Evidence-Based Management Of Neonatal Vomiting In The Emergency Department

Table of Contents

 

1. Abstract
2. Case Presentations
3. Introduction
4. Critical Appraisal Of The Literature
5. Etiology And Pathophysiology
6. Differential Diagnosis
   1. Obstructive Pathologies
      1. Bilious Etiologies
      2. Nonbilious Etiologies
   2. Nonobstructive Pathologies
      1. Gastroesophageal Reflux And Gastroesophageal Reflux Disease
      2. Overfeeding
      3. Feeding Intolerance
      4. Necrotizing Enterocolitis
      5. Sepsis And Infection
      6. Kernicterus
      7. Inborn Errors Of Metabolism
      8. Increased Intracranial Pressure
      9. Other Nonobstructive Etiologies
7. Prehospital Care
8. Emergency Department Evaluation
   1. History
      1. Quality Of Emesis
      2. Feeding Patterns
      3. Growth
      4. Gastroesophageal Reflux Disease
      5. Hydration Status, Urine Output, And Stooling
   2. Physical Examination
9. Diagnostic Studies
   1. Bedside Tests
   2. Laboratory Studies
   3. Radiographic Imaging Studies
      1. Bilious Emesis
   4. Nonbilious Emesis
      1. Hypertrophic Pyloric Stenosis
      2. Gastroesophageal Reflux Disease
10. Treatment
    1. Management Of Obstructive Etiologies
       1. Malrotation With Midgut Volvulus
       2. Hypertrophic Pyloric Stenosis
       3. Incarcerated Inguinal Hernia
       4. Intestinal Atresias
       5. Hirschsprung Disease
       6. Intussusception
    2. Management Of Nonobstructive Etiologies
       1. Gastroesophageal Reflux Disease
          • Nonpharmacologic Treatment
          • Pharmacologic Treatment
          • Acid Suppressants
          • Prokinetic Agents
       2. Surgical Management
       3. Necrotizing Enterocolitis
       4. Management Of Other Nonobstructive Causes Of Neonatal Vomiting
11. Special Populations
12. Controversies And Cutting Edge
13. Disposition
14. Summary
15. Risk Management Pitfalls For Neonatal Vomiting
16. Time- And Cost-Effective Strategies
17. Case Conclusions
18. Tables and Figures
    1. Table 1. Differential Diagnosis Of Vomiting In The Neonate
    2. Figure 1. Radiographic 'Double Bubble' Sign Associated With Duodenal Atresia
    3. Figure 2. Malrotation On Upper Gastrointestinal Study
    4. Figure 3. Ultrasound Of Hypertrophic Pyloric Stenosis
19. Clinical Pathway For Management Of Neonatal Vomiting In The Emergency Department
20. References

Abstract

Vomiting accounts for up to 36% of neonatal visits to the emergency department. The causes of vomiting can range from benign to life-threatening. Evidence to guide the diagnosis and management of neonatal vomiting in the emergency department is limited. History and physical examination are extremely important in these cases, especially in identifying red flags such as bilious or projectile emesis. A thorough review is presented, discussing various imaging modalities, including plain abdominal radiography, upper gastrointestinal studies, ultrasonography, and contrast enema. A systematic approach in the emergency department, as outlined in this review, is required to identify the serious causes of vomiting in the neonate.

Case Presentations

A 3-week-old boy with emesis is brought to the ED by his parents. He has had persistent nonbilious vomiting occurring after nearly every feed for the past 2 weeks. The parents have changed his formula 3 times, but there has been no change in symptoms. Although the baby has gained weight, he has not gained as expected. No fever has been noted. The remainder of the review of systems is negative. On physical examination, the patient is well-appearing and is not dehydrated. His abdomen is soft, nontender, and nondistended. You observe a brief episode where he arches his back, grimaces, and seems to “tighten up” while lying supine. Considering all the possible diagnoses, you debate what your workup should be...

A 2-day-old girl is then brought to the ED by her parents. The infant has had 5 episodes of vomiting that day. The mother reports that the vomit has changed from the color of colostrum to a green color. The mother and baby had an uncomplicated delivery and were discharged from the hospital earlier that day. The infant passed meconium on day 1 of life and has had 5 wet diapers since birth. The mother has noted that the infant has not been as vigorous when attempting breastfeeding since that morning. The remainder of the review of systems is negative. The physical examination reveals a lethargic neonate who reacts minimally to examination. Her abdomen is distended with quiet bowel sounds, and a slight whimper is elicited with palpation. The patient appears dehydrated, and there is a light green stain on the mother’s shoulder from the emesis. You tell the patient’s mother that you have concerns and that you need to work fast to uncover the cause of her vomiting. What can be the cause of vomiting in this neonate? All bilious emesis is bad, right? Should you call the surgeon right away, or wait until you have the diagnosis? Should you get an x-ray, an ultrasound, or a UGI study?

A 4-week-old boy is sent to the ED after being seen in his pediatrician’s office for vomiting and weight loss. He is noted to have lost 8 ounces since his last office visit 1 week prior. His mother reports that, for the past 2 weeks, he has been spitting up, it has become progressively more frequent, and is now forceful. She states that the color of the emesis is the formula she has been feeding him, and the vomiting occurs after every feed. He still has 4 to 5 wet diapers per day and no diarrhea. The remainder of the review of systems is negative. On physical examination, you find a sleeping neonate who reacts to the examination by crying. You notice that he does not produce many tears and his diaper is dry. On abdominal examination, you palpate a possible small mass in the right upper quadrant, but the baby moves frequently, and the examination is difficult to reproduce. The remainder of the examination is noncontributory. As you think about the orders you want to place, you wonder if a set of electrolytes would be helpful. Should you attempt a bedside ultrasound? Which test is first-line – an ultrasound or a UGI study?

Introduction

Vomiting in the neonate is a common presenting complaint in the emergency department (ED), with etiologies ranging from benign to life-threatening. Vomiting and feeding difficulties have been reported in 11% to 36% of neonates who visit the ED.^1,2 Vomiting (particularly bilious emesis) must be considered a surgical emergency until proven otherwise. The incidence of bilious emesis indicative of a surgical obstruction is reported to be between 20% and 38%.^3-7 A timely and accurate diagnosis is the key to successful management.⁸ Determining the etiology of vomiting in the neonate can be difficult and may involve multiple imaging modalities as well as consultation with subspecialists. This review will focus on the evaluation and treatment of neonates with gastrointestinal causes of vomiting, particularly the life-threatening etiologies.

Critical Appraisal Of The Literature

A literature search was performed in PubMed and Ovid MEDLINE®, using the search terms vomiting, neonate, bilious, emesis, gastroesophageal reflux disease, GERD, malrotation, midgut volvulus, Hirschsprung disease, hypertrophic pyloric stenosis, necrotizing enterocolitis, and incarcerated inguinal hernia. Significant, well-designed, randomized controlled trials and meta-analyses were included as well as older publications that have been frequently referenced in the medical community. A search of the Cochrane Database of Systematic Reviews yielded 1 pertinent publication related to the treatment of neonatal vomiting.⁹ One relevant review was not included in this issue, as it had been withdrawn from the Cochrane Library because the authors were unable to update the review.¹⁰ Guidelines released through the National Guideline Clearinghouse by the American College of Radiology in 2011¹¹ and guidelines from the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) in conjunction with the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) in 2009¹² were reviewed. Both of these guidelines are consensus statements and not systematic, evidence-based guidelines. A search of the American Academy of Pediatrics website did not reveal any clinical practice guidelines on this topic. There is a wide range in the quality of clinical evidence available for the diagnosis and management of neonatal vomiting, with most falling into the moderately strong category. There are limited prospective studies focused on ED management.

Risk Management Pitfalls For Neonatal Vomiting

1. “The infant had bilious vomiting and did not look well, but I decided to wait until completion of the diagnostic study before calling the surgeon.” In a toxic-appearing neonate with bilious vomiting, the diagnosis of a malrotation with midgut volvulus must be considered. Evaluation by a pediatric surgeon as soon as this diagnosis is suspected is warranted, as bowel necrosis is correlated with increased mortality.
2. “I evaluated a well-appearing infant with a history of vomiting. When asked, the mother confirmed the emesis was “bile.” The patient appeared well and had a completely normal examination, but because of the history of bilious vomiting, I proceeded to place an NG tube, call a surgeon, and order a UGI study.” Most caregivers (71%) equate “bile” with the color yellow. Asking the caregiver to describe the color of the emesis and not prompting them with the term “bile” could avoid an unnecessary workup in a well-appearing infant.
3. “I admitted an infant with abdominal distension, irritability, and vomiting, but did not consider a surgical abdomen, as the vomiting was nonbilious and nonprojectile.” Surgical etiologies for neonates with vomiting should still be considered with nonbilious vomiting in the presence of other concerning signs and symptoms, such as abdominal distention and irritability.
4. “For this infant with bilious vomiting, the initial abdominal radiograph did not show air fluid levels, so I determined that further imaging was not necessary.” The sensitivity and specificity of abdominal plain radiographs for obstruction in the presence of bilious emesis have been reported to be 44% to 50% and 80% to 97%, respectively, indicating that > 50% of cases would be missed if the diagnosis is based on radiographs alone.
5. “The infant had been spitting up since birth, so I didn’t think of considering a surgical issue, although the vomiting had become more frequent and more forceful.” In a study of return ED visits, patients diagnosed with reflux and/or vomiting at the first visit had a high frequency of admission (55%) and diagnosis of pyloric stenosis at the second visit (26%).
6. “I made the clinical diagnosis of GERD in a well-appearing infant and started treatment with metoclopramide.” The recommendations for treatment of GERD in well-appearing infants include nonpharmacologic treatments and consideration of pharmacologic treatment. Considerations include avoidance of cow’s milk protein and postprandial position changes. When nonpharmacologic treatment fails, H₂-receptor blockers can be considered. Due to significant side effects and lack of evidence of effectiveness in the treatment of GERD, prokinetic agents (such as metoclopramide) are no longer recommended for the treatment of GERD in infants.
7. “I discharged a 3-week-old baby with vomiting with a diagnosis of GERD because the infant was too young to consider HPS and the laboratory studies did not show hypokalemia, hypochloremia, or metabolic alkalosis.” Several authors have demonstrated that the majority of patients with HPS have normal electrolytes. Up to 88% of patients have no electrolyte abnormalities on admission. If the diagnosis of HPS is suspected, ultrasound should be ordered.
8. “I always recommend mothers with infants with suspected GERD to thicken formula and sit the infant in a car seat after feeds.” Although this was traditionally thought to decrease reflux symptoms, sitting upright in car seats after feeds has been shown to increase reflux symptoms in infants.
9. “I did not feel a palpable olive-sized mass in the abdomen, so I discharged the vomiting infant home with diagnosis of reflux.” Since the advent of ultrasonography for diagnosing HPS, the portion of patients with a clinical finding of a palpable olive-sized mass has fallen from previous reports of 78% to 83% to only 50%. This may be due to earlier diagnosis, which renders the mass smaller and not as palpable.
10. “I suspected the diagnosis of an incarcerated hernia in an infant with a painful inguinal mass and abdominal distension and ordered an abdominal ultrasound to confirm the diagnosis.” Incarcerated inguinal hernia is a diagnosis requiring prompt recognition and involvement of pediatric surgeons to optimize bowel salvage. Typically, history and physical examination are all the clinician needs to diagnose this entity and manual reduction should be attempted in the ED.

Tables and Figures

References

Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of subjects. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.

To help the reader judge the strength of each reference, pertinent information about the study will be included in bold type following the reference, where available. The most informative references cited in this paper, as determined by the author, will be noted by an asterisk (*) next to the number of the reference.

1. Fernandez Ruiz C, Trenchs Sainz de la Maza V, Curcoy Barcenilla AI, et al. [Neonatal management in the emergency department of a tertiary children’s hospital]. An Pediatr (Barc). 2006;65(2):123-128. (Retrospective chart review; 1481 patients)
2. Flanagan CF, Stewart M. Factors associated with early neonatal attendance to a paediatric emergency department. Arch Dis Child. 2014;99(3):239-243. (Retrospective chart review; 208 patients)
3. * Malhotra A, Lakkundi A, Carse E. Bilious vomiting in the newborn: 6 years data from a Level III Centre. J Paediatr Child Health. 2010;46(5):259-261. (Retrospective chart review; 61 patients)
4. Kao HA. Bilious vomiting during the first week of life. Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi. 1994;35(3):202- 207. (Retrospective chart review; 45 patients)
5. * Lilien LD, Srinivasan G, Pyati SP, et al. Green vomiting in the first 72 hours in normal infants. Am J Dis Child. 1986;140(7):662-664. (Retrospective chart review; 45 patients)
6. Owen R, Long AM, Grady A, et al. Outcomes of referrals for bilious aspirates and vomiting to a tertiary neonatal surgical unit. Int J Surg. 2011;9(7):508-509. (Prospective cohort study; 22 patients)
7. * Godbole P, Stringer MD. Bilious vomiting in the newborn: how often is it pathologic? J Pediatr Surg. 2002;37(6):909-911. (Prospective cohort study; 63 patients)
8. Grosfeld JS. Jejunoileal atresia and stenosis. In: Grosfeld JS, O’Neil JA, Fonkalsrud EW, et al, eds. Pediatric Surgery. 6th ed. Philadelphia, PA: Mosby; 2006:1269-1287. (Textbook)
9. Rao SC, Basani L, Simmer K, et al. Peritoneal drainage versus laparotomy as initial surgical treatment for perforated necrotizing enterocolitis or spontaneous intestinal perforation in preterm low birth weight infants. Cochrane Database Syst Rev. 2011(6):CD006182. (Systematic review; 2 studies, 185 patients)
10. Craig WR, Hanlon-Dearman A, Sinclair C, et al. Metoclopramide, thickened feedings, and positioning for gastrooesophageal reflux in children under two years. Cochrane Database Syst Rev. 2004(4):CD003502. (Systematic review; 20 studies; 771 patients)
11. Bulas D, McGrane SL, Coley BD, et al. ACR Appropriateness Criteria: vomiting in infants up to 3 months of age. American College of Radiology. 2011. Available at: http://www.acr.org/~/media/ACR/Documents/AppCriteria/Diagnostic/ VomitingInInfantsUpTo3MonthsOfAge.pdf. (Practice guideline)
12. Vandenplas Y, Rudolph CD, Di Lorenzo C, et al. Pediatric gastroesophageal reflux clinical practice guidelines: joint recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). J Pediatr Gastroenterol Nutr. 2009;49(4):498-547. (Practice guideline)
13. Hegar B, Dewanti NR, Kadim M, et al. Natural evolution of regurgitation in healthy infants. Acta Paediatr. 2009;98(7):1189-1193. (Prospective study; 130 patients)
14. Osatakul S, Sriplung H, Puetpaiboon A, et al. Prevalence and natural course of gastroesophageal reflux symptoms: a 1-year cohort study in Thai infants. J Pediatr Gastroenterol Nutr. 2002;34(1):63-67. (Prospective study; 216 patients)
15. Miyazawa R, Tomomasa T, Kaneko H, et al. Prevalence of gastro-esophageal reflux-related symptoms in Japanese infants. Pediatr Int. 2002;44(5):513-516. (Prospective study; 921 patients)
16. Nelson SP, Chen EH, Syniar GM, et al. Prevalence of symptoms of gastroesophageal reflux during infancy. A pediatric practice-based survey. Pediatric Practice Research Group. Arch Pediatr Adolesc Med. 1997;151(6):569-572. (Cross-sectional study; 948 patients)
17. Berdon WE, Baker DH, Bull S, et al. Midgut malrotation and volvulus. Which films are most helpful? Radiology. 1970;96(2):375-384. (Retrospective chart review; 77 patients)
18. Bonadio WA, Clarkson T, Naus J. The clinical features of children with malrotation of the intestine. Pediatr Emerg Care. 1991;7(6):348-349. (Retrospective chart review; 33 patients)
19. Messineo A, MacMillan JH, Palder SB, et al. Clinical factors affecting mortality in children with malrotation of the intestine. J Pediatr Surg. 1992;27(10):1343-1345. (Retrospective chart review; 182 children)
20. Schmidt H, Abolmaali N, Vogl TJ. Double bubble sign. Eur Radiol. 2002;12(7):1849-1853. (Descriptive study of radiologic finding)
21. Aboagye J, Goldstein SD, Salazar JH, et al. Age at presentation of common pediatric surgical conditions: reexamining dogma. J Pediatr Surg. 2014;49(6):995-999. (Retrospective chart review; 63,750 patients)
22. Piroutek MJ, Brown L, Thorp AW. Bilious vomiting does not rule out infantile hypertrophic pyloric stenosis. Clin Pediatr (Phila). 2012;51(3):214-218. (Retrospective chart review; 354 patients)
23. Shaoul R, Enav B, Steiner Z, et al. Clinical presentation of pyloric stenosis: the change is in our hands. Isr Med Assoc J. 2004;6(3):134-137. (Retrospective chart review; 70 patients)
24. Mahon BE, Rosenman MB, Kleiman MB. Maternal and infant use of erythromycin and other macrolide antibiotics as risk factors for infantile hypertrophic pyloric stenosis. J Pediatr. 2001;139(3):380-384. (Retrospective cohort study; 43 patients)
25. Honein MA, Paulozzi LJ, Himelright IM, et al. Infantile hypertrophic pyloric stenosis after pertussis prophylaxis with erythromcyin: a case review and cohort study. Lancet. 1999;354(9196):2101-2105. (Retrospective cohort study; 7 patients)
26. Cooper WO, Griffin MR, Arbogast P, et al. Very early exposure to erythromycin and infantile hypertrophic pyloric stenosis. Arch Pediatr Adolesc Med. 2002;156(7):647-650. (Retrospective cohort study; 804 patients)
27. Lund M, Pasternak B, Davidsen RB, et al. Use of macrolides in mother and child and risk of infantile hypertrophic pyloric stenosis: nationwide cohort study. BMJ. 2014;348:g1908. (Retrospective cohort study; 880 patients)
28. Hulka F, Campbell TJ, Campbell JR, et al. Evolution in the recognition of infantile hypertrophic pyloric stenosis. Pediatrics. 1997;100(2):E9. (Retrospective chart review; 901 patients)
29. Benson CD, Lloyd JR. Infantile pyloric stenosis. A review of 1,120 cases. Am J Surg. 1964;107:429-433. (Retrospective chart review; 1120 patients)
30. Moss RL, Hatch EI Jr. Inguinal hernia repair in early infancy. Am J Surg. 1991;161(5):596-599. (Retrospective chart review; 384 patients)
31. Kuhny D, Pukas A, Suda W, et al. Management and outcome of Hirschsprung’s disease diagnosed in neonatal period. Early Human Development. 2010;86(Supplement):S109. (Retrospective chart review; 9 patients)
32. Lee CC, Lien R, Chiang MC, et al. Clinical impacts of endelayed diagnosis of Hirschsprung’s disease in newborn infants. Pediatr Neonatol. 2012;53(2):133-137. (Retrospective cohort study; 51 patients)
33. Ziegler MM. Meconium ileus. In: Coran AG, Adzick NS, Krummel TM, et al, eds. Pediatric Surgery. Vol 2. 7th ed. Philadelphia, PA: Elsevier-Saunders; 2012:1073-1083. (Textbook)
34. Caty MG, Escobar Jr. MA. Meconium disease. In: Holcomb GW, Murphy JP, Ostlie DJ, eds. Ashcraft’s Pediatric Surgery. 6th ed. Philadelphia, PA: Elsevier-Saunders; 2014:439-453. (Textbook)
35. Kong FT, Liu WY, Tang YM, et al. Intussusception in infants younger than 3 months: a single center’s experience. World J Pediatr. 2010;6(1):55-59. (Retrospective cohort study; 39 patients)
36. Shad J, Biswas R. Ileo-colic intussusception in premature neonate. BMJ Case Rep. 2011;2011. (Case report)
37. Loukas I, Baltogiannis N, Plataras C, et al. Intussusception in a premature neonate: a rare often misdiagnosed cause of intestinal obstruction. Case Rep Med. 2009;2009:607989. (Case report)
38. Beres AL, Baird R. An institutional analysis and systematic review with meta-analysis of pneumatic versus hydrostatic reduction for pediatric intussusception. Surgery. 2013;154(2):328- 334. (Meta-analysis; 19 studies, 5559 patients)
39. Martin AJ, Pratt N, Kennedy JD, et al. Natural history and familial relationships of infant spilling to 9 years of age. Pediatrics. 2002;109(6):1061-1067. (Prospective cohort study; 693 patients)
40. Rudolph CD, Mazur LJ, Liptak GS, et al. Guidelines for evaluation and treatment of gastroesophageal reflux in infants and children: recommendations of the North American Society for Pediatric Gastroenterology and Nutrition. J Pediatr Gastroenterol Nutr. 2001;32 Suppl 2:S1-31. (Practice guideline)
41. * Lightdale JR, Gremse DA. Gastroesophageal reflux: management guidance for the pediatrician. Pediatrics. 2013;131(5):e1684-e1695. (Pratice guideline)
42. Bell MJ, Ternberg JL, Feigin RD, et al. Neonatal necrotizing enterocolitis: therapeutic decisions based upon clinical staging. Ann Surg. 1978;187(1):1-7. (Prospective cohort study; 48 patients)
43. American College of Emergency Physicians Clinical Policies Committee; American College of Emergency Physicians Clinical Policies Subcommittee on Pediatric Fever. Clinical policy for children younger than three years presenting to the emergency department with fever. Ann Emerg Med. 2003;42(4):530-545. (Clinical policy)
44. * Maherzi M, Guignard JP, Torrado A. Urinary tract infection in high-risk newborn infants. Pediatrics. 1978;62(4):521-523. (Cross-sectional study; 1762 patients)
45. * Vilanova Juanola JM, Canos Molinos J, Rosell Arnold E, et al. [Urinary tract infection in the newborn infant]. An Esp Pediatr. 1989;31(2):105-109. (Retrospective chart review; 28 patients)
46. Walker GM, Neilson A, Young D, et al. Colour of bile vomiting in intestinal obstruction in the newborn: questionnaire study. BMJ. 2006;332(7554):1363. (Cross-sectional study; 165 participants)
47. Gotley LM, Blanch A, Kimble R, et al. Pyloric stenosis: a retrospective study of an Australian population. Emerg Med Australas. 2009;21(5):407-413. (Retrospective chart review; 329 children)
48. Cafarotti A, Bascietto C, Salvatore R, et al. A 6-month-old boy with uncontrollable dystonic posture of the neck. Sandifer syndrome. Pediatr Ann. 2014;43(1):17-19. (Case report)
49. Chen A, Du J, Du LZ. [Clinical characteristics of abdominal distention in early newborns]. Zhongguo Dang Dai Er Ke Za Zhi. 2013;15(12):1074-1078. (Retrospective chart review; 201 patients)
50. Wyllie R. Motility disorders and Hirschsprung disease. In: Kliegman R, Stanton BF, St. Geme JW, et al, eds. Nelson Textbook of Pediatrics. 19th ed. Philadelphia, PA: Elsevier- Saunders; 2011:1283-1287. (Textbook)
51. * Wyllie R. Pyloric stenosis and congenital anomalies of the stomach. In: Kliegman R, Behrman R, eds. Nelson Textbook of Pediatrics. 18th ed. Philadelphia, PA: Elsevier-Saunders; 2007:1555-1558. (Textbook)
52. Papadakis K, Chen EA, Luks FI, et al. The changing presentation of pyloric stenosis. Am J Emerg Med. 1999;17(1):67-69. (Retrospective chart review; 283 patients)
53. Tutay GJ, Capraro G, Spirko B, et al. Electrolyte profile of pediatric patients with hypertrophic pyloric stenosis. Pediatr Emerg Care. 2013;29(4):465-468. (Retrospective chart review; 205 patients)
54. Smith GA, Mihalov L, Shields BJ. Diagnostic aids in the differentiation of pyloric stenosis from severe gastroesophageal reflux during early infancy: the utility of serum bicarbonate and serum chloride. Am J Emerg Med. 1999;17(1):28-31. (Retrospective case-control study; 150 patients)
55. Simpson AJ, Leonidas JC, Krasna IH, et al. Roentgen diagnosis of midgut malrotation: value of upper gastrointestinal radiographic study. J Pediatr Surg. 1972;7(2):243-252. (Retrospective chart review; 32 patients)
56. Dilley AV, Pereira J, Shi EC, et al. The radiologist says malrotation: does the surgeon operate? Pediatr Surg Int. 2000;16(1- 2):45-49. (Retrospective chart review; 71 patients)
57. Long FR, Kramer SS, Markowitz RI, et al. Intestinal malrotation in children: tutorial on radiographic diagnosis in difficult cases. Radiology. 1996;198(3):775-780. (Retrospective chart review; 81 patients)
58. Prasil P, Flageole H, Shaw KS, et al. Should malrotation in children be treated differently according to age? J Pediatr Surg. 2000;35(5):756-758. (Retrospective chart review; 110 patients)
59. Torres AM, Ziegler MM. Malrotation of the intestine. World J Surg. 1993;17(3):326-331. (Retrospective chart review; 22 patients)
60. Sizemore AW, Rabbani KZ, Ladd A, et al. Diagnostic performance of the upper gastrointestinal series in the evaluation of children with clinically suspected malrotation. Pediatr Radiol. 2008;38(5):518-528. (Retrospective chart review; 229 patients)
61. * Hsiao M, Langer JC. Value of laparoscopy in children with a suspected rotation abnormality on imaging. J Pediatr Surg. 2011;46(7):1347-1352. (Retrospective chart review; 51 patients)
62. Powell DM, Othersen HB, Smith CD. Malrotation of the intestines in children: the effect of age on presentation and therapy. J Pediatr Surg. 1989;24(8):777-780. (Retrospective chart review; 70 patients)
63. O’Donovan AN, Habra G, Somers S, et al. Diagnosis of Hirschsprung’s disease. AJR Am J Roentgenol. 1996;167(2):517- 520. (Retrospective chart review; 38 patients)
64. Taxman TL, Yulish BS, Rothstein FC. How useful is the barium enema in the diagnosis of infantile Hirschsprung’s disease? Am J Dis Child. 1986;140(9):881-884. (Retrospective chart review; 58 patients)
65. de Lorijn F, Kremer LCM, Reitsma JB, et al. Diagnostic tests in Hirschsprung disease: a systematic review. J Pediatr Gastroenterol Nutr. 2006;42(5):496-505. (Systematic review; 24 studies, 1818 patients)
66. Diamond IR, Casadiego G, Traubici J, et al. The contrast endelayed ema for Hirschsprung disease: predictors of a false-positive result. J Pediatr Surg. 2007;42(5):792-795. (Retrospective chart review; 129 patients)
67. Loening-Baucke V, Pringle KC, Ekwo EE. Anorectal manometry for the exclusion of Hirschsprung’s disease in neonates. J Pediatr Gastroenterol Nutr. 1985;4(4):596-603. (Prospective cohort study; 25 patients)
68. Teele RL, Smith EH. Ultrasound in the diagnosis of idiopathic hypertrophic pyloric stenosis. N Engl J Med. 1977;296(20):1149-1150. (Prospective study)
69. Iqbal CW, Rivard DC, Mortellaro VE, et al. Evaluation of ultrasonographic parameters in the diagnosis of pyloric stenosis relative to patient age and size. J Pediatr Surg. 2012;47(8):1542- 1547. (Retrospective chart review; 304 patients)
70. Hernanz-Schulman M, Sells LL, Ambrosino MM, et al. Hypertrophic pyloric stenosis in the infant without a palpable olive: accuracy of sonographic diagnosis. Radiology. 1994;193(3):771-776. (Prospective study; 152 patients)
71. Godbole P, Sprigg A, Dickson JA, et al. Ultrasound compared with clinical examination in infantile hypertrophic pyloric stenosis. Arch Dis Child. 1996;75(4):335-337. (Prospective study; 116 patients)
72. Niedzielski J, Kobielski A, Sokal J, et al. Accuracy of sonographic criteria in the decision for surgical treatment in infantile hypertrophic pyloric stenosis. Arch Med Sci. 2011;7(3):508-511. (Retrospective chart review; 115 patients)
73. Leaphart CL, Borland K, Kane TD, et al. Hypertrophic pyloric stenosis in newborns younger than 21 days: remodeling the path of surgical intervention. J Pediatr Surg. 2008;43(6):998- 1001. (Retrospective chart review; 314 patients)
74. Deal L, Gold BD, Gremse DA, et al. Age-specific questionnaires distinguish GERD symptom frequency and severity in infants and young children: development and initial validation. J Pediatr Gastroenterol Nutr. 2005;41(2):178-185. (Prospective study; 128 patients)
75. Lewis GC, Crapo SA, Williams JG. Critical skills and procedures in emergency medicine: vascular access skills and procedures. Emerg Med Clin North Am. 2013;31(1):59-86. (Review)
76. Alkalay AL, Sarnat HB, Flores-Sarnat L, et al. Population meta-analysis of low plasma glucose thresholds in full-term normal newborns. Am J Perinatol. 2006;23(2):115-119. (Metaanalysis; 6 studies, 723 patients)
77. Ladd WE. Surgical diseases of the alimentary tract in infants. N Engl J Med. 1936(215):705. (Review)
78. Stanfill AB, Pearl RH, Kalvakuri K, et al. Laparoscopic Ladd’s procedure: treatment of choice for midgut malrotation in infants and children. J Laparoendosc Adv Surg Tech A. 2010;20(4):369-372. (Retrospective chart review; 156 patients)
79. Hagendoorn J, Vieira-Travassos D, van der Zee D. Laparoscopic treatment of intestinal malrotation in neonates and infants: retrospective study. Surg Endosc. 2011;25(1):217-220. (Retrospective chart review; 45 patients)
80. Miozzari HH, Tonz M, von Vigier RO, et al. Fluid resuscitation in infantile hypertrophic pyloric stenosis. Acta Paediatr. 2001;90(5):511-514. (Retrospective chart review; 139 patients)
81. Hall NJ, Van Der Zee J, Tan HL, et al. Meta-analysis of laparoscopic versus open pyloromyotomy. Ann Surg. 2004;240(5):774-778. (Meta-analysis; 8 studies, 595 patients)
82. * Sola JE, Neville HL. Laparoscopic vs open pyloromyotomy: a systematic review and meta-analysis. J Pediatr Surg. 2009;44(8):1631-1637. (Meta-analysis; 6 studies, 625 patients)
83. Jia WQ, Tian JH, Yang KH, et al. Open versus laparoscopic pyloromyotomy for pyloric stenosis: a meta-analysis of randomized controlled trials. Eur J Pediatr Surg. 2011;21(2):77-81. (Meta-analysis; 3 studies; 492 patients)
84. Oomen MW, Hoekstra LT, Bakx R, et al. Open versus laparo scopic pyloromyotomy for hypertrophic pyloric stenosis: a systematic review and meta-analysis focusing on major complications. Surg Endosc. 2012;26(8):2104-2110. (Meta-analysis; 4 studies, 502 patients)
85. Elanahas A, Pemberton J, Yousef Y, et al. Investigating the use of preoperative nasogastric tubes and postoperative outcomes for infants with pyloric stenosis: a retrospective cohort study. J Pediatr Surg. 2010;45(5):1020-1023. (Retrospective chart review; 109 patients)
86. Koivusalo A, Pakarinen MP, Rintala RJ. Laparoscopic herniorrhaphy after manual reduction of incarcerated inguinal hernia. Surg Endosc. 2007;21(12):2147-2149. (Retrospective chart review; 40 patients)
87. Puri P, Guiney EJ, O’Donnell B. Inguinal hernia in infants: the fate of the testis following incarceration. J Pediatr Surg. 1984;19(1):44-46. (Retrospective chart review; 158 patients)
88. Goldman RD, Balasubramanian S, Wales P, et al. Pediatric surgeons and pediatric emergency physicians’ attitudes towards analgesia and sedation for incarcerated inguinal hernia reduction. J Pain. 2005;6(10):650-655. (Questionnaire; 245 respondents)
89. Al-Ansari K, Sulowski C, Ratnapalan S. Analgesia and sedation practices for incarcerated inguinal hernias in children. Clin Pediatr (Phila). 2008;47(8):766-769. (Retrospective chart review; 99 patients)
90. Koivusalo AI, Korpela R, Wirtavuori K, et al. A singleblinded, randomized comparison of laparoscopic versus open hernia repair in children. Pediatrics. 2009;123(1):332-337. (Randomized controlled trial; 89 patients)
91. Li B, Chen WB, Wang SQ, et al. [Transumbilical laparoendoscopic single-site surgery in the treatment of neonatal intestinal atresia and stenosis]. Zhonghua Wei Chang Wai Ke Za Zhi. 2013;16(1):44-47. (Prospective study; 20 patients)
92. Li B, Chen WB, Wang SQ, et al. Laparoscopy-assisted surgery for neonatal intestinal atresia and stenosis: a report of 35 cases. Pediatr Surg Int. 2012;28(12):1225-1228. (Prospective study; 35 patients)
93. Abhyankar A, Mukhtar Z. Laparoscopy-assisted surgery for neonatal intestinal atresia: single-center experience. Asian J Endosc Surg. 2011;4(2):90-93. (Prospective study; 3 patients)
94. Marquez TT, Acton RD, Hess DJ, et al. Comprehensive review of procedures for total colonic aganglionosis. J Pediatr Surg. 2009;44(1):257-265. (Meta-analysis; 19 studies, 161 patients)
95. Whitehouse JS, Gourlay DM, Winthrop AL, et al. Is it safe to discharge intussusception patients after successful hydrostatic reduction? J Pediatr Surg. 2010;45(6):1182-1186. (Retrospective chart review; 309 patients)
96. * Herwig K, Brenkert T, Losek JD. Enema-reduced intussusception management: is hospitalization necessary? Pediatr Emerg Care. 2009;25(2):74-77. (Retrospective cross-sectional study; 45 patients)
97. Horvath A, Dziechciarz P, Szajewska H. The effect of thickened-feed interventions on gastroesophageal reflux in infants: systematic review and meta-analysis of randomized, controlled trials. Pediatrics. 2008;122(6):e1268-1277. (Metaanalysis; 14 studies, 877 patients)
98. Khoshoo V, Ross G, Brown S, et al. Smaller volume, thickened formulas in the management of gastroesophageal reflux in thriving infants. J Pediatr Gastroenterol Nutr. 2000;31(5):554-556. (Prospective study; 6 patients)
99. Vandenplas Y, Sacre L. Milk-thickening agents as a treatment for gastroesophageal reflux. Clin Pediatr (Phila). 1987;26(2):66-68. (Prospective study; 30 patients)
100. Orenstein SR, Magill HL, Brooks P. Thickening of infant feedings for therapy of gastroesophageal reflux. J Pediatr. 1987;110(2):181-186. (Prospective study; 20 patients)
101. Xinias I, Mouane N, Le Luyer B, et al. Cornstarch thickened formula reduces oesophageal acid exposure time in infants. Dig Liver Dis. 2005;37(1):23-27. (Prospective study; 96 patients)
102. Hegar B, Rantos R, Firmansyah A, et al. Natural evolution of infantile regurgitation versus the efficacy of thickened formula. J Pediatr Gastroenterol Nutr. 2008;47(1):26-30. (Prospective study; 60 patients)
103. Miyazawa R, Tomomasa T, Kaneko H, et al. Effect of formula thickened with reduced concentration of locust bean gum on gastroesophageal reflux. Acta Paediatr. 2007;96(6):910-914. (Prospective study; 20 patients)
104. Chao HC, Vandenplas Y. Comparison of the effect of a cornstarch thickened formula and strengthened regular formula on regurgitation, gastric emptying and weight gain in infantile regurgitation. Dis Esophagus. 2007;20(2):155-160. (Prospective study; 81 patients)
105. Shalaby TM, Orenstein SR. Efficacy of telephone teaching of conservative therapy for infants with symptomatic gastroesophageal reflux referred by pediatricians to pediatric gastroenterologists. J Pediatr. 2003;142(1):57-61. (Retrospective study; 394 patients)
106. Meyers WF, Herbst JJ. Effectiveness of positioning therapy for gastroesophageal reflux. Pediatrics. 1982;69(6):768-772. (Case-control study; 128 patients)
107. Vandenplas Y, Sacre-Smits L. Seventeen-hour continuous esophageal pH monitoring in the newborn: evaluation of the influence of position in asymptomatic and symptomatic babies. J Pediatr Gastroenterol Nutr. 1985;4(3):356-361. (Prospective study; 82 patients)
108. Tobin JM, McCloud P, Cameron DJ. Posture and gastro-oesophageal reflux: a case for left lateral positioning. Arch Dis Child. 1997;76(3):254-258. (Prospective study; 24 patients)
109. Corvaglia L, Rotatori R, Ferlini M, et al. The effect of body positioning on gastroesophageal reflux in premature infants: evaluation by combined impedance and pH monitoring. J Pediatr. 2007;151(6):591-596. (Prospective study; 22 patients)
110. Orenstein SR, Whitington PF, Orenstein DM. The infant seat as treatment for gastroesophageal reflux. N Engl J Med. 1983;309(13):760-763. (Prospective study; 9 patients)
111. Carroll AE, Garrison MM, Christakis DA. A systematic review of nonpharmacological and nonsurgical therapies for gastroesophageal reflux in infants. Arch Pediatr Adolesc Med. 2002;156(2):109-113. (Systematic review; 10 studies, 602 patients)
112. Iacono G, Carroccio A, Cavataio F, et al. Gastroesophageal reflux and cow’s milk allergy in infants: a prospective study. J Allergy Clin Immunol. 1996;97(3):822-827. (Prospective study; 204 patients)
113. Hill DJ, Cameron DJ, Francis DE, et al. Challenge confirmation of late-onset reactions to extensively hydrolyzed formulas in infants with multiple food protein intolerance. J Allergy Clin Immunol. 1995;96(3):386-394. (Prospective study; 18 patients)
114. Sutphen JL, Dillard VL. Effect of ranitidine on twenty-fourhour gastric acidity in infants. J Pediatr. 1989;114(3):472-474. (Prospective study; 33 patients)
115. Orenstein SR, Shalaby TM, Devandry SN, et al. Famotidine for infant gastro-oesophageal reflux: a multi-centre, randomized, placebo-controlled, withdrawal trial. Aliment Pharmacol Ther. 2003;17(9):1097-1107. (Randomized controlled trial; 35 patients)
116. Cucchiara S, Gobio-Casali L, Balli F, et al. Cimetidine treatment of reflux esophagitis in children: an Italian multicentric study. J Pediatr Gastroenterol Nutr. 1989;8(2):150-156. (Prospective study; 32 patients)
117. Orenstein SR, Hassall E, Furmaga-Jablonska W, et al. Multicenter, double-blind, randomized, placebo-controlled trial assessing the efficacy and safety of proton pump inhibitor lansoprazole in infants with symptoms of gastroesophageal reflux disease. J Pediatr. 2009;154(4):514-520. (Multicenter doubleblind randomized placebo-controlled trial; 162 patients)
118. van der Pol RJ, Smits MJ, van Wijk MP, et al. Efficacy of proton- pump inhibitors in children with gastroesophageal reflux disease: a systematic review. Pediatrics. 2011;127(5):925- 935. (Systematic review; 12 studies, 437 patients)
119. Canani RB, Cirillo P, Roggero P, et al. Therapy with gastric acidity inhibitors increases the risk of acute gastroenteritis and community-acquired pneumonia in children. Pediatrics. 2006;117(5):e817-e820. (Prospective study; 186 patients)
120. Guillet R, Stoll BJ, Cotten CM, et al. Association of H2-blocker therapy and higher incidence of necrotizing enterocolitis in very low birth weight infants. Pediatrics. 2006;117(2):e137- 142. (Retrospective chart review; 11,072 patients)
121. Saiman L, Ludington E, Dawson JD, et al. Risk factors for Candida species colonization of neonatal intensive care unit patients. Pediatr Infect Dis J. 2001;20(12):1119-1124. (Prospective study; 2157 patients)
122. Chung EY, Yardley J. Are there risks associated with empiric acid suppression treatment of infants and children suspected of having gastroesophageal reflux disease? Hosp Pediatr. 2013;3(1):16-23. (Systematic review; 14 studies)
123. Hibbs AM, Lorch SA. Metoclopramide for the treatment of gastroesophageal reflux disease in infants: a systematic review. Pediatrics. 2006;118(2):746-752. (Systematic review; 12 studies, 343 patients)
124. Siddiqui MR, Abdulaal Y, Nisar A, et al. A meta-analysis of outcomes after open and laparoscopic Nissen’s fundoplication for gastro-oesophageal reflux disease in children. Pediatr Surg Int. 2011;27(4):359-366. (Meta-analysis; 6 studies, 721 patients)
125. Diaz DM, Gibbons TE, Heiss K, et al. Antireflux surgery outcomes in pediatric gastroesophageal reflux disease. Am J Gastroenterol. 2005;100(8):1844-1852. (Retrospective chart review; 762 patients)
126. Eltayeb AA, Mostafa MM, Ibrahim NH, et al. The role of surgery in management of necrotizing enterocolitis. Int J Surg. 2010;8(6):458-461. (Prospective study; 35 patients)
127. Moss RL, Dimmitt RA, Barnhart DC, et al. Laparotomy versus peritoneal drainage for necrotizing enterocolitis and perforation. N Engl J Med. 2006;354(21):2225-2234. (Randomized controlled trial; 117 patients)
128. Deshpande G, Rao S, Patole S, et al. Updated meta-analysis of probiotics for preventing necrotizing enterocolitis in preterm neonates. Pediatrics. 2010;125(5):921-930. (Meta-analysis; 11 studies, 2176 patients)
129. Aiken JJ, Oldham KT. Inguinal Hernias. In: Kliegman R, Stanton BF, St. Geme JW, et al, eds. Nelson Textbook of Pediatrics. 19th ed. Philadelphia, PA: Elsevier-Saunders; 2011:1362- 1368. (Textbook)
130. Antonoff MB, Kreykes NS, Saltzman DA, et al. American Academy of Pediatrics Section on Surgery hernia survey revisited. J Pediatr Surg. 2005;40(6):1009-1014. (Questionnaire study; 395 participants)
131. Alehossein M, Abdi S, Pourgholami M, et al. Diagnostic accuracy of ultrasound in determining the cause of bilious vomiting in neonates. Iran J Radiol. 2012;9(4):190-194. (Prospective study; 23 patients)
132. Pracros JP, Sann L, Genin G, et al. Ultrasound diagnosis of midgut volvulus: the “whirlpool” sign. Pediatr Radiol. 1992;22(1):18-20. (Prospective cohort study; 24 patients)
133. Chao HC, Kong MS, Chen JY, et al. Sonographic features related to volvulus in neonatal intestinal malrotation. J Ultrasound Med. 2000;19(6):371-376. (Prospective study; 31 patients)
134. Quail MA. Question 2. Is Doppler ultrasound superior to upper gastrointestinal contrast study for the diagnosis of malrotation? Arch Dis Child. 2011;96(3):317-318. (Systematic review; 4 studies, 1025 patients)
135. Silva CT, Daneman A, Navarro OM, et al. Correlation of sonographic findings and outcome in necrotizing enterocolitis. Pediatr Radiol. 2007;37(3):274-282. (Retrospective chart review; 40 patients)
136. Silva CT, Daneman A, Navarro OM, et al. A prospective comparison of intestinal sonography and abdominal radiographs in a neonatal intensive care unit. Pediatr Radiol. 2013;43(11):1453-1463. (Prospective cohort study; 75 patients)
137. Kim WY, Kim WS, Kim IO, et al. Sonographic evaluation of neonates with early-stage necrotizing enterocolitis. Pediatr Radiol. 2005;35(11):1056-1061. (Prospective cohort study; 40 patients)
138. Sivitz AB, Tejani C, Cohen SG. Evaluation of hypertrophic pyloric stenosis by pediatric emergency physician sonography. Acad Emerg Med. 2013;20(7):646-651. (Prospective study; 67 patients)
139. Perry AM, Caviness AC, Allen JY. Characteristics and diagnoses of neonates who revisit a pediatric emergency center. Pediatr Emerg Care. 2013;29(1):58-62. (Retrospective chart review; 147 patients)