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Delayed gastric emptying in infants with gastroesophageal reflux
190
February 1981 TheJournalofPEDIATRICS
Delayed gastric emptying in infants with gastroesophageal reflux The purpose of this study was to investigate the rate of gastric emptying of a liquid meal in young children with symptomatic gastroesophageal reflux o f varying intensity. Twenty-three infants (mean age 7.0 • 1.4 [SEM] months, range 2 to 14 months) were evaluated for reflux by esophageal manometrv, a five-hour p H probe study, and barium swallow. The rate o f gastric emptying was determined by using a liquid meal of 4 ounces of cow milk formula labeled with ..... Tc sulfur colloid. In seven infants with failure to thrive and objective criteria for severe reflux, the mean gastric emptying was 21.3 + 6.4% at one hour. In six infants with reflux and recurrent pulmonary disease, the mean gastric emptying was 19.8 +_ 5.4%. Ten infants with mild reflux, adequate weight gain, and no pulmonary symptoms emptied 44.3 +_ 6.tT/o of formula at one hour, and six normal adults (mean age 28.3 +_ 2 years) emptied 56.2 • 6.5% of formula at one hour. These data suggest that infants with severe GER have significantly delayed gastric emptying, that gastric retention may contribute to the F T T and pulmonary symptoms in these infants, and that abnormal motor fimction of the gastric fundus may be a significant factor in the pathogenesis of gastroesophageal reflux of infancy.
A. Craig Hillemeier, M.D.,* Robert Lange, Ph.D., Richard McCallum, M.D., John Seashore, M.D., and Joyce Gryboski, M.D.,
New Haven, Conn.
GASTROESOPHAGEAL REFLUX of infancy and early childhood is associated with considerable morbidity. The most frequent and severe manifestations are recurrent pulmonary disease and failure to thrive/, ~ Numerous diagnostic studies have been proposed to evaluate the severity of reflux and it has become apparent that the various modifications of the acid reflux (pH probe) test are the most sensitive means to quantitate this entity objectively?" The observation that decreased lower esophageal sphincter pressure may actually be a result of esophagitis From the Departments of Pediatrics, Nuclear Medicine, Internal Medicine, and Pediatric Surgery, Yale University School o f Medicine and Yale-New Haven Medical Center. Supported in part by National Institutes o f Health grant No. 00125. Dr Hillemeier is a recipient of National Research Service award No F32 HD05892-0131. *Reprint address: Department of Pediatrics, Yale University School of Medicine, 333 Cedar St., New Haven, CT 06510.
Vol. 98, No. 2, pp. 190-193
rather than its cause ~ has cast doubt that the sphincter is the major anatomic determinant of gastroesophageal reflux. The present study was designed to evaluate another aspect of motor function of the upper gastrointestinal tract of infants with reflux, namely, gastric emptying. Abbreviations used GER: gastroesophageal reflux FTT: failure to thrive RT: refluxtime LESP: loweresophageal sphincter pressure OD: outer diameter METHODS Twenty-three children less than 2 years of age were investigated for symptoms suggestive of GER. All those in whom anatomic obstruction or metabolic disease was responsible for the symptoms were excluded from the study. Group A consisted of seven children (mean age 7.2 months ___ 1.5 SEM, and range 3 to 13 months) with severe vomiting who were failing to thrive, with weights
0022-3476/81/020190+04500.40/0 9 1981 The C. V. Mosby Co.
Volume 98 Number 2
Delayed gastric emptying with gastroesophageal reflux
19 1
Table I. Results of five-hour pH probe test in infants with GER
Group
No. patients
>8 rain
x Longest episode of reflux (olin)
A. Failure to thrive B. Pulmonary abnormalities C. Reflux only
7 6 10
7/7 6/6 I / 10
16 • 2.5* 21.7 • 3.7 5.9 +- 1.4
Longest ep&ode
of reflux
Reflux time 2 hr postprandial I%)
Reflux lime while nothing (by mouth) (%)
38.4 -+ 3.7"[" 49.5 • 5.0t 16.2 +-- 3.0t
13% + 4.4 8.1 --+ 9.4 5.8 --+ 3.3
*Mean + SEM. tA--* C P < 0.05; B---~C P < 0.05. less than the third percentile. Group B consisted of six children (mean age 8.8 months • 1.9 SEM, range 3 to 14 months) with recurrent pulmonary disease and severe reflux symptoms. Group C consisted of ten children (mean age 6.8 months • 1.3 SEM, range 2 to 14 months) with normal growth but with histories suggesting mildto-moderate regurgitation; none had pulmonary symptoms. All children were observed in the hospital for a minimum of three days and had esophageal manometry, five-hour pH probe studies, barium swallow with water siphon test, and gastric emptying studies. Six normal adults (three men, three women; mean age 28.3 y e a r s _ 2.3 SEM, range 20 to 36 years) were screened by history and found to be free of symptoms of GER. Gastric emptying studies were performed in an identical manner. No subjects were taking medication. All studies were undertaken in a prospective fashion with approval of the Human Investigation Committee. Esophageal manometry was performed using a triple lumen polyvinyl tube assembly (individual OD 1.2 mm) with pressure sensing orifices perfused with distilled water at 0.5 ml/minute by pneumatic-hydraulic capillary infusion system" which has a response of greater than 800 mm Hg/sec. Pressures were transmitted to transducers (Statham Instruments, Inc., Oxnard, CA.) connected to an amplifying recording system (Beckman Instruments, Inc., Mountainside, N J). The station pull-through technique was utilized to determine lower esophageal sphincter pressure. All patients were studied without sedation. The pH probe studies were performed with a microelectrode No. 1506 (Microelectrodes, Inc., Grenadier, NH) of 1.6 inm OD placed 13% of the distance orad from the manometrically defined lower esophageal sphincter. Measurements were determined during a two-hour period after fasting for three hours, and for two hours after drinking 4 ounces of apple juice (pH 4). Reflux time was calculated as the percent of time the intraluminal pH was below four. The longest period- of time in which the pH was below 4 was noted. Monitoring began 15 minutes after juice consumption. In the fasting state the children were studied in the supine position, but while drinking
and for two hours afterward, they were sitting at a 45 degree angle. Barium swallow was performed while the children were supine and rolled from side to side. The water siphon test was performed with the children in the right lateral position. (After the stomach was distended by barium the infants were fed water in an effort to induce gastroesophageal reflux.) Gastric emptying studies were performed after a threehour fast. The meal consisted of 4 ounces of a standard cow milk formula to which 100 microcuries of .......Tc sulfur colloid was added. All subjects were placed in a supine position within five minutes of initiating ingestion. They were maintained in the same position for 60 minutes and imaging of the upper gastrointestinal tract was performed using a gamma camera and dedicated computer. An area of interest defining the stomach was used to obtain counts of "~mTc label in the stomach as a function of time from the computerized data. Gastric emptying was expressed as a percentage
(
CTo - CTt CTo
x 100),
where CTt is the count rate of ~"'mTc at any time in the stomach after correction for ~'"mTcdecay, and CTo is the initial count rate of isotope in the stomach. 7 All results are expressed as a mean value • the standard error of the mean. All statistical analyses were performed with the two-sample Student t test. RESULTS All infants in both the FTT and recurrent pulmonary disease groups had significantly more reflux time during the two-hour postprandial period than did the group with mild reflux (Table I). Each of these infants had an episode of a reflux longer than eight minutes, whereas only one of ten with mild reflux had such a prolonged episode. Esophageal manometrics demonstrated that three of 13 infants with FTT or pulmonary disease had a LESP of < 10 mm Hg, and no infant with mild reflux had a LESP
19 2
Hillemeier et al.
The Journal of Pediatrics February 1981
Table I1. Lower esophageal sphincter pressure and barium swallow results in infants with GER
Group
No. patients
LESP (ram Hg)
A. Failure to thrive B. Pulmonary abnormalities C. Reflux only
7 6 10
14.5 • 3,6 16 • 2,6 20.4 • 5.2
LESP <10
Barium swallow (+) without H,,O siphon
Barium swallow (+) with H,O
Total positive barium swallow
2/7 1/6 0/9
4/6 4/6 3/10
6/7 6/6 5/10
6/7 6/6 ~/10
4, m,nJ
60m,o
Table IlL Percentage of gastric emptying during first hour (%mean +_ SEM) after ingestion of cow milk formula
I A. B. C. D.
Failure to thrive Pulmonary abnormalities Reflux only Adult controls
N~ 7 6 10 6
I
,,m,n 11.5 • 10.4 _ 12.1 • 10.6 ~
3.4 3.4 3.9 4.2
-1
I 15.6 + 13.8 + 30.7 • 28.1 •
5.2 4.6 4.3 5.7
19.4 • 6.2 17.9 _+ 5.3 35.3 • 5.8 44.2 _+ 6.3
21.3 • 19,8 • 44.3 • 56.2 •
6.4* 5,4* 6* 7.5*
*A---~C P<: 0.05; B--~C P < 0.05; A--*D P ,< 0.01; B---*D P -< 0.01. below 12 mm Hg. Barium swallow with water siphon test was positive in 12 of 13 patients with FTT and recurrent pulmonary disease (Table II). Five of these infants had reflux of barium to the hypopharynx, whereas none of those with mild reflux had this finding. The gastric emptying rates at one hour in infants with FTT and recurrent pulmonary disease were 19.8 and 21.3%, respectively. These rates were significantly slower (P -< 0.05) than that of 44.3% in infants with mild disease. More significant (P < 0.01) was the difference between those infants and the normal adult controls, whose gastric emptying at one hour was 56,0% (Table III). The 14 infants who had at least one episode of reflux longer than eight minutes had gastric emptying of 19.5% in one hour, which is significantly slower (P < 0.05) than the gastric emptying of 48.1% measured in the nine patients who had no reflux episode of greater than eight minutes. Twelve of 14 infants with episodes of reflux longer than eight minutes had gastric emptying of less than 30% at one hour, whereas only one of nine with all episodes of reflux less than eight minutes had gastric emptying o f less than 30% (Means: 19.5 +_ 4.2% vs 48.1 +_ 5.3%, P < 0.05). DISCUSSION Our data indicate that infants who have the serious sequelae of GER are likely to have significantly delayed gastric emptying of a liquid meal compared to those with mild GER or to adults who have no symptoms of GER. GER of infancy is distinct from that of older children and adults since it occurs at a time when the primary nutritional source is a liquid and since the majority of cases respond to medical therapy and do not recur? Infants
with severe reflux have been shown to have abnormal esophageal peristaltic function in the distal esophagus. '. " Our study suggests that delayed gastric emptying may play a significant role in the pathogenesis of reflux in these infants and provides evidence that, in many infants, GER is part of a disturbance in intestinal motility which extends distal to the esophagus. Gastric emptying has previously been assessed by intubation and withdrawal techniques, contrast roentgenographs, and more recently by radionuclide scanning. Contrast studies using barium have proven limited in their usefulness because of their nonphysiologic nature and the inability to quantitate the amount emptied from the stomach. In adults, intubation techniques have proven extremely useful in delineating factors which control gastric emptying, such as osmolality, pH, fat, and possibly amino acids. Increased osmolality, decreased pH, and increased fat content or elongation of the carbon chain on the fatty acid will decrease gastric emptying?T M Studies of gastric emptying in the human infant have centered around ways to improve alimentation. The effect of increased osmolality in retarding gastric emptying has been shown by withdrawal techniques comparing the effects of 10'7odextrose to 5% dextrose feeds2 ~ Gestational age has proven to be a more important factor in determining gastric emptying than birth weight"; preterm infants have delayed gastric emptying, and a study suggests that breast milk empties more rapidly than infant formula. 15 The finding that liquid meals empty significantly faster than solid meals has led to the observation that the fundus is of primary importance in the emptying of liquids (by regulation of a gastroduodenal pressure gradient) and the antrum is of more importance in the emptying of sol-
Volume 98 Number 2
ids.,~. 17 Other experiments have confirmed that in adult dogs liquids are rapidly emptied and solids are broken into small particles and then emptied much in the same way as liquids. '~ Gastric emptying has recently been studied in adults with gastroesophageal reflux utilizing a semisolid meal and a g a m m a camera technique through the use of a gamma counter and radioisotope technique. A significant proportion of adults with gastroesophageal reflux do have delayed gastric emptying of this mixed solid-liquid meal? 9 Metoclopramide, a drug which enhances gastric emptying, ~~ has been shown to provide symptomatic relief in adults with gastroesophageal reflux. -~1 The delayed gastric emptying noted in our infants with severe complications of G E R has several possible explanations. Our liquid meal consisted of 1.5 gm of protein per 100 ml, 3.7 gm of fat per 100 ml, and 7 gm of carbohydrate per 100 ml (Enfamil, Mead Johnson Laboratories), and it is possible that an abnormality in the various duodenal receptors that control gastric emptying may exist. One indication that different regulatory factors may be operational in the infant comes from Pascale et al -~2 who demonstrated that the length of the fatty acid side-chain seems to have no effect on gastric emptying during infancy. This contrasts with the adult in whom mediumchain triglycerides slow gastric emptying. ~3 A developmental malfunction of the gastric musculature may explain delayed gastric emptying; Behar et al 2~ have suggested that adults with reflux esophagitis have defective antral contractility. Tornwall et al ~ have shown radiographically that the stomach of the normal newborn infant does not have a normal peristaltic wave and that it tends to perform in one tonic contraction until several weeks of age. An inability of the fundus to generate sufficient tone to result in an adequate gastroduodenal gradient may retard gastric emptying. Further studies are indicated to define upper gastrointestinal development in infants and children and to evaluate the long-term implications of delayed gastric emptying associated with gastroesophageal reflux early in life.
Delayed gastric emptying with gastroesophageal reflux
5.
6.
7. 8. 9.
10,
11.
12.
13. 14. 15. 16.
17.
18. 19.
20. 21.
22. REFERENCES 1. Euler AE, and Ament ME: Value of esophageal manometric studies in gastroesophageal reflux of infancy, Pediatrics 59:58, 1977. 2. Darius O, Casar C, Larrain A, and Pope CE II: Esophageal reflux-an unrecognized cuase of recurrent obstructive bronchitis in children, J PEOIATR89:220, 1976. 3. Arasu TS, Wyllie R, Fitzgerald JF, Franken EA, Siddigui AR, Lenman GA, Eigen H, and Grosfeld JL: Gastroesophageal reflux in infants and children-comparative accuracy of diagnostic methods, J PEDIATR96:798, 1980. 4. Sondheimer JM: Continuous monitoring of distal esopha-
23.
24.
25.
19 3
geal pH: A diagnostic test for gastroesophageal reflux in infants, J PEDIATR96:804, 1980. Biancani P, Dodds J, Storer E, Selling J, and McCallum R: Acute experimental esophagitis affects mechanical properties of the lower esophageal sphincter, Gastroenterology 76:1100, 1979 (abstr). Arndoffer RC, Steff J J, Dodds W J, et al: Improved infusion system for intraluminal esophageal manometry, Gastroenterology 73:23, 1977. Chandheim K: Use of ~"mTc-DTPA for measuring gastric emptying time. J Nucl Med 15:391, 1974. Gryboski J: Gastrointestinal problems in the infant, Philadelphia, 1975, WB Saunders Company, pp 92-94. Hillemeier AC, Gryboski JD, and McCallum R: Esophageal manometry and physiological pH probe studies in the evaluation of infants with GER, Pediatr Res 14:501, 1980 (abstr). Hunt JN, and Pathak JD: The osmotic effects of some simple molecules and ions on gastric emptying, J Physiol 154:254, 1968. Hunt JN, and Knox MT: The slowing of gastric emptying by four strong acids and three weak ones, J Physiol 201:161, 1969. Hunt JN, and Knox MT: A relation between the chain length of fatty acids and the slowing of gastric emptying, J Physiol 194:327, 1968. Husband J, and Husband P: Gastric emptying of water and glucose solutions in the newborn, Lancet 1:409, 1969. Gupta M, and Brans YW: Gastric retention in neonates, Pediatrics 62:26, 1978. Cavell B: Gastric emptying in preterm infants, Acta Paediatr Scand 68:725, 1979. Dozois RR, Kelly KA, and Code CF: Effects of distal antrectomy on gastric emptying of liquids and solids, Gastroenterology 61:675, 1971. Wilbur BG, and Kelly KA: Effect of proximal gastric, complete gastric, and truncal vagotomy on canine gastric electric activity, motility and emptying, An Surg 178:295, 1973. Hinder RA, and Kelly KA: Canine gastric emptying of solids and liquids, Am J Physiol 233:E335, 1977. McCallum RW, Berkowitz DM, and Lerner E: Gastric emptying in patients with gastroesophageal reflux, Gastroenterology (in press). Cornell AM, and George JD: Effects ofmetoclopramide on gastric function in man, Gut 10:673, 1969. McCallum RW, Ippoliti AF, Cooney C, and Sturdevant RAL: A controlled trial of metoclopramide on symptomatic gastroesophageal reflux, N Engl J Med 27:354, 1977. Pascale JA, Mims LC, Greenberg MG, and Alexander JB: Gastric response in low birth weight infants fed various formulas, Biol Neonate 34:150, 1978. Feldman M, Shapiro BJ, and Berkowitz D: Comparitive effects of medium chain and long chain triglycerides on the rate of gastric emptying, Gastroenterology 60:774, 1971. Behar J, and Ramsby G: Gastric emptying and antral motility in reflux esophagitis, Gastroenterology 74:253, 1978. Tornwall L, Lind J, Peltonen T, and Wegebis C: The gastrointestinal tract of the newborn, Ann Paediatr Finn 4:219, 1958.
February 1981 TheJournalofPEDIATRICS
Delayed gastric emptying in infants with gastroesophageal reflux The purpose of this study was to investigate the rate of gastric emptying of a liquid meal in young children with symptomatic gastroesophageal reflux o f varying intensity. Twenty-three infants (mean age 7.0 • 1.4 [SEM] months, range 2 to 14 months) were evaluated for reflux by esophageal manometrv, a five-hour p H probe study, and barium swallow. The rate o f gastric emptying was determined by using a liquid meal of 4 ounces of cow milk formula labeled with ..... Tc sulfur colloid. In seven infants with failure to thrive and objective criteria for severe reflux, the mean gastric emptying was 21.3 + 6.4% at one hour. In six infants with reflux and recurrent pulmonary disease, the mean gastric emptying was 19.8 +_ 5.4%. Ten infants with mild reflux, adequate weight gain, and no pulmonary symptoms emptied 44.3 +_ 6.tT/o of formula at one hour, and six normal adults (mean age 28.3 +_ 2 years) emptied 56.2 • 6.5% of formula at one hour. These data suggest that infants with severe GER have significantly delayed gastric emptying, that gastric retention may contribute to the F T T and pulmonary symptoms in these infants, and that abnormal motor fimction of the gastric fundus may be a significant factor in the pathogenesis of gastroesophageal reflux of infancy.
A. Craig Hillemeier, M.D.,* Robert Lange, Ph.D., Richard McCallum, M.D., John Seashore, M.D., and Joyce Gryboski, M.D.,
New Haven, Conn.
GASTROESOPHAGEAL REFLUX of infancy and early childhood is associated with considerable morbidity. The most frequent and severe manifestations are recurrent pulmonary disease and failure to thrive/, ~ Numerous diagnostic studies have been proposed to evaluate the severity of reflux and it has become apparent that the various modifications of the acid reflux (pH probe) test are the most sensitive means to quantitate this entity objectively?" The observation that decreased lower esophageal sphincter pressure may actually be a result of esophagitis From the Departments of Pediatrics, Nuclear Medicine, Internal Medicine, and Pediatric Surgery, Yale University School o f Medicine and Yale-New Haven Medical Center. Supported in part by National Institutes o f Health grant No. 00125. Dr Hillemeier is a recipient of National Research Service award No F32 HD05892-0131. *Reprint address: Department of Pediatrics, Yale University School of Medicine, 333 Cedar St., New Haven, CT 06510.
Vol. 98, No. 2, pp. 190-193
rather than its cause ~ has cast doubt that the sphincter is the major anatomic determinant of gastroesophageal reflux. The present study was designed to evaluate another aspect of motor function of the upper gastrointestinal tract of infants with reflux, namely, gastric emptying. Abbreviations used GER: gastroesophageal reflux FTT: failure to thrive RT: refluxtime LESP: loweresophageal sphincter pressure OD: outer diameter METHODS Twenty-three children less than 2 years of age were investigated for symptoms suggestive of GER. All those in whom anatomic obstruction or metabolic disease was responsible for the symptoms were excluded from the study. Group A consisted of seven children (mean age 7.2 months ___ 1.5 SEM, and range 3 to 13 months) with severe vomiting who were failing to thrive, with weights
0022-3476/81/020190+04500.40/0 9 1981 The C. V. Mosby Co.
Volume 98 Number 2
Delayed gastric emptying with gastroesophageal reflux
19 1
Table I. Results of five-hour pH probe test in infants with GER
Group
No. patients
>8 rain
x Longest episode of reflux (olin)
A. Failure to thrive B. Pulmonary abnormalities C. Reflux only
7 6 10
7/7 6/6 I / 10
16 • 2.5* 21.7 • 3.7 5.9 +- 1.4
Longest ep&ode
of reflux
Reflux time 2 hr postprandial I%)
Reflux lime while nothing (by mouth) (%)
38.4 -+ 3.7"[" 49.5 • 5.0t 16.2 +-- 3.0t
13% + 4.4 8.1 --+ 9.4 5.8 --+ 3.3
*Mean + SEM. tA--* C P < 0.05; B---~C P < 0.05. less than the third percentile. Group B consisted of six children (mean age 8.8 months • 1.9 SEM, range 3 to 14 months) with recurrent pulmonary disease and severe reflux symptoms. Group C consisted of ten children (mean age 6.8 months • 1.3 SEM, range 2 to 14 months) with normal growth but with histories suggesting mildto-moderate regurgitation; none had pulmonary symptoms. All children were observed in the hospital for a minimum of three days and had esophageal manometry, five-hour pH probe studies, barium swallow with water siphon test, and gastric emptying studies. Six normal adults (three men, three women; mean age 28.3 y e a r s _ 2.3 SEM, range 20 to 36 years) were screened by history and found to be free of symptoms of GER. Gastric emptying studies were performed in an identical manner. No subjects were taking medication. All studies were undertaken in a prospective fashion with approval of the Human Investigation Committee. Esophageal manometry was performed using a triple lumen polyvinyl tube assembly (individual OD 1.2 mm) with pressure sensing orifices perfused with distilled water at 0.5 ml/minute by pneumatic-hydraulic capillary infusion system" which has a response of greater than 800 mm Hg/sec. Pressures were transmitted to transducers (Statham Instruments, Inc., Oxnard, CA.) connected to an amplifying recording system (Beckman Instruments, Inc., Mountainside, N J). The station pull-through technique was utilized to determine lower esophageal sphincter pressure. All patients were studied without sedation. The pH probe studies were performed with a microelectrode No. 1506 (Microelectrodes, Inc., Grenadier, NH) of 1.6 inm OD placed 13% of the distance orad from the manometrically defined lower esophageal sphincter. Measurements were determined during a two-hour period after fasting for three hours, and for two hours after drinking 4 ounces of apple juice (pH 4). Reflux time was calculated as the percent of time the intraluminal pH was below four. The longest period- of time in which the pH was below 4 was noted. Monitoring began 15 minutes after juice consumption. In the fasting state the children were studied in the supine position, but while drinking
and for two hours afterward, they were sitting at a 45 degree angle. Barium swallow was performed while the children were supine and rolled from side to side. The water siphon test was performed with the children in the right lateral position. (After the stomach was distended by barium the infants were fed water in an effort to induce gastroesophageal reflux.) Gastric emptying studies were performed after a threehour fast. The meal consisted of 4 ounces of a standard cow milk formula to which 100 microcuries of .......Tc sulfur colloid was added. All subjects were placed in a supine position within five minutes of initiating ingestion. They were maintained in the same position for 60 minutes and imaging of the upper gastrointestinal tract was performed using a gamma camera and dedicated computer. An area of interest defining the stomach was used to obtain counts of "~mTc label in the stomach as a function of time from the computerized data. Gastric emptying was expressed as a percentage
(
CTo - CTt CTo
x 100),
where CTt is the count rate of ~"'mTc at any time in the stomach after correction for ~'"mTcdecay, and CTo is the initial count rate of isotope in the stomach. 7 All results are expressed as a mean value • the standard error of the mean. All statistical analyses were performed with the two-sample Student t test. RESULTS All infants in both the FTT and recurrent pulmonary disease groups had significantly more reflux time during the two-hour postprandial period than did the group with mild reflux (Table I). Each of these infants had an episode of a reflux longer than eight minutes, whereas only one of ten with mild reflux had such a prolonged episode. Esophageal manometrics demonstrated that three of 13 infants with FTT or pulmonary disease had a LESP of < 10 mm Hg, and no infant with mild reflux had a LESP
19 2
Hillemeier et al.
The Journal of Pediatrics February 1981
Table I1. Lower esophageal sphincter pressure and barium swallow results in infants with GER
Group
No. patients
LESP (ram Hg)
A. Failure to thrive B. Pulmonary abnormalities C. Reflux only
7 6 10
14.5 • 3,6 16 • 2,6 20.4 • 5.2
LESP <10
Barium swallow (+) without H,,O siphon
Barium swallow (+) with H,O
Total positive barium swallow
2/7 1/6 0/9
4/6 4/6 3/10
6/7 6/6 5/10
6/7 6/6 ~/10
4, m,nJ
60m,o
Table IlL Percentage of gastric emptying during first hour (%mean +_ SEM) after ingestion of cow milk formula
I A. B. C. D.
Failure to thrive Pulmonary abnormalities Reflux only Adult controls
N~ 7 6 10 6
I
,,m,n 11.5 • 10.4 _ 12.1 • 10.6 ~
3.4 3.4 3.9 4.2
-1
I 15.6 + 13.8 + 30.7 • 28.1 •
5.2 4.6 4.3 5.7
19.4 • 6.2 17.9 _+ 5.3 35.3 • 5.8 44.2 _+ 6.3
21.3 • 19,8 • 44.3 • 56.2 •
6.4* 5,4* 6* 7.5*
*A---~C P<: 0.05; B--~C P < 0.05; A--*D P ,< 0.01; B---*D P -< 0.01. below 12 mm Hg. Barium swallow with water siphon test was positive in 12 of 13 patients with FTT and recurrent pulmonary disease (Table II). Five of these infants had reflux of barium to the hypopharynx, whereas none of those with mild reflux had this finding. The gastric emptying rates at one hour in infants with FTT and recurrent pulmonary disease were 19.8 and 21.3%, respectively. These rates were significantly slower (P -< 0.05) than that of 44.3% in infants with mild disease. More significant (P < 0.01) was the difference between those infants and the normal adult controls, whose gastric emptying at one hour was 56,0% (Table III). The 14 infants who had at least one episode of reflux longer than eight minutes had gastric emptying of 19.5% in one hour, which is significantly slower (P < 0.05) than the gastric emptying of 48.1% measured in the nine patients who had no reflux episode of greater than eight minutes. Twelve of 14 infants with episodes of reflux longer than eight minutes had gastric emptying of less than 30% at one hour, whereas only one of nine with all episodes of reflux less than eight minutes had gastric emptying o f less than 30% (Means: 19.5 +_ 4.2% vs 48.1 +_ 5.3%, P < 0.05). DISCUSSION Our data indicate that infants who have the serious sequelae of GER are likely to have significantly delayed gastric emptying of a liquid meal compared to those with mild GER or to adults who have no symptoms of GER. GER of infancy is distinct from that of older children and adults since it occurs at a time when the primary nutritional source is a liquid and since the majority of cases respond to medical therapy and do not recur? Infants
with severe reflux have been shown to have abnormal esophageal peristaltic function in the distal esophagus. '. " Our study suggests that delayed gastric emptying may play a significant role in the pathogenesis of reflux in these infants and provides evidence that, in many infants, GER is part of a disturbance in intestinal motility which extends distal to the esophagus. Gastric emptying has previously been assessed by intubation and withdrawal techniques, contrast roentgenographs, and more recently by radionuclide scanning. Contrast studies using barium have proven limited in their usefulness because of their nonphysiologic nature and the inability to quantitate the amount emptied from the stomach. In adults, intubation techniques have proven extremely useful in delineating factors which control gastric emptying, such as osmolality, pH, fat, and possibly amino acids. Increased osmolality, decreased pH, and increased fat content or elongation of the carbon chain on the fatty acid will decrease gastric emptying?T M Studies of gastric emptying in the human infant have centered around ways to improve alimentation. The effect of increased osmolality in retarding gastric emptying has been shown by withdrawal techniques comparing the effects of 10'7odextrose to 5% dextrose feeds2 ~ Gestational age has proven to be a more important factor in determining gastric emptying than birth weight"; preterm infants have delayed gastric emptying, and a study suggests that breast milk empties more rapidly than infant formula. 15 The finding that liquid meals empty significantly faster than solid meals has led to the observation that the fundus is of primary importance in the emptying of liquids (by regulation of a gastroduodenal pressure gradient) and the antrum is of more importance in the emptying of sol-
Volume 98 Number 2
ids.,~. 17 Other experiments have confirmed that in adult dogs liquids are rapidly emptied and solids are broken into small particles and then emptied much in the same way as liquids. '~ Gastric emptying has recently been studied in adults with gastroesophageal reflux utilizing a semisolid meal and a g a m m a camera technique through the use of a gamma counter and radioisotope technique. A significant proportion of adults with gastroesophageal reflux do have delayed gastric emptying of this mixed solid-liquid meal? 9 Metoclopramide, a drug which enhances gastric emptying, ~~ has been shown to provide symptomatic relief in adults with gastroesophageal reflux. -~1 The delayed gastric emptying noted in our infants with severe complications of G E R has several possible explanations. Our liquid meal consisted of 1.5 gm of protein per 100 ml, 3.7 gm of fat per 100 ml, and 7 gm of carbohydrate per 100 ml (Enfamil, Mead Johnson Laboratories), and it is possible that an abnormality in the various duodenal receptors that control gastric emptying may exist. One indication that different regulatory factors may be operational in the infant comes from Pascale et al -~2 who demonstrated that the length of the fatty acid side-chain seems to have no effect on gastric emptying during infancy. This contrasts with the adult in whom mediumchain triglycerides slow gastric emptying. ~3 A developmental malfunction of the gastric musculature may explain delayed gastric emptying; Behar et al 2~ have suggested that adults with reflux esophagitis have defective antral contractility. Tornwall et al ~ have shown radiographically that the stomach of the normal newborn infant does not have a normal peristaltic wave and that it tends to perform in one tonic contraction until several weeks of age. An inability of the fundus to generate sufficient tone to result in an adequate gastroduodenal gradient may retard gastric emptying. Further studies are indicated to define upper gastrointestinal development in infants and children and to evaluate the long-term implications of delayed gastric emptying associated with gastroesophageal reflux early in life.
Delayed gastric emptying with gastroesophageal reflux
5.
6.
7. 8. 9.
10,
11.
12.
13. 14. 15. 16.
17.
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