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Hirschsprung disease in the premature newborn: A population based study and 40-year single center experience
Journal of Pediatric Surgery 50 (2015) 123–125
Contents lists available at ScienceDirect
Journal of Pediatric Surgery journal homepage: www.elsevier.com/locate/jpedsurg
Hirschsprung disease in the premature newborn: A population based study and 40-year single center experience Earl C. Downey a, Elizabeth Hughes a, Angelica R. Putnam b, Henry J. Baskin c, Michael D. Rollins a,⁎ a b c
Division of Pediatric Surgery, Primary Children’s Medical Center and the University of Utah, Salt Lake City, UT, USA Division of Pathology, Primary Children’s Medical Center and the University of Utah, Salt Lake City, UT, USA Division of Radiology, Primary Children’s Medical Center and the University of Utah, Salt Lake City, UT, USA
a r t i c l e
i n f o
Article history: Received 3 October 2014 Accepted 6 October 2014 Key words: Hirschsprung disease Prematurity
a b s t r a c t Background/Purpose: Understanding of Hirschsprung disease (HD) in premature newborns (PHD) is anecdotal. We have sought in this study to identify the demographic and clinical features of PHD. Methods: All patients with HD 1970–2011 treated at our tertiary care children’s hospital were identified. Patients with biopsy confirmed HD and EGA b 37 weeks were selected for further review. Prenatal and birth data, demographics, clinical signs, radiologic and pathologic data, and operative interventions were examined. The occurrence of PHD was observed using data from the Utah Department of Health database 1997–2011. Results: 404 patients with HD from 1970 to 2011 were treated. Twenty-seven (6.7%) had PHD. Mean birth weight in PHD was 2196 grams and mean gestational age 34 (range 29–36) weeks. Seven patients had Down syndrome. Nonchromosomal anomalies occurred in 25%. Median time from birth to biopsy diagnosis was 42 days (range 2–316 days). The most common presenting signs were abdominal distension and bilious emesis. The HD incidence in Utah for all births was 1/4322 (0.023%) and for premature infants 1/3885 (0.027%). Conclusions: PHD are similar to term infants with HD. Diagnosis of HD is often delayed in premature newborns, and associated anomalies are more common. © 2015 Elsevier Inc. All rights reserved.
The occurrence of Hirschsprung disease (HD) in premature babies (PHD) is uncommon and has been infrequently reported. One recent series described a small cohort of premature newborns with HD treated at a single center [1]; however, no large population based study has been performed. We sought to report the demographics of HD in premature neonates and more completely describe the clinical features of this group in a stable and geographically well-defined population. We hypothesized that HD in premature newborns is clinically similar to HD in term newborns and has a similar incidence.
1. Methods Inpatient databases of Primary Children’s Hospital and Intermountain Healthcare as well as the University of Utah for the years 1970–2011 were queried for all patients with diagnosis codes of both Hirschsprung disease and prematurity. In addition, the outpatient clinical records of the Division of Pediatric Surgery of the University of Utah were similarly examined for any data regarding patients with these two diagnosis codes. The Institutional Review Board of the University of Utah and Primary Children’s Hospital approved this study. ⁎ Corresponding author at: Primary Children’s Medical Center, 100 North Mario Capecchi Drive, Suite 2600, Salt Lake City, Utah 84113, USA. Tel.: +1 801 662 2950; fax: +1 801 662 2980. E-mail address: [email protected] (M.D. Rollins). http://dx.doi.org/10.1016/j.jpedsurg.2014.10.013 0022-3468/© 2015 Elsevier Inc. All rights reserved.
A pediatric pathologist confirmed Hirschsprung disease including absent ganglion cells and the presence of hypertrophic nerves in an adequate rectal biopsy. This was also correlated with operative findings including any additional biopsy results. A single pediatric radiologist reviewed radiologic studies. Prematurity was defined as a gestational age at birth less than 37 weeks. Patients who did not meet the above criteria were excluded from review. 1.1. Patient cohorts 1.1.1. All patients treated at PCH Our tertiary care free-standing children’s hospital provides care to five states in the intermountain west and is the only facility that provides care to newborns with surgical disorders in Utah. We reviewed patient demographics of all premature patients with HD treated at PCH during the period 1970–2011 in order to examine the characteristics of this patient population. This included prenatal course, birth data, clinical presentation, imaging studies and pathologic findings. Operative interventions were also reviewed. 1.1.2. Utah-born patients The subset cohort of patients allowed us to examine the occurrence of PHD in a single population. Only patients born in Utah from 1997 to 2011 were included in this analysis [2]. This time period and location was selected because of availability and accuracy of medical records. Birth data for premature and low birth weight infants from the State of Utah were
124
E.C. Downey et al. / Journal of Pediatric Surgery 50 (2015) 123–125
available through the Utah Department of Health Center of Health Data, Office of Vital Records and Statistics. These data on premature newborns have been reported centrally and published since 1997. Data include the annual total numbers of births, term births and premature births. Only live births were included. This registry subdivided premature births as gestational age ≤28 weeks, 28–35 weeks, and 36 weeks. The occurrence of PHD in our database was subdivided similarly. Incidence of HD in the term and premature populations were then calculated. 2. Results A total of 404 patients with HD were treated at PCH from 1970 to 2011. Twenty-seven of these patients (23 male) were born b 37 weeks gestational age (6.7%). The average incidence of premature births in the general population during this time period was 11.3% (69,931/617,690). Twenty-three of the 27 PHD treated at our hospital during 1970–2011 were born in Utah. 2.1. Demographics of PHD: Utah-born patients A total of 129 patients with HD from Utah were treated at PCH from 1997 to 2011. Of all premature births during this period, 18 were diagnosed with HD (incidence = 0.027% or 1/3885 births). The average incidence of HD in the live birth population during this period was 1/4788 births or 0.023% (Tables 1 and 2). PHD represented an average incidence of 10.7% of the HD patients each year. There were no patients born less than 28 weeks gestation that had HD. Of the 18 PHD less than 37 weeks gestation, 11 were 28–35 weeks and 7 were 36 weeks.
Table 2 Incidence of HD among live premature births (PHD) in Utah (1997–2011). Year
Premature births
Total PHD
%PHD
1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 TOTAL
4239 4547 4322 4244 4242 4421 4474 4814 5004 5041 4921 5118 5010 4715 4819 69,931
1 1 1 2 2 0 0 3 0 2 0 2 1 1 2 18
0.024 0.022 0.023 0.047 0.11 0 0 0.062 0 0.091 0 0.04 0.02 0.021 0.042 0.027
(1), esophageal atresia (1), duodenal atresia (1), omphalocele (1), renal duplication (1). Presenting signs observed in PHD are shown in Table 3. A contrast enema was obtained in 25 patients at a median of 17 days of age (2–270 days). Fifteen suggested rectosigmoid disease (60%), 3 long segment disease (12%) and seven failed to show a transition zone (28%). An initial rectal biopsy at the bedside was obtained in 21 patients (5 repeated). Average time to diagnosis by rectal biopsy was 42 days (range 2–371 days). 2.3. Operative data
2.2. Clinical features of PHD 2.2.1. Identification and diagnosis Prenatal evaluation was available for 18/27 patients. One pregnancy was complicated by polyhydramnios and one by oligohydramnios. Prenatal amniocentesis with full chromosomal analysis was performed in 15 mothers. Abnormal chromosomes were detected in 8 (7 Down syndrome, 1 Turners syndrome). The average maternal gravida was 2.6 (range 1–6) and parity was 2.2 (range 1–6). A family history of HD was present in 4 (14.8%) patients. The average gestational age was 33.6 weeks (range 29–36 weeks) and birth weight 2196 grams (1300–3479 grams). Five patients were the product of a multiple gestation including 3 dizygotic twins, each with an unaffected twin. Two affected patients were part of triplets resulting from in vitro fertilization. The third baby died and no autopsy was performed. Associated nonchromosomal anomalies included congenital heart defects (n = 4.14.8%), central hypoventilation syndrome
Table 1 Incidence of Hirschsprung disease (HD) (all live births only) in Utah (1997–2011). Year
Total births
Total HD
%HD
1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 TOTAL
43,009 45,126 46,243 47,331 47,915 49,140 49,834 50,653 51,517 53,475 55,063 55,605 53,849 52,164 51,144 617,690
13 8 11 17 11 16 9 13 11 9 10 11 16 6 13 129
0.03 0.018 0.024 0.036 0.023 0.033 0.018 0.026 0.021 0.017 0.018 0.02 0.03 0.016 0.025 0.023
Laparoscopic assisted primary endorectal pullthrough was performed in 8 patients (Table 4). Median postconceptual age at the time of surgery and age was 41.3 weeks and 37 days (range 16–240 days) respectively. Fifteen patients underwent leveling colostomy at a median postconceptual age of 38.6 weeks and median age of 60 days (range 7–270 days). An ileostomy was performed in three patients for total colon HD. Pullthrough was accomplished in 24 patients (12 Soave and 12 Duhamel operations). Three patients did not have a pullthrough. Age at pullthrough was 3.5 weeks to 14 months. HD was confirmed on review of all 27 resected specimens. The transition zone was rectosigmoid 21 (77.8%), splenic flexure 2 (7.4%) and total colonic involvement in 4 (14.8%). Three of the four patients (all male) with total colonic aganglionosis also had involvement of the small bowel. Two of the four eventually underwent Duhamel pullthrough at the level of the ileum, one has an ileostomy and one died prior to definitive pullthrough. Seven (28%) patients developed enterocolitis postoperatively. Four of these had been treated with primary pullthrough for a rectosigmoid transition zone at 16–43 days of age (2 patients with Down syndrome). Three underwent initial leveling colostomy before definitive pullthrough (Duhamel 2, Soave 1) for rectosigmoid disease. Three (12%) patients developed an anastomotic stricture managed with dilations. These patients had undergone definitive pullthrough between 6 months and one year of age (Duhamel 2, Soave 1). These were not the same patients who suffered from postoperative enterocolitis. One patient required a redo pullthrough for
Table 3 Signs at presentation in PHD. Signs Delayed passage of meconium Abdominal distention Bilious emesis Enterocolitis Jaundice
Number
Percentage of cohort
15/26 25/26 24/26 7/24 3/22
58% 96% 92% 29% 14%
E.C. Downey et al. / Journal of Pediatric Surgery 50 (2015) 123–125 Table 4 Operative details in patients without total colon involvement.
Gestational age (median) Birth weight (median) Chromosomal anomaly (n) Congenital heart disease Median postconceptional age (weeks) at surgery (range) Transition zone Rectosigmoid Splenic flexure Definitive operation (n)
Primary pullthrough
Leveling colostomy
35 2657 grams 2 0 41.3 (38.3–63.3)
33 2080 grams 6 3 38.6 (32.3–73.6)
8 0 Soave (8)
13 2 Duhamel (11) Soave (4)
an initial transition zone pullthrough. Five (18.5%) late deaths occurred following discharge (1 pneumonia, 2 malignancy, 1 cerebrovascular accident, 1 unknown cause). Three of the five deaths occurred in patients with total colon involvement. 3. Discussion Our series represents the largest description of premature infants with Hirschsprung disease. This study is unique in that it represents a well-defined population in a geographically stable location. We found a similar incidence of HD within our premature population compared to the term population in Utah (0.027%, 1/3885 vs. 0.023%, 1/4322). However, this incidence is slightly higher than 1 in 5000 that is commonly quoted [3–5]. Twenty-seven (6.7%) of the 404 patients with HD treated at our institution from 1970 to 2011 were born at b 37 weeks gestational age. This finding is similar to that reported by Sharp et al. [1] which included 6/85 (7%) premature patients with HD and 17/250 (6.8%) reported by Klein and Philippart [6]. The clinical presentation of HD was similar in our premature infants to that reported in term infants with HD [3,7] with the exception that most of our patients presented with bilious emesis [8–10]. Furthermore, thirty percent of our PHD patients had Trisomy 21, which is nearly three times that reported in term infants with HD [3,10–12]. The diagnosis of PHD was made after the first week of life in 74% (20/ 27). Most children with HD will fail to pass meconium within the first 48 hours of life [3] as was seen in 58% of our PHD. However, many premature infants will present with abnormal stooling patterns owing to decreased gastrointestinal motility [13,14]. This may have accounted for the somewhat delayed diagnosis in our premature population. Although we are unable to calculate the true sensitivity and specificity of the contrast enema in this study, findings consistent with a rectosigmoid transition zone Hirschsprung disease were seen on contrast enema in 60% of our patients. Total colon aganglionosis occurred with a similar frequency (14.8%) in our premature patients as that reported for term infants with HD [15]. Complications including postoperative enterocolitis and stricture formation occurred with a similar frequency to that reported for term infants [3]. The three patients who developed an anastomotic stricture were managed with dilations. These patients had undergone a definitive pullthrough between 6 months and one year of age (Duhamel 2, Soave 1). Interestingly, these patients did not experience postoperative enterocolitis. Mortality rates of 5–17% have been reported for term HD [2]. Five
125
of our PHD patients (three with total colon involvement) died. We were unable to attribute any of these nonoperative late deaths directly to gastrointestinal causes, specifically enterocolitis. The aim of this study was not to evaluate long term outcome in this patient population but to describe the clinical features of the premature newborn and to determine the occurrence of HD in the premature population. This study has several limitations, many of which are inherent to a retrospective review. Patients with HD, both term and premature, were identified through our hospital and clinic records and it is possible that there were patients with HD who may have died prior to transfer to our center. Not all patients in some extraction tables could be included because of inadequate records. This was particularly prevalent in the prenatal and birth record tables. Also, signs considered consistent with enterocolitis varied which likely affected our preoperative and postoperative rates of enterocolitis. While the surgical management PHD is similar to that of term newborns, delayed passage of meconium may not be a reliable trigger for investigation. Bilious emesis seems to be a more reliable sign to prompt investigation in this cohort. A high index of suspicion for premature newborns with otherwise unexplained obstructive signs is also a trigger for a rectal biopsy (particularly if the patient has Down syndrome or other anomalies). 4. Conclusions The results of this study dispute the common belief that HD is rare in premature infants. Hirschsprung disease occurs with a similar frequency in premature newborns. Clinical features and the level of aganglionosis are also similar to term infants with the disease although an increased association with Down syndrome may exist. References [1] Sharp NE, Pettiford-Cunningham J, Shah SR, et al. The prevalence of Hirschsprung disease in premature infants after suction rectal biopsy. J Surg Res 2013;184:374–7. [2] Utah Department of Health, Center for Health Data. Office of Healthcare Statistics, Utah Heath Data Committee. http://health.utah.gov/chd/. [Last accessed Dec 2012]. [3] Haricharan RN, Georgeson KE. Hirschsprung disease. Sem Pediatr Surg 2008;17: 266–75. [4] Spouge D, Baird PA. Hirschsprung disease in a large birth cohort. Teratology 1985; 32:171–7. [5] Suita S, Taguchi T, Ieiri S, et al. Hirschsprung’s disease in Japan: Analysis of 3852 patients based on a nationwide survey in 30 years. J Pediatr Surg 2005;40:197–201. [6] Klein MD, Philippart AI. Hirschsprung’s disease: Three decades’ experience at a single institution. J Pediatr Surg 1993;28:1291–3. [7] Pini Prato A, Gentilino V, Giunta C, et al. Hirschsprung disease: Do risk factors of poor surgical outcome exist? J Pediatr Surg 2008;43:612–9. [8] Diamond IR, Casadiego G, Traubici J, et al. The contrast enema for Hirschsprung disease: Predictors of a false-positive result. J Pediatr Surg 2007;42:792–5. [9] Hackam DJ, Reblock KK, Redlinger RE, et al. Diagnosis and outcome of Hirschsprung’s disease: Does age really matter? Pediatr Surg Int 2004;20:319–22. [10] Teitelbaum DH, Cilley RE, Sherman NJ, et al. A decade of experience with the primary pull-through for Hirschsprung disease in the newborn period: A multicenter analysis of outcomes. Ann Surg 2000;232:372–80. [11] Amiel J, Sproat-Emison E, Garcia-Barcelo M, et al. Hirschsprung disease, associated syndromes and genetics: A review. J Med Genet 2008;45:1–14. [12] Stensrud KJ, Emblem R, Bjornland K. Functional outcome after operation for Hirschsprung disease — transanal vs transabdominal approach. J Pediatr Surg 2010;45:1640–4. [13] Berseth CL. Gastrointestinal motility in the neonate. Clin Perinatol 1996;23:179–90. [14] Kenny SE, Tam PK, Garcia-Barcelo M. Hirschsprung’s disease. Sem Pediatr Surg 2010; 19:194–200. [15] Moore SW. Total colonic aganglionosis in Hirschsprung disease. Sem Pediatr Surg 2012;21:302–9.
Contents lists available at ScienceDirect
Journal of Pediatric Surgery journal homepage: www.elsevier.com/locate/jpedsurg
Hirschsprung disease in the premature newborn: A population based study and 40-year single center experience Earl C. Downey a, Elizabeth Hughes a, Angelica R. Putnam b, Henry J. Baskin c, Michael D. Rollins a,⁎ a b c
Division of Pediatric Surgery, Primary Children’s Medical Center and the University of Utah, Salt Lake City, UT, USA Division of Pathology, Primary Children’s Medical Center and the University of Utah, Salt Lake City, UT, USA Division of Radiology, Primary Children’s Medical Center and the University of Utah, Salt Lake City, UT, USA
a r t i c l e
i n f o
Article history: Received 3 October 2014 Accepted 6 October 2014 Key words: Hirschsprung disease Prematurity
a b s t r a c t Background/Purpose: Understanding of Hirschsprung disease (HD) in premature newborns (PHD) is anecdotal. We have sought in this study to identify the demographic and clinical features of PHD. Methods: All patients with HD 1970–2011 treated at our tertiary care children’s hospital were identified. Patients with biopsy confirmed HD and EGA b 37 weeks were selected for further review. Prenatal and birth data, demographics, clinical signs, radiologic and pathologic data, and operative interventions were examined. The occurrence of PHD was observed using data from the Utah Department of Health database 1997–2011. Results: 404 patients with HD from 1970 to 2011 were treated. Twenty-seven (6.7%) had PHD. Mean birth weight in PHD was 2196 grams and mean gestational age 34 (range 29–36) weeks. Seven patients had Down syndrome. Nonchromosomal anomalies occurred in 25%. Median time from birth to biopsy diagnosis was 42 days (range 2–316 days). The most common presenting signs were abdominal distension and bilious emesis. The HD incidence in Utah for all births was 1/4322 (0.023%) and for premature infants 1/3885 (0.027%). Conclusions: PHD are similar to term infants with HD. Diagnosis of HD is often delayed in premature newborns, and associated anomalies are more common. © 2015 Elsevier Inc. All rights reserved.
The occurrence of Hirschsprung disease (HD) in premature babies (PHD) is uncommon and has been infrequently reported. One recent series described a small cohort of premature newborns with HD treated at a single center [1]; however, no large population based study has been performed. We sought to report the demographics of HD in premature neonates and more completely describe the clinical features of this group in a stable and geographically well-defined population. We hypothesized that HD in premature newborns is clinically similar to HD in term newborns and has a similar incidence.
1. Methods Inpatient databases of Primary Children’s Hospital and Intermountain Healthcare as well as the University of Utah for the years 1970–2011 were queried for all patients with diagnosis codes of both Hirschsprung disease and prematurity. In addition, the outpatient clinical records of the Division of Pediatric Surgery of the University of Utah were similarly examined for any data regarding patients with these two diagnosis codes. The Institutional Review Board of the University of Utah and Primary Children’s Hospital approved this study. ⁎ Corresponding author at: Primary Children’s Medical Center, 100 North Mario Capecchi Drive, Suite 2600, Salt Lake City, Utah 84113, USA. Tel.: +1 801 662 2950; fax: +1 801 662 2980. E-mail address: [email protected] (M.D. Rollins). http://dx.doi.org/10.1016/j.jpedsurg.2014.10.013 0022-3468/© 2015 Elsevier Inc. All rights reserved.
A pediatric pathologist confirmed Hirschsprung disease including absent ganglion cells and the presence of hypertrophic nerves in an adequate rectal biopsy. This was also correlated with operative findings including any additional biopsy results. A single pediatric radiologist reviewed radiologic studies. Prematurity was defined as a gestational age at birth less than 37 weeks. Patients who did not meet the above criteria were excluded from review. 1.1. Patient cohorts 1.1.1. All patients treated at PCH Our tertiary care free-standing children’s hospital provides care to five states in the intermountain west and is the only facility that provides care to newborns with surgical disorders in Utah. We reviewed patient demographics of all premature patients with HD treated at PCH during the period 1970–2011 in order to examine the characteristics of this patient population. This included prenatal course, birth data, clinical presentation, imaging studies and pathologic findings. Operative interventions were also reviewed. 1.1.2. Utah-born patients The subset cohort of patients allowed us to examine the occurrence of PHD in a single population. Only patients born in Utah from 1997 to 2011 were included in this analysis [2]. This time period and location was selected because of availability and accuracy of medical records. Birth data for premature and low birth weight infants from the State of Utah were
124
E.C. Downey et al. / Journal of Pediatric Surgery 50 (2015) 123–125
available through the Utah Department of Health Center of Health Data, Office of Vital Records and Statistics. These data on premature newborns have been reported centrally and published since 1997. Data include the annual total numbers of births, term births and premature births. Only live births were included. This registry subdivided premature births as gestational age ≤28 weeks, 28–35 weeks, and 36 weeks. The occurrence of PHD in our database was subdivided similarly. Incidence of HD in the term and premature populations were then calculated. 2. Results A total of 404 patients with HD were treated at PCH from 1970 to 2011. Twenty-seven of these patients (23 male) were born b 37 weeks gestational age (6.7%). The average incidence of premature births in the general population during this time period was 11.3% (69,931/617,690). Twenty-three of the 27 PHD treated at our hospital during 1970–2011 were born in Utah. 2.1. Demographics of PHD: Utah-born patients A total of 129 patients with HD from Utah were treated at PCH from 1997 to 2011. Of all premature births during this period, 18 were diagnosed with HD (incidence = 0.027% or 1/3885 births). The average incidence of HD in the live birth population during this period was 1/4788 births or 0.023% (Tables 1 and 2). PHD represented an average incidence of 10.7% of the HD patients each year. There were no patients born less than 28 weeks gestation that had HD. Of the 18 PHD less than 37 weeks gestation, 11 were 28–35 weeks and 7 were 36 weeks.
Table 2 Incidence of HD among live premature births (PHD) in Utah (1997–2011). Year
Premature births
Total PHD
%PHD
1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 TOTAL
4239 4547 4322 4244 4242 4421 4474 4814 5004 5041 4921 5118 5010 4715 4819 69,931
1 1 1 2 2 0 0 3 0 2 0 2 1 1 2 18
0.024 0.022 0.023 0.047 0.11 0 0 0.062 0 0.091 0 0.04 0.02 0.021 0.042 0.027
(1), esophageal atresia (1), duodenal atresia (1), omphalocele (1), renal duplication (1). Presenting signs observed in PHD are shown in Table 3. A contrast enema was obtained in 25 patients at a median of 17 days of age (2–270 days). Fifteen suggested rectosigmoid disease (60%), 3 long segment disease (12%) and seven failed to show a transition zone (28%). An initial rectal biopsy at the bedside was obtained in 21 patients (5 repeated). Average time to diagnosis by rectal biopsy was 42 days (range 2–371 days). 2.3. Operative data
2.2. Clinical features of PHD 2.2.1. Identification and diagnosis Prenatal evaluation was available for 18/27 patients. One pregnancy was complicated by polyhydramnios and one by oligohydramnios. Prenatal amniocentesis with full chromosomal analysis was performed in 15 mothers. Abnormal chromosomes were detected in 8 (7 Down syndrome, 1 Turners syndrome). The average maternal gravida was 2.6 (range 1–6) and parity was 2.2 (range 1–6). A family history of HD was present in 4 (14.8%) patients. The average gestational age was 33.6 weeks (range 29–36 weeks) and birth weight 2196 grams (1300–3479 grams). Five patients were the product of a multiple gestation including 3 dizygotic twins, each with an unaffected twin. Two affected patients were part of triplets resulting from in vitro fertilization. The third baby died and no autopsy was performed. Associated nonchromosomal anomalies included congenital heart defects (n = 4.14.8%), central hypoventilation syndrome
Table 1 Incidence of Hirschsprung disease (HD) (all live births only) in Utah (1997–2011). Year
Total births
Total HD
%HD
1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 TOTAL
43,009 45,126 46,243 47,331 47,915 49,140 49,834 50,653 51,517 53,475 55,063 55,605 53,849 52,164 51,144 617,690
13 8 11 17 11 16 9 13 11 9 10 11 16 6 13 129
0.03 0.018 0.024 0.036 0.023 0.033 0.018 0.026 0.021 0.017 0.018 0.02 0.03 0.016 0.025 0.023
Laparoscopic assisted primary endorectal pullthrough was performed in 8 patients (Table 4). Median postconceptual age at the time of surgery and age was 41.3 weeks and 37 days (range 16–240 days) respectively. Fifteen patients underwent leveling colostomy at a median postconceptual age of 38.6 weeks and median age of 60 days (range 7–270 days). An ileostomy was performed in three patients for total colon HD. Pullthrough was accomplished in 24 patients (12 Soave and 12 Duhamel operations). Three patients did not have a pullthrough. Age at pullthrough was 3.5 weeks to 14 months. HD was confirmed on review of all 27 resected specimens. The transition zone was rectosigmoid 21 (77.8%), splenic flexure 2 (7.4%) and total colonic involvement in 4 (14.8%). Three of the four patients (all male) with total colonic aganglionosis also had involvement of the small bowel. Two of the four eventually underwent Duhamel pullthrough at the level of the ileum, one has an ileostomy and one died prior to definitive pullthrough. Seven (28%) patients developed enterocolitis postoperatively. Four of these had been treated with primary pullthrough for a rectosigmoid transition zone at 16–43 days of age (2 patients with Down syndrome). Three underwent initial leveling colostomy before definitive pullthrough (Duhamel 2, Soave 1) for rectosigmoid disease. Three (12%) patients developed an anastomotic stricture managed with dilations. These patients had undergone definitive pullthrough between 6 months and one year of age (Duhamel 2, Soave 1). These were not the same patients who suffered from postoperative enterocolitis. One patient required a redo pullthrough for
Table 3 Signs at presentation in PHD. Signs Delayed passage of meconium Abdominal distention Bilious emesis Enterocolitis Jaundice
Number
Percentage of cohort
15/26 25/26 24/26 7/24 3/22
58% 96% 92% 29% 14%
E.C. Downey et al. / Journal of Pediatric Surgery 50 (2015) 123–125 Table 4 Operative details in patients without total colon involvement.
Gestational age (median) Birth weight (median) Chromosomal anomaly (n) Congenital heart disease Median postconceptional age (weeks) at surgery (range) Transition zone Rectosigmoid Splenic flexure Definitive operation (n)
Primary pullthrough
Leveling colostomy
35 2657 grams 2 0 41.3 (38.3–63.3)
33 2080 grams 6 3 38.6 (32.3–73.6)
8 0 Soave (8)
13 2 Duhamel (11) Soave (4)
an initial transition zone pullthrough. Five (18.5%) late deaths occurred following discharge (1 pneumonia, 2 malignancy, 1 cerebrovascular accident, 1 unknown cause). Three of the five deaths occurred in patients with total colon involvement. 3. Discussion Our series represents the largest description of premature infants with Hirschsprung disease. This study is unique in that it represents a well-defined population in a geographically stable location. We found a similar incidence of HD within our premature population compared to the term population in Utah (0.027%, 1/3885 vs. 0.023%, 1/4322). However, this incidence is slightly higher than 1 in 5000 that is commonly quoted [3–5]. Twenty-seven (6.7%) of the 404 patients with HD treated at our institution from 1970 to 2011 were born at b 37 weeks gestational age. This finding is similar to that reported by Sharp et al. [1] which included 6/85 (7%) premature patients with HD and 17/250 (6.8%) reported by Klein and Philippart [6]. The clinical presentation of HD was similar in our premature infants to that reported in term infants with HD [3,7] with the exception that most of our patients presented with bilious emesis [8–10]. Furthermore, thirty percent of our PHD patients had Trisomy 21, which is nearly three times that reported in term infants with HD [3,10–12]. The diagnosis of PHD was made after the first week of life in 74% (20/ 27). Most children with HD will fail to pass meconium within the first 48 hours of life [3] as was seen in 58% of our PHD. However, many premature infants will present with abnormal stooling patterns owing to decreased gastrointestinal motility [13,14]. This may have accounted for the somewhat delayed diagnosis in our premature population. Although we are unable to calculate the true sensitivity and specificity of the contrast enema in this study, findings consistent with a rectosigmoid transition zone Hirschsprung disease were seen on contrast enema in 60% of our patients. Total colon aganglionosis occurred with a similar frequency (14.8%) in our premature patients as that reported for term infants with HD [15]. Complications including postoperative enterocolitis and stricture formation occurred with a similar frequency to that reported for term infants [3]. The three patients who developed an anastomotic stricture were managed with dilations. These patients had undergone a definitive pullthrough between 6 months and one year of age (Duhamel 2, Soave 1). Interestingly, these patients did not experience postoperative enterocolitis. Mortality rates of 5–17% have been reported for term HD [2]. Five
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of our PHD patients (three with total colon involvement) died. We were unable to attribute any of these nonoperative late deaths directly to gastrointestinal causes, specifically enterocolitis. The aim of this study was not to evaluate long term outcome in this patient population but to describe the clinical features of the premature newborn and to determine the occurrence of HD in the premature population. This study has several limitations, many of which are inherent to a retrospective review. Patients with HD, both term and premature, were identified through our hospital and clinic records and it is possible that there were patients with HD who may have died prior to transfer to our center. Not all patients in some extraction tables could be included because of inadequate records. This was particularly prevalent in the prenatal and birth record tables. Also, signs considered consistent with enterocolitis varied which likely affected our preoperative and postoperative rates of enterocolitis. While the surgical management PHD is similar to that of term newborns, delayed passage of meconium may not be a reliable trigger for investigation. Bilious emesis seems to be a more reliable sign to prompt investigation in this cohort. A high index of suspicion for premature newborns with otherwise unexplained obstructive signs is also a trigger for a rectal biopsy (particularly if the patient has Down syndrome or other anomalies). 4. Conclusions The results of this study dispute the common belief that HD is rare in premature infants. Hirschsprung disease occurs with a similar frequency in premature newborns. Clinical features and the level of aganglionosis are also similar to term infants with the disease although an increased association with Down syndrome may exist. References [1] Sharp NE, Pettiford-Cunningham J, Shah SR, et al. The prevalence of Hirschsprung disease in premature infants after suction rectal biopsy. J Surg Res 2013;184:374–7. [2] Utah Department of Health, Center for Health Data. Office of Healthcare Statistics, Utah Heath Data Committee. http://health.utah.gov/chd/. [Last accessed Dec 2012]. [3] Haricharan RN, Georgeson KE. Hirschsprung disease. Sem Pediatr Surg 2008;17: 266–75. [4] Spouge D, Baird PA. Hirschsprung disease in a large birth cohort. Teratology 1985; 32:171–7. [5] Suita S, Taguchi T, Ieiri S, et al. Hirschsprung’s disease in Japan: Analysis of 3852 patients based on a nationwide survey in 30 years. J Pediatr Surg 2005;40:197–201. [6] Klein MD, Philippart AI. Hirschsprung’s disease: Three decades’ experience at a single institution. J Pediatr Surg 1993;28:1291–3. [7] Pini Prato A, Gentilino V, Giunta C, et al. Hirschsprung disease: Do risk factors of poor surgical outcome exist? J Pediatr Surg 2008;43:612–9. [8] Diamond IR, Casadiego G, Traubici J, et al. The contrast enema for Hirschsprung disease: Predictors of a false-positive result. J Pediatr Surg 2007;42:792–5. [9] Hackam DJ, Reblock KK, Redlinger RE, et al. Diagnosis and outcome of Hirschsprung’s disease: Does age really matter? Pediatr Surg Int 2004;20:319–22. [10] Teitelbaum DH, Cilley RE, Sherman NJ, et al. A decade of experience with the primary pull-through for Hirschsprung disease in the newborn period: A multicenter analysis of outcomes. Ann Surg 2000;232:372–80. [11] Amiel J, Sproat-Emison E, Garcia-Barcelo M, et al. Hirschsprung disease, associated syndromes and genetics: A review. J Med Genet 2008;45:1–14. [12] Stensrud KJ, Emblem R, Bjornland K. Functional outcome after operation for Hirschsprung disease — transanal vs transabdominal approach. J Pediatr Surg 2010;45:1640–4. [13] Berseth CL. Gastrointestinal motility in the neonate. Clin Perinatol 1996;23:179–90. [14] Kenny SE, Tam PK, Garcia-Barcelo M. Hirschsprung’s disease. Sem Pediatr Surg 2010; 19:194–200. [15] Moore SW. Total colonic aganglionosis in Hirschsprung disease. Sem Pediatr Surg 2012;21:302–9.