objectives than this study(4, 12–14).

One Year Follow Post AP for GI Symptoms and HRQOL

Participants were contacted either via telephone survey or in person at their follow-up clinic visit one year after the initial attack. This visit was recommended universally for patients. Patients were surveyed for first AP attacks between February 2013 and October 2020. Due to a protocol change in July 2018, patients were systematically screened at the one year mark for symptoms. These patients were surveyed with a questionnaire (Supplementary Digital Content 1) regarding presence of abdominal pain, other GI symptoms,, interval hospitalizations, as well as suspected episodes of pancreatitis managed at home in the 12 months following initial hospitalization. Development of ARP was also documented based on review of EMR, which was defined as at least one subsequent AP attack at least four weeks apart with absence of pain in between episodes(10). Due to the COVID-19 pandemic, in person clinic visits and subsequent study recruitment was limited, so additional patients were contacted via telephone survey. At least three separate attempts were made to contact patient’s caregivers. Patients and their caregivers were also asked to each complete both the Pediatric Quality of Life Inventory^™ (PedsQL^™ ) and PedsQL^™ Gastrointestinal Symptoms and Worry Scales. Thirty participants and their caregivers from the cohort completed these measures at one year follow-up. (Supplementary Digital Content 2)

A healthy controls comparison sample was derived from legacy data (6). An age, gender, and race/ethnicity sample was uniquely derived to match the present study’s AP sample. Parental informed consent and child assent as required were obtained(6).

For the PedsQL^™ 4.0 Generic Core Scales, an age, gender, and race/ethnicity matched healthy sample was uniquely derived from the PedsQL^™ 4.0 Generic Core Scales initial field test study (15, 16). The 23-item PedsQL^™ 4.0 Generic Core Scales encompass: 1) Physical Functioning (8 items), 2) Emotional Functioning (5 items), 3) Social Functioning (5 items), and 4) School Functioning (5 items)(15). The instructions ask how much of a problem each item has been during the past one month. Items are reverse-scored and linearly transformed to a 0–100 scale so that higher scores indicate better HRQOL. Scale Scores are computed as the sum of the items divided by the number of items answered (this accounts for missing data).

The PedsQL^™ Gastrointestinal Symptoms Scales, derived from the PedsQL^™ Gastrointestinal Symptoms Module(17), encompass 10 individual multi-item scales: 1) Stomach Pain and Hurt Scale (6 items), 2) Stomach Discomfort When Eating Scale (5 items), 3) Food and Drink Limits Scale (6 items), 4) Trouble Swallowing Scale (3 items), 5) Heartburn and Reflux Scale (4 items), 6) Nausea and Vomiting Scale (4 items), 7) Gas and Bloating Scale (7 items), 8) Constipation Scale (14 items), 9) Blood in Poop Scale (2 items), and 10) Diarrhea Scale (7 items). The two PedsQL^™ Gastrointestinal Worry Scales from the PedsQL^™ Gastrointestinal Symptoms Module were also included(17). The format, instructions, Likert response scale, and scoring method for the PedsQL^™ Gastrointestinal Symptoms and Worry Scales are identical to the PedsQL^™ 4.0 Generic Core Scales(15). Higher scores indicate better HRQOL corresponding to lower symptoms(17).

Items are reverse-scored and linearly transformed to a 0–100 scale (0=100, 1=75, 2=50, 3=25, 4=0), so that lower scores demonstrate more (worse) GI symptoms and hence lower (worse) GI-specific HRQOL. Scale Scores are computed as the sum of the items divided by the number of items answered (accounting for missing data). If more than 50% of the items in the scale are missing, the Scale Score is not computed(18). This computation is consistent with the previous PedsQL^™ peer-reviewed publications as well as other well-established HRQOL measures(19). This accounts for the differences in sample sizes for scales reported in the Tables.

Statistical Analysis for post AP clinical data:

Data were analyzed using SAS^®, version 9.4 (SAS Institute, Cary, North Carolina, USA). Due to the distribution of variables, continuous data were summarized as medians with interquartile ranges (IQR: 25^th-75^th percentiles) and categorical data were summarized as frequency counts and percentages. For continuous data, group comparisons were done using Wilcoxon-Mann-Whitney tests and Chi-square or Fisher’s exact tests were used for analysis between groups for categorical data, as appropriate. A p-value <0.05 was considered statistically significant.

Statistical Analysis for post AP PedsQL data:

Independent samples t-tests and chi-square analyses were conducted to determine any group differences in age, gender, and race/ethnicity between the comparison groups. Cronbach’s coefficient alpha was utilized to determine scale internal consistency reliability(20). Scales with internal consistency reliabilities of 0.70 or greater are recommended for comparing patient groups, while an internal consistency reliability criterion of 0.90 is recommended for analyzing individual patient scores(21).

Clinical interpretability using the known-groups validity method compares scale scores across groups known to differ in the health construct being investigated(22–24). PedsQL^™ Gastrointestinal Symptoms Scales and Worry Scales, and PedsQL^™ 4.0 Generic Core Scales scores in groups differing in known health condition (i.e., AP or healthy participants) were computed using independent samples t-tests (Bonferroni familywise correction for multiple comparisons). In order to determine the magnitude of the anticipated differences, effect sizes were calculated(25). Effect sizes as used in these analyses were calculated by taking the difference between the healthy sample mean and the AP sample mean divided by the pooled standard deviations for each set of analyses. Effect sizes for differences in means are designated as small (0.20), medium (0.50), and large (0.80) in magnitude(25). Statistical analyses were conducted using IBM SPSS Statistics 28 (Armonk, New York, USA).

Results

Clinical Factors and Demographics

A total of 74 subjects had data collected at one year follow-up post AP. Fifty-six subjects were reached via random surveys and clinical visits at the one year follow-up mark and had data on the symptomatology survey post AP (Figure 1).

Figure 1:

Flow Chart of study enrollment of one year follow up survey visits, and health-related quality of life (HRQOL).

From July 2018 to October 2019 when patients were systemically approached via recommended annual clinic visits and/or telephone survey, 18 families responded out of a total of 39 approached patients for a 46% response rate. Among responders, 9/18 (50%) were male. The median age at time of first attack was 13.9 (IQR: 7.4 – 17.3) years and 9/18 (50%) had a mild AP attack. There was no statistically significant difference in age at initial attack, sex, race, BMI percentile, weight percentile or severity of attack between survey responders and non-responders (Table 1).

Table 1.

Acute Pancreatitis with no recurrence vs Acute Recurrent Pancreatitis: 1 year Follow-up Survey

	AP N=60	ARP N=14	P-value
Age 1st AP attack (years)	13.6 (8.3–16.2)	12.3 (6.1–14.0)	0.21
Sex (male)	32 (53%)	8 (57%)	0.80
Race			0.61
White/Caucasian	55 (92%)	12 (86%)
Black/African American	5 (8%)	2 (14%)
BMI percentile 1st AP attack	70.3 (27.3–92.3)	38.4 (17.0–89.4) n=12	0.58
Weight percentile 1st AP attack	47.9 (17.2–88.9)	23.1 (5.4–83.6)	0.48
Severity of attack			0.87
Mild	46 (77%)	12 (86%)
Moderately severe	9 (15%)	1 (7%)
Severe	5 (8%)	1 (7%)
Risk Factors			0.39
Divisum/Obstructive	8 (13%)	1 (7%)
Biliary/Gallstones	7 (12%)	2 (14%)
Trauma	1 (2%)	0 (0%)
Genetic*	2 (3%)	3 (21%)
Systemic/Metabolic/Toxic	6 (10%)	0 (0%)
Drug induced	10 (17%)	1 (7%)
Multiple	9 (15%)	2 (14%)
Idiopathic	17 (28%)	5 (36%)
Admitted to hospital in last 12 months	6 (10%)	10 (71%)	<0.0001
# admissions	2.5 (1.0–4.0)	2.0 (2.0–3.0)
Suspected AP episode in last 12 months	22 (37%)	6 (43%)	0.67
Abdominal pain from pancreatitis	26 (43%)	10 (71%)	0.08
# times hospitalized for abdominal pain	0.0 (0.0–0.0)	2.0 (2.0–3.0)
Vomiting	28 (47%)	7 (50%)	0.82
Diarrhea	22 (37%)	5 (36%)	1.00
Both vomiting and diarrhea	13 (22%)	4 (29%)	0.72
Weight loss	17 (28%)	6 (43%)	0.34

AP = acute pancreatitis without recurrence in first year

ARP = acute recurrent pancreatitis Data presented as n (%) or median (25^th–75^th percentile).

^*17/74 (23%) had genetic testing done: 8/60 (13%) AP group, 9/14 (64%) ARP group

Acute Pancreatitis vs Acute Recurrent Pancreatitis

From our cohort, 14/74 (19%) went on to have at least one recurrent attack of AP within the first year post AP follow-up. The ARP group was also similar in age, sex, BMI percentile and race distribution to the single AP group. The ARP group had a significantly higher proportion who were re-hospitalized within the first year 10/14 (71%) vs 6/60 (10%) (P <0.0001) and a higher proportion who experienced abdominal pain 10/14 (71%) vs 26/60 (43%) though this did not reach statistical significance (P =0.08). The proportion of ARP patients with GI symptoms (vomiting, diarrhea, weight loss) was not significantly different from the non-ARP group (Table 1). Risk factors for first AP episodes are also shown in Table 1. Of note, genetic testing was not systematically performed and was obtained more preferentially in the ARP group based on providers’ practices and clinical indications (9/14 (64%) had genetic testing in the ARP group vs 8/60 (13%) in the AP group).

During the 1 year follow-up period, 36/74 (49%) patients reported the presence of abdominal pain. Patients with abdominal pain had a higher proportion of suspected AP attacks at home (26/36, 72%) compared to those without abdominal pain (2/38, 5%) (P <0.0001). Patients with abdominal pain also had a higher rate of reporting both vomiting and diarrhea during the follow-up period (P =0.002).

In addition, patients with any GI symptoms had a higher proportion of suspected attacks (28/61, 46%) compared to those without GI symptoms (0/13, 0%) (P =0.001). 35/74 (47%) reported vomiting, 27/74 (36%) reported diarrhea and 23/74 (31%) reported weight loss.

HRQOL Measures

For the PedsQL^™ 4.0 Generic Core Scales, there were no significant differences between the AP sample and the matched healthy sample for age (t[1209] = 0.00, P > 0.05), gender (χ² [1] = 0.00, P > 0.05) or race/ethnicity (χ² [2] = 0.00, P > 0.05). For the PedsQL^™ Gastrointestinal and Worry Scales, there were no significant differences between the AP sample and the matched healthy sample for age (t[558] = 0.04, P > 0.05), gender (χ² [1] = 0.00, P > 0.05) or race/ethnicity (χ² [2] = 0.00, P > 0.05). Supplementary Table 1 contains the demographic patient characteristics of the AP participants who completed the PedsQL^™ scales one year post their first AP attack as well as for healthy controls. Study participants were asked to complete the PedsQL^™ 4.0 Generic Core Scales and PedsQL^™ Gastrointestinal and Worry Scales at that annual visit.PedsQL^™ 4.0 Generic Core Scales scores were significantly lower for child self-report and parent proxy-report across all dimensions in comparison to the healthy controls (Table 2). The largest effects sizes were for the Generic Core Scales Total Scale Score, Physical Functioning Scale, and the School Functioning Scale (all P<0.001).

Table 2.

PedsQL^™ 4.0 Generic Core Scales Scores Comparisons between Pediatric Patients with Acute Pancreatitis and Healthy Controls for Child Self-Report and Parent Proxy-Report

Generic Core Scales		Acute Pancreatitis		Healthy Controls		Differences (95% CI)	Effect Size
	Items	α	Mean ± SD	α	Mean ± SD
Child Self-Report		N = 24		N = 981
Total Score	23	0.96	70.88 ± 23.84	0.88	85.66 ± 11.74	14.8 (9.9 to 19.7)***	1.22
Physical Functioning	8	0.93	72.94 ± 26.16	0.75	89.87 ± 11.67	16.9 (12.0 to 21.9)***	1.39
Emotional Functioning	5	0.88	72.50 ± 25.32	0.77	81.43 ± 17.55	8.9 (1.7 to 16.1)*	0.50
Social Functioning	5	0.92	77.08 ± 28.81	0.78	87.02 ± 15.92	9.9 (3.3 to 16.6)**	0.61
School Functioning	5	0.87	59.79 ± 27.52	0.71	81.89 ± 16.13	22.1 (15.4 to 28.8)***	1.34
Parent Proxy-Report		N = 30		N = 1172
Total Score	23	0.97	68.78 ± 26.74	0.91	85.17 ± 12.80	16.4 (11.1 to 21.6)***	1.24
Physical Functioning	8	0.96	69.27 ± 33.50	0.85	88.55 ± 15.56	19.3 (13.4 to 25.2)***	1.19
Emotional Functioning	5	0.89	70.33 ± 25.56	0.80	82.03 ± 16.15	11.7 (5.7 to 17.7)***	0.71
Social Functioning	5	0.91	71.33 ± 32.59	0.81	87.08 ± 16.48	15.8 (9.6 to 21.9)***	0.92
School Functioning	5	0.93	60.00 ± 31.95	0.76	80.82 ± 17.19	20.8 (13.8 to 27.8)***	1.18

Note:

^*P<0.05

^**P<0.01

^***P<0.001, based on independent samples t-tests (Bonferroni familywise correction for multiple comparisons, P = 0.01).

α = Cronbach’s alpha internal consistency reliability. SD = standard deviation. CI = confidence interval.

Effect sizes are designated as small (0.20), medium (0.50), and large (0.80).

Higher scores equal better generic health-related quality of life.

For child self-report, all of the Gastrointestinal Symptoms Scales and the Worry About Stomach Aches Scale demonstrated significantly greater symptoms (i.e., lower scale scores) except for the Trouble Swallowing Scale and the Worry About Going Poop Scale. The Stomach Pain and Hurt, Stomach Discomfort When Eating, Nausea and Vomiting, and Worry About Stomach Aches Scales demonstrated the largest effect size differences. For parent proxy-report, all the scales demonstrated significantly greater symptoms (i.e., lower scale scores) than the healthy controls with mostly large effects sizes. The largest effect sizes were demonstrated for the Stomach Pain and Hurt Scale, Stomach Discomfort When Eating Scale, Nausea and Vomiting Scale, the Food and Drink Limits Scale, Heartburn and Reflux Scale, the Gas and Bloating Scale, Diarrhea Scale, and the Worry About Stomach Aches Scale. Comparisons between pediatric patients with AP to the matched healthy controls (Table 3).

Table 3.

PedsQL^™ Gastrointestinal Symptoms Scales and Worry Scales Scores Comparisons between Pediatric Patients with Acute Pancreatitis and Healthy Controls for Child Self-Report and Parent Proxy-Report

Gastrointestinal Symptoms Scales and Worry Scales		Acute Pancreatitis		Healthy Controls		Differences (95% CI)	Effect Size
	Items	α	Mean ± SD	α	Mean ± SD
Child Self-Report		N = 24		N = 477
Stomach Pain and Hurt	6	0.93	59.55 ± 24.25	0.90	80.92 ± 17.99	21.4 (13.8 to 28.9)***	1.17
Stomach Discomfort When Eating	5	0.90	69.53 ± 25.96	0.90	89.57 ± 16.39	20.0 (13.1 to 27.0)***	1.18
Food and Drink Limits	6	0.93	76.04 ± 26.84	0.91	89.72 ± 17.32	13.7 (6.3 to 21.0)***	0.77
Trouble Swallowing	3	0.73	93.06 ± 12.45	0.89	95.67 ± 11.36	2.6 (2.1 to 7.3)	0.23
Heartburn and Reflux	4	0.60	79.17 ± 18.95	0.79	90.51 ± 14.61	11.4 (5.3 to 17.4)***	0.77
Nausea and Vomiting	4	0.89	77.60 ± 21.49	0.88	91.74 ± 14.87	14.1 (7.9 to 20.4)***	0.93
Gas and Bloating	7	0.87	67.41 ± 27.71	0.93	83.12 ± 19.93	15.7 (7.4 to 24.1)***	0.77
Constipation	14	0.91	78.35 ± 18.15	0.95	86.84 ± 17.10	8.5 (1.3 to 15.7)*	0.50
Blood in Poop	2	0.92	91.30 ± 17.85	0.87	96.47 ± 11.67	5.2 (0.1 to 10.2)*	0.43
Diarrhea	7	0.88	83.54 ± 17.12	0.91	94.17 ± 11.75	10.6 (5.6 to 15.7)***	0.88
Worry About Going Poop	5	0.74	88.91 ± 15.15	0.87	94.23 ± 12.99	5.3 (1.3 to 12.0)	0.41
Worry About Stomach Aches	2	0.81	68.75 ± 30.17	0.78	91.10 ± 16.42	22.4 (15.2 to 29.5)***	1.29
Parent Proxy-Report		N = 30		N = 291
Stomach Pain and Hurt	6	0.95	60.20 ± 23.69	0.95	80.79 ± 19.50	20.6 (13.0 to 28.2)***	1.03
Stomach Discomfort When Eating	5	0.94	67.33 ± 26.25	0.94	88.81 ± 17.80	21.5 (14.4 to 28.6)***	1.15
Food and Drink Limits	6	0.97	70.55 ± 33.79	0.92	91.35 ± 15.46	20.8 (14.0 to 27.6)***	1.17
Trouble Swallowing	3	0.85	88.39 ± 19.02	0.95	96.68 ± 11.76	8.3 (3.4 to 13.2)***	0.66
Heartburn and Reflux	4	0.84	75.86 ± 22.33	0.79	93.51 ± 12.88	17.7 (9.0 to 26.3)***	1.26
Nausea and Vomiting	4	0.95	74.58 ± 26.05	0.92	91.97 ± 15.62	17.4 (11.0 to 23.7)***	1.03
Gas and Bloating	7	0.97	69.08 ± 27.22	0.94	87.30 ± 18.95	18.2 (10.7 to 25.7 )***	0.92
Constipation	14	0.95	78.27 ± 20.18	0.97	89.20 ± 15.97	10.9 (4.7 to 17.1)***	0.67
Blood in Poop	2	0.85	90.00 ± 16.87	0.91	96.93 ± 11.64	6.9 (2.3 to 11.5)**	0.57
Diarrhea	7	0.89	81.49 ± 18.90	0.90	95.09 ± 10.71	13.6 (9.2 to 18.0)***	1.16
Worry About Going Poop	5	0.81	89.83 ± 17.09	0.89	95.96 ± 11.14	6.1 (1.7 to 10.6)**	0.52
Worry About Stomach Aches	2	0.75	75.42 ± 23.78	0.83	93.39 ± 16.12	18.0 (11.6 to 24.4)***	1.06

Note:

^*P<0.05

^**P<0.01

^***P<0.001, based on independent samples t-tests (Bonferroni familywise correction for multiple comparisons, P = 0.004).

α = Cronbach’s alpha internal consistency reliability. SD = standard deviation. CI = confidence interval.

Effect sizes are designated as small (0.20), medium (0.50), and large (0.80).

Lower scores demonstrate more (worse) gastrointestinal symptoms and hence lower (worse) gastrointestinal-specific HRQOL.

Internal Consistency Reliability

Cronbach’s alpha internal consistency reliability coefficients for the PedsQL^™ 4.0 Generic Score Scales as shown in Table 2 exceeded the minimum reliability standard of 0.70 required for group comparisons. Most of the AP child self-report and parent proxy-report scales approached or exceeded the reliability criterion of 0.90 recommended for analyzing individual patient scores.

Cronbach’s alpha internal consistency reliability coefficients for the PedsQL^™ Gastrointestinal Symptoms and Worry Scales are shown in Table 3. All scales exceeded the minimum reliability standard of 0.70 required for group comparisons except for the Heartburn and Reflux Scale for AP child self-report. For the AP sample, the majority of scales approached or exceeded the reliability criterion of 0.90 recommended for analyzing individual patient scores.

Discussion

This is a unique pediatric AP cohort followed under a longitudinal observational study designed to follow patients after their first pancreatitis attack which includes prospective follow-up of patients at an annual interval to incorporate both subjective symptoms and objective data paired with PRO measures based on validated tools for pediatric patients. Our novel findings show that abdominal pain and other GI symptoms affect approximately half of patients within the first year after their first episode of AP. We also show that subjects with and without ARP in the first year have similar trends in having vomiting, diarrhea and weight loss and continue to experience troublesome GI symptoms.

We have incorporated into our study the concept of evaluating PRO in post AP in children utilizing validated measures for quality of life in children but not tested in AP setting previously. Our findings demonstrate that there were significant differences in most of the PedsQL^™ 4.0 Generic Core Scales and the PedsQL^™ Gastrointestinal Symptoms Scales between pediatric patients with AP compared to their age, gender, and race/ethnicity matched healthy controls.

While prior AP studies found that there are decreased quality of life metrics in adults as well as increased disability at follow-up(3, 26), this approach has not been previously investigated in children with AP. Up to this time, it was known that ARP and chronic pancreatitis in children are considered debilitating diseases with frequent hosptializations and pain that can impact quality of life adversely (27–32). The effect of a single AP episode without ARP on longitudinal follow up has not been well investigated prior. Our data shows that presence of abdominal and gastrointestinal symptoms of vomiting, diarrhea and weight loss were present in subjects with and without ARP post first attack of AP.

PRO measures of health-related quality of life (HRQOL) and multidimensional gastrointestinal symptoms are essential processes in establishing treatment effects for GI disorders(33, 34). Pediatric patients with functional or organic GI diseases have been shown to manifest significantly impaired overall generic HRQOL compared to matched healthy controls in a large multisite national study (5). Further research with the PedsQL^™ Gastrointestinal Symptoms Scales has also shown that pediatric patients with functional or organic GI diseases demonstrate significantly greater GI symptoms when compared to matched healthy controls across multiple GI symptoms(6, 35–37). Nevertheless, multidimensional measurement of patient-reported GI symptoms of pediatric patients with AP compared to matched healthy controls benchmark group has not been previously investigated.

This study does have limitations. First, it relies on a small sample size of patients from a single center which may limit its generalizability. Additionally, this study lacks data on the patients and families who chose not to participate, although on subanalysis the non-responders had similar baseline characteristics to the responders. Our database reflects a center that provides a quaternary level of care, which may reflect a referral bias in a sample of a sicker population of patients, nonetheless these findings are worth follow up. Lastly, as already discussed, genetic testing was completed on a subset of subjects, based on providers discretion as opposed to a standardized approach for the entire cohort.

Strengths of the study include the use of a prospective cohort design following the patients from the first attack onward. Moreover, the use of the multi-center validated PedsQL^™ Gastrointestinal Symptoms Scales and Worry Scales represents a strength to our design(17). Additionally, the PedsQL^™ 4.0 Generic Core Scales is one of the most widely used pediatric generic HRQOL measurement instruments in the world, as confirmed by recent international meta-analysis reviews(38, 39), and provides a relatively solid benchmark for comparing these generic scales across acute, chronic, and healthy pediatric populations internationally.

In conclusion, we report that after a single episode of AP, pediatric patients suffer from abdominal pain, gastrointestinal symptoms of vomiting, diarrhea and weight loss during the first year post attack even in the absence of progression to ARP. We also show that these symptoms post AP affect their HRQOL outcomes at the one year interval. Future studies should focus on identification of risk factors predisposing to burdensome symptoms that may warrant closer follow-up, as well as strategies to interventions to improve management of AP patients during their initial presentation to optimize their quality of life measures. More research is needed to study the progression of disease following a first attack of AP in children.

What is Known

• Pain and disability affect adults up to one year following their initial acute pancreatitis (AP) attack

• Health-related quality of life (HRQOL) is negatively impacted in adult patients after an episode of AP

What is New

• Pediatric patients with one AP attack have no difference in the burden of gastrointestinal symptoms than those who develop acute recurrent pancreatitis (ARP) in the first year post AP

• Patients with one AP attack have worse reported gastrointestinal symptoms and HRQOL scores compared to healthy controls

Abbreviations:

AP

Acute Pancreatitis

PedsQL

Pediatric Quality of Life Inventory

HRQOL

health-related quality of life

GI

Gastrointestinal

PRO

Patient-Reported Outcome