It Is a Wrap! Or Is It?: The Role of Fundoplication in Infant Feeding Intolerance

Abstract

Purpose:

Fundoplication is one of the most common procedures performed by pediatric surgeons, frequently for gastroesophageal reflux with feeding intolerance. No consensus exists in its management, with multiple institutions opting for medical therapy over surgical intervention.

Methods:

A case-based survey was administered at a national pediatric surgery conference. Clinical vignettes described former-premature infants with reflux and feeding intolerance with or without failure to thrive (FTT), neurological impairment, complex cardiopathy, and respiratory symptoms. Odds ratios (ORs) for fundoplication were calculated from participants' responses.

Results:

Surgeons elected to perform fundoplication in 14%–74% of cases. The OR for performing fundoplication in the presence of FTT was 1.84 (confidence interval [CI] 1.34–2.54, P = .0002) overall, achieving significance in subgroup analysis for cardiopathy (OR 3.56, CI 1.88–6.71, P = .0001) and neurological impairment (OR 1.79, CI 1.04–3.07, P = .04), but not in the absence of these comorbidities (OR 1.05, CI 0.61–1.83, P = .86). The OR for fundoplication in the presence of neurological impairment was 1.97 (CI 1.34–2.90, P = .0005) and that for cardiopathy was 1.70 (CI 1.20–2.40, P = .003), independent of FTT status. In subgroup analysis, the greatest predictors for fundoplication were neurological impairment with FTT (OR 2.63, CI 1.55–4.48, P = .0004) and complex cardiopathy with FTT and cough/syncope (OR 7.14, CI 4.05–12.58, P < .0001). Presence of cardiopathy without FTT had the overall lowest odds of fundoplication (OR 0.40, CI 0.21–0.78, P = .006).

Conclusion:

Surgeons tend to perform fundoplication in the presence of FTT and other comorbidities, particularly when these are concurrent. Respiratory symptoms are a strong predictor for fundoplication in patients with complex cardiopathies.

Introduction

Gastroesophageal reflux disease (GERD) is one of the most common foregut disorders, impacting 7%–20% of the pediatric population.^1,2 The incidence is believed to be higher in patients with additional medical comorbidities including prematurity, neurologic impairment, and complex cardiac disease.^2,3 In previous studies in the United Kingdom and the United States, a diagnosis of GERD was made in 10%–22% of premature infants cared for in neonatal intensive care units.^1,2,4 Differentiating benign gastroesophageal reflux from clinically significant GERD is challenging, as the associated symptoms are prevalent in infancy.^1,3 Equally challenging is determining which cases will improve and potentially resolve with medical management, modified enteral feeds, and patient growth and development and which would benefit from an antireflux procedure.

Experts across disciplines continue to debate the best approach to manage these complex patients, with practice varying based on physician specialty and training environment.^4–6 Per the Pediatric Gastroesophageal Reflux Clinical Practice Guidelines, initial management should involve medication trials, alterations in feeding schedule, formula thickeners, prokinetic agents, and patient positioning.³ Surgical intervention is reserved for refractory symptoms or life-threatening complications despite optimal medical management and for chronic conditions with significant risk of GERD-associated complications.³

From a surgical standpoint, the Nissen fundoplication is the most common operation for management of infantile GERD. However, although some surgical centers perform hundreds of antireflux operations a year, others debate the necessity and efficacy of the fundoplication, instead advocating for increased medical management, noninvasive feeding methods, or other surgical interventions such as gastrostomy or gastrojejunal feeds.^3,5,7–9 In 2017, the American Pediatric Surgical Association (APSA) Outcomes and Evidence-Based Practice Committee evaluated the efficacy of surgical intervention for GERD based on current literature. The committee found insufficient evidence to show improvement in most of the symptoms usually considered indications for Nissen fundoplication, including cough, aspiration, apnea, and pneumonia-related hospitalizations. Although intervention may improve subjective gastrointestinal and asthma symptoms, there is insufficient evidence to establish the success rates of fundoplication; therefore, the current recommendation is for more rigorous evaluation based on individual patient characteristics.⁹

Owing to a lack of established consensus in the management of these patients, we sought to analyze the current practice patterns of clinically active pediatric surgeons in the United States.

Materials and Methods

A case-based survey was administered on May 3, 2018, at the Case Debates and Controversies session of the APSA Annual Meeting in Palm Desert, CA. Anonymous audience member responses were collected through an electronic polling system.

The root clinical vignette described a 2-month-old former premature infant with gastroesophageal reflux, normal upper gastrointestinal series, and persistent vomiting after adjusted feeds and prokinetic therapy. The variables adjusted for subsequent cases were the presence or absence of failure to thrive (FTT), neurological impairment, complex cardiopathy, and respiratory symptoms (Table 1).

Table 1.

Clinical Vignettes

Clinical vignettes (cases)
1. Otherwise healthy child without FTT.
2. Otherwise healthy child with FTT.
3. Neurological impairment without FTT.
4. Neurological impairment with FTT.
5. Complex cardiopathy without FTT.
6. Complex cardiopathy with FTT.
7. Complex cardiopathy with FTT and respiratory symptoms.

Root case is a 2-month-old former premature infant with gastroesophageal reflux, normal upper gastrointestinal series, and persistent vomiting after adjusted feeds and prokinetic therapy.

FTT, failure to thrive.

The odds ratios (ORs) and 95% confidence intervals (CIs) for fundoplication were calculated using MedCalc Statistical Software version 18.11.3 (MedCalc^® Software bvba, Ostend, Belgium). Statistical significance was established as a P-value of <.05.

Results

The number of responses ranged between 101 and 124 recorded audience participations per clinical vignette. Surgeons elected to perform fundoplication in 14%–74% of cases (Table 2).

Table 2.

Participant Responses

	Infant feeding intolerance/persistent vomiting on NG feeds
	Otherwise healthy		Neurological impairment		Complex cardiopathy
	No FTT	FTT	No FTT	FTT	No FTT	FTT	FTT + cough
	Case 1	Case 2	Case 3	Case 4	Case 5	Case 6	Case 7
Home on NG feeds (%)	17.74	0.00	21.78	0.83	33.06	3.36	0.85
Additional studies (%)	20.97	36.59	6.93	10.00	4.03	4.20	10.17
H2 blockers or PPI (%)	8.06	4.88	1.98	1.67	1.61	2.52	0.85
NJ tube (%)	13.71	21.95	9.90	9.17	1.61	14.29	5.93
G tube (%)	7.26	3.25	16.83	12.50	41.13	26.89	3.39
GJ tube (%)	4.03	4.07	5.94	13.33	4.84	12.61	5.08
Fundoplication ± G tube (%)	28.23	29.27	36.63	50.83	13.71	36.13	73.73
Esophageal disconnection (%)	N/A	N/A	N/A	1.67	N/A	N/A	N/A
No. of observations	124	123	101	120	124	119	118

FTT, failure to thrive; G, gastrostomy; GJ, gastrojejunostomy; H2, histamine type 2; NG, nasogastric; NJ, nasojejunal; PPI, proton pump inhibitors.

The OR for fundoplication in the presence of FTT was 1.84 (CI 1.34–2.54, P = .0002) overall, achieving significance in subgroup analysis for cardiopathy (OR 3.56, CI 1.88–6.71, P = .0001) and neurological impairment (OR 1.79, CI 1.04–3.07, P = .04), but not in the absence of comorbidities (OR 1.05, CI 0.61–1.83, P = .86).

The OR for performing fundoplication in the presence of neurological impairment was 1.97 (CI 1.34–2.90, P = .0005); in the presence of cardiopathy, it was 1.70 (CI 1.20–2.40, P = .003); both of these findings were independent of FTT status. In further subgroup analysis, the greatest predictors for fundoplication were neurological impairment with FTT (OR 2.63, CI 1.55–4.48, P = .0004) and complex cardiopathy with FTT and cough/syncope (OR 7.14, CI 4.05–12.58, P < .0001). Presence of cardiopathy without FTT had the lowest OR for fundoplication (OR 0.40, CI 0.21–0.78, P = .006) (Table 3).

Table 3.

Statistical Analysis

Exposure group	Negative control	OR	CI	P
All FTT except cough (2, 4, 6)	All without FTT (1, 3, 5)	1.84	1.34–2.54	.0002^**
Otherwise healthy with FTT (2)	Otherwise healthy without FTT (1)	1.05	0.61–1.83	.86
NI with FTT (4)	NI without FTT (3)	1.79	1.04–3.07	.04^**
CC with FTT (6)	CC without FTT (5)	3.56	1.88–6.71	.0001^**
All NI (3, 4)	All otherwise healthy (1, 2)	1.97	1.34–2.90	.0005^**
All CC (5, 6, 7)	All otherwise healthy (1, 2)	1.70	1.20–2.40	.003^**
NI without FTT (3)	Otherwise healthy without FTT (1)	1.47	0.83–2.58	.18
NI with FTT (4)	Otherwise healthy without FTT (1)	2.63	1.55–4.48	.0004^**
CC without FTT (5)	Otherwise healthy without FTT (1)	0.40	0.21–0.78	.006^**
CC with FTT (6)	Otherwise healthy without FTT (1)	1.44	0.84–2.47	.19
CC with FTT plus cough (7)	Otherwise healthy without FTT (1)	7.14	4.05–12.58	<.0001^**

Case numbers presented in parentheses ().

Statistically significant at P < .05.

CC, complex cardiopathy; CI, confidence interval; FTT, failure to thrive; NI, neurological impairment; OR, odds ratio.

Discussion

Fundoplications are one of the most commonly performed operations among pediatric surgeons, with >5000 cases performed annually.¹⁰ However, outcomes of this common procedure are difficult to predict, as there is a lack of high-quality evidence in existing literature.⁹ The current Pediatric Gastroesophageal Reflux Clinical Practice Guidelines give only a weak recommendation for considering antireflux surgery in the setting of life-threatening complications, symptoms refractory to medical therapy, and in chronic conditions wherein there is a high risk of complications (such as neurologic impairment or cystic fibrosis).³ The lack of clear guidelines has resulted in significant regional variability in the number of fundoplications performed.¹¹

Our study sought to evaluate how pediatric surgeons would manage three different groups of infants with feeding intolerance that could potentially benefit from a fundoplication: otherwise healthy patients, patients with neurologic impairment, and patients with complex cardiopathy. It also evaluated how the presence of FTT and respiratory symptoms impacted their decision.

In patients with feeding intolerance who are otherwise healthy, our study showed that fewer than a third of pediatric surgeons would perform a fundoplication, even when the patient has FTT (28.23% without FTT, 29.27% with FTT). This relative reluctance is reflected in practice, where patients with complex comorbidities who undergo fundoplication make up a much larger proportion than they do in the general population. In a series of 277 patients who underwent primary fundoplication, only 22% were otherwise healthy, with many patients having either neurologic impairment (28%) or esophageal atresia (23%).¹² In evaluating national trends in fundoplication, 45% of patients had neurologic impairment and 62% had some type of complex chronic condition.¹³

In patients with both feeding intolerance and neurologic impairment, our survey found that pediatric surgeons were only more likely to perform a fundoplication if there was also FTT (OR 2.63, CI 1.55–4.48, P = .0004). For patients with neurologic impairment without FTT, surgeons were no more likely to operate than if the patient was otherwise healthy (OR 1.47, CI 0.83–2.58, P = .18). Since patients with neurologic impairment are more likely to require reoperation than neurologically normal patients (15.4% ± 4.2% versus 7.0% ± 3.3% respectively, χ² P = .003),¹⁴ surgeons may be less inclined to perform a fundoplication in the absence of increased risk of GERD complications secondary to an additional comorbidity. However, there is no clear evidence that surgery for GERD in this patient population alters the risk for poor outcomes, which are more common than in the non-neurologically impaired population.⁹

Similar to patients with neurologic impairment, conflicting evidence exists pertaining to the impact of fundoplication in children with congenital heart disease. Although some studies note a correlation between high morbidity and mortality with fundoplication,^15,16 others saw no difference in mortality between patients with congenital heart disease who had fundoplication and those who did not.^17,18

This controversy may help explain the finding that patients with feeding intolerance and complex cardiopathy but no FTT had the lowest overall odds of fundoplication (OR 0.40, CI 0.21–0.78, P = .006). The preferred management in this patient population was instead largely split between placement of a G-tube alone (41.13%) and sending the patient home on nasogastric (NG) feeds (33.06%). This result also reflects a split in the literature, which is divided between those who suggest a potential benefit of G-tubes in patients with severe congenital heart disease^19–21 and those wherein there is no benefit²² or even possible harm.^23–25

Management of patients with feeding intolerance and congenital heart disease continues to vary by physician preference, with some seeking to avoid any procedure that involves exposure to general anesthesia and additional trauma,²⁶ whereas others are more aggressive in operative enteral access to minimize potential aspiration risks.¹⁹ Our finding that the greatest predictor for performing a fundoplication was the patient with complex cardiopathy, FTT, and cough/syncope (OR 7.14, CI 4.05–12.58, P < .0001) suggests that potential minimization of aspiration risk may influence a surgeon's decision to operate. Of interest, however, there have been no high-quality studies evaluating how fundoplication affects cough.^9,27 Current evidence shows no reduction in aspiration pneumonia or apnea, although there is a potentially decreased risk of acute life-threatening events if these symptoms are clearly correlated with reflux episodes.⁹

The chief limitation to our study is its foundation on survey results from a series of standardized patients. In practice, there are a multitude of factors that would influence a surgeon's decision to operate. Another major limitation to our analysis is that the presence of respiratory symptoms was only evaluated in a clinical vignette with complex cardiopathy; therefore, we cannot establish further between-group comparisons. More meaningful comparisons would have been feasible if the presence of respiratory symptoms was also an option in the other groups, particularly because one of the few studies that evaluates outcomes in otherwise healthy children found that 22 of its 24 patients with respiratory symptoms had resolution after laparoscopic Nissen fundoplication.²⁸ Although this survey helps identify which patients pediatric surgeons think would most benefit from fundoplication, further studies are needed to evaluate whether such a benefit exists.

Conclusion

Pediatric surgeons are more likely to perform a fundoplication in patients with persistent vomiting on NG feeds in the presence of FTT and other comorbidities, especially when these factors are concurrent. The presence of respiratory symptoms was a strong predictor for fundoplication in patients with complex cardiopathy. No consensus exists for the management of these clinical scenarios, which likely reflects the lack of high-quality evidence related to outcomes after fundoplication. Further studies are needed to better identify treatment algorithms in these populations.

Footnotes

Acknowledgments

This project was made possible thanks to the session facilitators, all participating surgeons sharing their current practices, and the American Pediatric Surgical Association (APSA) for providing a platform for ongoing conversations and continuous improvement in the practice of pediatric surgery.

Disclosure Statement

A.M.C.B., A.G., R.E.H., and C.M.H. have no competing financial interests. T.A.P. is consultant for Conmed.

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