Gastroschisis in the United States : analysis and risk categorization of 4344 patients

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1 (2007) 27, r 2007 Nature Publishing Group All rights reserved /07 $30 ORIGINAL ARTICLE Gastroschisis in the United States : analysis and risk categorization of 4344 patients F Abdullah 1, MA Arnold 1, R Nabaweesi 1, AC Fischer 1, PM Colombani 1, KD Anderson 2, H Lau 1 and DC Chang 3 1 Division of Pediatric Surgery, Center for Pediatric Surgery Outcomes Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA; 2 University of Southern California, Los Angeles, CA, USA and 3 Department of Surgery, Center for Surgical Trials and Outcomes Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA Objective: Gastroschisis is a rare congenital abdominal wall defect through which intraabdominal organs herniate and it requires surgical management soon after birth. The objectives of this study were to profile patient characteristics of this anomaly utilizing data from two large national databases and to validate previous risk stratification categories of infants born with this condition. Methods: An analysis was performed using 13 years of the National Inpatient Sample database ( , 1998, 1999, 2001, 2002) and 3 years of the Kids Inpatient Database (1997, 2000, 2003). These combined databases contain information from nearly 93 million discharges in the United States. Infants with gastroschisis were identified by International Classification of Disease-9 procedure code (repair of gastroschisis) and an age at admission of <8 days. Variables of gender, race, geographic region, co-existing diagnoses, length of stay, hospital charges adjusted to 2005 dollars, complications and inpatient mortality were collected from the databases. Infants were divided into simple and complex categories based on the absence or presence of intestinal atresia, stenosis, perforation, necrosis or volvulus. Comparisons between groups were performed using Pearson s w 2 for categorical outcomes and the Kruskal Wallis test for non-normally distributed continuous variables. Results: A total of 4344 infants with gastroschisis were identified. These were comprised of 44.0% female infants (n ¼ 1910), 46.4% male infants (n ¼ 2017) whereas 9.6% were not reported (n ¼ 415). Racial analysis showed the largest subset being white in 40.9% of infants (n ¼ 1775) with Hispanic infants being the next highest group reported at 17.2% (n ¼ 745). Co-existing intestinal anomalies were the most common, affecting 9.9% (n ¼ 429) infants, whereas certain cardiac (6.8%, n ¼ 294) and pulmonary (1.7%, n ¼ 72) conditions were also identified. Simple gastroschisis represented 89.1% (n ¼ 3870) of the group whereas 10.9% (n ¼ 474) were complex in nature. Simple and complex patients Correspondence: Dr F Abdullah, Division of Pediatric Surgery, Center for Pediatric Surgery Outcomes Research, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Harvey 319, Baltimore, MD , USA. fa@jhmi.edu Received 28 June 2006; revised 23 August 2006; accepted 18 September 2006; published online 12 October 2006 differed in median length of stay (28 vs 67 days, P<0.01), inpatient mortality (2.9 vs 8.7%, P<0.01) and median inflation-adjusted hospital charges ($ vs $ , P<0.01). Conclusions: These data represent a national analysis of the largest group of infants with gastroschisis to date which further aids the characterization and understanding of this serious congenital condition. (2007) 27, doi: /sj.jp ; published online 12 October 2006 Keywords: gastroschisis; congenital anomaly; abdominal wall defects; infants; outcomes Introduction Gastroschisis is a congenital anomaly of newborns characterized by an abdominal wall defect usually situated to the right of the umbilicus. Organs that may protrude through the defect include the stomach, small and large bowel, liver, spleen and bladder. These infants require surgical correction of the condition to minimize abdominal fluid losses and infection as well as to prevent further damage to the exposed intestine. Although gastroschisis and omphalocele were not defined as distinct clinical entities until 50 years ago, 1,2 one of the first reported survivals of an infant with gastroschisis was published by William Fear of England in The modern era of treatment is one of the remarkable success stories of medicine in which advances in neonatal critical care, parenteral nutrition and pediatric surgical techniques have contributed to a documented survival of greater than 90% in the United States. 4,5 Gastroschisis can occur as an isolated abnormality (simple) or it can be associated with other gastrointestinal anomalies such as intestinal atresia, perforation, necrosis or volvulus (complex). Although extensive literature is available regarding the surgical treatment of gastroschisis, 4,6 9 few reports have focused on the categorization and risk stratification of this abnormality. 10 This study addresses the lack of comprehensive national information about patients with gastroschisis. It is also the first study to analyze data from two large national inpatient databases

2 Gastroschisis in the US 51 in order to validate an existing risk stratification scheme of this disease. This analysis provides the largest profile of this disease to date along with more precise predictions of the clinical course of affected infants. Methods Databases An analysis was performed using 13 years of the National Inpatient Sample (NIS) file ( , 1998, 1999, 2001, 2002) and 3 years of the Kids Inpatient Database (KID) file (1997, 2000, 2003) as outlined schematically in Figure 1. Both databases are produced as part of the Healthcare Cost and Utilization Project (HCUP) of the Agency for Healthcare Research and Quality. The NIS is an all-payer database that annually contains information from up to 8 million inpatient discharges from approximately 1000 hospitals across the United States. Hospitals are sampled to represent a 20% stratified sample of all community hospitals. The number of states for which data are available has increased from eight states in 1988 to 37 states in The KID contains a sample of pediatric (age 20 years or less) discharges from all community, non-rehabilitation hospitals in states which participate in the HCUP. Unlike the NIS, which samples at the hospital level, the KID samples patient discharges which are then weighted to obtain national estimates. The sampling algorithm involves systematic random sampling to select 10% of uncomplicated in-hospital births and 80% of complicated in-hospital births as well as other selected pediatric cases. The KID contains information from up to 36 states. 12 Information collected on patients in both databases includes age at admission, gender, race, diagnosis and procedure information, total hospital charges, disposition, length of stay, median household income for the patient s zip code and descriptive hospital information (state, urbanicity, teaching status and bed size). Patient selection Inclusion criteria for the analysis were an International Classification of Disease (ICD)-9 procedure code of (repair of gastroschisis) and an age at admission of less than 8 days. The use of this procedure code to acquire gastroschisis patients has been validated previously. 13 Data management and analysis A descriptive analysis was performed using variables of gender, race, inpatient mortality, geographic region (Northeast, Midwest, South, West) and type of hospital (urban teaching, urban non-teaching and rural). Summary statistics for length of stay and inflation-adjusted total hospital charges were calculated. The prevalence of certain co-existing diagnoses, congenital abnormalities and in-hospital complications was determined by searching ICD-9 codes. Patients were divided into those with simple Figure 1 National inpatient database schematic. Table 1 Demographics Characteristic n (%) Gender Male 2017 (46.4) Female 1910 (44.0) Unknown 415 (9.6) Race White 1775 (40.9) Black 334 (7.7) Hispanic 745 (17.2) Other 267 (6.2) Unknown 1223 (28.2) a a Not all states collected information on race. and complex gastroschisis according to the definition of Molik et al. 10 Comparisons between groups were performed using Pearson s w 2 for categorical outcomes or the Kruskal Wallis test for non-normally distributed continuous variables. Total hospital charges were adjusted for inflation to reflect 2005 dollars. 14 Results Demographic data A total of 4344 patients were identified after combining the two databases. Gender was evenly divided within the study group with 1910 (44.0%) female infants and 2017 (46.4%) males (Table 1). Gender was not reported for 415 infants (9.6%). The racial makeup was 40.9% white, 17.2% Hispanic and 7.7% black (Table 1). Two hundred and sixty-seven were classified as other (including Asian, Pacific Islander, Hawaiian and Native American). Race data were not available for 28.2% of participants because not all hospitals and states report this information to HCUP. 11

3 52 Gastroschisis in the US Co-existing diagnoses The prevalence of co-existing conditions and congenital abnormalities among the infants was determined (Table 2). Overall, intestinal anomalies were the most common (8.1%) with total absence, atresia, stenosis or stricture of the small bowel being the most frequently encountered. Co-existing cardiopulmonary disease was less common. Specifically, bronchopulmonary dysplasia was found in 1.4% of the infants whereas only fifteen infants (0.4%) had a diagnosis of lung agenesis, hypoplasia or dysplasia. The most common cardiac anomalies were patent ductus arteriosus (4.9%), atrial septal defect (4.1%) and ventricular septal defect (1.8%). Undescended testis was relatively common (6.8%) whereas hydronephrosis and trisomies were exceedingly rare (1.3 and 0.1%, respectively). Hospitalization characteristics and inpatient mortality Most infants were hospitalized in the South and West (36.5 and 31.4%, respectively) with 20.5% in the Midwest and 11.7% in the Northeast (Table 3). These data are of limited value as they are not adjusted for differences in population distribution. The majority of infants were either born in or quickly transferred to urban teaching hospitals (78.0%). Few patients were treated at rural centers. Table 2 Co-existing diagnoses Diagnosis n a (%) Intestinal 354 (8.1) Meckel s diverticulum 27 (0.6) Small bowel atresia, stenosis, stricture or absence 220 (5.1) Large bowel atresia or stenosis 81 (1.9) Enteric duplication 72 (1.7) Pulmonary 72 (1.7) Agenesis, hypoplasia and dysplasia 15 (0.4) Bronchopulmonary dysplasia 59 (1.4) Cardiac 379 (8.7) ASD 180 (4.1) VSD 77 (1.8) PDA 214 (4.9) Genitourinary Undescended testis 138 (6.8) Hydronephrosis 58 (1.3) Trisomies 4 (0.1) 18 2 (0.05) 21 2 (0.05) Abbreviations: ASD, atrial septal defect; PDA, patent ductus arteriosus; VSD, ventricular septal defect. a Patients with more than one diagnosis within a category are only counted once in the total. All-cause inpatient mortality was low (3.5%). The median length of stay was 30 days (interquartile range days) with 10.3% of infants being hospitalized for fewer than 15 days. Nearly half required a prolonged hospitalization of greater than 30 days. Length of stay was not found to differ by hospital type (data not shown). The median inflation-adjusted total hospital charge was $ In-hospital complications and transfusion requirement Sepsis (16.2%) and ileus (11.3%) were the most common complications (Table 4). Other infectious disease complications were unusual. Small bowel resections were relatively common (9.9%), although there are no data to show whether resection was performed at the initial surgery or at a later laparotomy. Subsequent laparotomy was required in 41 (0.9%) patients, although the reason cannot be determined from the data. Although relatively few infants were found to have respiratory failure (1.7%), respiratory distress was more commonly encountered (7.4%). Anemia (8.4%) was common, but 19.2% of patients with anemia were not transfused and 14.4% of those who were transfused did not have an ICD-9 code consistent with anemia. Characteristics of simple and complex groups Relatively few infants in this analysis were categorized as complex (n ¼ 474; 10.9%) compared to simple (Table 5). Patients with complex disease were more likely to be male (61.0 vs 55.4%; P ¼ 0.03) and treated in urban, teaching hospitals (P<0.01). The geographic distribution, however, was the same for both groups. Median length of stay, hospital charges and in-hospital mortality, Table 3 Hospitalization characteristics Geographic region, n (%) Northeast 506 (11.7) Midwest 889 (20.5) South 1584 (36.5) West 1365 (31.4) Type of hospital, n (%) Urban, teaching 3386 (78.0) Urban, non-teaching 830 (19.1) Rural 53 (1.2) Unknown 75 (1.7) In-hospital mortality, n (%) 152 (3.5) Length of stay Median (IQR) 30 (20 50) Total hospital charges ($) Median (IQR) ( ) Abbreviaton: IQR, interquartile range.

4 Gastroschisis in the US 53 Table 4 In-hospital complications and transfusion requirements Complication n a (%) Gastrointestinal 934 (21.5) NEC 136 (3.1) Prolonged ileus 360 (8.3) Malabsorption 148 (3.4) Intestinal perforation 97 (2.2) Volvulus 8 (0.2) Exploratory laparotomy as a 2nd procedure 41 (0.9) Ostomy 174 (4.0) Small bowel resection 362 (8.3) Acute vascular insufficiency of the intestine 102 (2.4) Respiratory 124 (2.9) Pneumonia 55 (1.3) Respiratory failure 74 (1.7) Infectious disease 1154 (26.6) Trunk cellulitis 111 (2.6) Wound complications 82 (1.9) Bacteremia 595 (13.7) Septicemia 700 (16.1) Septic shock 3 (0.1) Cardiovascular 50 (1.2) Cardiac arrest 20 (0.5) Cardiovascular shock 32 (0.7) Fistulae 17 (0.4) Enterocutaneous, enterocolic, enteroenteric or ileorectal 9 (0.2) Persistent postoperative fistula 10 (0.2) Acute renal failure 23 (0.5) Anemia 878 (20.2) Transfusion required 486 (11.2) Abbreviation: NEC, necrotizing enterocolitis. a Patients with more than one diagnosis within each category are only counted once in the total. on the other hand, were markedly different. Complex patients were typically hospitalized more than twice as long as their simple counterparts (67 vs 28 days; P<0.01). As a result, complex patients had significantly higher median inflation-adjusted hospital costs ($ vs $90 788; P<0.01). Finally, infants in the complex category were three times more likely to die during the hospitalization (8.7 vs 2.9%; P<0.01). Discussion In treating patients with a rare congenital anomaly, it is important to have a precise description of patient demographics, co-existing diagnoses, hospital course and outcome, not only with an aim of Table 5 Division of gastroschisis into simple and complex a Simple (n ¼ 3870; 89.1%) Complex (n ¼ 474; 10.9%) P-value Gender, n (%) 0.03 Male 1785 (46.1) 232 (49.0) Female 1727 (44.6) 185 (39.0) Unknown 358 (9.3) 57 (12.0) Geographic region, n (%) 0.13 Northeast 437 (11.3) 69 (14.6) Midwest 803 (20.8) 86 (18.1) South 1418 (36.6) 166 (35.0) West 1212 (31.3) 153 (32.3) Type of hospital, n (%) <0.01 Urban, teaching 3000 (78.7) 386 (84.1) Urban, non-teaching 764 (20.1) 66 (14.4) Rural 46 (1.2) 7 (1.5) Missing 60 (1.6) 15 (3.2) Length of stay, median (IQR) 28 (20 44) 67 (37 101) <0.01 Total hospital charges ($) Median (IQR) <0.01 ( ) ( ) In-hospital mortality, n (%) 111 (2.9) 41 (8.7) <0.01 Abbreviaton: IQR, interquartile range. a Complex defined by those infants with intestinal atresias, perforations, necrotic segments and volvulus. improving patient care, but also to aid in the counseling of parents as to prognosis. The study of rare congenital anomalies such as gastroschisis remains challenging, as all previous studies have generally depended on the limited experience of a single-center or regional database. This study seeks to profile infants with gastroschisis using a nationwide sample and to use this information to validate the risk classification system that divides them into simple and complex categories. 10 The data for this analysis were drawn from a national sample of discharges compiled from two de-identified national databases spanning 16 years and 37 states. Although the NIS database contains a 20% sample of all pediatric and adult discharges, the KID is a more comprehensive pediatric database as it is derived exclusively from discharges in patients 20 years of age and younger. Although the NIS is available for all 16 years, the KID has been issued only three times (1997, 2000, 2003). The KID was used, therefore, each year for which it was available and the NIS was used for the remaining 13 years. Thus, in total, we analyzed

5 54 Gastroschisis in the US 16 consecutive years from two national databases in order to minimize institutional and regional variations. With these combined data sets, we have created a comprehensive description of the demographics, co-existing diagnoses and hospital course of infants with gastroschisis. As the ICD-9 diagnosis code for gastroschisis and omphalocele are identical (756.7), we used the ICD-9 procedure code of (repair of gastroschisis) to identify patients for the analysis, a technique that has been has been previously validated for this diagnosis. 13 Our analysis has confirmed prior epidemiological studies which have shown that infants with gastroschisis typically have few co-existing congenital abnormalities and that overall survival is excellent. 10,15 17 The second major objective of this study was to validate the risk stratification categories of simple and complex as they relate to gastroschisis. As the understanding of the pathophysiology of gastroschisis has evolved over the last half century, numerous authors have made substantial contributions to the surgical treatment of gastroschisis while also noting differing clinical outcomes among a specific subset of patients. 4,6 9 An uneventful hospital course and improved outcome was observed in infants with gastroschisis who had no other anomaly or complication. The terms used by previous authors to describe these patients include simple, 10 isolated 18 and uncomplicated. 9 The negative impact on survival of specific factors and defined subgroups relating to the presence or absence of small bowel continuity 19 or the larger category of intestinal atresia were also recognized. 4,6 Molik and Grosfeld 10 formally defined simple and complex gastroschisis, and demonstrated that these are two clinically distinct subsets of patients with different hospital courses. The data we have analyzed support this classification and show that patients with complex defects (intestinal atresias, perforations, necrotic segments and volvulus) are more likely to require extensive hospital resources and have diminished survival. There are a number of limitations to our study that relate primarily to the data collection methods that are associated with national administrative databases. First, observations within the databases are dependent on accurate coding and recording of diagnoses and procedures using ICD-9 codes. These may not be nearly as accurate as a comprehensive medical chart reviews. However, error distribution is likely to be random as data are recorded by clerical and coding staff remote from the patient or study question. Furthermore, data recording errors and bias are also averaged over a large sample with information being gathered from independent hospitals in different states. Thus, sporadic errors should be evenly distributed throughout the data set. Second, the precise timing of clinical observations, diagnoses and procedures cannot be determined using the NIS and the KID. The inability to identify the precise timing of clinical events limits our ability to fully interpret data relating to a particular patient s hospital course. For example, we are only able to state that intestinal perforation or volvulus occurred during the hospitalization but cannot determine the exact timing of either event (e.g. at birth, preoperatively or postoperatively during the hospitalization). Third, certain fields in the NIS and KID are missing significant data (race, for instance), which may limit any substantial conclusions based on those characteristics. Fourth, because of limitations in the data sets and in ICD-9 coding, we were unable to investigate maternal characteristics, the incidence of antenatal diagnosis or specific details relating to birth history. Finally, the type and timing of surgical repair (primary or delayed) as well as details of the operative procedure central to surgical therapy and management (quality of bowel, presence of peel, location of atresia) could not be determined. Despite these limitations, the results from our study regarding the relative frequency of co-existing diagnoses, duration of hospitalization and outcome are generally consistent with previous studies using smaller sample sizes of non-national data. 10,15 17,20,21 Interestingly, our overall rate of intestinal atresia (n ¼ 265, 6.1%) is lower than the greater than 10% prevalence that is typically reported. 20,22,23 By combining two large national databases of hospital discharges, this study is the largest national study to date to profile the demographics of infants with gastroschisis. Additionally, we have also validated the categorization of these patients into simple and complex subgroups which differ in their use of hospital resources and subsequent survival. These data may be useful in assisting medical providers to treat these patients in a cost-effective way, guide health-care payers towards appropriate reimbursements and provide useful information to patient families. Acknowledgments We express our appreciation to Dr J Alex Haller, Jr for his review of this paper. References 1 Watkins DE. Gastroschisis with case report. Virginia Med Monthly 1943; 78: Moore TC, Stokes GE. Report of two cases treated by a modification of the Gross operation for omphalocele. Surgery 1953; 33: Fear W. Congenital extrusion of abdominal viscera:return:recovery. BMJ II 1878; Snyder CL, Miller KA, Sharp RJ, Murphy JP, Andrews WA, Holcomb III GW et al. Management of intestinal atresia in patients with gastroschisis. J Pediatr Surg 2001; 36: Wilson RD, Johnson MP. 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