Theresa M. Shalaby

Reflux Symptoms in 100 Normal Infants: Diagnostic Validity of the Infant Gastroesophageal Reflux Questionnaire

To identify the prevalence of reflux symptoms in normal infants, to characterize the diagnostic validity of a previously described 138-item Infant Gastroesophageal Reflux Questionnaire (I-GERQ) for separating normal infants from those with gastroesophageal reflux disease (GERD), and to identify potentially provocative caretaking practices, we administered the questionnaire to 100 infants attending a well-baby clinic (normals) and to 35 infants referred to the Gastroenterology Division for evaluation for GERD and testing positive on esophageal pH probe or biopsy (GERD infants). Differences were analyzed by Chi-square, and odds ratios were defined. The diagnostic validity of a 25-point I-GERQ GERD score based on 11 items on the questionnaire was evaluated by calculating its sensitivity, specificity, and positive and negative predictive values. We found that normal infants had a high prevalence of reflux symptoms, such as daily regurgitation (40%), respiratory symptoms, crying more than an hour a day (17%), arching (10%), or daily hiccups (36%) but that many symptoms were significantly more prevalent in the GERD than in the normal infants (Chi-square P<.05), and odds ratios were above 3 for nearly 20 items. The positive and negative predictive values for the 25-point I-GERQ score were 1.00 and .94-.98, respectively. Environmental smoke exposure did not quite reach significance as a provocative factor for GERD. Although normal infants have a high prevalence of symptoms suggesting GERD, a simple questionnaire-based score is a valid diagnostic test with high positive and negative predictive values.

Reliability and Validity of an Infant Gastroesophageal Reflux Questionnaire

To improve history-taking of infants with suspected gastroesophageal reflux, we developed an Infant Gastroesophageal Reflux Questionnaire consisting of 161 items covering demographics, symptoms (regurgitation, weight deficit, respiratory difficulties, fussiness, apnea, and pain or bleeding of esophagitis), and possible causes (feeding volume and frequency, allergy, infection, colic, central nervous system abnormalities, positioning, and smoke exposure). The questionnaire was completed by primary caretakers of 69 infants aged 1 to 58 weeks suspected of having reflux. Median time to complete the questionnaire was 20 minutes. The median internal consistency of 29 pairs of redundant questions was 0.94. Median test-retest consistency of 110 items for nine respondents was 0.88. Median interobserver consistency, evaluated for 129 items in 35 questionnaires also filled out by secondary caretakers, was 0.85. The median accuracy of four externally validated items was 1.00. This questionnaire can aid pediatricians in making decisions regarding diagnoses and treatment in this common but complex disorder.

Genetics of gastroesophageal reflux disease: a review.

In the past few years, attention has focused on the possibility that gastroesophageal reflux disease (GERD) may have a genetic basis. A specific locus associated with pediatric GERD has been identified on chromosome 13. This article reviews the literature to date that supports a familial or genetic basis for GERD, examines evidence for a specific locus for pediatric GERD at 13q14, and analyzes the rationale for suspecting genetic heterogeneity within pediatric GERD. The suspicion that GERD might have a familial component is not a new one. The first reports of familial hiatal hernia were published nearly forty years ago. In the subsequent decades, two dozen publications have identified familial segregation of hiatal hernia (HH), Barrett’s esophagus (BE), esophageal adenocarcinoma, and GERD. Differences between adult and pediatric GERD (1) prompt one to be somewhat cautious in extrapolating data from one to the other. However, as a genetic basis has been considered in the literature for both ends of the age spectrum recently, it is worthwhile to reflect on the literature as a whole, particularly given our own cadre of families containing both infants and adults with significant GERD. Nonetheless, it may be that distinct genetic predispositions will be identified for different presentations, including presentations in different age groups.

Sandifer Syndrome Posturing: Relation to Abdominal Wall Contractions, Gastroesophageal Reflux, and Fundoplication

Sandifer syndrome designates abnormal posturing in patients with gastroesophageal reflux. To explore its mechanisms via examining relationships among Sandifer syndrome posturing, abdominal wall contractions, and reflux episodes, we studied an affected child in detail. The study utilized esophageal pHmetry, surface electromyography, and split-screen videography. The multichannel physiologic study demonstrated association of rectus abdominis contraction with onset of reflux episodes (P < 0.001) and association of reflux episodes with Sandifer syndrome posturing. This child’s subsequent course confirmed his diagnosis and suggested mechanisms of the association of reflux and Sandifer syndrome. We conclude that abdominal wall contractions may induce reflux episodes. Sandifer syndrome may be due to gastroesophageal reflux even without hiatal hernia, macroscopic esophagitis, or reflux symptoms. Despite the absence of more typical reflux symptoms and failure to respond to very aggressive medical therapy, Sandifer syndrome may resolve after fundoplication.

Autosomal dominant infantile gastroesophageal reflux disease: exclusion of a 13q14 locus in five well characterized families

OBJECTIVES:A genetic locus for pediatric reflux was proposed on chromosome 13q14, but is unconfirmed in independent kindreds. We sought to test this locus in families with multiple affected infants from our database of well characterized infants with reflux.METHODS:We screened the database for families with multiple affected infants. Affected proband phenotype required histological esophagitis; affected sibling/cousin phenotype required a threshold score on a diagnostic questionnaire. Screened families were reduced to five based on pedigree, consent, and phenotypic clarity. Linkage of the phenotype with the four previously reported markers (D13S218, D13S1288, D13S1253, and D13S263) was tested, using an autosomal dominant, 70% penetrance model. Linkage required logarithm-of-odds score ≥3.RESULTS:Of 54 individuals in the five probands’ generation, 21 (39%) were affected based on questionnaire, of whom nearly one half also had histological confirmation of esophagitis. Linkage to the defined region was excluded for the five families by two-point LOD scores (−1.47 at D13S218, −1.32 at D13S1288, −3.43 at D13S1253, and −3.92 at D13S263) and by multipoint (multipoint LOD scores less than −2 between D13S218 and D13S263) linkage analysis. No family demonstrated even suggestive positive linkage (i.e., LOD score >1).CONCLUSIONS:In five rigorously phenotyped families with autosomal dominant pattern infantile reflux, we excluded genetic linkage to the region of 13q14 previously identified responsible for an autosomal dominant form of pediatric reflux. These results suggest genetic heterogeneity, possibly related to phenotypic heterogeneity, in familial pediatric gastroesophageal reflux disease.

Regurgitant reflux, vs non‐regurgitant reflux, is preceded by rectus abdominis contraction in infants

Abstract Infants commonly regurgitate during some, but not all, gastro‐oesophageal reflux episodes. As several different mechanisms for reflux episodes have been identified, it was hypothesized that the mechanisms for regurgitant and non‐regurgitant reflux differ. To test whether regurgitant episodes are associated with, and perhaps propelled by, rectus abdominis contraction, ten infants, aged 9–30 weeks (median 16.5 weeks), with regurgitant reflux and no other cause for their regurgitation, were studied with concurrent distal oesophageal pH probe monitoring and surface electromyography of the rectus abdominis muscles. Reflux episodes with material emanating from the mouth (regurgitant reflux) were distinguished from those without visible regurgitation, and were characterized as being, or not being, temporally associated with rectus abdominis activity.

Morphometric histology for infant gastroesophageal reflux disease : Evaluation of reliability in 497 esophageal biopsies

Objectives: We sought to determine the reliability of morphometric measurements on infant esophageal biopsies using a light microscope with eyepiece micrometer. Methods: We measured epithelial thickness, basal layer thickness (B), papillary height (P) and epithelial lymphocyte and eosinophil numbers on ≈500 existing esophageal suction biopsies from infants previously evaluated for reflux esophagitis. We tested these measurements for interobserver, test-retest and internal consistency reliability. Results: Infants ages 0.25 to 23.75 (median, 6.25) months provided 497 biopsies. Both investigators scoring the biopsies independently judged 93% of them scorable. Of the biopsies scored by both, the 2 readings were within 0.15 of each other for P in 97% and for B in 81%. In addition to these correlative measures of consistency, categoric measures demonstrated that 373 (89%) of the 420 scorable biopsies with visible papillae produced agreement as to P being abnormal (317, 85%) or normal (56, 15%). Similarly, 360 (78%) of the 463 scorable biopsies produced agreement as to B being abnormal (339, 94%) or normal (21, 6%). P values were 0.17 to 0.94 (median, 0.67), and B values were 0.13 to 0.91 (median, 0.34). Lymphocytes numbered 0 to 40 (median 5) per high-power field. Only 12% had any eosinophils; none of those with completely normal morphometrics had any eosinophils; and only 2% had >5 eosinophils per high-power field. Conclusions: Simple quantitative esophageal histological morphometric parameters are reliably measurable on suction biopsies from infants using a light microscope fitted with an ocular micrometer, even by nonpathologists.

The Effects of Increasing Doses of Ranitidine on Gastric pH in Children

BACKGROUND Ranitidine is widely used for gastroesophageal reflux disease (GERD) in children, but optimal dosing is unclear. We compared effects of weight-based doses of oral ranitidine on gastric pH in children with clinical GERD. METHODS Children ages 4-11 years with clinical GERD were enrolled in a multi-center prospective randomized study comparing a fixed dose of ranitidine (Zantac 75) with placebo after an overnight fast; gastric pH was measured for 6 h after the fixed dose (Phase 1). Of the six enrollees from our center, four received active drug during Phase 1; 12 h after the fixed dose, these four children received ranitidine 5 mg/kg (maximum 150 mg) and gastric pH was measured for another 6-12 hours (Phase 2). This report details the effects of two dose ranges (Low Dose, < 3 mg/kg/dose, and High Dose, ≥ 3 mg/kg/dose) on gastric pH in children. RESULTS The four children were 6.9-11.3 years old and weighed 20.4-49.5 kg. The Low Doses were 1.5-2.7 mg/kg; the High Doses were 3-5 mg/kg. Although the mean percentage of time with gastric pH > 4 during the entire 6 hours following dosing was similar after Low and High Dose (50% vs. 57%, NS), during the last two hours of this interval the mean percentage of time with gastric pH > 4 was only 29% for Low Dose vs. 89% for High Dose (P = 0.006). Moreover, during those two hours, none of the Low Doses kept gastric pH above 4 for > 60% of the time, while all of the High Doses kept pH above 4 for > 60% of the time (P = 0.03). In three of four patients who underwent extended (9-12 h) gastric pH monitoring after High Dose ranitidine, gastric pH was above 4 for more than 40% of total time. CONCLUSIONS Doses of ranitidine ≥ 3 mg/kg/dose may be required for acid suppression lasting beyond 6 hours.