Infectious Complications and Antibiotic Use in Gastroschisis

Abstract

Background:

Gastroschisis is a challenging neonatal condition often with prolonged hospitalizations, need for parenteral nutrition, infectious complications, and can even result in death. Infection is reported to occur in up to two-thirds of patients with gastroschisis and is a strong risk factor for increased morbidity and mortality. Increased days with a central venous catheter, complex gastroschisis, and delayed abdominal wall closure have been consistently found to be associated with increased risk of infection, whereas sutureless gastroschisis closure has been associated with fewer infections. Although one of the most common complications of gastroschisis is infection, the use of antibiotic agents varies widely with variability in the literature to guide management. Antibiotic usage should be selective and short-term, especially in neonates with simple gastroschisis regardless of method for abdominal wall closure.

Conclusions:

Future initiatives should focus on development of evidence-based guidelines on the care of these patients with the goal of reducing variability and improve outcomes within and across institutions.

Gastroschisis is a congenital disease in which there is a right-sided paraumbilical defect of the abdominal wall allowing intra-abdominal contents to protrude at birth. There has been an increasing prevalence of gastroschisis both nationally and worldwide over the last two decades.^1,2 It is the most common congenital abdominal wall defect with an estimated incidence of more than four per 10,000 live births.¹ Despite this, gastroschisis remains a challenging condition often with prolonged hospitalizations, need for parenteral nutrition, infectious complications, and even death.³ The continued increase in prevalence along with improved advancements in neonatal critical care and surgical management strategies for gastroschisis have led these communities to evaluate opportunities to improve clinical outcomes. One of the most common complications of gastroschisis is infection, which can lead to substantial morbidity. We therefore sought to review the literature to outline the current antibiotic strategies in the management of gastroschisis, incidence of infections, the effect of different surgical approaches on infection and morbidity, and opportunities as a community to focus quality improvement initiatives and antibiotic stewardship.

Definitions

To compare outcomes between disparate groups and analyses most effectively, it is essential to establish accepted working definitions for key terms. The U.S. Centers for Disease Control and Prevention (CDC) has established standardized definitions for key terms of particular relevance to this review: surgical site infection (SSI), central line-associated blood stream infection (CLABSI), and catheter-associated urinary tract infection (CAUTI).^4–6 Using the CDC convention, SSI will be defined here as infection occurring 30 (superficial and organ/space SSI) or 90 (deep SSI) days after an operative procedure, involving the superficial or deep soft tissues of the incision or organ/space, with at least one of the following: purulent drainage, pathologic organism identified in the wound, abscess or evidence of infection on clinical examination.⁴ Central line-associated blood stream infection is defined as a laboratory-confirmed blood stream infection in which an eligible blood stream organism is identified, and an eligible central line is present on or before the date of diagnosis.⁵ Catheter-associated urinary tract infection is defined as an infection involving any part of the urinary system developed in association with a urinary catheter.⁶ Where possible, studies that use CDC definitions have been discussed and are clearly articulated in Tables 1 through 3. However, the relative paucity of studies relevant to this topic that explicitly use CDC definitions is an inherent limitation when attempting to compare study results.

Table 1.

Infectious Complications in Neonates with Gastroschisis: SSI

Author	Year	Sample size	Retrospective/prospective	Number of sites	CDC definition	Empiric antibiotic exposure and regimen	SSI rate	Highlighted findings
Bence et al.⁵⁵	2021	256	Retrospective	7 children's hospitals	Yes	Not described.	20%	Silo placement (OR, 2.62) and prosthetic patch (OR, 3.42) were associated with SSI
Sangkhathat et al.¹⁰	2008	68	Retrospective	Single institution	Yes	All received 7-14 days of ampicillin, gentamicin and metronidazole.	32%	Higher rate of SSI in a staged closure versus primary closure (48% vs. 22%)
Schlueter et al.¹⁴	2015	155	Retrospective	Single institution	Yes	Mean antibiotic duration = 9.8 days, 97% received ampicillin and gentamicin.	5%
Gurien et al.¹⁵	2017	627	Retrospective	2012-2014 NSQIP	Yes	Not described.	4%	Those who underwent primary repair (0–1 d) had less SSI than those with staged repair (4–14 d) (2% vs. 7%)
Witt et al.¹⁷	2019	90	Retrospective	Single institution	Yes	Average duration = 12.4 days in sutured closure, 7.4 days in sutureless closure. No regimen specified.	26%	No significant difference in SSI rate between sutured and sutureless closure
Ravikumar et al.¹⁸	2020	64	Retrospective	Single institution	Yes	All received preoperative ampicillin and gentamicin. Median duration = 8 days.	17%
Palatnik et al.¹⁹	2020	199	Retrospective	Single institution	No	Not described.	11%	Decreased odds of SSI with primary closure (OR, 0.37)
Raymond et al.²⁰	2020	566	Retrospective	8 children's hospitals	No	Not described.	2%
Behram et al.²¹	2021	29	Retrospective	Single institution	No	Not described.	25%	100% SSI rate in complex gastroschisis, 4.5% in simpleSimilar SSI rate in primary closure vs. silo placement
Riddle et al.²²	2022	2,021	Retrospective	Children's Hospital Neonatal Database (CHND)	No	Median antibiotic duration = 7 days. No regimen specified.	5%
Ergün et al.⁸	2005	75	Retrospective	Single institution	No	Not described.	7%
Khalil et al.¹¹	2008	72	Retrospective	Single institution	No	Cefotaxime and metronidazole, median exposure = 5 days.	20%	8 × higher SSI rate in males
Baird et al.¹²	2012	395	Prospective	16 centers (Canadian Pediatric Surgery Network database)	No	Mean antibiotic duration = 6.1 days, 65% received ampicillin and gentamicin.	13%	SSI rate was higher for patients with a delayed closure (21% vs. 8%)No difference in SSI rate between closure in operating room vs. NICU

SSI = surgical site infection; CDC = U.S. Centers for Disease Control and Prevention; OR = odds ratio; NICU = neonatal intensive care.

Incidence of Infectious Complications in Infants With Gastroschisis

Infectious complications in neonates with gastroschisis are one of the most frequent morbidities encountered in this challenging patient population. While the large majority of the current literature includes retrospective analyses of varying sample sizes, the evidence overwhelmingly demonstrates that infections are common and have significant impact (Tables 1–3).^3,7–22 Infections can occur primarily from a multitude of sites, including the surgical or gastroschisis wound site, blood stream, and urinary tract.

Surgical site infections are a relatively common complication in the management of gastroschisis. Studies using the CDC definition for SSI show highly variable rates of SSI, ranging from 4% to 32%, whereas studies using related definitions show overall SSI rates ranging from 2% to 25% (Table 1).^{3,8,10–12,14,15,17–22} This inter-study variability appears likely to be secondary to a combination of small sample sizes, variable SSI definitions, and disparate methods of diagnosis. One common theme between studies was the higher incidence of SSIs in neonates undergoing delayed closure (often defined as over 24 hours) compared with primary closure.^10,12,15,19 For example, Sangkhathat et al.¹⁰ found that a staged, or delayed, closure was associated with a 48% incidence of SSI compared with 22% incidence with primary closure. This study was limited by its retrospective, single-center experience in a small cohort of 68 patients.

Baird et al.¹² improved upon this study by capturing infection events in patients with gastroschisis prospectively across 16 institutions in a total of 395 patients, finding that SSI was again higher in patients with a delayed closure (21.2% compared with 8.2%). In 2017, Gurien et al.¹⁵ replicated these findings as well with a more than three-fold increase in SSIs with delayed closure. Surgical site infections have also been shown to be increased in individuals with silo placement (odds ratio [OR], 2.6), which is likely representative of a delayed wound closure as well.³ These studies in combination provide strong evidence of a greatly increased risk of SSI in the setting of delayed abdominal wall closure.

Neonates with gastroschisis often require parenteral nutrition for a variable length of time because of the inability to tolerate enteral feeding. This results in a frequent requirement for central venous access and subsequent risk of CLABSI. In studies using the CDC definition for CLABSI, rates range from 3% to 7%, whereas studies using related definitions demonstrate ranges of 6% to 34% (Table 2).^{3,7,8,10–12,14,20,22} The total number of days in which an indwelling central venous catheter is present is greatly associated with the incidence of a CLABSI.¹² Interestingly, several studies have demonstrated that CLABSIs were more common than wound or SSIs in neonates with gastroschisis.^8,12,20 In a retrospective, single-center study, Schlatter et al.⁷ found CLABSI occurred in 48.7% of patients undergoing primary operative repair but much less frequently (11.5%) in patients who underwent silo placement and delayed closure.

Table 2.

Infectious Complications in Neonates with Gastroschisis: CLABSI

Author	Year	Sample size	Retrospective/prospective	Number of sites	CDC definition	Empiric antibiotic exposure and regimen	CLABSI rate	Highlighted findings
Bence et al.³	2021	256	Retrospective	7 children's hospitals	Yes	Not described.	3%
Schlueter et al.¹⁴	2015	155	Retrospective	Single institution	Yes	Mean antibiotic duration = 9.8 d, 97% received ampicillin and gentamicin.	6%	Prematurity and low birth weight associated with higher incidence of infection.
Sangkhathat et al.¹⁰	2008	68	Retrospective	Single institution	Yes	All received 7–14 d of ampicillin, gentamicin and metronidazole.	7%
Khalil et al.¹¹	2008	72	Retrospective	Single institution	No	Cefotaxime and metronidazole, median exposure = 5 d.	21%	CLABSI rate not affected by patient gender, weight, type of surgery performed or method of venous access.
Baird et al.¹²	2012	395	Prospective	16 centers (Canadian Pediatric Surgery Network database)	No	Mean antibiotic duration = 6.1 days, 65% received ampicillin and gentamicin.	15%	No difference between delayed & early closure groups.
Raymond et al.²⁰	2020	566	Retrospective	8 children's hospitals	No	Not described.	6%	Higher rate of CLABSI in complex (17%) compared to simple (4%) gastroschisis
Riddle et al.²²	2022	2,021	Retrospective	Children's Hospital Neonatal Database (CHND)	No	Median antibiotic duration = 7 d. No regimen specified.	7%	CLABSI rate was highest in complex gastroschisis (18%) compared with simple (5%)
Schlatter et al.⁷	2003	65	Retrospective	Single institution	No	Not described.	34%	Lower CLABSI rate with delayed closure (11.5% vs. 48.7%)
Ergün et al.⁸	2005	75	Retrospective	Single institution	No	Not described.	22%

CLABSI = central line associated blood stream infection; CDC = U.S. Centers for Disease Control and Prevention.

Neonates with gastroschisis may require placement of a urinary catheter for close monitoring of urine output. Catheter-associated urinary tract infection rates in neonates with gastroschisis range from 1.5% to 3% in studies using the CDC definition and 3% to 6% in studies using similar definitions of CAUTI (Table 3).^10,14,18,22

Table 3.

Infectious Complications in Neonates With Gastroschisis: CAUTI

Author	Year	Sample Size	Retrospective/prospective	Number of sites	CDC definition	Empiric antibiotic exposure and regimen	CAUTI rate
Sangkhathat et al.¹⁰	2008	68	Retrospective	Single institution	Yes	All received 7–14 d of ampicillin, gentamicin and metronidazole.	3%
Schlueter et al.¹⁴	2015	155	Retrospective	Single institution	Yes	Mean antibiotic duration = 9.8 d, 97% received ampicillin and gentamicin.	1.5%
Ravikumar et al.¹⁸	2020	64	Retrospective	Single institution	No	All received pre-operative ampicillin and gentamicin. Median duration = 8 d.	6%
Riddle et al.²²	2022	2,021	Retrospective	Children's Hospital Neonatal Database (CHND)	No	Median antibiotic duration = 7 d. No regimen specified.	3%

CAUTI = catheter-associated urinary tract infection; CDC = U.S. Centers for Disease Control and Prevention.

Impact of Simple Versus Complex Gastroschisis

An important differentiation exists between simple, isolated gastroschisis and complex gastroschisis, which is associated with the presence of atresia, perforation, ischemia, or volvulus. Those neonates with complex gastroschisis are known to have more complicated clinical courses with higher rates of morbidity and mortality.²⁰ This classification of gastroschisis as either simple or complex was first described by Molik et al.²³ in 2001. The classification system was then validated in 2007 by Arnold et al.⁹ through the use of a retrospective analysis of 4,344 infants from the National Inpatient Sample and Kids' Inpatient Database. Using this large sample size, the authors demonstrated that patients with complex gastroschisis had increased morbidities, including infectious complications (24.3% vs. 45.4%; p < 0.01), and increased mortality (2.9% vs. 8.7%; p < 0.01).⁹ Since then, Raymond et al.²⁰ validated these findings in a multi-institutional review of 566 neonates and identified complex gastroschisis (77/489 neonates) to be associated with increased sepsis (OR, 3.9; 95% confidence interval [CI], 2.1–7.2) and mortality (OR, 3.5; 95% CI, 1.4–8.7) compared with infants with simple gastroschisis. Central line-associated blood stream infections were more frequent in infants with complex compared with simple gastroschisis (17% compared with 4%, respectively). Interestingly there was no difference in the incidence of SSIs between simple and complex gastroschisis in this study.²⁰ In 2021, Riddle et al.²² retrospectively reviewed 2021 neonates in the Children's Hospital Neonatal Database also finding that CLABSI was more than three-fold higher in complex gastroschisis compared with simple.

Others have provided additional granularity into differences in the peri-operative characteristics and morbidities between simple and complex gastroschisis. Dekonenko et al.²⁴ retrospectively reviewed 394 neonates (315 simple and 79 complex) with gastroschisis from 11 children's hospitals, demonstrating that patients with complex gastroschisis were more likely to have patch closure of their abdominal wall (9% vs. 28%; p < 0.001). Interestingly, antibiotic use prior to closure was no different between neonates with simple versus complex gastroschisis; however, antibiotics were found to be used for more days post-closure in those with complex gastroschisis (4 vs. 7 days; p < 0.001).²⁴

Effect of Surgical Approach

First described in 2004 by Sandler et al.,²⁵ the sutureless closure (also referred to as “plastic” or “flap” closure) technique for gastroschisis repair involves using an intentionally long umbilical cord remnant as a biological dressing, facilitating abdominal wall defect closure by secondary intention. After the manual reduction of intra-abdominal contents into the abdomen, either in a primary or staged (using a silo) fashion, the umbilical cord remnant is secured over the defect using a plastic adhesive dressing. This technique has gradually gained popularity by pediatric surgeons for its theoretical benefits of reduced costs and resource utilization, improved cosmetics, and the ability to perform the procedure at the patient bedside without general anesthesia. As sutureless closure causes less iatrogenic tissue trauma and involves using the umbilical cord stump as a biological dressing, it is plausible to surmise that it may be associated with fewer infectious complications, which is supported by accumulating evidence suggesting its association with improvements in multiple infection and antibiotic use metrics.

In a 2016 systematic review and meta-analysis by Youssef et al.,²⁶ which analyzed 1,124 patients from 12 studies, sutureless (flap) closure was associated with lower SSI rates compared with sutured (fascial) closure techniques (OR, 0.40). This trend was similarly demonstrated in a 2019 systematic review and meta-analysis by Miyake et al.,²⁷ which analyzed 128 patients from three retrospective studies, and demonstrated lower SSI rates with sutureless closure after staged repair using a silo (OR, 0.24).

Similarly, a 2020 retrospective review by Fraser et al.²⁸ of 315 patients who underwent gastroschisis repair at 11 participating centers, 67 of whom underwent sutureless repair, demonstrated a significant reduction in SSI (both superficial and deep) after sutureless repair when compared with sutured repair (3% vs. 13%; p = 0.02). Most convincing, however, is the 2017 prospective randomized control trial by Bruzoni et al.²⁹ that compared 19 patients undergoing sutureless repair with 20 patients undergoing sutured repair. Here, they demonstrated a lower rate of SSI in the sutureless repair group compared with the sutured group (21% vs. 55%; p = 0.048).

In addition to evidence of reduced SSI rates in neonates undergoing sutureless gastroschisis repair, there appears to be a coinciding reduction in antibiotic use in this group. First shown in a 97-patient single center retrospective review by Witt et al.,¹⁷ sutureless repair appears to be associated with fewer total antibiotic days (7.2 vs. 12.4 days; p = 0.003). However, the rigor of this study's conclusions are significantly tempered by a local antibiotic prescribing practice pattern change occurring during the 10-year study period. Despite this, the 2020 retrospective review by Fraser et al.²⁸ demonstrated a similar finding, in which they found lower post-procedure total antibiotic use in the sutureless repair group (67% vs. 83%; p = 0.004). This reduction in antibiotic use was demonstrated in a three-year time period across 11 different centers, and was thus less likely to be skewed by local antibiotic prescribing practices.

Collectively, the accumulating evidence to date suggests that sutureless gastroschisis repair is associated with reduced SSI rates and in turn, reduced antibiotic use and exposure. The rigor of these conclusions could be boosted by further prospective and randomized evaluations, as only one prospective randomized control trial, comparing a total of 39 patients, has been performed to date.²⁹

Identifiable Risk Factors for Infection in Gastroschisis

Although the literature over the last two decades clearly demonstrates a high risk of infection in infants with gastroschisis, more recent studies have been aimed at identification of modifiable risk factors to reduce this complication and its subsequent outcomes. Explored risk factors in this review include mode of delivery, location of delivery, gestational age at delivery, type of repair (as discussed in the preceding section), and postnatal factors such as nutrition, feeding protocols, hypothermia, and fluid resuscitation.

Several studies have explored the optimal mode of delivery, such as vaginal delivery or cesarean section, for known gastroschisis patients. Consistently, the mode of delivery has not been shown to be associated with long-term complications including necrotizing enterocolitis (NEC) and sepsis.^30,31 Nasr and Langer³² retrospectively reviewed 395 infants to determine if location of birth impacted outcomes. They found that infants outborn (not born at a surgical center) as compared to inborn infants had statistically significant increased complications including SSI and necrotizing enterocolitis (OR, 1.6; p = 0.05).

Schlueter et al.¹⁴ retrospectively reviewed 129 patients with uncomplicated gastroschisis and found those who were born earlier in gestation or with a lower birthweight had increased infections and more often required a staged approach to abdominal wall closure. Others have previously shown delivery earlier in gestation is associated with other negative clinical outcomes including longer time to enteral feeds and length of stay.⁸ Palatink et al.¹⁹ retrospectively reviewed 199 infants born with gastroschisis at a single center across 17 years and found that later gestational age at delivery was associated with shorter duration of ventilatory support and parenteral nutrition dependence. They found no difference in the rate of primary closure based on gestational age at delivery. Contradictory to this, Landisch et al.³³ performed a meta-analysis of publications to analyze outcomes of early delivery with gastroschisis and found that elective preterm delivery may be favorable in terms of less sepsis, fewer days to full feeds, and fewer days of parenteral nutrition. Riddle et al.³⁴ performed a more recent multicenter retrospective cohort analysis from Children's Hospitals Neonatal Consortium data and found lower rates of CLABSI and necrotizing enterocolitis in infants born at or beyond 37 weeks. With this conflicting literature, the Gastroschisis Outcomes of Delivery (GOOD) study is ongoing with the goal of improving the knowledge surrounding the optimal gestational age of delivery for fetuses with prenatally diagnosed gastroschisis.³⁵

Bence et al.³ retrospectively reviewed at total of 256 infants from seven children's hospitals between 2013 and 2017 and identified silo placement (OR, 2.62) and use of a prosthetic patch for closure (OR, 3.42) to be independent predictors of SSIs. Palatink et al.¹⁹ retrospectively reviewed 199 infants born with gastroschisis and found primary closure to be associated with lower odds of SSI (OR, 0.37; 95% CI, 0.15–0.97). Similarly, Allin et al.³⁶ retrospectively reviewed data from Ireland, Canada, and Great Britain of a cohort of patients with uncomplicated gastroschisis, finding a decreased infection risk with primary closure (adjusted OR, 2.06; 95% CI, 1.10–3.87; p = 0.025).

Regarding post-natal factors, Dekonenko et al.³⁷ retrospectively analyzed 315 neonates across 11 children's hospitals and found infants fed with an institutional-specific feeding protocol had fewer SSIs (7% vs 16%; p = 0.019). Walter-Necolet et al.³⁸ described reduced incidence of nosocomial infections in an internal cohort (9% vs. 40% in the control group; p = 0.016) with early minimal enteral feeding by a standard protocol. Hogdson et al.³⁹ investigated the impact of breast milk on gastroschisis outcomes. Although infectious complications were not directly assessed, the exclusive use of breast milk was associated with decreased time to full feeds (median 18 vs. 25 days; p = 0.037) and therefore fewer central line days (median 20 vs. 26 days; p = 0.037). Similarly, others have also found improved time to full feeds with use of mother's own milk in gastroschisis patients.^40–42 Jayanthi et al.⁴³ suggested after review of single-center retrospective data that breast milk may confer protection against NEC development.

There have been several studies to evaluate the risk of peri-operative hypothermia and potential for increased infectious complications. Landisch et al.⁴⁴ reported in a retrospective review of 43 neonates that 48.8% of neonates had peri-operative hypothermia, but they identified no association between hypothermia and infectious complications. Similarly in a more recent study, Bence et al.³ found in a retrospective review of 256 patients across seven institutions, 42% of neonates had peri-operative hypothermia; however, there was no association of hypothermia with infectious complications. Jansen et al.⁴⁵ investigated another modifiable postnatal factor, fluid resuscitation, in a retrospective cohort of 407 patients by multivariable analysis. In this study, they found for each 17 mL/kg of resuscitative fluids the odds increased by 0.02 (p = 0.03) for one or more bacteremia episodes.

Utilization of Antibiotic Agents and Development of Clinical Management Pathways

Currently there is no universal protocol to direct the antibiotic choice or duration for children with gastroschisis. Instead, institutions have independently developed clinical practice guidelines in attempts to standardize care. In neonates, coagulase-negative staphylococcus is the most common causative agent for both early and late onset infections.^12,46,47 The initial choice of antibiotic agent has traditionally been the combination of a β-lactamase–resistant penicillin and aminoglycoside.^46,48,49 A pathway recommending antibiotic choice and duration was proposed by the British Columbia Children's Hospital in 2018. In this, children were differentiated based on clinical concern for early onset sepsis, with cloxacillin and tobramycin/gentamicin used for all patients and ampicillin added for those of highest risk.⁵⁰ As Laituri and Arnold⁵¹ described in 2019, gastroschisis is technically a clean operative case, and their recommendation was for no peri-operative antibiotic prophylaxis. Ting et al.⁵² described a detailed practice summary compiled by a consortium of Canadian providers. Although they agreed gastroschisis closure to be a clean procedure, they noted the high incidence of SSI in this population and thus recommended a separate wound classification and antibiotic recommendation to include ampicillin or cloxacillin with gentamicin until wound closure.

The University of California Fetal Consortium implemented a gastroschisis clinical practice guideline across their multi-institutional university consortium in 2015 to standardize and improve care of gastroschisis neonates with a protocol that promoted avoidance of routine intubation and paralysis during silo placement, expeditious abdominal wall closure, discontinuation of antibiotics and narcotics within 48 hours of closure in the absence of culture-positive sepsis or clinical instability, and early initiation/advancement of feeds. Of the 70 patients with uncomplicated gastroschisis, they found an 80% adherence to antibiotic termination at 48 hours and 90% usage of the recommended antibiotic regimen of ampicillin and gentamicin.⁵³ Notably, they were able to reduce their total average number of antibiotic days from nine days prior to implementation of the clinical practice guideline to 5.5 days after use of the clinical practice guideline (p < 0.01).

Similarly, researchers at Doernbecher Children's Hospital in Oregon developed and instituted a care protocol in 2014 to standardize antibiotic usage, fluid management, central line placement, and feeding progression in neonates with uncomplicated gastroschisis. They also implemented a practice of discontinuation of antibiotic agents at 48 hours after the initial surgical intervention if there are no clinical signs (culture positive, clinical instability) of an infection. Antibiotic agents continued solely for presence of a silo were considered as non-compliant to the protocol, of which they noted they had five patients. Overall, they were able to decrease the use of antibiotics beyond 48 hours from 50% to 24% after the protocol initiative.⁵⁴

It is well known that antibiotic stewardship reduces the risk of antibiotic toxicity, drug resistance, and intestinal dysbiosis. Ultimately, the decision of antibiotic usage and type must be determined by weighing the risk of antibiotic resistance against ensuring adequate coverage. Ultimately, evidence and practice suggest antibiotic usage should be selective and short-term, especially in neonates with simple gastroschisis and no clinical signs of infection.

Influence of Infection on Healthcare Utilization and Cost

Addressing identifiable and modifiable risk factors for infectious complications has the potential to improve overall outcomes and reduce costs.¹¹ The most demonstrable impact of wound or CLABSI in infants with gastroschisis is the significant increase in hospital length of stay. Baird et al.¹² found that average length of stay was at least double in neonates with either an SSI or CLABSI.^1–3 Others have also shown that length of hospital stay is increased in patients with gastroschisis with infectious complications. Uribe-Leitz et al.¹⁶ reviewed 1,378 patients in the Kids' Inpatient Database and identified an increase in hospital stay by 4.5 days with any infectious complication, seven days with a SSI, and 11 days with sepsis. Others have estimated that infectious complications of gastroschisis on average lead to a 32-day longer hospital stay, estimated to increase the overall hospital cost by $63,713 per child.¹⁴ When categorized individually, they found SSI, sepsis, and CLABSI each increased hospital costs, although the cost increase was most significant for CLABSI at $57,180.¹⁶ Although there is little surprise in their finding that increased morbidities with infectious complications increase hospital stay and cost, it is important to consider the downstream effects of this common morbidity in gastroschisis neonates to fully demonstrate the importance of striving for improved outcomes.

Limitations

The authors note three main limitations when evaluating the existing body of data related to infectious complications and antibiotic use in the management of gastroschisis. First, the ability to compare rates of infectious complication between studies using different definitions for complications such as SSI, CLABSI, and CAUTI is limited. A subset of studies was found to use the gold standard CDC definition, whereas others used similar definitions or did not cite a definition at all. Second, evaluation of studies analyzing large aggregate databases retrospectively such as the Kids' Inpatient Database, National Quality Improvement Project, and Children's Hospital Neonatal Database databases is limited by the lack of standardization of practices at the institutions supplying data. Finally, there exists a paucity of prospective trials employing standardized definitions and methodologies, from which to draw conclusions.

Conclusions

Collectively, the current evidence demonstrates that simple gastroschisis has an overall significantly lower risk of infectious complications compared to complex gastroschisis. The most common infectious complication in most analyses is CLABSI, which are significantly more frequent in complex gastroschisis. SSI is the second most frequent infectious complication, with the greatest risk factors being delayed closure, silo placement, and patch closure. The current data supports that sutureless closure of gastroschisis has an overall reduced risk of infectious wound complications compared to operative fascial closure. Unfortunately, the majority of data consist of retrospective, single-center, or small sample size studies, often with varying definitions for key infection measures, significantly limiting the strength of many conclusions. However, we strongly advocate for guidelines supporting limited prophylactic antibiotic usage in simple gastroschisis and infants who undergo primary or sutureless closure. The development of clinical practice guidelines to help providers care for these neonates has been shown to decrease variability and improve outcomes. Further studies to improve the rigor of data, including prospective and randomized trials employing standardized definitions and methodologies, around the care of this complex neonatal population with high complications rates are needed to aid pediatric surgeons and neonatologists in the development of generalizable guidelines that can be utilized across institutions.

Footnotes

Authors' Contributions

Writing—original draft: Wallace, Danko, Zamora, Morris, Li, Froehlich, Robinson. Writing—review and editing: Wallace, Danko, Zamora, Morris, Froehlich, Project administration: Wallace, Robinson. Conceptualization: Robinson. Methodology: Robinson. Supervision: Robinson.

Funding Information

There are no external sources of funding associated with the preparation of this manuscript.

Author Disclosure Statement

The authors declare no conflicts of interest related to the preparation of this manuscript.

References

Kirby

, Marshall

, Tanner

, et al. Prevalence and correlates of gastroschisis in 15 states, 1995 to 2005. Obstet Gynecol, 2013; 122(2 Pt 1):275–281; doi: 10.1097/AOG.0b013e31829cbbb4

Kong

, Yeo

, Abdel-Latif

, et al. Outcomes of infants with abdominal wall defects over 18 years. J Pediatr Surg, 2016; 51(10):1644–1649; doi: 10.1016/j.jpedsurg.2016.06.003

Bence

, Landisch

, Wu

, et al. Risk factors for perioperative hypothermia and infectious outcomes in gastroschisis patients. J Pediatr Surg, 2021; 56(7):1107–1112; doi: 10.1016/j.jpedsurg.2021.03.020

CDC National Healthcare Safety Network. CDC NHSN Surgical Site Infection. 2023. Available from: https://www.cdc.gov/nhsn/pdfs/pscmanual/9pscssicurrent.pdf [Last accessed: March 21, 2023].

CDC National Healthcare Safety Network. CDC NHSN Bloodstream Infection Event (Central Line-Associated Bloodstream Infection and Non-Central Line Associated Bloodstream Infection). 2023. Available from: https://www.cdc.gov/nhsn/pdfs/pscmanual/4psc_clabscurrent.pdf [Last accessed: March 21, 2023].

CDC National Healthcare Safety Network. CDC NHSN Urinary Tract Infection (Catheter-Associated Urinary Tract Infection [CAUTI] and Non-Catheter-Associated Urinary Tract Infection [UTI]) Events. 2023. Available from: https://www.cdc.gov/nhsn/pdfs/pscmanual/7psccauticurrent.pdf [Last accessed: March 21, 2023].

Schlatter

, Norris

, Uitvlugt

, et al. Improved outcomes in the treatment of gastroschisis using a preformed silo and delayed repair approach. J Pediatr Surg, 2003; 38(3):459–464; doi: 10.1053/jpsu.2003.50079

Ergün

, Barksdale

, Ergün

, et al. The timing of delivery of infants with gastroschisis influences outcome. J Pediatr Surg, 2005; 40(2):424–428; doi: 10.1016/j.jpedsurg.2004.10.013

Arnold

, Chang

, Nabaweesi

, et al. Risk stratification of 4344 patients with gastroschisis into simple and complex categories. J Pediatr Surg, 2007; 42(9):1520–1525; doi: 10.1016/j.jpedsurg.2007.04.032

10.

Sangkhathat

, Patrapinyokul

, Chiengkriwate

, et al. Infectious complications in infants with gastroschisis: An 11-year review from a referral hospital in southern Thailand. J Pediatr Surg, 2008; 43(3):473–478; doi: 10.1016/j.jpedsurg.2007.10.026

11.

Khalil

, Baath

, Baillie

, et al. Infections in gastroschisis: Organisms and factors. Pediatr Surg Int, 2008; 24(9):1031–1035; doi: 10.1007/s00383-008-2210-0

12.

Baird

, Puligandla

, Skarsgard

, et al. Infectious complications in the management of gastroschisis. Pediatr Surg Int, 2012; 28(4):399–404; doi: 10.1007/s00383-011-3038-6

13.

Orion

, Krein

, Liao

, et al. Outcomes of plastic closure in gastroschisis. Surgery, 2011; 150(2):177–185; doi: 10.1016/j.surg.2011.05.001

14.

Schlueter

, Azarow

, Hines

, et al. Identifying strategies to decrease infectious complications of gastroschisis repair. J Pediatr Surg, 2015; 50(1):98–101; doi: 10.1016/j.jpedsurg.2014.10.001

15.

Gurien

, Dassinger

, Burford

, et al. Does timing of gastroschisis repair matter? A comparison using the ACS NSQIP pediatric database. J Pediatr Surg, 2017; 52(11):1751–1754; doi: 10.1016/j.jpedsurg.2017.02.008

16.

Uribe-Leitz

, McCracken

, Heiss

, et al. The influence of infectious complications in gastroschisis on costs and length of stay. Am J Perinatol, 2017; 34(1):62–69; doi: 10.1055/s-0036-1584299

17.

Witt

, Zobel

, Padilla

, et al. Evaluation of clinical outcomes of sutureless vs sutured closure techniques in gastroschisis repair. JAMA Surg, 2019; 154(1):33–39; doi: 10.1001/jamasurg.2018.3216

18.

Ravikumar

, Mitchell

, Cantey

. Antibiotic utilization and infection among infants with abdominal wall defects. Pediatr Infect Dis J, 2020; 39(12):1116–1120; doi: 10.1097/INF.0000000000002867

19.

Palatnik

, Loichinger

, Wagner

, et al. The association between gestational age at delivery, closure type and perinatal outcomes in neonates with isolated gastroschisis. J Matern Fetal Neonatal Med, 2020; 33(8):1393–1399; doi: 10.1080/14767058.2018.1519538

20.

Raymond

, Hawkins

, St Peter

, et al. Predicting morbidity and mortality in neonates born with gastroschisis. J Surg Res, 2020; 245:217–224; doi: 10.1016/j.jss.2019.07.065

21.

Behram

, Oğlak

, Özaydın

, et al. What is the main factor in predicting the morbidity and mortality in patients with gastroschisis: Delivery time, delivery mode, closure method, or the type of gastroschisis (simple or complex)?. Turk J Med Sci, 2021; 51(3):1587–1595; doi: 10.3906/sag-2011-166

22.

Riddle

, Agarwal

, Haberman

, et al. Gastroschisis and low incidence of early-onset infection: A case for antimicrobial stewardship. J Perinatol Off J Calif Perinat Assoc, 2022; doi: 10.1038/s41372-022-01494-3

23.

Molik

, Gingalewski

, West

, et al. Gastroschisis: A plea for risk categorization. J Pediatr Surg, 2001; 36(1):51–55; doi: 10.1053/jpsu.2001.20004

24.

Dekonenko

, Fraser

, Deans

, et al. Outcomes in gastroschisis: expectations in the postnatal period for simple vs complex gastroschisis. J Perinatol Off J Calif Perinat Assoc, 2021; 41(7):1755–1759; doi: 10.1038/s41372-021-01093-8

25.

Sandler

, Lawrence

, Meehan

, et al. A “plastic” sutureless abdominal wall closure in gastroschisis. J Pediatr Surg, 2004; 39(5):738–741; doi: 10.1016/j.jpedsurg.2004.01.040

26.

Youssef

, Gorgy

, Arbash

, et al. Flap versus fascial closure for gastroschisis: A systematic review and meta-analysis. J Pediatr Surg, 2016; 51(5):718–725; doi: 10.1016/j.jpedsurg.2016.02.010

27.

Miyake

, Seo

, O'Connell

, et al. Safety and usefulness of plastic closure in infants with gastroschisis: A systematic review and meta-analysis. Pediatr Surg Int, 2019; 35(1):107–116; doi: 10.1007/s00383-018-4381-7

28.

Fraser

, Deans

, Fallat

, et al. Sutureless vs sutured abdominal wall closure for gastroschisis: Operative characteristics and early outcomes from the Midwest Pediatric Surgery Consortium. J Pediatr Surg, 2020; 55(11):2284–2288; doi: 10.1016/j.jpedsurg.2020.02.017

29.

Bruzoni

, Jaramillo

, Dunlap

, et al. Sutureless vs sutured gastroschisis closure: A prospective randomized controlled trial. J Am Coll Surg, 2017; 224(6):1091–1096.; doi: 10.1016/j.jamcollsurg.2017.02.014

30.

Kirollos

, Abdel-Latif

. Mode of delivery and outcomes of infants with gastroschisis: A meta-analysis of observational studies. Arch Dis Child Fetal Neonatal Ed, 2018; 103(4):F355–F363; doi: 10.1136/archdischild-2016-312394

31.

Segel

, Marder

, Parry

, et al. Fetal abdominal wall defects and mode of delivery: a systematic review. Obstet Gynecol, 2001; 98(5 Pt 1):867–873; doi: 10.1016/s0029-7844(01)01571-x

32.

Nasr

, Langer

, Canadian Paediatric Surgery

Network

. Influence of location of delivery on outcome in neonates with gastroschisis. J Pediatr Surg, 2012; 47(11):2022–2025; doi: 10.1016/j.jpedsurg.2012.07.037

33.

Landisch

, Yin

, Christensen

, et al. Outcomes of gastroschisis early delivery: A systematic review and meta-analysis. J Pediatr Surg, 2017; 52(12):1962–1971; doi: 10.1016/j.jpedsurg.2017.08.068

34.

Riddle

, Acharya

, Agarwal

, et al. Gestational age at delivery and neonatal outcomes among infants with gastroschisis in the Children's Hospitals Neonatal Consortium (CHNC). Am J Perinatol [Epub ahead of print: DOI: 10.1055/s-0042-1744510.] [Last accessed: August 12, 2022].

35.

Wagner

Gastroschisis Outcomes of Delivery (GOOD) Study. Clinical trial registration. clinicaltrials.gov; 2022.

36.

Allin

BSR

, Opondo

, Kurinczuk

, et al. Management of gastroschisis: Results From the NETS2G Study, a Joint British, Irish, and Canadian Prospective Cohort Study of 1268 Infants. Ann Surg, 2021; 273(6):1207–1214; doi: 10.1097/SLA.0000000000004217

37.

Dekonenko

, Fraser

, Deans

, et al. Does use of a feeding protocol change outcomes in gastroschisis? A report from the Midwest Pediatric Surgery Consortium. Eur J Pediatr Surg, 2022; 32(2):153–159; doi: 10.1055/s-0040-1721074

38.

Walter-Nicolet

, Rousseau

, Kieffer

, et al. Neonatal outcome of gastroschisis is mainly influenced by nutritional management. J Pediatr Gastroenterol Nutr, 2009; 48(5):612–617; doi: 10.1097/MPG.0b013e31818c5281

39.

Hodgson

, Livingston

, Robinson

, et al. Use of breast milk in infants with uncomplicated gastroschisis: A retrospective cohort study. J Pediatr Surg, 2022; 57(5):840–845; doi: 10.1016/j.jpedsurg.2021.12.045

40.

Storm

, Bowker

, Klonoski

, et al. Mother's own milk dose is associated with decreased time from initiation of feedings to discharge and length of stay in infants with gastroschisis. J Perinatol, 2020; 40(8):1222–1227; doi: 10.1038/s41372-020-0595-3

41.

Kohler

, Perkins

, Bass

. Human milk versus formula after gastroschisis repair: Effects on time to full feeds and time to discharge. J Perinatol Off J Calif Perinat Assoc, 2013; 33(8):627–630; doi: 10.1038/jp.2013.27

42.

Gulack

, Laughon

, Clark

, et al. Enteral feeding with human milk decreases time to discharge in infants following gastroschisis repair. J Pediatr, 2016; 170:85–89; doi: 10.1016/j.jpeds.2015.11.046

43.

Jayanthi

, Seymour

, Puntis

, et al. Necrotizing enterocolitis after gastroschisis repair: A preventable complication?. J Pediatr Surg, 1998; 33(5):705–707; doi: 10.1016/s0022-3468(98)90191-9

44.

Landisch

, Massoumi

, Christensen

, et al. Infectious outcomes of gastroschisis patients with intraoperative hypothermia. J Surg Res, 2017; 215:93–97; doi: 10.1016/j.jss.2017.03.053

45.

Jansen

, Safavi

, Lin

, et al. Preclosure fluid resuscitation influences outcome in gastroschisis. Am J Perinatol, 2012; 29(4):307–312; doi: 10.1055/s-0031-1295639

46.

Klingenberg

, Aarag

, Rønnestad

, et al. Coagulase-negative staphylococcal sepsis in neonates. Association between antibiotic resistance, biofilm formation and the host inflammatory response. Pediatr Infect Dis J, 2005; 24(9):817–822; doi: 10.1097/01.inf.0000176735.20008.cd

47.

Stoll

, Hansen

, Fanaroff

, et al. Late-onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network. Pediatrics, 2002; 110(2 Pt 1):285–291; doi: 10.1542/peds.110.2.285

48.

Tiley

, MacDonald

, Doherty

, et al. Active promotion of antibiotic guidelines: An intensive program. Commun Dis Intell Q Rep, 2003; 27(Suppl):S13–18.

49.

Blayney

, Al Madani

. Coagulase-negative staphylococcal infections in a neonatal intensive care unit: In vivo response to cloxacillin. Paediatr Child Health, 2006; 11(10):659–663.

50.

Haddock

, Al Maawali

, Ting

, et al. Impact of multidisciplinary standardization of care for gastroschisis: Treatment, outcomes, and cost. J Pediatr Surg, 2018; 53(5):892–897; doi: 10.1016/j.jpedsurg.2018.02.013

51.

Laituri

, Arnold

. A standardized guideline for antibiotic prophylaxis in surgical neonates. Semin Pediatr Surg, 2019; 28(1):53–56; doi: 10.1053/j.sempedsurg.2019.01.009

52.

Ting

, Autmizguine

, Dunn

, et al. Practice Summary of antimicrobial therapy for commonly encountered conditions in the neonatal intensive care unit: A Canadian perspective. Front Pediatr, 2022; 10:894005; doi: 10.3389/fped.2022.894005

53.

DeUgarte

, Calkins

, Guner

, et al. Adherence to and outcomes of a University-Consortium gastroschisis pathway. J Pediatr Surg, 2020; 55(1):45–48; doi: 10.1016/j.jpedsurg.2019.09.048

54.

Gilliam

, Vu

, Rao

, et al. Minimizing variance in gastroschisis management leads to earlier full feeds in delayed closure. J Surg Res, 2021; 257:537–544; doi: 10.1016/j.jss.2020.07.072

55.

Bence

, Landisch

, Wu

, et al. Risk factors for perioperative hypothermia and infectious outcomes in gastroschisis patients. J Pediatr Surg, 2021; 56(7):1107–1112; doi: 10.1016/j.jpedsurg.2021.03.020