PEDIATRICS Vol. 120 No. 5 November 2007, pp. 946-949 (doi:10.1542/peds.2007-1146)
ARTICLE |
Are We Overprescribing Antireflux Medications for Infants With Regurgitation?
Pediatric Specialty Center, West Jefferson Medical Center, New Orleans, Louisiana
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ABSTRACT |
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 TOP ABSTRACT METHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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OBJECTIVE. Our goal was to evaluate the diagnosis and treatment of infants with persistent regurgitation who were referred to a pediatric gastroenterology service.
METHODS. The records of 64 infants with persistent regurgitation and without any neurodevelopmental abnormalities, underlying illness, or cigarette smoke exposure were evaluated for diagnostic workup and treatment. Forty-four infants underwent extended esophageal pH monitoring.
RESULTS. Only 8 of 44 pH studies showed abnormal acid reflux. Forty-two of these 44 infants were already on antireflux medications. Other etiologies included hypertrophic pyloric stenosis (4) and renal tubular acidosis (1). Discontinuation of medication did not result in worsening of symptoms in most infants with normal pH studies.
CONCLUSIONS. The majority of infants who were prescribed antireflux drugs did not meet diagnostic criteria for gastroesophageal reflux disease.
Key Words: gastroesophageal reflux • infant
Abbreviations: GERD—gastroesophageal reflux disease
During 1998–1999, infants with regurgitation accounted for 14% of our total patient referrals, and 40% of these infants were already on anti–gastroesophageal reflux disease (GERD) medications and/or an extensively hydrolyzed formula. During 2006–2007, such infants accounted for 23% of all referrals, and 90% of them were already receiving anti-GERD medications and/or extensively hydrolyzed formulas. This shift prompted us to evaluate the diagnosis and treatment of infants with regurgitation.
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METHODS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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We evaluated the medical charts of infants who were referred to the Pediatric Specialty Center at West Jefferson Medical Center during a 3-year period for symptoms of regurgitation lasting for >2 weeks. The following groups of infants were excluded: (1) those who were born preterm or small for gestational age; (2) those with any underlying illness, especially diarrhea; (3) those with neurodevelopmental abnormalities or dysmorphic features; (4) those with a lower respiratory tract illness; (5) those who were exposed directly or indirectly to cigarette smoke; and (6) those whose care was provided by anyone other than the mother.
For the sake of studying a homogeneous population with comparable growth patterns, energy intake and maturity, we included only those infants who were born at term, appropriate for gestational age, and of normal neurodevelopmental status. Cigarette smoke exposure and lower respiratory tract illnesses, especially asthma, can exacerbate reflux, so such children were excluded to maintain consistency in clinical status. For achieving reliability in assessing oral intake and formula preparation, infants who were provided care by caregivers other than their mother were excluded. Chart reviews and data collection were performed after approval was obtained from the institutional review board. The data were gathered on a standardized form designed in our clinic and used to collect information on all patients as part of our ongoing research on GERD.
The diagnostic tests that were performed either before or after referral were radiology, ultrasonography, extended esophageal pH monitoring, blood chemistry, and blood gas analysis. The pH study was performed after withdrawal of the prokinetics or H2-receptor antagonists for at least 5 days and proton-pump inhibitors for at least 10 days. A pH of <4 in the distal esophagus for >5% of the time was regarded as an abnormal study and a marker of GERD. The upper gastrointestinal barium studies were used only for diagnosing structural abnormalities, and any mention of reflux by the radiologist was not considered diagnostic of GERD.
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RESULTS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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Ninety-two infants were identified, and 64 fulfilled all entry criteria. The main reasons for exclusion were caregivers other than the mother (n = 8), shorter duration of symptoms (n = 3), exposure to cigarette smoke (n = 3), underlying illness (n = 3), prematurity (n = 2), and multiple factors (n = 9). We received referrals from 132 physicians, and 42 of them accounted for referring 84% of the infants included in this study. The clinical presentation, patient details, and results of diagnostic tests are given in Table 1.
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Most (89%) infants were gaining weight at a rate of >15 g/day. Feeding >504 kJ/kg per day (>120 kcal/kg per day) was noted in 40.6% infants. Thickening of feeds (81.3%) and antireflux medication (90.6%) were common interventions used for control of symptoms before referral. Dry rice cereal (84.6%) and dry oatmeal cereal (15.4%) were the 2 thickening agents used. Inappropriate thickening with <1 tablespoon of cereal per ounce of formula was very common (70.3%). In 85.9% of the infants, the formula had been changed in the 2 weeks before the referral. A completely or extensively hydrolyzed formula was commonly used (60.9%).
Diagnostic tests yielded abnormal results in 13 (20.3%) infants and were as follows: (1) GERD (n = 8) based on abnormal esophageal pH with or without impedance studies; (2) hypertrophic pyloric stenosis (n = 4) based on ultrasonography; (3) metabolic alkalosis (n = 4) and metabolic acidosis (n = 1) based on blood gas analysis; the 4 infants with metabolic alkalosis had hypertrophic pyloric stenosis, and the 1 with metabolic acidosis had renal tubular acidosis; and (4) gastric outlet obstruction (n = 2) based on radiology; both had hypertrophic pyloric stenosis.
A total of 44 extended esophageal pH/impedance monitoring studies were performed on 44 infants. Forty-two of these 44 infants were already on anti-GERD medications. The results of only 8 (18.2%) of 44 of these studies were abnormal. Of the remaining 20 infants who did not get a pH-probe study, 4 had pyloric stenosis and 1 had renal tubular acidosis. The 15 remaining infants were thriving and had only regurgitation without any accompanying symptoms and were expected to have a low probability for an abnormal pH-probe study and so did not get one.
Regurgitation alone as the presenting symptom was more common in infants with a normal pH-probe study (69%) as compared with those with an abnormal pH-probe study (25%). Seven infants had weight gains of <15 g/day, and these included the 4 infants with pyloric stenosis, 1 with renal tubular acidosis, and 2 others with abnormal pH-probe study results.
As part of our standard of care, follow-up of all patients is through clinic visits, e-mails, and telephone calls. All infants included in this study had a follow-up scheduled for 1 to 4 weeks after their evaluation. The 8 infants with abnormal pH-probe–study results and 1 infant with renal tubular acidosis stayed on treatment with anti-GERD medications. Four infants underwent pyloromyotomy for hypertrophic pyloric stenosis. After surgery, 1 infant became asymptomatic and did not require any medication. Of the remaining 3 infants, 2 had persistent regurgitation postoperatively and were treated with metoclopramide and unthickened feeds for presumed delayed gastric emptying, and 1 infant with regurgitation and irritability was treated with unthickened feeds along with metoclopramide and nizatidine for a clinical diagnosis of GERD and delayed gastric emptying.
All anti-GERD medications were withdrawn in the remaining 51 infants, but they continued on their existing formula. The parents of all of these infants were counseled on appropriate thickening and intake of formula as well as positioning. There was no follow-up for 6 of 51 infants, 6 infants showed worsening of symptoms, and 39 had improvement/no worsening of symptoms.
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DISCUSSION |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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On the basis of the data of this study, we believe that most infants who had reflux symptoms and were referred to our pediatric specialty service did not meet the strict diagnostic criteria for GERD yet had received some anti-GERD medications. Withdrawal of the medications did not result in any worsening in the majority of these infants. Only
20% of the infants in the study had evidence of an underlying pathology to explain their symptoms, such as GERD, pyloric stenosis, or renal tubular acidosis. This is similar to the findings of Condino et al,1 who reported the occurrence of normal pH-probe and impedance studies in most infants who were referred for reflux symptoms. Overfeeding and underthickening of the formula were noted frequently. Feeding intakes of >504 kJ/kg per day (>120 kcal/kg per day) were common and could have contributed to the symptoms. Thickening of feeds was commonly advised, but concomitant reduction in the volume was not made, resulting in excessive volume/energy intake. Overfeeding results in gastric distension that is a precipitating factor for inappropriate relaxation of lower esophageal sphincter, a hallmark of reflux. We previously described the efficacy and composition of smaller volume thickened feeds that will reduce the frequency of reflux by 50%.2 Such feeds need to be small volume and thickened with 1 tablespoon of dry rice cereal per ounce of formula, keeping in mind not only the volume but also the total energy intake for weight and age. Similar findings also were reported by Orenstein et al,3 who used 1 tablespoon of rice cereal per ounce of formula. In our patients, acid-suppressing drugs were used frequently for reflux symptoms, although no objective diagnosis of GERD was established. The persistence of regurgitation despite anti-GERD medications was no surprise because these drugs are unlikely to reduce the frequency of reflux.4 Moreover, the simple use of appropriate conservative therapy alone instituted via a telephone triage system can lead to improvement of symptoms in 24% of such infants.5 It was interesting to note that for infants with abnormal pH-probe results, the presenting complaints often included other symptoms in addition to regurgitation, whereas for infants with normal pH-probe results, regurgitation alone was usually the only presenting symptom. Also, a weight gain of <15 g/day was always associated with an underlying pathology such as pyloric stenosis, renal tubular acidosis, or GERD.
In evaluating our results, 2 concerns should be kept in mind. First, the patients in this study were a select population of infants who had persistence of symptoms and were referred for subspecialist care. Second, there may be regional differences in the way certain conditions are managed by primary care physicians.
This early use of anti-GERD medications in infants with regurgitation could be for several reasons: (1) lack of a simple diagnostic tool for GERD in infants for the primary care physician may prompt the use of a therapeutic trial, (2) parental anxiety at persistence of symptoms may prompt the use of a therapeutic trial, and (3) aggressive marketing by the manufacturers of acid-suppressing drugs seems to have blurred the dividing line between gastroesophageal reflux and GERD.
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CONCLUSIONS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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We have shown that the parental perception of the volume of their child's emesis is greatly exaggerated, usually by fivefold to sixfold (eg, 5 mL of emesis is perceived as 30 mL).6 Parent–doctor communication, parent education, and reassurance are very important tools in treating such infants. For an infant with persistent regurgitation and no red flags (poor weight gain, excessive crying, irritability, feeding problems, recurrent respiratory symptoms, hoarseness, chronic cough, disturbed sleep, or hematemesis), the physician should be able to persist with conservative treatment (eg, appropriate small-volume thickened feeds, correct positioning, avoidance of cigarette smoke, trial of a hypoallergenic formula) without parental anxiety. The recently simplified and validated Infant Gastroesophageal Reflux Questionnaire–Revised may be a consideration for primary care physicians to use as a fairly accurate and a noninvasive tool for not only diagnosing GERD in infants but also following symptom progression.7 The North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (www.naspghan.org) has provided a very helpful and comprehensive statement that can assist primary care physicians in treating infants and children with gastroesophageal reflux.8
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FOOTNOTES |
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Accepted May 24, 2007.
Address correspondence to Vikram Khoshoo, MD, PhD, Pediatric Specialty Center, 1111 Medical Center Blvd, South 650, Marrero, LA 70072. E-mail: vkhoshoo{at}sbcglobal.net
The authors have indicated they have no financial relationships relevant to this article to disclose.
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REFERENCES |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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- Condino AA, Sondheimer J, Pan Z, Gralla J, Perry D, O'Connor JA. Evaluation of infantile acid and nonacid gastroesophageal reflux using combined pH monitoring and impedance measurement. J Pediatr Gastroenterol Nutr. 2006;42 :16 –21[CrossRef][Web of Science][Medline]
- Khoshoo V, Ross G, Brown S, Edell D. Smaller volume thickened feeds in the management of gastroesophageal reflux in thriving infants. J Pediatr Gastroenterol Nutr. 2000;31 :554 –556[Web of Science][Medline]
- Orenstein SR, Magill HL, Brooks P. Thickening of infant feedings for therapy of gastroesophageal reflux. J Pediatr. 1987;110 :181 –186[CrossRef][Web of Science][Medline]
- Kaul A, Campbell W. Evaluating efficacy of acid suppression therapy in infants using combined pH-impedance measurements [abstract]. J Pediatr Gastroenterol Nutr. 2006;43 :E16
- 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 :57 –61[CrossRef][Web of Science][Medline]
- Pillo-Blocka F, Jurimae K, Khoshoo V, Zlotkin S. How much is "a lot" of emesis? Lancet. 1991;337 :311 –312[Web of Science][Medline]
- Kleinman L, Rothman M, Staruss R, et al. Infant gastroesophageal reflux questionnaire revised: development and validation as an evaluative instrument. Clin Gastroenterol Hepatol. 2006;4 :588 –596[CrossRef][Web of Science][Medline]
- 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, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr. 2001;32(suppl 2) :S1 –S31
PEDIATRICS (ISSN 1098-4275). ©2007 by the American Academy of Pediatrics
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- Gastric acid suppression as treatment for GERD is not a benign intervention
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