Is gastroesophageal reflux disease really a life-long disease: do babies who regurgitate grow up to be adults with GERD complications?

There are a number of chronic digestive diseases in adults which have symptom and/or disease onset in childhood. Examples of childhood-onset chronic diseases include Helicobacter pylori-associated gastroduodenal disease and gastroesophageal reflux disease (GERD). Unfortunately, there is a paucity of well-designed longitudinal studies that characterize the natural history of each of these conditions and more importantly identify individuals (i.e., children) who are at risk for serious, long-term adult sequelae. Gastroesophageal reflux (GER), the physiological condition, and GERD, the disease, occur frequently during the first 2 yr of life. However, commonly held "dogma" by pediatricians is the belief that the majority of these children "grew out of their GER or GERD symptoms." On the contrary, recent evidence suggests that GERD in some subjects is a chronic, potentially life-long condition that begins in childhood, and in those in whom disease onset is early, there may be a higher risk for long-term severe disease sequelae. The article by Orenstein et al., although small in cohort size (N = 19), is the first systematic, longitudinal prospective study that employs both a validated GERD symptom assessment instrument and a histological characterization of esophageal inflammation via mucosal biopsies of infants during the first year of life. The infants, part of a larger therapeutic trial, were originally referred to the investigators for GERD evaluation, failed a 2-wk lifestyle modification trial, and were randomized to placebo or intervention (acid suppression and prokinetic therapy). This placebo cohort was evaluated in follow-up via assessment of symptoms using a validated Infant-Gastroesophageal-Reflux-Questionnaire (I-GERQ) and esophageal suction biopsy; morphometric characterization of mucosal histology and symptom scores were performed at 2, 4, 6, and 12 months. At the 12-month endpoint, 10 of 19 completed the study without rescue medication and overall symptom scores improved in all 10 completers. However, none of the 10 completers had normalization of biopsy assessments, i.e., basal cell layer <25% and papillary height <53% of epithelial thickness. The authors concluded that although symptoms improved in more than half of infants with reflux esophagitis followed longitudinally, esophageal mucosal histology remained abnormal at the 1-yr evaluation in the absence of pharmacotherapy. The lack of concordant improvement of the esophageal histology should raise concern regarding sub-clinical persistence of ongoing esophageal insult, which might in the long-term, predispose the individual to GERD-related complications, such as strictures, Barrett's esophagus, and/or esophageal adenocarcinoma. In this editorial, the implications of GERD being a life-long disease based on the findings described by Orenstein et al. are discussed. In addition, a description of areas where further research is critically needed is provided namely: (1) population-based, epidemiological studies of GERD with appropriate case and control definitions, (2) characterization of genetically "at-risk" individuals (i.e., with childhood-onset GERD) for severe GERD sequelae (e.g., Barrett's esophagus, esophageal adenocarcinoma), or potentially, (3) longitudinal, family cohort natural history studies with index pediatric GERD cases.