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Outcomes of infants with abdominal wall defects over 18 years
Journal of Pediatric Surgery xxx (2016) xxx–xxx
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Outcomes of infants with abdominal wall defects over 18 years Juin Yee Kong a,b,⁎, Kee Thai Yeo a,b, Mohamed E. Abdel-Latif c,d, Barbara Bajuk e, Andrew J.A. Holland f,g, Susan Adams g,h, Ashish Jiwane g,h, Sandra Heck f, Michael Yeong a, Kei Lui a,g, Ju Lee Oei a,gon behalf of the New South Wales and Australian Capital Territory Neonatal Intensive Care Units' Data Collection a
Department of Newborn Care, Royal Hospital for Women, Randwick, NSW, Australia Department of Neonatology, KK Women's and Children's Hospital, Singapore c Department of Neonatology, Centenary Hospital for Women and Children, Garran, ACT, Australia d School of Clinical Medicine, Australian National University, Woden, ACT, Australia e Neonatal Intensive Care Units' Data Collection, NSW Pregnancy and Newborn Services Network, Westmead, NSW, Australia f The Children's Hospital at Westmead, The University of Sydney, NSW, Australia; g School of Women's and Children's Health, University of New South Wales, Randwick, NSW, Australia; h Department of Pediatric Surgery, Sydney Children's Hospital, Randwick, NSW, Australia b
a r t i c l e
i n f o
Article history: Received 30 December 2015 Received in revised form 20 April 2016 Accepted 5 June 2016 Available online xxxx Key words: Abdominal wall defect Gastroschisis Omphalocele Neonate Outcomes Mortality
a b s t r a c t Background/Purpose: Infants with abdominal wall defects (AWD) are at risk of poor outcomes including prolonged hospitalization, infections and mortality. Our objective was to describe and compare the outcomes of infants admitted with gastroschisis and omphalocele over 18 years. Methods: Population-based study of clinical data and outcomes of live-born infants with AWD admitted to all tertiary-level neonatal intensive care units in New South Wales and Australian Capital Territory from 1992 to 2009. Result: There were 502 infants with AWD – 336 gastroschisis, 166 omphalocele. Infants with gastroschisis required a longer duration of total parenteral nutrition (19 vs 4 days, p b 0.05), longer hospitalization (28 vs 15 days, p b 0.05) and had a higher rate of systemic infection [23.5% vs 13.3%, OR 1.77 (1.15–2.74), p b 0.05] compared to infants with omphalocele. Overall, omphalocele infants had higher mortality rate compared to gastroschisis infants [OR 2.77 (1.53, 5.04), p b 0.05]. Gastroschisis mortality rates increased from epoch 1 to epoch 3 (4.2% to 8.8%). Conclusion: Compared to infants with omphalocele, infants with gastroschisis required significantly longer hospitalization and parenteral nutrition with higher rates of infection. Infants with omphalocele had higher overall mortality rates. However, there has been an increase in the gastroschisis mortality rates but the cause for this is unclear. © 2016 Elsevier Inc. All rights reserved.
Gastroschisis (GS) and omphalocele (OM) are the most common congenital abdominal wall defects (AWD). Both conditions may be diagnosed prenatally by a combination of maternal serum screening and fetal ultrasound [1–5]. While the incidence varies between countries, the overall global incidence of GS has been increasing (1–5 per 10,000) [6–10], while OM rates have remained stable (1–3 per 10,000) [7,11,12]. Children with AWD are at risk of prolonged hospitalization, feeding intolerance, infections and mortality [13–16]. Single center reports
Abbreviations: AWD, abdominal wall defect; ACT, Australian Capital Territory; ART, assisted reproductive technology; BW, birth weight; CLD, chronic lung disease; OM, omphalocele; GS, gastroschisis; ICD-9, International Classification of Diseases Ninth Revision; IUGR, intrauterine growth restriction; NEC, necrotizing enterocolitis; NICU, neonatal intensive care unit; NSW, New South Wales; ROM, rupture of membranes; SGA, small for gestational age; TPN, total parenteral nutrition. ⁎ Corresponding author at: Department of Neonatology, KK Women's and Children's Hospital, 100 Bukit Timah Road, Singapore 229899, Singapore. Tel.: +65 84327531; fax: +65 62919079. E-mail addresses: [email protected], [email protected] (J.Y. Kong).
suggest that advances in perinatal management, nutrition and surgical techniques have improved outcomes, particularly for GS infants [6,17–19]. Whether this is true on a population level remains uncertain but important, as factors associated with short and long-term outcomes guide management and decision-making. In this study, we aimed to describe and compare the outcomes of infants admitted with GS and OM to neonatal intensive care units (NICU) in New South Wales (NSW) and the Australian Central Territory (ACT) more than an 18-year period (1992–2009). We also aimed to identify risk factors associated with adverse short term outcomes and mortality. We hypothesized that the outcomes and survival of these infants have improved as a result of changes and improvement in neonatal and surgical practice over the 18-year period. 1. Methods This study included all infants with AWD who survived to be admitted to one of the ten NICUs and were born over an 18 year period
http://dx.doi.org/10.1016/j.jpedsurg.2016.06.003 0022-3468/© 2016 Elsevier Inc. All rights reserved.
Please cite this article as: Kong JY, et al, Outcomes of infants with abdominal wall defects over 18 years, J Pediatr Surg (2016), http://dx.doi.org/ 10.1016/j.jpedsurg.2016.06.003
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J.Y. Kong et al. / Journal of Pediatric Surgery xxx (2016) xxx–xxx
between 1 January 1992 and 31 December 2009. The following information were extracted for the purposes of this study including maternal demographic data (maternal age, aboriginal status), perinatal information (maternal antenatal issues, provision of antenatal steroids, delivery information), neonatal data (gender, birthweight, gestational age), details of AWD management (surgical management, length of parenteral nutrition) and selected outcomes of AWD (length of stay, necrotizing enterocolitis, systemic infections, mortality).
3. Small for gestational age (SGA) was defined as a birth weight less than 10th percentile for gender and gestation. 4. Out born status denoted neonates who were born in a non-tertiary hospital who required transfer to one of the ten NICUs for specialist treatment. 5. Death before discharge referred to deaths occurring prior to discharge of infants from NICUs, while overall death include any death occurring prior to and after discharge reported to the audit officers. 6. The classification of necrotizing enterocolitis (NEC) was based on published clinical and radiographic definitions [22]. 7. To determine the complexity of GS, cases were divided into ‘simple’ or ‘complex’ disease based on the dates and types of operations using ICD-9 coding. From 1999 onwards, additional descriptions and code for the GS cases were recorded in the database. GS cases were categorized as ‘complex’ if there was additional coding for ‘resection of atresia’, ‘bowel resection’, ‘volvulus’, and ‘adhesion’ on the same day of primary operation. Cases were also categorized as ‘primary closure’ versus ‘delayed closure’ based on ICD-9 coding as well as dates of operations.
1.1. Data source This study was a retrospective review of data extracted from the neonatal intensive care units' (NICUS) data collection, which is a populationbased, prospective state-wide audit of infants admitted to all ten NICUs (eight perinatal centers and two children's hospitals) within NSW and the ACT in Australia. The NICUS database commenced in 1992 and collects data on all neonatal patients who are admitted to a NICU during the neonatal period for one of the following reasons: (1) gestation age b 32 weeks, (2) birth weight ≤ 1500 g, (3) assisted ventilation (mechanical ventilation or continuous positive airways pressure) for 4 h or more commenced during the first 28 days of life, or (4) major surgery (opening of a body cavity first performed in the first 28 days of life), (5) insertion of a central line (6) therapeutic hypothermia. Neonatal, maternal and perinatal data were prospectively collected and collated within each NICU by a designated clinical nurse specialist. Standard definitions were used across the entire network. Data were compiled into a central database located at the NSW Pregnancy and Newborn Services Network, Sydney and were subjected to rigorous quality control measures. The definitions and accuracy of this database has been previously documented [20]. Study period was divided into three 6-year epochs: epoch 1 (1992–1997), epoch 2 (1998–2003), and epoch 3 (2004–2009). The study was approved by the NSW Population and Health Services Research Ethics Committee.
1.3. Statistical analysis We utilized χ 2 test and t test for categorical and continuous data, where appropriate. One way ANOVA and Kruskal–Wallis test was used for multiple group comparisons. A multiple logistic regression analysis was used to establish the independent influence of AWD on neonatal mortality, after controlling for significant confounding factors identified in the bivariate comparisons. Separate logistic regression analyses were also performed on the subgroups of GS and OM to determine the factors associated with mortality in these groups. Odds ratio (OR) and adjusted odds ratio (AOR) were expressed with 95% confidence intervals (95% CI). A level of significance of α b 0.05 using a two-tailed comparison was used in this study. Analysis was performed using SPSS Statistics (IBM Corp., Released 2013. IBM SPSS Statistics for Windows, Version 22.0. Armonk, NY: IBM Corp).
1.2. Definitions
2. Results
The following definitions were used for the purposes of this study:
A total of 36,571 infants were admitted to the 10 NICUs in NSW and ACT during the study period, including 10,052 (27.5%) in epoch 1, 12,038 (32.9%) in epoch 2 and 14,481 (39.6%) in epoch 3. Over the 18year period, 502 (1.4%) infants with AWD were identified and treated. Of these, 336 (67%) had GS and 166 (23%) had OM. The incidence of
1. Growth percentiles were derived from Australian population-based growth charts [21]. 2. Intrauterine growth restriction (IUGR) was diagnosed by antenatal ultrasounds where the fetus failed to reach its predetermined growth potential. 6.0
per 10,000 live births
5.0
4.0 Gastroschisis
3.0
Omphalocele AWD
2.0
1.0
0.0 2009
2008
2007
2006
2005
2004
2003
2002
2001
2000
1999
1998
1997
1996
1995
1994
1993
1992
Fig. 1. Incidence of abdominal wall defect cases admitted to NICUs in NSW and ACT from 1992 to 2009. Data expressed as incidence per 10,000 live births (based on live births reported by the Australian Bureau of Statistics for NSW and ACT) [Total livebirths by year – 1992: 94534; 1993: 92393; 1994: 92159; 1995: 90466; 1996: 89517; 1997: 91364; 1998: 89481; 1999: 91037; 2000: 90817; 2001: 88516; 2002: 90695; 2003: 90472; 2004: 90068; 2005: 90795; 2006: 91815; 2007: 94248; 2008: 99488; 2009: 97641]
Please cite this article as: Kong JY, et al, Outcomes of infants with abdominal wall defects over 18 years, J Pediatr Surg (2016), http://dx.doi.org/ 10.1016/j.jpedsurg.2016.06.003
J.Y. Kong et al. / Journal of Pediatric Surgery xxx (2016) xxx–xxx
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Table 1 Maternal and infant clinical characteristics.
Median maternal age Aboriginal ethnicity Assisted reproduction Multiple gestation Antenatal steroids Preterm labor Rupture of membrane N 24 h Pathologically proven chorioamnionitis1 Maternal illicit substance use1 Median gestational age, weeks Male gender Caesarean section Median birthweight, gm Intrauterine growth restriction Small for gestational age 5 min Apgar b 7
Gastroschisis (GS) (n = 336)
Omphalocele (OM) (n = 166)
Odds ratio (CI)
p value
22 [19,27] 14 (4.2) 2 (0.6) 11 (3.3) 48 (14.3) 96 (28.6) 15 (4.5) 0 (0) 8 (2.4) 36 [35, 37] 182 (54.2) 118 (35.1) 2550 [2133,2828] 38 (11.3) 110 (32.7) 21 (6.3)
31 [26,35] 4 (2.4) 9 (5.4) 11 (6.6) 22 (13.3) 26 (15.7) 12 (7.2) 1 (0.9) 2 (1.2) 37 [36, 39] 98 (59.0) 59 (33.3) 2980 [2558, 3500] 9 (5.4) 26 (15.7) 9 (5.4)
N/A N/A 0.11 (0.02,0.50) 0.49 (0.22,1.12) 1.08 (0.67,1.72) 1.82 (1.23,2.70) 0.62 (0.30,1.29) N/A 1.98 (0.42,9.20) N/A 0.92 (0.78,1.08) 1.01 (0.88,1.16) N/A 2.09 (1.03,4.21) 2.09 (1.42,3.07) 1.16 (0.54,2.48)
b0.001 0.32 0.001 0.08 0.76 0.002 0.20 0.18 0.38 b0.001 0.30 0.93 b0.001 0.03 b0.001 0.84
Values are numbers (percentage) with odd ratio (95% confidence interval) or median [interquartile range]. 1 Data collected from 2001 onwards.
AWD cases admitted to NICU increased across the 3 epochs (Fig. 1), from 2.6 per 10,000 live births in epoch 1 to 3.6 per 10,000 in epoch 3. The rate of GS doubled from a rate of 1.5 per 10,000 livebirths in 1992 to 3.3 in 2009 compared to the rate of OM, where the rate increased marginally from 1.1 per 10,000 livebirths to 1.7 in 2009. 2.1. Maternal–Infant clinical characteristics The median age of mothers of infants born with GS were significantly lower than mothers of infants born with OM [22 vs 31 years, p b 0.001) (Table 1). In the OM group, 26.1% were born to mothers N35 years of age, compared with 5.1% in GS group (p b 0.01). Only 3.6% of OM mothers were b 20 years of age, compared with 36.1% in GS group. (p b 0.01). Mothers of infants born with GS were also more likely to present with preterm labor [28.6% vs 15.7%, OR 1.82 (1.23,2.70)] and were less likely to have conceived via assisted conception techniques [0.6% vs 5.4%, OR 0.11 (0.02,0.50)]. GS infants had lower median birth weights (2550 g vs 2980 g, p b 0.001), lower gestational age (36 wks vs 37 wks, p b 0.001) and twice the odds of being SGA [32.7% vs 15.7%, OR 2.09 (1.42, 3.07)]. The rates of Caesarean section were similar between both groups (35.1% versus 33.3%, p = 0.93). There was also similar proportion of infants of aboriginal ethnicity, male gender, multiple gestation, and similar rates of antenatal steroids, prolonged rupture of membranes and maternal illicit substance usage. 2.2. Outcomes between GS and OM The comparison of outcomes between GS and OM infants is summarized in Table 2. During the course of hospitalization, GS infants were more likely to require central venous lines [96.7% vs 56.3%, OR 1.59
(1.21, 2.10)], TPN for a longer duration (19 days versus 4 days, p = 0.001), develop more systemic infections (23.5% versus 13.3%, OR 1.77 (1.15–2.74)]) and require longer hospitalization (28 days versus 15 days, p = 0.01). Mortality rates were significantly higher in OM infants [16.3% vs 6.5%, OR 2.78(1.52–5.26)]. Deaths because of congenital anomalies accounted for 14 (14.1%) deaths in the GS group and 19 (27.9%) in the OM group [OR 2.4 (1.1, 5.1), p = 0.03]. Deaths because of infectious causes were similar: 5 (5.1%) in the GS group and 1(1.5%) in the OM group [OR 0.3 (0.03, 2.5), p = 0.4]. When controlling for known confounding factors (including maternal age, assisted reproduction, gender, prematurity and epoch), small for gestational age status and OM were associated with increased risk for mortality in AWD infants (Table 3). Infants who were SGA had 2 times the risk of mortality compared to non-SGA infants [AOR 2.10 (1.08,4.10)] and the OM group had 3 times the risk compared to the GS group [AOR 3.36 (1.57,7.17)]. 2.3. Comparison between epochs 2.3.1. Gastroschisis There were 96 GS infants in epoch 1, 104 in epoch 2 and 136 in epoch 3 (Table 4). This increase in admitted GS cases to NICUs was also reflected in an increase in the overall incidence (per 10,000 live births) over the years in the region (Fig. 1). There were no notable differences in the antenatal characteristics of infants across the three epochs with the exception for increased antenatal steroid administration to in epoch 3. The rate of Caesarean section was lower in epoch 3. There was an increase in the rate of proven systemic infection and length of stay for the two most recent epochs. A non-significant increase in mortality was noted from epoch 1 to epoch 3 (4.2% to 8.8%, p = 0.3), with
Table 2 Comparison of outcomes between GS and OM infants.
Median duration of total parenteral nutrition, days Any proven systemic infection Central lines1 Necrotizing enterocolitis Median length of stay, days Mean Gestational age at discharge, weeks Death prior to discharge Overall death2
Gastroschisis (GS) (n = 336)
Omphalocele (OM) (n = 166)
Odds Ratio (CI)
p value
19 [12,27] 79 (23.5) 145 (43.2) 10 (3.0) 28 [20,47] 41.0 [39.3,43.0] 20 (6.0) 22 (6.5)
4 [0,12] 22 (13.3) 45 (27.1) 3 (1.8) 15 [8,33] 40.0 [38.6,42.2] 25 (15.1) 27 (16.3)
N/A 1.77 (1.15,2.74) 1.59 (1.21,2.10) 1.65 (0.46,5.90) N/A N/A 0.40 (0.23,0.69) 0.40 (0.24, 0.69)
0.001 0.01 0.001 0.74 0.01 0.01 0.001 0.001
Values are numbers (percentage) with odd ratio (95% confidence interval) or median [interquartile range]. 1 Data collected from 2003 onwards. 2 Overall death includes reported death after discharge.
Please cite this article as: Kong JY, et al, Outcomes of infants with abdominal wall defects over 18 years, J Pediatr Surg (2016), http://dx.doi.org/ 10.1016/j.jpedsurg.2016.06.003
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J.Y. Kong et al. / Journal of Pediatric Surgery xxx (2016) xxx–xxx
Table 3 Multiple logistic regression analysis of mortality in infants with anterior abdominal wall defects. Β coefficient (SE) Admission Epoch Epoch 2 vs epoch 1 Epoch 3 vs epoch 1 Omphalocele Gastrochisis Maternal age b 20 years Maternal age ≥ 20 years Assisted reproduction Non-assisted conception Female gender Male gender Term gestation Preterm gestation Small for gestational age Appropriate for gestational age
When comparing characteristics of OM survivors and deceased, several factors were associated with increased risk of mortality including lower birth weight and lower gestational age. Caesarean section rates were significantly higher (55.6% vs 31.7%) in the deceased group (Table 5). NEC incidence was also associated with increased mortality although the number of cases was very low. After controlling for potential confounding factors, only lower birth weight was found to be associated with increased risk of mortality in this group.
Adjusted odds ratio (95%CI)
p value
0.03 (0.42) 0.14 (0.38) 1.21 (0.39)
1.03 (0.46,2.32) 1.15 (0.55,2.41) 3.36 (1.57,7.17)
0.90 0.70 0.002
0.01 (0.03)
1.01 (0.96,1.07)
0.60
3. Discussion
−0.82 (1.09)
0.44 (0.05,3.74)
0.50
0.11 (0.31)
1.12 (0.61,2.06)
0.70
−0.60 (0.32)
0.55 (0.29, 1.03)
0.06
0.47 (0.34)
2.10 (1.08,4.10)
0.03
This study represents one of the larger contemporary studies of AWD outcomes, spanning a total of 18 years. The overall incidence of AWD has increased from 2.6 per 10,000 live births in the first 6-year epoch to 3.6 per 10,000 in epoch 3. The increasing trend of AWD is because of the increase seen in cases in GS admitted to the NICUs during the time period studied. An increase in the incidence of GS has also been observed in several parts of the world [23,24]. The increase in caseload may reflect changing antenatal practices that lead to early detection of AWD, expectant management and successful transfer of liveborns to the NICU. One of the known major risk factors associated with the occurrence of AWD (especially GS) is young maternal age, typically below 20 years [11,25,26]. This was consistent with the findings in our study. The proposed explanation for this association is the possibility of increased use of recreational drugs, cigarette smoking, low socioeconomic status and poor nutritional status of the mothers of these infants [27–29]. In our study, the rates of substance abuse in GS and OM mothers were not significantly different (2.4% and 1.2%), but were lower than the overall rate of drug use in mothers of infants requiring NICU admission in our setting (approximately 5.1%) [30]. A significant proportion of OM mothers have been reported to be at the two ends of the reproductive age, b20 years or N 40 years. [24]. The optimal mode of delivery for infants with GS and OM remains controversial, although recent literature advocates avoidance of elective Caesarean deliveries [31–35]. The reported mortality rates and shortterm outcomes have not been shown to be affected by the mode of delivery [36]. Caesarean section rates in our study were equal in both groups and there was a trend towards a lower rate of Caesarean section in the most recent epoch. Conception through assisted reproduction therapy (ART) was found to be higher in the OM group. This is likely a reflection of the advanced
most deaths occurring before discharge from hospital. The presence of congenital anomalies was coded as a cause for majority of the deaths and infections were a notable factor only in the most recent epoch. Further analysis was performed to compare clinical characteristics of survivors and non-survivors in the GS group (Table 5). No significant difference was observed between rates of secondary closure between survivors and deceased GS infants. Lower birth weight, systemic infections and development of necrotizing enterocolitis were noted to be associated with the deaths in the GS infants. 2.3.2. Omphalocele There were 46 cases of OM in epoch 1, 50 cases in epoch 2 and 70 in epoch 3 (Table 3). As for GS, this trend represented an overall increase in incidence (per 10,000 live births) over the study period in the region (Fig. 1). There was an increase in the rate of preterm labor in the last 2 epochs. Antenatal steroid use and delivery room resuscitation were significantly higher in epoch 3 but Caesarean section rates were lower. Rates of proven systemic infections decreased from epoch 1 to epoch 2 and remained stable over epoch 3. A non-significant decrease in mortality rates for OM was observed from epoch 1 to epoch 3 (19.6% to 14.3%, p = 0.8).
Table 4 Comparison of infants with gastroschisis and omphalocele between epochs. Gastroschisis
Median maternal age Assisted reproduction Multiple gestation Antenatal steroids Preterm labor Rupture of membrane N 24 h Median birth weight, gm Median gestational age, wks Male gender Caesarean section Median duration of TPN, days Proven systemic infection Necrotizing enterocolitis Median length of stay, days Median gestation at discharge, wks Overall death1 Because of congenital anomalies Because of infections Because of other causes
Omphalocele
Epoch 1 (n = 96)
Epoch 2 (n = 104)
Epoch 3 (n = 136)
Epoch 1 (n = 46)
Epoch 2 (n = 50)
Epoch 3 (n = 70)
20.5 [17,24] 2 (2.1) 4 (4.2) 5 (5.3) 50 (52.1) 5 (5.2) 2366 [2038,2694] 36 [35,37] 52 (54.2) 35 (36.5) 18 [11,25] 16 (16.7) 1 (1.0) 27 [13,41] 41 [39,43] 4 (4.2) 2 (2.1) 0 2(2.1)
23 [19.5,26.5] 0 2 (1.9) 16 (15.4) 51 (49.0) 3 (2.9) 2568 [2224,2912] 37 [35.5,38.5] 63 (60.6) 50 (48.1) 17.5 [10,35] 30 (28.8) 4 (3.8) 27.5 [15.5,39.5] 41 [39,43] 6 (5.8) 4 (3.8) 1 (1.0) 1 (1.0)
23 [19.5,26.5] 0 5 (3.7) 27 (19.9)⁎
30 [26,34] 1 (2.2) 4 (8.7) 4 (8.8) 12 (26.1) 5 (10.9) 2915 [2471,3408] 38 [36,39] 32 (69.6) 21 (45.7) 3.5 [0,13] 10 (21.7) 2 (4.3) 16 [10,39] 40.5 [39,43] 9 (19.6) 7 (15.2) 0 2 (4.3)
29 [25,35] 3 (6.0) 2 (4.0) 3 (6.0) 19 (38.0) 2 (4.0) 2983 [2546,3424] 37 [36,39] 27 (54.0) 21 (42.0) 2.5 [0,7] 5 (10.0) 0 14.5 [7,23.5] 40 [39,42] 8 (16.0) 6 (12.0) 0 2 (4.0)
31 [27,36] 5 (7.1) 5 (7.1) 15 (21.4)⁎
68 (50.0) 7 (5.1) 2443 [2060,2826] 36.5 [35.5,37.5] 67 (49.3) 33 (24.3)⁎ 19.5 [11,28] 33 (24.3) 5 (3.7) 30 [15.5,44.5] 41 [39,43] 12 (8.8)⁎ 8 (5.9) 4 (2.9) 1 (0.7)
26 (37.1) 5 (7.1) 3010 [2630,3570] 37 [36,38] 39 (55.7) 17 (24.3)⁎ 6 [0,14] 7 (10.0) 1 (1.4) 13.5 [8,36] 40 [38,42] 10 (14.3)⁎ 6 (8.6) 1 (1.4) 4 (5.7)
Values are numbers (percentage) with odd ratio (95% confidence interval) or median [interquartile range]. 1 Overall death includes reported death after discharge. ⁎ Comparison between epochs by ANOVA or Kruskal–Wallis test p b 0.05.
Please cite this article as: Kong JY, et al, Outcomes of infants with abdominal wall defects over 18 years, J Pediatr Surg (2016), http://dx.doi.org/ 10.1016/j.jpedsurg.2016.06.003
J.Y. Kong et al. / Journal of Pediatric Surgery xxx (2016) xxx–xxx
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Table 5 Comparison of survivors and deceased AWD infants. Gastroschisis
Median birth weight (g) Median gestational age (weeks) Male gender Preterm Caesarean section Proven systemic infection Median TPN duration (days) Necrotizing enterocolitis Secondary closure⁎
Omphalocele
Survivors N = 314
Deceased N = 22
Odds ratio (CI)
p value
Survivors N = 139
Deceased N = 27
Odds ratio (CI)
p value
2500 [2150–2840] 37 [35–37)] 170 (54.1%) 156 (49.7%) 112 (35.7%) 69 (22.0%) 19 (13–27) 7 (2.2%) 41 (19.9%)
2255 [1966–2421] 36 [34–37] 12 (54.5%) 13 (59.1) 6 (37.3%) 10 (45.5%) 11 (0–36) 3 (13.6%) 5 (27.8%)
N/A N/A 1.00 (0.94,1.06) 0.84 (0.58,1.21) 0.89 (0.68,1.16) 0.48 (0.29,0.80) N/A 0.16 (0.05,0.59) 0.72 (0.32,1.59)
0.002 0.39 1.00 0.39 0.43 0.01 0.34 0.002 0.43
3120 [2750–3560] 38 [36–39] 84 (60.4%) 44 (31.7%) 44 (31.7%) 16 (11.5%) 4 (0–12) 1 (0.7%)
2380 [1850–2735] 37 [34–38] 14 (51.9%) 13 (48.1%) 15 (55.6%) 6 (22.2%) 0 (0–28) 2 (7.4%)
N/A N/A 1.17 (0.79,1.72) 0.66 (0.41,1.04) 1.54 (1.00,2.38) 0.52 (0.22,1.20) N/A 0.10 (0.01,1.03)
b0.001 0.04 0.41 0.10 0.02 0.13 0.06 0.02
Data are presented in numbers (percentage) or median [interquartile range]. ⁎ Data available for analysis from year 1999.
maternal age in this group. ART has been associated with increased risk of syndromes such as Beckwith–Wiedemann Syndrome (BWS), which commonly presents with OM [37]. In some reports, up to 22% of cases of OM have been associated with BWS and of which, 50% were the result of ART [38,39]. Genetic testing for this imprinting disorder, however, was not routinely done in the OM infants in our cohort and further examination of this association is warranted. Incomplete data on other associated anomalies and syndromes did not allow for further analysis on the contribution of congenital conditions on clinical presentation and potential outcomes of AWD. Not surprisingly, AWD was associated with significant morbidity, mortality and prolonged hospitalization. The burden of intensive care remains with GS infants, which were more likely to require prolonged central venous lines for TPN and were at a higher risk for systemic infections and prolonged hospitalizations. Contrary to previous reports [7,14,19], we found a non-significant increase in mortality rate for GS infants over the study period, from 4.2% in epoch 1 to 8.1% in epoch 3 (p = 0.3). Small bowel atresia, perforation and stenosis have been established as important factors in the survival and development of morbidities in GS infants [6,40–42]. A recent meta-analysis of 13 studies performed by Bergholz et al., demonstrated that complex gastroschisis (defined as gastroschisis with atresia, necrosis, perforation or volvulus) was associated with significantly increased morbidity and mortality when compared to simple gastroschisis (16.7% vs 2.18%, p b 0.001) [43]. We believe that the increasing mortality rate in our study might be attributed to an increase in complexity of cases in recent years. The lack of information regarding complexity of cases in the database limits our ability to investigate this association further. In contrast, the mortality rates of OM infants, although higher than GS infants, decreased over the study period, from 19.6% to 14.3% and were significantly lower than other studies [11,12,15]. Whether this may be because of antenatal terminations of complex cases, parental choices and selective process or because of improved care of co-morbidities is uncertain and requires further analysis. The lack of data on the antenatal diagnosis of abdominal wall defects in the database precludes the ability to determine any potential effect and differences in the management of infants born with these conditions. There are several limitations that must be considered in interpreting the findings of our study. Because of the nature of the database and case inclusion, we were also unable to obtain information on AWD infants who were not admitted to a NICU or who did not survive to NICU admission. This may predispose the study to selection bias that may lead to overestimation of the outcomes measures. Variation in NICU practices between units and case mix across the different NICUs may have influenced the outcomes of infants as reported to the network. Incomplete data from earlier years (e.g. the lack of description of defect and surgical management on GS infants) limited our ability to perform more detailed analyses to identify potential factors responsible for changes in the trends of outcomes and mortality rate in both GS and OM.
4. Conclusion The overall incidence of AWD has increased more than the 18 year timespan. GS infants required significantly longer hospitalizations and parenteral nutrition with higher rates of infection compared to infants with OM. Mortality rates have decreased for OM but rates for GS infants appear to have increased over time. Further studies are needed to determine the effects of stillbirths, complexity of the defect as well as operative strategies of infants with AWD on short term as well as long term outcomes. Conflict of interest None. References [1] Sebire NJ, Spencer K, Noble PL, et al. Maternal serum alpha-fetoprotein in fetal neural tube and abdominal wall defects at 10 to 14 weeks of gestation. Br J Obstet Gynaecol 1997;104:849–51. [2] Saller Jr DN, Canick JA, Palomaki GE, et al. Second-trimester maternal serum alphafetoprotein, unconjugated estriol, and hCG levels in pregnancies with ventral wall defects. Obstet Gynecol 1994;84:852–5. [3] Grande M, Arigita M, Borobio V, et al. First-trimester detection of structural abnormalities and the role of aneuploidy markers. Ultrasound Obstet Gynecol 2012;39:157–63. [4] Joo JG, Csatlos E, Rigo Jr J. Abdominal wall malformations in a 15-year fetopathological study: accuracy of prenatal ultrasonography diagnosis. Prenat Diagn 2010;30:1015–8. [5] Barisic I, Clementi M, Hausler M, et al. Evaluation of prenatal ultrasound diagnosis of fetal abdominal wall defects by 19 European registries. Ultrasound Obstet Gynecol 2001;18:309–16. [6] Baerg J, Kaban G, Tonita J, et al. Gastroschisis: a sixteen-year review. J Pediatr Surg 2003;38:771–4. [7] Suita S, Okamatsu T, Yamamoto T, et al. Changing profile of abdominal wall defects in Japan: results of a national survey. J Pediatr Surg 2000;35:66–71 [discussion 72]. [8] Overton TG, Pierce MR, Gao H, et al. Antenatal management and outcomes of gastroschisis in the U.K. Prenat Diagn 2012;32:1256–62. [9] Kirby RS, Marshall J, Tanner JP, et al. Prevalence and correlates of gastroschisis in 15 states, 1995 to 2005. Obstet Gynecol 2013;122:275–81. [10] Mastroiacovo P, Lisi A, Castilla EE. The incidence of gastroschisis: research urgently needs resources. BMJ 2006;332:423–4. [11] Rankin J, Dillon E, Wright C. Congenital anterior abdominal wall defects in the north of England, 1986-1996: occurrence and outcome. Prenat Diagn 1999;19:662–8. [12] Salihu HM, Pierre-Louis BJ, Druschel CM, et al. Omphalocele and gastroschisis in the state of New York, 1992-1999. Birth Defects Res A Clin Mol Teratol 2003;67:630–6. [13] Novotny DA, Klein RL, Boeckman CR. Gastroschisis: an 18-year review. J Pediatr Surg 1993;28:650–2. [14] Snyder CL. Outcome analysis for gastroschisis. J Pediatr Surg 1999;34:1253–6. [15] Vachharajani AJ, Rao R, Keswani S, et al. Outcomes of exomphalos: an institutional experience. Pediatr Surg Int 2009;25:139–44. [16] Durfee SM, Benson CB, Adams SR, et al. Postnatal outcome of fetuses with the prenatal diagnosis of gastroschisis. J Ultrasound Med 2013;32:407–12. [17] Davies MW, Kimble RM, Cartwright DW. Gastroschisis: ward reduction compared with traditional reduction under general anesthesia. J Pediatr Surg 2005;40:523–7. [18] Leadbeater K, Kumar R, Feltrin R. Ward reduction of gastroschisis: risk stratification helps optimise the outcome. Pediatr Surg Int 2010;26:1001–5. [19] Guida E, Pini-Prato A, Mattioli G, et al. Abdominal wall defects: a 33-year unicentric experience. Minerva Pediatr 2013;65:179–85.
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[20] Bajuk B. Validation of the neonatal intensive care units' data collection. Presented at the proceedings of the 5th annual congress of the perinatal Society of Australia and New Zealand, Canberra, Australia; 2001. [21] Dobbins TA, Sullivan EA, Roberts CL, et al. Australian national birthweight percentiles by sex and gestational age, 1998-2007. Med J Aust 2012;197:291–4. [22] Bell MJ, Ternberg JL, Feigin RD, et al. Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann Surg 1978;187:1–7. [23] Reid KP, Dickinson JE, Doherty DA. The epidemiologic incidence of congenital gastroschisis in Western Australia. Am J Obstet Gynecol 2003;189:764–8. [24] Byron-Scott R, Haan E, Chan A, et al. A population-based study of abdominal wall defects in South Australia and Western Australia. Paediatr Perinat Epidemiol 1998;12:136–51. [25] Loane M, Dolk H, Bradbury I, et al. Increasing prevalence of gastroschisis in Europe 1980-2002: a phenomenon restricted to younger mothers? Paediatr Perinat Epidemiol 2007;21:363–9. [26] Tan KH, Kilby MD, Whittle MJ, et al. Congenital anterior abdominal wall defects in England and Wales 1987-93: retrospective analysis of OPCS data. BMJ 1996;313:903–6. [27] Torfs CP, Velie EM, Oechsli FW, et al. A population-based study of gastroschisis: demographic, pregnancy, and lifestyle risk factors. Teratology 1994;50:44–53. [28] Hoyme HE, Jones MC, Jones KL. Gastroschisis: abdominal wall disruption secondary to early gestational interruption of the omphalomesenteric artery. Semin Perinatol 1983;7:294–8. [29] Holland AJ, Walker K, Badawi N. Gastroschisis: an update. Pediatr Surg Int 2010;26:871–8. [30] Abdel-Latif ME, Bajuk B, Lui K, et al. Short-term outcomes of infants of substanceusing mothers admitted to neonatal intensive care units in new South Wales and the Australian Capital Territory. J Paediatr Child Health 2007; 43:127–33. [31] Gomez Alcala AV. The "routine" use of cesarean section (CS) for delivery of infants with gastroschisis (Gs) is not warranted. J Pediatr Surg 2004;39:1885–6.
[32] Lurie S, Sherman D, Bukovsky I. Omphalocele delivery enigma: the best mode of delivery still remains dubious. Eur J Obstet Gynecol Reprod Biol 1999;82:19–22. [33] Kitchanan S, Patole SK, Muller R, et al. Neonatal outcome of gastroschisis and exomphalos: a 10-year review. J Paediatr Child Health 2000;36:428–30. [34] Puligandla PS, Janvier A, Flageole H, et al. Routine cesarean delivery does not improve the outcome of infants with gastroschisis. J Pediatr Surg 2004;39:742–5. [35] Baud D, Lausman A, Alfaraj MA, et al. Expectant management compared with elective delivery at 37 weeks for gastroschisis. Obstet Gynecol 2013;121:990–8. [36] Abdel-Latif ME, Bolisetty S, Abeywardana S, et al. Mode of delivery and neonatal survival of infants with gastroschisis in Australia and New Zealand. J Pediatr Surg 2008;43:1685–90. [37] Halliday J, Oke K, Breheny S, et al. Beckwith-Wiedemann syndrome and IVF: a case– control study. Am J Hum Genet 2004;75:526–8. [38] Wilkins-Haug L, Porter A, Hawley P, et al. Isolated fetal omphalocele, BeckwithWiedemann syndrome, and assisted reproductive technologies. Birth Defects Res A Clin Mol Teratol 2009;85:58–62. [39] Boyd PA, Bhattacharjee A, Gould S, et al. Outcome of prenatally diagnosed anterior abdominal wall defects. Arch Dis Child Fetal Neonatal Ed 1998;78:F209–13. [40] Cusick E, Spicer RD, Beck JM. Small-bowel continuity: a crucial factor in determining survival in gastroschisis. Pediatr Surg Int 1997;12:34–7. [41] Arnold MA, Chang DC, Nabaweesi R, et al. Risk stratification of 4344 patients with gastroschisis into simple and complex categories. J Pediatr Surg 2007;42:1520–5. [42] Arnold MA, Chang DC, Nabaweesi R, et al. Development and validation of a risk stratification index to predict death in gastroschisis. J Pediatr Surg 2007;42:950–5 [discussion 955–956]. [43] Bergholz R, Boettcher M, Reinshagen K, et al. Complex gastroschisis is a different entity to simple gastroschisis affecting morbidity and mortality-a systematic review and meta-analysis. J Pediatr Surg 2014;49:1527–32.
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Journal of Pediatric Surgery journal homepage: www.elsevier.com/locate/jpedsurg
Outcomes of infants with abdominal wall defects over 18 years Juin Yee Kong a,b,⁎, Kee Thai Yeo a,b, Mohamed E. Abdel-Latif c,d, Barbara Bajuk e, Andrew J.A. Holland f,g, Susan Adams g,h, Ashish Jiwane g,h, Sandra Heck f, Michael Yeong a, Kei Lui a,g, Ju Lee Oei a,gon behalf of the New South Wales and Australian Capital Territory Neonatal Intensive Care Units' Data Collection a
Department of Newborn Care, Royal Hospital for Women, Randwick, NSW, Australia Department of Neonatology, KK Women's and Children's Hospital, Singapore c Department of Neonatology, Centenary Hospital for Women and Children, Garran, ACT, Australia d School of Clinical Medicine, Australian National University, Woden, ACT, Australia e Neonatal Intensive Care Units' Data Collection, NSW Pregnancy and Newborn Services Network, Westmead, NSW, Australia f The Children's Hospital at Westmead, The University of Sydney, NSW, Australia; g School of Women's and Children's Health, University of New South Wales, Randwick, NSW, Australia; h Department of Pediatric Surgery, Sydney Children's Hospital, Randwick, NSW, Australia b
a r t i c l e
i n f o
Article history: Received 30 December 2015 Received in revised form 20 April 2016 Accepted 5 June 2016 Available online xxxx Key words: Abdominal wall defect Gastroschisis Omphalocele Neonate Outcomes Mortality
a b s t r a c t Background/Purpose: Infants with abdominal wall defects (AWD) are at risk of poor outcomes including prolonged hospitalization, infections and mortality. Our objective was to describe and compare the outcomes of infants admitted with gastroschisis and omphalocele over 18 years. Methods: Population-based study of clinical data and outcomes of live-born infants with AWD admitted to all tertiary-level neonatal intensive care units in New South Wales and Australian Capital Territory from 1992 to 2009. Result: There were 502 infants with AWD – 336 gastroschisis, 166 omphalocele. Infants with gastroschisis required a longer duration of total parenteral nutrition (19 vs 4 days, p b 0.05), longer hospitalization (28 vs 15 days, p b 0.05) and had a higher rate of systemic infection [23.5% vs 13.3%, OR 1.77 (1.15–2.74), p b 0.05] compared to infants with omphalocele. Overall, omphalocele infants had higher mortality rate compared to gastroschisis infants [OR 2.77 (1.53, 5.04), p b 0.05]. Gastroschisis mortality rates increased from epoch 1 to epoch 3 (4.2% to 8.8%). Conclusion: Compared to infants with omphalocele, infants with gastroschisis required significantly longer hospitalization and parenteral nutrition with higher rates of infection. Infants with omphalocele had higher overall mortality rates. However, there has been an increase in the gastroschisis mortality rates but the cause for this is unclear. © 2016 Elsevier Inc. All rights reserved.
Gastroschisis (GS) and omphalocele (OM) are the most common congenital abdominal wall defects (AWD). Both conditions may be diagnosed prenatally by a combination of maternal serum screening and fetal ultrasound [1–5]. While the incidence varies between countries, the overall global incidence of GS has been increasing (1–5 per 10,000) [6–10], while OM rates have remained stable (1–3 per 10,000) [7,11,12]. Children with AWD are at risk of prolonged hospitalization, feeding intolerance, infections and mortality [13–16]. Single center reports
Abbreviations: AWD, abdominal wall defect; ACT, Australian Capital Territory; ART, assisted reproductive technology; BW, birth weight; CLD, chronic lung disease; OM, omphalocele; GS, gastroschisis; ICD-9, International Classification of Diseases Ninth Revision; IUGR, intrauterine growth restriction; NEC, necrotizing enterocolitis; NICU, neonatal intensive care unit; NSW, New South Wales; ROM, rupture of membranes; SGA, small for gestational age; TPN, total parenteral nutrition. ⁎ Corresponding author at: Department of Neonatology, KK Women's and Children's Hospital, 100 Bukit Timah Road, Singapore 229899, Singapore. Tel.: +65 84327531; fax: +65 62919079. E-mail addresses: [email protected], [email protected] (J.Y. Kong).
suggest that advances in perinatal management, nutrition and surgical techniques have improved outcomes, particularly for GS infants [6,17–19]. Whether this is true on a population level remains uncertain but important, as factors associated with short and long-term outcomes guide management and decision-making. In this study, we aimed to describe and compare the outcomes of infants admitted with GS and OM to neonatal intensive care units (NICU) in New South Wales (NSW) and the Australian Central Territory (ACT) more than an 18-year period (1992–2009). We also aimed to identify risk factors associated with adverse short term outcomes and mortality. We hypothesized that the outcomes and survival of these infants have improved as a result of changes and improvement in neonatal and surgical practice over the 18-year period. 1. Methods This study included all infants with AWD who survived to be admitted to one of the ten NICUs and were born over an 18 year period
http://dx.doi.org/10.1016/j.jpedsurg.2016.06.003 0022-3468/© 2016 Elsevier Inc. All rights reserved.
Please cite this article as: Kong JY, et al, Outcomes of infants with abdominal wall defects over 18 years, J Pediatr Surg (2016), http://dx.doi.org/ 10.1016/j.jpedsurg.2016.06.003
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between 1 January 1992 and 31 December 2009. The following information were extracted for the purposes of this study including maternal demographic data (maternal age, aboriginal status), perinatal information (maternal antenatal issues, provision of antenatal steroids, delivery information), neonatal data (gender, birthweight, gestational age), details of AWD management (surgical management, length of parenteral nutrition) and selected outcomes of AWD (length of stay, necrotizing enterocolitis, systemic infections, mortality).
3. Small for gestational age (SGA) was defined as a birth weight less than 10th percentile for gender and gestation. 4. Out born status denoted neonates who were born in a non-tertiary hospital who required transfer to one of the ten NICUs for specialist treatment. 5. Death before discharge referred to deaths occurring prior to discharge of infants from NICUs, while overall death include any death occurring prior to and after discharge reported to the audit officers. 6. The classification of necrotizing enterocolitis (NEC) was based on published clinical and radiographic definitions [22]. 7. To determine the complexity of GS, cases were divided into ‘simple’ or ‘complex’ disease based on the dates and types of operations using ICD-9 coding. From 1999 onwards, additional descriptions and code for the GS cases were recorded in the database. GS cases were categorized as ‘complex’ if there was additional coding for ‘resection of atresia’, ‘bowel resection’, ‘volvulus’, and ‘adhesion’ on the same day of primary operation. Cases were also categorized as ‘primary closure’ versus ‘delayed closure’ based on ICD-9 coding as well as dates of operations.
1.1. Data source This study was a retrospective review of data extracted from the neonatal intensive care units' (NICUS) data collection, which is a populationbased, prospective state-wide audit of infants admitted to all ten NICUs (eight perinatal centers and two children's hospitals) within NSW and the ACT in Australia. The NICUS database commenced in 1992 and collects data on all neonatal patients who are admitted to a NICU during the neonatal period for one of the following reasons: (1) gestation age b 32 weeks, (2) birth weight ≤ 1500 g, (3) assisted ventilation (mechanical ventilation or continuous positive airways pressure) for 4 h or more commenced during the first 28 days of life, or (4) major surgery (opening of a body cavity first performed in the first 28 days of life), (5) insertion of a central line (6) therapeutic hypothermia. Neonatal, maternal and perinatal data were prospectively collected and collated within each NICU by a designated clinical nurse specialist. Standard definitions were used across the entire network. Data were compiled into a central database located at the NSW Pregnancy and Newborn Services Network, Sydney and were subjected to rigorous quality control measures. The definitions and accuracy of this database has been previously documented [20]. Study period was divided into three 6-year epochs: epoch 1 (1992–1997), epoch 2 (1998–2003), and epoch 3 (2004–2009). The study was approved by the NSW Population and Health Services Research Ethics Committee.
1.3. Statistical analysis We utilized χ 2 test and t test for categorical and continuous data, where appropriate. One way ANOVA and Kruskal–Wallis test was used for multiple group comparisons. A multiple logistic regression analysis was used to establish the independent influence of AWD on neonatal mortality, after controlling for significant confounding factors identified in the bivariate comparisons. Separate logistic regression analyses were also performed on the subgroups of GS and OM to determine the factors associated with mortality in these groups. Odds ratio (OR) and adjusted odds ratio (AOR) were expressed with 95% confidence intervals (95% CI). A level of significance of α b 0.05 using a two-tailed comparison was used in this study. Analysis was performed using SPSS Statistics (IBM Corp., Released 2013. IBM SPSS Statistics for Windows, Version 22.0. Armonk, NY: IBM Corp).
1.2. Definitions
2. Results
The following definitions were used for the purposes of this study:
A total of 36,571 infants were admitted to the 10 NICUs in NSW and ACT during the study period, including 10,052 (27.5%) in epoch 1, 12,038 (32.9%) in epoch 2 and 14,481 (39.6%) in epoch 3. Over the 18year period, 502 (1.4%) infants with AWD were identified and treated. Of these, 336 (67%) had GS and 166 (23%) had OM. The incidence of
1. Growth percentiles were derived from Australian population-based growth charts [21]. 2. Intrauterine growth restriction (IUGR) was diagnosed by antenatal ultrasounds where the fetus failed to reach its predetermined growth potential. 6.0
per 10,000 live births
5.0
4.0 Gastroschisis
3.0
Omphalocele AWD
2.0
1.0
0.0 2009
2008
2007
2006
2005
2004
2003
2002
2001
2000
1999
1998
1997
1996
1995
1994
1993
1992
Fig. 1. Incidence of abdominal wall defect cases admitted to NICUs in NSW and ACT from 1992 to 2009. Data expressed as incidence per 10,000 live births (based on live births reported by the Australian Bureau of Statistics for NSW and ACT) [Total livebirths by year – 1992: 94534; 1993: 92393; 1994: 92159; 1995: 90466; 1996: 89517; 1997: 91364; 1998: 89481; 1999: 91037; 2000: 90817; 2001: 88516; 2002: 90695; 2003: 90472; 2004: 90068; 2005: 90795; 2006: 91815; 2007: 94248; 2008: 99488; 2009: 97641]
Please cite this article as: Kong JY, et al, Outcomes of infants with abdominal wall defects over 18 years, J Pediatr Surg (2016), http://dx.doi.org/ 10.1016/j.jpedsurg.2016.06.003
J.Y. Kong et al. / Journal of Pediatric Surgery xxx (2016) xxx–xxx
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Table 1 Maternal and infant clinical characteristics.
Median maternal age Aboriginal ethnicity Assisted reproduction Multiple gestation Antenatal steroids Preterm labor Rupture of membrane N 24 h Pathologically proven chorioamnionitis1 Maternal illicit substance use1 Median gestational age, weeks Male gender Caesarean section Median birthweight, gm Intrauterine growth restriction Small for gestational age 5 min Apgar b 7
Gastroschisis (GS) (n = 336)
Omphalocele (OM) (n = 166)
Odds ratio (CI)
p value
22 [19,27] 14 (4.2) 2 (0.6) 11 (3.3) 48 (14.3) 96 (28.6) 15 (4.5) 0 (0) 8 (2.4) 36 [35, 37] 182 (54.2) 118 (35.1) 2550 [2133,2828] 38 (11.3) 110 (32.7) 21 (6.3)
31 [26,35] 4 (2.4) 9 (5.4) 11 (6.6) 22 (13.3) 26 (15.7) 12 (7.2) 1 (0.9) 2 (1.2) 37 [36, 39] 98 (59.0) 59 (33.3) 2980 [2558, 3500] 9 (5.4) 26 (15.7) 9 (5.4)
N/A N/A 0.11 (0.02,0.50) 0.49 (0.22,1.12) 1.08 (0.67,1.72) 1.82 (1.23,2.70) 0.62 (0.30,1.29) N/A 1.98 (0.42,9.20) N/A 0.92 (0.78,1.08) 1.01 (0.88,1.16) N/A 2.09 (1.03,4.21) 2.09 (1.42,3.07) 1.16 (0.54,2.48)
b0.001 0.32 0.001 0.08 0.76 0.002 0.20 0.18 0.38 b0.001 0.30 0.93 b0.001 0.03 b0.001 0.84
Values are numbers (percentage) with odd ratio (95% confidence interval) or median [interquartile range]. 1 Data collected from 2001 onwards.
AWD cases admitted to NICU increased across the 3 epochs (Fig. 1), from 2.6 per 10,000 live births in epoch 1 to 3.6 per 10,000 in epoch 3. The rate of GS doubled from a rate of 1.5 per 10,000 livebirths in 1992 to 3.3 in 2009 compared to the rate of OM, where the rate increased marginally from 1.1 per 10,000 livebirths to 1.7 in 2009. 2.1. Maternal–Infant clinical characteristics The median age of mothers of infants born with GS were significantly lower than mothers of infants born with OM [22 vs 31 years, p b 0.001) (Table 1). In the OM group, 26.1% were born to mothers N35 years of age, compared with 5.1% in GS group (p b 0.01). Only 3.6% of OM mothers were b 20 years of age, compared with 36.1% in GS group. (p b 0.01). Mothers of infants born with GS were also more likely to present with preterm labor [28.6% vs 15.7%, OR 1.82 (1.23,2.70)] and were less likely to have conceived via assisted conception techniques [0.6% vs 5.4%, OR 0.11 (0.02,0.50)]. GS infants had lower median birth weights (2550 g vs 2980 g, p b 0.001), lower gestational age (36 wks vs 37 wks, p b 0.001) and twice the odds of being SGA [32.7% vs 15.7%, OR 2.09 (1.42, 3.07)]. The rates of Caesarean section were similar between both groups (35.1% versus 33.3%, p = 0.93). There was also similar proportion of infants of aboriginal ethnicity, male gender, multiple gestation, and similar rates of antenatal steroids, prolonged rupture of membranes and maternal illicit substance usage. 2.2. Outcomes between GS and OM The comparison of outcomes between GS and OM infants is summarized in Table 2. During the course of hospitalization, GS infants were more likely to require central venous lines [96.7% vs 56.3%, OR 1.59
(1.21, 2.10)], TPN for a longer duration (19 days versus 4 days, p = 0.001), develop more systemic infections (23.5% versus 13.3%, OR 1.77 (1.15–2.74)]) and require longer hospitalization (28 days versus 15 days, p = 0.01). Mortality rates were significantly higher in OM infants [16.3% vs 6.5%, OR 2.78(1.52–5.26)]. Deaths because of congenital anomalies accounted for 14 (14.1%) deaths in the GS group and 19 (27.9%) in the OM group [OR 2.4 (1.1, 5.1), p = 0.03]. Deaths because of infectious causes were similar: 5 (5.1%) in the GS group and 1(1.5%) in the OM group [OR 0.3 (0.03, 2.5), p = 0.4]. When controlling for known confounding factors (including maternal age, assisted reproduction, gender, prematurity and epoch), small for gestational age status and OM were associated with increased risk for mortality in AWD infants (Table 3). Infants who were SGA had 2 times the risk of mortality compared to non-SGA infants [AOR 2.10 (1.08,4.10)] and the OM group had 3 times the risk compared to the GS group [AOR 3.36 (1.57,7.17)]. 2.3. Comparison between epochs 2.3.1. Gastroschisis There were 96 GS infants in epoch 1, 104 in epoch 2 and 136 in epoch 3 (Table 4). This increase in admitted GS cases to NICUs was also reflected in an increase in the overall incidence (per 10,000 live births) over the years in the region (Fig. 1). There were no notable differences in the antenatal characteristics of infants across the three epochs with the exception for increased antenatal steroid administration to in epoch 3. The rate of Caesarean section was lower in epoch 3. There was an increase in the rate of proven systemic infection and length of stay for the two most recent epochs. A non-significant increase in mortality was noted from epoch 1 to epoch 3 (4.2% to 8.8%, p = 0.3), with
Table 2 Comparison of outcomes between GS and OM infants.
Median duration of total parenteral nutrition, days Any proven systemic infection Central lines1 Necrotizing enterocolitis Median length of stay, days Mean Gestational age at discharge, weeks Death prior to discharge Overall death2
Gastroschisis (GS) (n = 336)
Omphalocele (OM) (n = 166)
Odds Ratio (CI)
p value
19 [12,27] 79 (23.5) 145 (43.2) 10 (3.0) 28 [20,47] 41.0 [39.3,43.0] 20 (6.0) 22 (6.5)
4 [0,12] 22 (13.3) 45 (27.1) 3 (1.8) 15 [8,33] 40.0 [38.6,42.2] 25 (15.1) 27 (16.3)
N/A 1.77 (1.15,2.74) 1.59 (1.21,2.10) 1.65 (0.46,5.90) N/A N/A 0.40 (0.23,0.69) 0.40 (0.24, 0.69)
0.001 0.01 0.001 0.74 0.01 0.01 0.001 0.001
Values are numbers (percentage) with odd ratio (95% confidence interval) or median [interquartile range]. 1 Data collected from 2003 onwards. 2 Overall death includes reported death after discharge.
Please cite this article as: Kong JY, et al, Outcomes of infants with abdominal wall defects over 18 years, J Pediatr Surg (2016), http://dx.doi.org/ 10.1016/j.jpedsurg.2016.06.003
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Table 3 Multiple logistic regression analysis of mortality in infants with anterior abdominal wall defects. Β coefficient (SE) Admission Epoch Epoch 2 vs epoch 1 Epoch 3 vs epoch 1 Omphalocele Gastrochisis Maternal age b 20 years Maternal age ≥ 20 years Assisted reproduction Non-assisted conception Female gender Male gender Term gestation Preterm gestation Small for gestational age Appropriate for gestational age
When comparing characteristics of OM survivors and deceased, several factors were associated with increased risk of mortality including lower birth weight and lower gestational age. Caesarean section rates were significantly higher (55.6% vs 31.7%) in the deceased group (Table 5). NEC incidence was also associated with increased mortality although the number of cases was very low. After controlling for potential confounding factors, only lower birth weight was found to be associated with increased risk of mortality in this group.
Adjusted odds ratio (95%CI)
p value
0.03 (0.42) 0.14 (0.38) 1.21 (0.39)
1.03 (0.46,2.32) 1.15 (0.55,2.41) 3.36 (1.57,7.17)
0.90 0.70 0.002
0.01 (0.03)
1.01 (0.96,1.07)
0.60
3. Discussion
−0.82 (1.09)
0.44 (0.05,3.74)
0.50
0.11 (0.31)
1.12 (0.61,2.06)
0.70
−0.60 (0.32)
0.55 (0.29, 1.03)
0.06
0.47 (0.34)
2.10 (1.08,4.10)
0.03
This study represents one of the larger contemporary studies of AWD outcomes, spanning a total of 18 years. The overall incidence of AWD has increased from 2.6 per 10,000 live births in the first 6-year epoch to 3.6 per 10,000 in epoch 3. The increasing trend of AWD is because of the increase seen in cases in GS admitted to the NICUs during the time period studied. An increase in the incidence of GS has also been observed in several parts of the world [23,24]. The increase in caseload may reflect changing antenatal practices that lead to early detection of AWD, expectant management and successful transfer of liveborns to the NICU. One of the known major risk factors associated with the occurrence of AWD (especially GS) is young maternal age, typically below 20 years [11,25,26]. This was consistent with the findings in our study. The proposed explanation for this association is the possibility of increased use of recreational drugs, cigarette smoking, low socioeconomic status and poor nutritional status of the mothers of these infants [27–29]. In our study, the rates of substance abuse in GS and OM mothers were not significantly different (2.4% and 1.2%), but were lower than the overall rate of drug use in mothers of infants requiring NICU admission in our setting (approximately 5.1%) [30]. A significant proportion of OM mothers have been reported to be at the two ends of the reproductive age, b20 years or N 40 years. [24]. The optimal mode of delivery for infants with GS and OM remains controversial, although recent literature advocates avoidance of elective Caesarean deliveries [31–35]. The reported mortality rates and shortterm outcomes have not been shown to be affected by the mode of delivery [36]. Caesarean section rates in our study were equal in both groups and there was a trend towards a lower rate of Caesarean section in the most recent epoch. Conception through assisted reproduction therapy (ART) was found to be higher in the OM group. This is likely a reflection of the advanced
most deaths occurring before discharge from hospital. The presence of congenital anomalies was coded as a cause for majority of the deaths and infections were a notable factor only in the most recent epoch. Further analysis was performed to compare clinical characteristics of survivors and non-survivors in the GS group (Table 5). No significant difference was observed between rates of secondary closure between survivors and deceased GS infants. Lower birth weight, systemic infections and development of necrotizing enterocolitis were noted to be associated with the deaths in the GS infants. 2.3.2. Omphalocele There were 46 cases of OM in epoch 1, 50 cases in epoch 2 and 70 in epoch 3 (Table 3). As for GS, this trend represented an overall increase in incidence (per 10,000 live births) over the study period in the region (Fig. 1). There was an increase in the rate of preterm labor in the last 2 epochs. Antenatal steroid use and delivery room resuscitation were significantly higher in epoch 3 but Caesarean section rates were lower. Rates of proven systemic infections decreased from epoch 1 to epoch 2 and remained stable over epoch 3. A non-significant decrease in mortality rates for OM was observed from epoch 1 to epoch 3 (19.6% to 14.3%, p = 0.8).
Table 4 Comparison of infants with gastroschisis and omphalocele between epochs. Gastroschisis
Median maternal age Assisted reproduction Multiple gestation Antenatal steroids Preterm labor Rupture of membrane N 24 h Median birth weight, gm Median gestational age, wks Male gender Caesarean section Median duration of TPN, days Proven systemic infection Necrotizing enterocolitis Median length of stay, days Median gestation at discharge, wks Overall death1 Because of congenital anomalies Because of infections Because of other causes
Omphalocele
Epoch 1 (n = 96)
Epoch 2 (n = 104)
Epoch 3 (n = 136)
Epoch 1 (n = 46)
Epoch 2 (n = 50)
Epoch 3 (n = 70)
20.5 [17,24] 2 (2.1) 4 (4.2) 5 (5.3) 50 (52.1) 5 (5.2) 2366 [2038,2694] 36 [35,37] 52 (54.2) 35 (36.5) 18 [11,25] 16 (16.7) 1 (1.0) 27 [13,41] 41 [39,43] 4 (4.2) 2 (2.1) 0 2(2.1)
23 [19.5,26.5] 0 2 (1.9) 16 (15.4) 51 (49.0) 3 (2.9) 2568 [2224,2912] 37 [35.5,38.5] 63 (60.6) 50 (48.1) 17.5 [10,35] 30 (28.8) 4 (3.8) 27.5 [15.5,39.5] 41 [39,43] 6 (5.8) 4 (3.8) 1 (1.0) 1 (1.0)
23 [19.5,26.5] 0 5 (3.7) 27 (19.9)⁎
30 [26,34] 1 (2.2) 4 (8.7) 4 (8.8) 12 (26.1) 5 (10.9) 2915 [2471,3408] 38 [36,39] 32 (69.6) 21 (45.7) 3.5 [0,13] 10 (21.7) 2 (4.3) 16 [10,39] 40.5 [39,43] 9 (19.6) 7 (15.2) 0 2 (4.3)
29 [25,35] 3 (6.0) 2 (4.0) 3 (6.0) 19 (38.0) 2 (4.0) 2983 [2546,3424] 37 [36,39] 27 (54.0) 21 (42.0) 2.5 [0,7] 5 (10.0) 0 14.5 [7,23.5] 40 [39,42] 8 (16.0) 6 (12.0) 0 2 (4.0)
31 [27,36] 5 (7.1) 5 (7.1) 15 (21.4)⁎
68 (50.0) 7 (5.1) 2443 [2060,2826] 36.5 [35.5,37.5] 67 (49.3) 33 (24.3)⁎ 19.5 [11,28] 33 (24.3) 5 (3.7) 30 [15.5,44.5] 41 [39,43] 12 (8.8)⁎ 8 (5.9) 4 (2.9) 1 (0.7)
26 (37.1) 5 (7.1) 3010 [2630,3570] 37 [36,38] 39 (55.7) 17 (24.3)⁎ 6 [0,14] 7 (10.0) 1 (1.4) 13.5 [8,36] 40 [38,42] 10 (14.3)⁎ 6 (8.6) 1 (1.4) 4 (5.7)
Values are numbers (percentage) with odd ratio (95% confidence interval) or median [interquartile range]. 1 Overall death includes reported death after discharge. ⁎ Comparison between epochs by ANOVA or Kruskal–Wallis test p b 0.05.
Please cite this article as: Kong JY, et al, Outcomes of infants with abdominal wall defects over 18 years, J Pediatr Surg (2016), http://dx.doi.org/ 10.1016/j.jpedsurg.2016.06.003
J.Y. Kong et al. / Journal of Pediatric Surgery xxx (2016) xxx–xxx
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Table 5 Comparison of survivors and deceased AWD infants. Gastroschisis
Median birth weight (g) Median gestational age (weeks) Male gender Preterm Caesarean section Proven systemic infection Median TPN duration (days) Necrotizing enterocolitis Secondary closure⁎
Omphalocele
Survivors N = 314
Deceased N = 22
Odds ratio (CI)
p value
Survivors N = 139
Deceased N = 27
Odds ratio (CI)
p value
2500 [2150–2840] 37 [35–37)] 170 (54.1%) 156 (49.7%) 112 (35.7%) 69 (22.0%) 19 (13–27) 7 (2.2%) 41 (19.9%)
2255 [1966–2421] 36 [34–37] 12 (54.5%) 13 (59.1) 6 (37.3%) 10 (45.5%) 11 (0–36) 3 (13.6%) 5 (27.8%)
N/A N/A 1.00 (0.94,1.06) 0.84 (0.58,1.21) 0.89 (0.68,1.16) 0.48 (0.29,0.80) N/A 0.16 (0.05,0.59) 0.72 (0.32,1.59)
0.002 0.39 1.00 0.39 0.43 0.01 0.34 0.002 0.43
3120 [2750–3560] 38 [36–39] 84 (60.4%) 44 (31.7%) 44 (31.7%) 16 (11.5%) 4 (0–12) 1 (0.7%)
2380 [1850–2735] 37 [34–38] 14 (51.9%) 13 (48.1%) 15 (55.6%) 6 (22.2%) 0 (0–28) 2 (7.4%)
N/A N/A 1.17 (0.79,1.72) 0.66 (0.41,1.04) 1.54 (1.00,2.38) 0.52 (0.22,1.20) N/A 0.10 (0.01,1.03)
b0.001 0.04 0.41 0.10 0.02 0.13 0.06 0.02
Data are presented in numbers (percentage) or median [interquartile range]. ⁎ Data available for analysis from year 1999.
maternal age in this group. ART has been associated with increased risk of syndromes such as Beckwith–Wiedemann Syndrome (BWS), which commonly presents with OM [37]. In some reports, up to 22% of cases of OM have been associated with BWS and of which, 50% were the result of ART [38,39]. Genetic testing for this imprinting disorder, however, was not routinely done in the OM infants in our cohort and further examination of this association is warranted. Incomplete data on other associated anomalies and syndromes did not allow for further analysis on the contribution of congenital conditions on clinical presentation and potential outcomes of AWD. Not surprisingly, AWD was associated with significant morbidity, mortality and prolonged hospitalization. The burden of intensive care remains with GS infants, which were more likely to require prolonged central venous lines for TPN and were at a higher risk for systemic infections and prolonged hospitalizations. Contrary to previous reports [7,14,19], we found a non-significant increase in mortality rate for GS infants over the study period, from 4.2% in epoch 1 to 8.1% in epoch 3 (p = 0.3). Small bowel atresia, perforation and stenosis have been established as important factors in the survival and development of morbidities in GS infants [6,40–42]. A recent meta-analysis of 13 studies performed by Bergholz et al., demonstrated that complex gastroschisis (defined as gastroschisis with atresia, necrosis, perforation or volvulus) was associated with significantly increased morbidity and mortality when compared to simple gastroschisis (16.7% vs 2.18%, p b 0.001) [43]. We believe that the increasing mortality rate in our study might be attributed to an increase in complexity of cases in recent years. The lack of information regarding complexity of cases in the database limits our ability to investigate this association further. In contrast, the mortality rates of OM infants, although higher than GS infants, decreased over the study period, from 19.6% to 14.3% and were significantly lower than other studies [11,12,15]. Whether this may be because of antenatal terminations of complex cases, parental choices and selective process or because of improved care of co-morbidities is uncertain and requires further analysis. The lack of data on the antenatal diagnosis of abdominal wall defects in the database precludes the ability to determine any potential effect and differences in the management of infants born with these conditions. There are several limitations that must be considered in interpreting the findings of our study. Because of the nature of the database and case inclusion, we were also unable to obtain information on AWD infants who were not admitted to a NICU or who did not survive to NICU admission. This may predispose the study to selection bias that may lead to overestimation of the outcomes measures. Variation in NICU practices between units and case mix across the different NICUs may have influenced the outcomes of infants as reported to the network. Incomplete data from earlier years (e.g. the lack of description of defect and surgical management on GS infants) limited our ability to perform more detailed analyses to identify potential factors responsible for changes in the trends of outcomes and mortality rate in both GS and OM.
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