Age at Presentation of Common Pediatric Surgical Conditions: Reexamining Dogma Jonathan Aboagye, Seth D. Goldstein, Jose H. Salazar, Dominic Papandria, Mekam T. Okoye, Khaled Al-Omar, Dylan Stewart, Jeffrey Lukish, Fizan Abdullah PII: DOI: Reference:
S0022-3468(14)00048-7 doi: 10.1016/j.jpedsurg.2014.01.039 YJPSU 56670
To appear in:
Journal of Pediatric Surgery
Received date: Accepted date:
25 January 2014 27 January 2014
Please cite this article as: Aboagye Jonathan, Goldstein Seth D., Salazar Jose H., Papandria Dominic, Okoye Mekam T., Al-Omar Khaled, Stewart Dylan, Lukish Jeffrey, Abdullah Fizan, Age at Presentation of Common Pediatric Surgical Conditions: Reexamining Dogma, Journal of Pediatric Surgery (2014), doi: 10.1016/j.jpedsurg.2014.01.039
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
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Age at Presentation of Common Pediatric Surgical Conditions: Reexamining Dogma
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Jonathan Aboagye, MBChB, MPH; Seth D. Goldstein, MD; Jose H Salazar, MD; Dominic Papandria, MD; Mekam T Okoye, MBBS, Khaled Al-Omar, MBBS, Dylan Stewart, MD, Jeffrey Lukish, MD, Fizan Abdullah, MD, PhD
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Center for Pediatric Surgical Clinical Trials & Outcomes Research, Division of Pediatric Surgery Johns Hopkins University School of Medicine
Address Correspondence to:
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Fizan Abdullah, MD, PhD Division of Pediatric Surgery Charlotte R. Bloomberg Children’s Center 1800 Orleans Street, Room 7337 Baltimore, MD 21287-0005 E-mail: [email protected] Telephone: (410) 955-1983 Fax: (410) 502-5314
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ABSTRACT Purpose: The commonly cited ages at presentation of many pediatric conditions have been
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based largely on single center or outdated epidemiologic evidence. Thus, we sought to examine
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the ages at presentation of common pediatric surgical conditions using cases from large national databases.
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Methods: A retrospective analysis was performed on Healthcare Cost and Utilization Project databases from 1988 to 2009. Pediatric discharges were selected using matched ICD9 diagnosis
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and procedure codes for malrotation, intussusception, hypertrophic pyloric stenosis (HPS), incarcerated inguinal hernia (IH), and Hirschsprung disease (HD). Descriptive statistics were
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computed.
Results: A total of 63,750 discharges were identified, comprising 2,744 cases of malrotation, 5,831 of intussusception, 36,499 of HPS, 8,564 of IH, and 10,112 of HD. About 58.2% of
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malrotation cases presented before age 1. Moreover, 92.8% of HPS presented between 3 and 10 weeks. For intussusception, 50.3% and 91.4% presented prior to ages 1 and 4 years,
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respectively. Also, 55.8% of IHD cases presented before their first birthday. For HD, 6.5% of
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cases presented within the neonatal period and 45.9% prior to age 1 year. Conclusion: Our findings support generally cited presenting ages for HPS and intussusception.
texts.
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However, the ages at presentation for HD, malrotation, and IH differ from commonly cited
Keywords: age at presentation; intussusception; pyloric stenosis; inguinal hernia; malrotation; Hirschsprung disease
ACCEPTED MANUSCRIPT
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INTRODUCTION
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The age at presentation of pediatric patients with certain symptoms is a critical part of establishing differential diagnoses and correctly identifying common surgical conditions. For
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example, refractory emesis in a 2-year-old is unlikely to be hypertrophic pyloric stenosis (HPS),
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but could conceivably be malrotation. [1, 2] In this context, common adages regarding age of
pediatricians and pediatric surgeons.
MA
presentation of common pediatric conditions are emphasized during the training of
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However, much of this dogma stems from isolated institutional experiences or outdated epidemiologic evidence, while the true age-related epidemiology of many pediatric diseases is
PT
not precisely known. Thus, we sought to re examine the age at presentation of common
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pediatric surgical conditions using admissions from large national databases over a 21 year
METHODS
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period.
Data Acquisition A retrospective analysis was performed using a non-overlapping combination of the Nationwide Inpatient Sample (NIS) (1988-1996, 1998, 1999, 2001, 2002, 2004, 2005, 2007, 2008 and 2009) and the Kids’ Inpatient Database (KID) (1997, 2000, 2003, 2006). Both the NIS and KID have been developed as part of the Healthcare Cost and Utilization Project (HCUP) of the Agency for Healthcare Research and Quality (AHRQ). [3] The NIS is an all-payer database that
ACCEPTED MANUSCRIPT currently compiles information on up to 8.16 million inpatient discharges from approximately 1,000 hospitals across the United States each year. Hospitals are selected to represent a 20%
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stratified sample of all community hospitals. Data from 1056 hospitals located in 42 states were available in the data set under study. The KID contains a sample of pediatric (age 20 or
SC
less) discharges from all community, non-rehabilitation hospitals from states which participate in HCUP. The KID samples 1.91 to 3.13 million patient discharges, rather than sampling at the
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hospital level like the NIS. Patient discharges are then weighted to obtain national estimates.
MA
The sampling algorithm involves systematic random sampling so that 10% of uncomplicated inhospital births and 80% of complicated in-hospital births are selected, as well as other selected
ED
pediatric cases. The KID contains information from 3,739 hospitals in 38 states over the period
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studied. [4] Included in the analysis were children younger than 18 years old. We used a combination of International Classification of Disease 9 th edition (ICD 9)
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diagnostic and procedure codes for malrotation, intussusception, hypertrophic pyloric stenosis
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(HPS), incarcerated inguinal hernia (IH) and Hirschprung disease (HD), to select patient discharges for the analysis. HCUP databases record previous and current admission diagnosis of patients using the ICD 9 codes per discharge; thus, to increase specificity we included records containing ICD9 diagnostic codes that matched corresponding procedure codes during the index admission (Table 1). The NIS and KID provide age in days for infants (less than one year old) and age in months for children younger than eleven years. Using the most precise value available for each record, the patients were divided into the different age groups for each diagnosis due to peculiarities in the presentation of each disease. To account for the ages at presentation for children who might have spent time in a neonatal intensive care unit prior to
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gestational age or prematurity were not available.
Information on patients’ gender and race were also obtained. Descriptive statistics were
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performed using Stata MP, version 11 (College Station, TX).
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RESULTS
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A total of 63,750 discharges were identified, which included 2,744 cases of malrotation, 5,831 of intussusception, 36,499 of HPS, 8,564 of IH and 10,112 of HD.
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Malrotation
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Out of the 2,744 cases of intestinal malrotation, 1,621 (59.1%) were males and 1,123 (40.9%) were females. The ages ranged from the neonatal period to 17 years with mean and median
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ages of 3.2 years and 5 months respectively. Also, 58.2% presented before their 1 st birthday and
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75% before age 5 years. The peak age of presentation was the 1st month of life (30%), with a steep decline by the end of the 3rd month to 10%. This was followed by a steady decline until 8 years. [Figure 1] Intussusception Among the 5,831 cases of intussusceptions identified were 3,767 (64.6%) males and 2,064 (35.4%) females, resulting in a male:female ratio of 2:1. The mean age was 20 months and the median age 1 year, range 1 month to 17 years. [Table 2] Presentation was rare prior to the 3 rd month. However, there was a sharp increase from the 3rd month onwards, with a peak in the 1
ACCEPTED MANUSCRIPT to 3-year-old interval and a sharp decline at age 7 years. Moreover, 91% of cases presented before age 4 years and 98.7% prior to age 13 years. [Figure 1]
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Infantile Hypertrophic Pyloric Stenosis
We identified a total of 36,499 cases of HPS, which comprised 30,244 (82.9%) males and 6,255
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(17.1%) females giving a ratio of 5:1. The ages of patients ranged from 1 week to 10 years. The
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mean and median ages were 5 weeks. [Table 2] Approximately half of the patients presented before 5 weeks, 80% before the 8 weeks and 97.5% by 12 weeks. There was a sharp increase in
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the incidence after the 2nd week and peaking at the 5th week. A steady decline was noted from
Incarcerated Inguinal Hernia
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there to the 10th week and leveling off to the 12th week of life. [Figure 1]
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Out of a total of 8,564 cases, 7,553 (88.2%) were males and 1,011 (11.8%) were females.
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(male:female ratio of 7:1). The mean and median ages at presentation were 2.4 years and 8 months respectively. [Table 2] Their ages ranged from the first month of life to 17 years. About
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55.8% of patients presented before their 1st birthday and 85.2% prior to their 5th birthday. Moreover, 90.5% presented prior to age 9 years. A bimodal distribution was noted. There was an initial peak at the 1-3 month age interval and then another at 1 year. Subsequently, there was a leveling off from 4 years to those beyond 9 years. [Figure 1] Hirschsprung Disease A total of 10,112 patients presenting with Hirschprung disease were identified. This included 7,588 (75.0%) males and 2,524 (25.0%) females. (male:female ratio of 3:1) The mean and median ages at presentation were 3 years and 1 year respectively. [Table 2] Only 6.5% of cases
ACCEPTED MANUSCRIPT presented by the 1st week of life, 60% and 93% presented before their 2nd and 13th birthdays respectively. A gradual increase in the incidence was noticed from the 1 st week of life with peak
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at 6-11 year age interval. [Figure 1] Discussion
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We have freshly examined the dogma surrounding the ages of presentation of intestinal
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malrotation, intussusception, hypertrophic pyloric stenosis, incarcerated inguinal hernia and Hirschsprung disease using national administrative databases. Our findings support
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traditionally cited presenting ages for intussusception and hypertrophic pyloric stenosis. However, the ages at presentation for malrotation, incarcerated inguinal hernia and
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Hirschsprung disease differ from commonly cited texts.
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Intestinal malrotation is said to have a varied clinical presentation from infancy through adulthood. Although it has often been regarded as a disease of infancy, there is increasing
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evidence of presentation at later years and into adulthood.[5] In the pediatric age group it is
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reported that between half to two thirds of cases present in the 1 st month of life, with most of these presenting in the neonatal period.[6] Other texts also posit that around 90% of cases occur in the 1st year of life. [7, 8, 9] However, in our study only 20% of cases presented within the 1st month of life and only 60% before 1 year. This may correlate with a single-center study by Nehra et. al., which reported that 31% of malrotation cases presented among patients less than 1 year of age, with 21% among those aged 1 year to 18 years. The remaining 48% were older than 18 years. [10] This implies that within the pediatric age group, about two thirds of malrotation cases present in children less than 1 year which is consistent with our findings.
ACCEPTED MANUSCRIPT Intussusception is traditionally regarded to present rarely before 3 months of life, with about 90% presenting before 3 years of age. [11][12] Most cases are thought to present
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between 6 – 9 months of life. [13] A population-wide study done in Denmark among a cohort of children under 5 years, showed the rarity of the condition before 2 months of life and a decline
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after 12 months of age. [14] Mandeville et. al. reported that, the majority of patients who presented with a diagnosis of intussusception in their facility in the US were between the ages
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of 6 to 36 months old. Moreover, 60% of cases presented before 1 year and 80-90% were
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younger than 2 years. [15] Our study results are consistent with these findings, with only 1.5% of cases presenting before 2 months of age, just over half of cases presenting before 1 year,
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70% before 2 years, and 91% at 3 years.
The presentation of a 3 week old infant presenting to the emergency department with
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non-bilious emesis will trigger a differential diagnosis of HPS. This is because HPS is known to
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occur commonly in children aged 3 to 12 weeks presenting with progressive, non bilious,
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projectile vomiting.[1] A nationwide study in the United States showed that the mean age at presentation was 41.1 days, with an age range of 1 day to 3 years. [16] Another case series also showed that the mean age at presentation with vomiting in HPS cases was about 35 days with a mean age at surgery of 39 days. [17] These are consistent with our findings, which demonstrated a mean age at presentation of 38 days with rare disease presentation before the 3rd week (1.6%) and 98% before the 12th week. Incarcerated inguinal hernia has been reported to occur in about 30% of cases before 2 months of age.[18] Other texts indicate that about two thirds of IH cases present in children under 1 year old.[19] In a series to investigate the incidence of incarcerated inguinal hernia,
ACCEPTED MANUSCRIPT Stylianos et. al., found that 85% of incarceration occurred before the 1st birthday.[20] However, our analysis reveals a mean age of 2.5 years, with only 55.8% of cases of presenting before their
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1st birthday, though between 30-40% of cases presented in the first 2 months of life. One possible reason could be our inability to capture patients who might have presented earlier
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with nonstrangulating incarceration, but had postponement of operative treatment due to scheduling difficulties or concerns of fitness for surgery. [21]
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Hirschsprung disease is often described as a disease of the neonatal period. Some
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studies have reported that about 80 – 90% of patients present during the neonatal period with abdominal distension and bilious vomiting. [22, 23] Our observations differ from this widely
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cited dogma. We observed that only 6.5% of cases presented in the neonatal period and only 60% of cases were seen before their 1st birthday. This deviation could be explained by our case
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selection criteria. Our use of ICD-9 diagnostic and procedure codes for HD means that patients
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selected had to have a biopsy or a procedure to treat HD. Patients undergoing staged repair for
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long-segment disease may be captured again by these methods when they re-present for their definitive operations. Still, we believe that the majority of patients in the time frame of this study would have been offered primary pullthrough. That leaves consideration that the disease may present later than conventionally thought, or that cases presenting later in life are those of missed diagnosis. In a study by Khan et al, the mean age of patients undergoing biopsy for HD was 2.9 years. [24] This mean age is relatively similar to the mean age of the selected admissions for HD in this study (2.4 years). Our study has various strengths compared to previous studies examining the age at presentation of these conditions. It leverages the largest sample of inpatient records that
ACCEPTED MANUSCRIPT describe age of onset for the conditions examined, representing a nationwide sample over a 21 year period. The analysis is limited by the unavailability of persistent patient identifiers in the
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NIS or KID databases, which limit the ability to detect and account for hospital-to-hospital transfer or repeated admissions. This has the potential to skew the resulting analysis through
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double-counting. In addition, the presence of the diagnosis code does not implicate the surgical condition as the source of the patient’s presenting symptoms, as the diagnosis may
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have been made incidentally. This is particularly true for malrotation where about 20% of cases
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are diagnosed intraoperatively, during surgery for other congenital anomalies. [25] We believe that the large nationwide sample included in the current study helps to shed
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light on the ages associated with common pediatric surgical conditions. Specifically, though we agree with the traditional teachings regarding pyloric stenosis and intussusception, we hope to
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shed light on potential inaccuracies addressing the age at presentation of malrotation,
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incarcerated inguinal hernia and Hirschsprung disease.
ACCEPTED MANUSCRIPT REFERENCES 1. Spicer RD. Infantile hypertrophic pyloric stenosis: A review. Br J Surg. 1982; 69:128-135.
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2. Clark LA, Oldham KT. Malrotation. In Ashcraft KW, Murphy JP, Sharp RJ, et al, eds.
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Pediatric surgery. 3rd ed. Philadelphia: Saunders, 2000, pp 425–442.
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3. NIS Technical Documentation, Agency for Healthcare Research and Quality, Rockville (Md) (2003 [February]), p. 135
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4. HCUP Databases. Healthcare Cost and Utilization Project (HCUP). June 2013. Agency for
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Healthcare Research and Quality, Rockville, MD
http://www.hcup-us.ahrq.gov/kidoverview.jsp. Accessed on July 4th, 2013
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5. Nagdeve NG, Qureshi AM, Bhingare PD, Shinde SK.Malrotation beyond infancy. - J
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Pediatr Surg. 2012 Nov;47(11):2026-32 6. Bales C, Liacouras CA. Intestinal atresia, stenosis and malrotation. In: Kliegman RM,
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Stanton BF, Geme JW, Schor NF, Berhman RE, eds. Nelson Textbook of Pediatrics. 19th
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ed. Philadelphia: Saunders; 2011.
7. Pierro A, Ong EGP. Malrotation. In: Puri P, Höllwarth ME, eds. Pediatric Surgery. Berlin Heidelberg: Springer; 2006:197-202. 8. Strouse P J. Disorders of intestinal rotation and fixation (“malrotation”). Pediatr Radiol2004;34:837–51 9. . Kapfer SA, Rappold JF. Intestinal malrotation—not just the pediatric surgeon’s problem. J Am Coll Surg 2004;199:628– 635 10. Nehra D, Goldstein AM. Intestinal malrotation: Varied clinical presentation from infancy through adulthood. Surgery. 2011;149:386-393
ACCEPTED MANUSCRIPT 11. Justice FA, Auldist AW, Bines JE. Intussusception: Trends in clinical presentation and management. J Gastroenterol Hepatol. 2006;21:842-846.
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12. Colombani PM, Scholz S. Intussusception. In: Coran GA, ed. Pediatric Surgery. 7th ed.
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Philadelphia: Saunders; 2012:1093-1109.
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13. 1. Doody DP, Foglia RP. Intussusception. In: Oldham KT, Colombani PM, Foglia RP, eds. Principles and Practice of Pediatric Surgery. 2nd ed. Philadelphia: Lippincott
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Williams & Wilkins; 2005:1297-1305.
14. Fischer TK, Bihrmann K, Perch M, Koch A, Wohlfahrt J, Kåre M, Melbye M.
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Intussusception in early childhood: A cohort study of 1.7 million children. Pediatrics.
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2004;114:782-785.
15. Mandeville K, Chien M, Willyerd FA, Mandell G, Hostetler MA, Bulloch B Pediatr Emerg
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Care. 2012;28: 842-844.
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16. Safford SD, Pietrobon R, Safford KM, Martins H, Skinner MA, Rice HE. A study of 11,003
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patients with hypertrophic pyloric stenosis and the association between surgeon and hospital volume and outcomes. - J Pediatr Surg. 2005;40:967-972 17. Jedd MB, Melton LJ, 3rd, Griffin MR, Kaufman BH, Hoffman AD, Broughton DD, O'Brien PC. Trends in infantile hypertrophic pyloric stenosis in Olmsted County, Minnesota, 1950-1984. Paediatr Perinat Epidemiol. 1988;2: 148–157. 18. Rowe MI, Clatworthy HW. Incarcerated and strangulated hernias in children. Arch Surg 1970;101:136 19. Aiken JJ, Oldham KT. Inguinal hernias. In: Kliegman RM, Stanton BF, Geme JW, Schor NF, Berhman RE, eds. Nelson Textbook of Pediatrics. 19th ed. Philadelphia: Saunders; 2011:1362-1368.
ACCEPTED MANUSCRIPT 20. Stylianos S, Jacir NN, Harris BH: Incarceration of inguinal hernia in infants prior to elective repair. J Pediatr Surg. 1993;28:582
35-year review. J Pediatr Surg. 2006; 41:980-986.
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21. Ein SH, Njere I, Ein A. Six thousand three hundred sixty-one pediatric inguinal hernias: A
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22. Langer JC. Hirschprungs disease. In: Oldham KT, Colombani PM, Foglia RP, eds.
Williams & Wilkins; 2005:1348-1364.
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Principles and Practice of Pediatric Surgery. Volume II ed. Philadelphia: Lippincott
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23. Langer JC. Hirshprungs disease. In: Coran GA, ed. Pediatric Surgery. 7th ed. Philadelphia: Suanders; 2012:1265-1278.
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24. Khan AR, Vujanic GM, Huddart S. The constipated child: how likely is Hirschsprung's disease? Pediatr Surg Int. 2003;19:439-42
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25. Powell DM, Othersen HB, Smith CD. Malrotation of the intestines in children: the effect
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of age on presentation and therapy. J Pediatr Surg. 1989; 24:777-80.
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Table 1 ICD 9 Diagnosis and Procedure codes used in Cases Selection
751.4
Procedure Codes
45.61, 45.62, 45.63, 46.01, 46.20, 46.21, 46.23, 46.81, 46.82, 54.11, 54.95
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433
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9629, 46.80, 46.81, 46.82, 46.85
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Incarcerated Inguinal Hernia 550.0, 550.00,550.01, 550.02, 550.03, 550.1, 550.10, 550.11, 550.12, 550.13 530, 53.00, 53.01, 53.02, 53.04, 53.05, 531, 53.12, 53.13, 53.14, 53.15, 53.16, 53.17
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Diagnosis Codes
Intussusception Hypertrophic Pyloric Stenosis 560.0 750.5
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Malrotation
Hirschsprung Disease 751.3
45.92, 45.95, 46.01, 46.03, 46.10, 46.11,46.13, 48.40,48.41, 48.42, 48.43, 48.49, 48.50, 48.52, 48.59, 48.65, 48.69
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Intussusception
Hypertrophic Pyloric Stenosis
Incarcerated Inguinal Hernia
Hirschsprung Disease
1,621 (59.1) 1,123 (40.9) 3.2(4.9)
3,767 (64.6) 2,064 (35.4) 1.7(2.2)
30,244 (82.9) 6,255 (17.10) 5.2(3.6)*
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7,553 (88.2) 1,011(11.8) 2.4(4.1)
7,588(75.0) 2,524 (25.0) 3.0(4.0)
1,418 ( 51.7 ) 297 (10.8) 278 (10.1) 65 (2.4)
2,322 (39.8) 726(12.5) 1,178 (20.2) 221 (3.8)
18,440 (50.5) 1,954 (5.4) 5,775 (15.8) 378 (1.0)
3,813 (44.5) 1,526 (17.8) 785 (9.2) 236 (2.7)
4,777(47.2) 1,311 (13.0 ) 1,154 (11.4) 342( 3.4)
336 (5.8) 1,048 (18.0)
1,601 (4.4) 8,351 (22.9)
283 (3.3) 1,921(22.4)
462 (4.6) 2,066 (20.4)
5,831
36,499
8,564
10,112
2,744
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119(4.3) 567 (20.7)
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Malrotation
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Sex N (%) Male Female Age(years) Mean (SD) Race N (%) White Black Hispanic Asian/Pacific Islander other Unspecified Total N
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Table 2 Patient Demographics by Cases
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S0022-3468(14)00048-7 doi: 10.1016/j.jpedsurg.2014.01.039 YJPSU 56670
To appear in:
Journal of Pediatric Surgery
Received date: Accepted date:
25 January 2014 27 January 2014
Please cite this article as: Aboagye Jonathan, Goldstein Seth D., Salazar Jose H., Papandria Dominic, Okoye Mekam T., Al-Omar Khaled, Stewart Dylan, Lukish Jeffrey, Abdullah Fizan, Age at Presentation of Common Pediatric Surgical Conditions: Reexamining Dogma, Journal of Pediatric Surgery (2014), doi: 10.1016/j.jpedsurg.2014.01.039
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
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Age at Presentation of Common Pediatric Surgical Conditions: Reexamining Dogma
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Jonathan Aboagye, MBChB, MPH; Seth D. Goldstein, MD; Jose H Salazar, MD; Dominic Papandria, MD; Mekam T Okoye, MBBS, Khaled Al-Omar, MBBS, Dylan Stewart, MD, Jeffrey Lukish, MD, Fizan Abdullah, MD, PhD
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Center for Pediatric Surgical Clinical Trials & Outcomes Research, Division of Pediatric Surgery Johns Hopkins University School of Medicine
Address Correspondence to:
AC
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Fizan Abdullah, MD, PhD Division of Pediatric Surgery Charlotte R. Bloomberg Children’s Center 1800 Orleans Street, Room 7337 Baltimore, MD 21287-0005 E-mail: [email protected] Telephone: (410) 955-1983 Fax: (410) 502-5314
ACCEPTED MANUSCRIPT
ABSTRACT Purpose: The commonly cited ages at presentation of many pediatric conditions have been
T
based largely on single center or outdated epidemiologic evidence. Thus, we sought to examine
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the ages at presentation of common pediatric surgical conditions using cases from large national databases.
SC
Methods: A retrospective analysis was performed on Healthcare Cost and Utilization Project databases from 1988 to 2009. Pediatric discharges were selected using matched ICD9 diagnosis
NU
and procedure codes for malrotation, intussusception, hypertrophic pyloric stenosis (HPS), incarcerated inguinal hernia (IH), and Hirschsprung disease (HD). Descriptive statistics were
MA
computed.
Results: A total of 63,750 discharges were identified, comprising 2,744 cases of malrotation, 5,831 of intussusception, 36,499 of HPS, 8,564 of IH, and 10,112 of HD. About 58.2% of
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malrotation cases presented before age 1. Moreover, 92.8% of HPS presented between 3 and 10 weeks. For intussusception, 50.3% and 91.4% presented prior to ages 1 and 4 years,
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respectively. Also, 55.8% of IHD cases presented before their first birthday. For HD, 6.5% of
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cases presented within the neonatal period and 45.9% prior to age 1 year. Conclusion: Our findings support generally cited presenting ages for HPS and intussusception.
texts.
AC
However, the ages at presentation for HD, malrotation, and IH differ from commonly cited
Keywords: age at presentation; intussusception; pyloric stenosis; inguinal hernia; malrotation; Hirschsprung disease
ACCEPTED MANUSCRIPT
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INTRODUCTION
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The age at presentation of pediatric patients with certain symptoms is a critical part of establishing differential diagnoses and correctly identifying common surgical conditions. For
SC
example, refractory emesis in a 2-year-old is unlikely to be hypertrophic pyloric stenosis (HPS),
NU
but could conceivably be malrotation. [1, 2] In this context, common adages regarding age of
pediatricians and pediatric surgeons.
MA
presentation of common pediatric conditions are emphasized during the training of
ED
However, much of this dogma stems from isolated institutional experiences or outdated epidemiologic evidence, while the true age-related epidemiology of many pediatric diseases is
PT
not precisely known. Thus, we sought to re examine the age at presentation of common
CE
pediatric surgical conditions using admissions from large national databases over a 21 year
METHODS
AC
period.
Data Acquisition A retrospective analysis was performed using a non-overlapping combination of the Nationwide Inpatient Sample (NIS) (1988-1996, 1998, 1999, 2001, 2002, 2004, 2005, 2007, 2008 and 2009) and the Kids’ Inpatient Database (KID) (1997, 2000, 2003, 2006). Both the NIS and KID have been developed as part of the Healthcare Cost and Utilization Project (HCUP) of the Agency for Healthcare Research and Quality (AHRQ). [3] The NIS is an all-payer database that
ACCEPTED MANUSCRIPT currently compiles information on up to 8.16 million inpatient discharges from approximately 1,000 hospitals across the United States each year. Hospitals are selected to represent a 20%
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T
stratified sample of all community hospitals. Data from 1056 hospitals located in 42 states were available in the data set under study. The KID contains a sample of pediatric (age 20 or
SC
less) discharges from all community, non-rehabilitation hospitals from states which participate in HCUP. The KID samples 1.91 to 3.13 million patient discharges, rather than sampling at the
NU
hospital level like the NIS. Patient discharges are then weighted to obtain national estimates.
MA
The sampling algorithm involves systematic random sampling so that 10% of uncomplicated inhospital births and 80% of complicated in-hospital births are selected, as well as other selected
ED
pediatric cases. The KID contains information from 3,739 hospitals in 38 states over the period
PT
studied. [4] Included in the analysis were children younger than 18 years old. We used a combination of International Classification of Disease 9 th edition (ICD 9)
CE
diagnostic and procedure codes for malrotation, intussusception, hypertrophic pyloric stenosis
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(HPS), incarcerated inguinal hernia (IH) and Hirschprung disease (HD), to select patient discharges for the analysis. HCUP databases record previous and current admission diagnosis of patients using the ICD 9 codes per discharge; thus, to increase specificity we included records containing ICD9 diagnostic codes that matched corresponding procedure codes during the index admission (Table 1). The NIS and KID provide age in days for infants (less than one year old) and age in months for children younger than eleven years. Using the most precise value available for each record, the patients were divided into the different age groups for each diagnosis due to peculiarities in the presentation of each disease. To account for the ages at presentation for children who might have spent time in a neonatal intensive care unit prior to
ACCEPTED MANUSCRIPT diagnosis or subsequent procedure, we calculated the age at presentation for children under 1 year by adding the coded hospital day of procedure to the admission date. Accurate data on
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gestational age or prematurity were not available.
Information on patients’ gender and race were also obtained. Descriptive statistics were
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performed using Stata MP, version 11 (College Station, TX).
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RESULTS
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A total of 63,750 discharges were identified, which included 2,744 cases of malrotation, 5,831 of intussusception, 36,499 of HPS, 8,564 of IH and 10,112 of HD.
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Malrotation
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Out of the 2,744 cases of intestinal malrotation, 1,621 (59.1%) were males and 1,123 (40.9%) were females. The ages ranged from the neonatal period to 17 years with mean and median
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ages of 3.2 years and 5 months respectively. Also, 58.2% presented before their 1 st birthday and
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75% before age 5 years. The peak age of presentation was the 1st month of life (30%), with a steep decline by the end of the 3rd month to 10%. This was followed by a steady decline until 8 years. [Figure 1] Intussusception Among the 5,831 cases of intussusceptions identified were 3,767 (64.6%) males and 2,064 (35.4%) females, resulting in a male:female ratio of 2:1. The mean age was 20 months and the median age 1 year, range 1 month to 17 years. [Table 2] Presentation was rare prior to the 3 rd month. However, there was a sharp increase from the 3rd month onwards, with a peak in the 1
ACCEPTED MANUSCRIPT to 3-year-old interval and a sharp decline at age 7 years. Moreover, 91% of cases presented before age 4 years and 98.7% prior to age 13 years. [Figure 1]
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Infantile Hypertrophic Pyloric Stenosis
We identified a total of 36,499 cases of HPS, which comprised 30,244 (82.9%) males and 6,255
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(17.1%) females giving a ratio of 5:1. The ages of patients ranged from 1 week to 10 years. The
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mean and median ages were 5 weeks. [Table 2] Approximately half of the patients presented before 5 weeks, 80% before the 8 weeks and 97.5% by 12 weeks. There was a sharp increase in
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the incidence after the 2nd week and peaking at the 5th week. A steady decline was noted from
Incarcerated Inguinal Hernia
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there to the 10th week and leveling off to the 12th week of life. [Figure 1]
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Out of a total of 8,564 cases, 7,553 (88.2%) were males and 1,011 (11.8%) were females.
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(male:female ratio of 7:1). The mean and median ages at presentation were 2.4 years and 8 months respectively. [Table 2] Their ages ranged from the first month of life to 17 years. About
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55.8% of patients presented before their 1st birthday and 85.2% prior to their 5th birthday. Moreover, 90.5% presented prior to age 9 years. A bimodal distribution was noted. There was an initial peak at the 1-3 month age interval and then another at 1 year. Subsequently, there was a leveling off from 4 years to those beyond 9 years. [Figure 1] Hirschsprung Disease A total of 10,112 patients presenting with Hirschprung disease were identified. This included 7,588 (75.0%) males and 2,524 (25.0%) females. (male:female ratio of 3:1) The mean and median ages at presentation were 3 years and 1 year respectively. [Table 2] Only 6.5% of cases
ACCEPTED MANUSCRIPT presented by the 1st week of life, 60% and 93% presented before their 2nd and 13th birthdays respectively. A gradual increase in the incidence was noticed from the 1 st week of life with peak
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at 6-11 year age interval. [Figure 1] Discussion
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We have freshly examined the dogma surrounding the ages of presentation of intestinal
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malrotation, intussusception, hypertrophic pyloric stenosis, incarcerated inguinal hernia and Hirschsprung disease using national administrative databases. Our findings support
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traditionally cited presenting ages for intussusception and hypertrophic pyloric stenosis. However, the ages at presentation for malrotation, incarcerated inguinal hernia and
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Hirschsprung disease differ from commonly cited texts.
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Intestinal malrotation is said to have a varied clinical presentation from infancy through adulthood. Although it has often been regarded as a disease of infancy, there is increasing
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evidence of presentation at later years and into adulthood.[5] In the pediatric age group it is
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reported that between half to two thirds of cases present in the 1 st month of life, with most of these presenting in the neonatal period.[6] Other texts also posit that around 90% of cases occur in the 1st year of life. [7, 8, 9] However, in our study only 20% of cases presented within the 1st month of life and only 60% before 1 year. This may correlate with a single-center study by Nehra et. al., which reported that 31% of malrotation cases presented among patients less than 1 year of age, with 21% among those aged 1 year to 18 years. The remaining 48% were older than 18 years. [10] This implies that within the pediatric age group, about two thirds of malrotation cases present in children less than 1 year which is consistent with our findings.
ACCEPTED MANUSCRIPT Intussusception is traditionally regarded to present rarely before 3 months of life, with about 90% presenting before 3 years of age. [11][12] Most cases are thought to present
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between 6 – 9 months of life. [13] A population-wide study done in Denmark among a cohort of children under 5 years, showed the rarity of the condition before 2 months of life and a decline
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after 12 months of age. [14] Mandeville et. al. reported that, the majority of patients who presented with a diagnosis of intussusception in their facility in the US were between the ages
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of 6 to 36 months old. Moreover, 60% of cases presented before 1 year and 80-90% were
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younger than 2 years. [15] Our study results are consistent with these findings, with only 1.5% of cases presenting before 2 months of age, just over half of cases presenting before 1 year,
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70% before 2 years, and 91% at 3 years.
The presentation of a 3 week old infant presenting to the emergency department with
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non-bilious emesis will trigger a differential diagnosis of HPS. This is because HPS is known to
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occur commonly in children aged 3 to 12 weeks presenting with progressive, non bilious,
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projectile vomiting.[1] A nationwide study in the United States showed that the mean age at presentation was 41.1 days, with an age range of 1 day to 3 years. [16] Another case series also showed that the mean age at presentation with vomiting in HPS cases was about 35 days with a mean age at surgery of 39 days. [17] These are consistent with our findings, which demonstrated a mean age at presentation of 38 days with rare disease presentation before the 3rd week (1.6%) and 98% before the 12th week. Incarcerated inguinal hernia has been reported to occur in about 30% of cases before 2 months of age.[18] Other texts indicate that about two thirds of IH cases present in children under 1 year old.[19] In a series to investigate the incidence of incarcerated inguinal hernia,
ACCEPTED MANUSCRIPT Stylianos et. al., found that 85% of incarceration occurred before the 1st birthday.[20] However, our analysis reveals a mean age of 2.5 years, with only 55.8% of cases of presenting before their
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1st birthday, though between 30-40% of cases presented in the first 2 months of life. One possible reason could be our inability to capture patients who might have presented earlier
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with nonstrangulating incarceration, but had postponement of operative treatment due to scheduling difficulties or concerns of fitness for surgery. [21]
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Hirschsprung disease is often described as a disease of the neonatal period. Some
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studies have reported that about 80 – 90% of patients present during the neonatal period with abdominal distension and bilious vomiting. [22, 23] Our observations differ from this widely
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cited dogma. We observed that only 6.5% of cases presented in the neonatal period and only 60% of cases were seen before their 1st birthday. This deviation could be explained by our case
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selection criteria. Our use of ICD-9 diagnostic and procedure codes for HD means that patients
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selected had to have a biopsy or a procedure to treat HD. Patients undergoing staged repair for
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long-segment disease may be captured again by these methods when they re-present for their definitive operations. Still, we believe that the majority of patients in the time frame of this study would have been offered primary pullthrough. That leaves consideration that the disease may present later than conventionally thought, or that cases presenting later in life are those of missed diagnosis. In a study by Khan et al, the mean age of patients undergoing biopsy for HD was 2.9 years. [24] This mean age is relatively similar to the mean age of the selected admissions for HD in this study (2.4 years). Our study has various strengths compared to previous studies examining the age at presentation of these conditions. It leverages the largest sample of inpatient records that
ACCEPTED MANUSCRIPT describe age of onset for the conditions examined, representing a nationwide sample over a 21 year period. The analysis is limited by the unavailability of persistent patient identifiers in the
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NIS or KID databases, which limit the ability to detect and account for hospital-to-hospital transfer or repeated admissions. This has the potential to skew the resulting analysis through
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double-counting. In addition, the presence of the diagnosis code does not implicate the surgical condition as the source of the patient’s presenting symptoms, as the diagnosis may
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have been made incidentally. This is particularly true for malrotation where about 20% of cases
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are diagnosed intraoperatively, during surgery for other congenital anomalies. [25] We believe that the large nationwide sample included in the current study helps to shed
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light on the ages associated with common pediatric surgical conditions. Specifically, though we agree with the traditional teachings regarding pyloric stenosis and intussusception, we hope to
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shed light on potential inaccuracies addressing the age at presentation of malrotation,
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incarcerated inguinal hernia and Hirschsprung disease.
ACCEPTED MANUSCRIPT REFERENCES 1. Spicer RD. Infantile hypertrophic pyloric stenosis: A review. Br J Surg. 1982; 69:128-135.
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2. Clark LA, Oldham KT. Malrotation. In Ashcraft KW, Murphy JP, Sharp RJ, et al, eds.
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Pediatric surgery. 3rd ed. Philadelphia: Saunders, 2000, pp 425–442.
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3. NIS Technical Documentation, Agency for Healthcare Research and Quality, Rockville (Md) (2003 [February]), p. 135
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4. HCUP Databases. Healthcare Cost and Utilization Project (HCUP). June 2013. Agency for
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Healthcare Research and Quality, Rockville, MD
http://www.hcup-us.ahrq.gov/kidoverview.jsp. Accessed on July 4th, 2013
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5. Nagdeve NG, Qureshi AM, Bhingare PD, Shinde SK.Malrotation beyond infancy. - J
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Pediatr Surg. 2012 Nov;47(11):2026-32 6. Bales C, Liacouras CA. Intestinal atresia, stenosis and malrotation. In: Kliegman RM,
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Stanton BF, Geme JW, Schor NF, Berhman RE, eds. Nelson Textbook of Pediatrics. 19th
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ed. Philadelphia: Saunders; 2011.
7. Pierro A, Ong EGP. Malrotation. In: Puri P, Höllwarth ME, eds. Pediatric Surgery. Berlin Heidelberg: Springer; 2006:197-202. 8. Strouse P J. Disorders of intestinal rotation and fixation (“malrotation”). Pediatr Radiol2004;34:837–51 9. . Kapfer SA, Rappold JF. Intestinal malrotation—not just the pediatric surgeon’s problem. J Am Coll Surg 2004;199:628– 635 10. Nehra D, Goldstein AM. Intestinal malrotation: Varied clinical presentation from infancy through adulthood. Surgery. 2011;149:386-393
ACCEPTED MANUSCRIPT 11. Justice FA, Auldist AW, Bines JE. Intussusception: Trends in clinical presentation and management. J Gastroenterol Hepatol. 2006;21:842-846.
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12. Colombani PM, Scholz S. Intussusception. In: Coran GA, ed. Pediatric Surgery. 7th ed.
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Philadelphia: Saunders; 2012:1093-1109.
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13. 1. Doody DP, Foglia RP. Intussusception. In: Oldham KT, Colombani PM, Foglia RP, eds. Principles and Practice of Pediatric Surgery. 2nd ed. Philadelphia: Lippincott
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Williams & Wilkins; 2005:1297-1305.
14. Fischer TK, Bihrmann K, Perch M, Koch A, Wohlfahrt J, Kåre M, Melbye M.
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Intussusception in early childhood: A cohort study of 1.7 million children. Pediatrics.
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2004;114:782-785.
15. Mandeville K, Chien M, Willyerd FA, Mandell G, Hostetler MA, Bulloch B Pediatr Emerg
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Care. 2012;28: 842-844.
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16. Safford SD, Pietrobon R, Safford KM, Martins H, Skinner MA, Rice HE. A study of 11,003
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patients with hypertrophic pyloric stenosis and the association between surgeon and hospital volume and outcomes. - J Pediatr Surg. 2005;40:967-972 17. Jedd MB, Melton LJ, 3rd, Griffin MR, Kaufman BH, Hoffman AD, Broughton DD, O'Brien PC. Trends in infantile hypertrophic pyloric stenosis in Olmsted County, Minnesota, 1950-1984. Paediatr Perinat Epidemiol. 1988;2: 148–157. 18. Rowe MI, Clatworthy HW. Incarcerated and strangulated hernias in children. Arch Surg 1970;101:136 19. Aiken JJ, Oldham KT. Inguinal hernias. In: Kliegman RM, Stanton BF, Geme JW, Schor NF, Berhman RE, eds. Nelson Textbook of Pediatrics. 19th ed. Philadelphia: Saunders; 2011:1362-1368.
ACCEPTED MANUSCRIPT 20. Stylianos S, Jacir NN, Harris BH: Incarceration of inguinal hernia in infants prior to elective repair. J Pediatr Surg. 1993;28:582
35-year review. J Pediatr Surg. 2006; 41:980-986.
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21. Ein SH, Njere I, Ein A. Six thousand three hundred sixty-one pediatric inguinal hernias: A
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22. Langer JC. Hirschprungs disease. In: Oldham KT, Colombani PM, Foglia RP, eds.
Williams & Wilkins; 2005:1348-1364.
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Principles and Practice of Pediatric Surgery. Volume II ed. Philadelphia: Lippincott
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23. Langer JC. Hirshprungs disease. In: Coran GA, ed. Pediatric Surgery. 7th ed. Philadelphia: Suanders; 2012:1265-1278.
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24. Khan AR, Vujanic GM, Huddart S. The constipated child: how likely is Hirschsprung's disease? Pediatr Surg Int. 2003;19:439-42
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25. Powell DM, Othersen HB, Smith CD. Malrotation of the intestines in children: the effect
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of age on presentation and therapy. J Pediatr Surg. 1989; 24:777-80.
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Table 1 ICD 9 Diagnosis and Procedure codes used in Cases Selection
751.4
Procedure Codes
45.61, 45.62, 45.63, 46.01, 46.20, 46.21, 46.23, 46.81, 46.82, 54.11, 54.95
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433
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9629, 46.80, 46.81, 46.82, 46.85
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Incarcerated Inguinal Hernia 550.0, 550.00,550.01, 550.02, 550.03, 550.1, 550.10, 550.11, 550.12, 550.13 530, 53.00, 53.01, 53.02, 53.04, 53.05, 531, 53.12, 53.13, 53.14, 53.15, 53.16, 53.17
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Diagnosis Codes
Intussusception Hypertrophic Pyloric Stenosis 560.0 750.5
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Malrotation
Hirschsprung Disease 751.3
45.92, 45.95, 46.01, 46.03, 46.10, 46.11,46.13, 48.40,48.41, 48.42, 48.43, 48.49, 48.50, 48.52, 48.59, 48.65, 48.69
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Intussusception
Hypertrophic Pyloric Stenosis
Incarcerated Inguinal Hernia
Hirschsprung Disease
1,621 (59.1) 1,123 (40.9) 3.2(4.9)
3,767 (64.6) 2,064 (35.4) 1.7(2.2)
30,244 (82.9) 6,255 (17.10) 5.2(3.6)*
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7,553 (88.2) 1,011(11.8) 2.4(4.1)
7,588(75.0) 2,524 (25.0) 3.0(4.0)
1,418 ( 51.7 ) 297 (10.8) 278 (10.1) 65 (2.4)
2,322 (39.8) 726(12.5) 1,178 (20.2) 221 (3.8)
18,440 (50.5) 1,954 (5.4) 5,775 (15.8) 378 (1.0)
3,813 (44.5) 1,526 (17.8) 785 (9.2) 236 (2.7)
4,777(47.2) 1,311 (13.0 ) 1,154 (11.4) 342( 3.4)
336 (5.8) 1,048 (18.0)
1,601 (4.4) 8,351 (22.9)
283 (3.3) 1,921(22.4)
462 (4.6) 2,066 (20.4)
5,831
36,499
8,564
10,112
2,744
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119(4.3) 567 (20.7)
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Malrotation
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Sex N (%) Male Female Age(years) Mean (SD) Race N (%) White Black Hispanic Asian/Pacific Islander other Unspecified Total N
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Table 2 Patient Demographics by Cases
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