“Infantile Colic” as the Sole Manifestation of Gastroesophageal Reflux

“Infantile colic” is a colloquial term that is used to designate frequent prolonged bouts of fussing, crying, restlessness, and increased motor activity for no apparent reason, in an otherwise healthy infant (1). Tradition has it that “infantile colic” tends to improve and disappear after 3-4 months of age, but in reality the condition is also noted to persist well into the second half of the 1 st year of life (2). A variety of conditions have been proposed to cause the clinical array that is labeled “infantile colic,” among them intrafamilial problems (3), malabsorption of sugar(s) (4), cow's milk protein allergy (5), neuroendocrine factors (6), depending on the specific viewpoint from which the condition is studied, and the modes of treatment vary accordingly. Bouts of crying, irritability, and restlessness can also be manifested by infants who have pathological gastroesophageal reflux (GER) (7). From accruing experience with lower esophageal pH monitoring, it has emerged that pathological GER can exist without overt evidence of regurgitation, vomiting, or respiratory disturbances (“silent” reflux), while still causing esophagitis (8), and evoking episodes of bitter crying and restlessness that may be construed as reflecting “infantile colic.” In effect, in the course of our experience with esophageal pH monitoring, we detected significant GER in infants whose sole clinical manifestations were episodes of fussing, crying, and restlessness, which had been diagnosed by the primary physician as “infantile colic.” We therefore undertook to perform esophageal pH studies in a prospective series of babies with a presumptive diagnosis of “infantile colic” that was severe and persistent enough to induce referral to our Pediatric Gastroenterology Clinic. PATIENTS AND METHODS Twenty-six consecutive babies, ages 2-9 months, had been labeled as having “infantile colic,” which featured daily prolonged episodes of bitter crying, with irritability, restlessness, and increased motor activity that included drawing up of the legs and stamping movements. The events went on for more than 4 weeks, and had not responded to parental reassurance, dietary manipulations, defoaming agents and herbal teas. There had been no deviation from normal health and development, and no apparent source for the distress. After a detailed history and physical examination, 24-h esophageal pH monitoring was performed with a pH-sensitive electrode placed 4 cm proximal to the lower esophageal sphincter and connected to a Digitrapper MK III recording and digitizing device (Synectics AB, Stockholm, Sweden). The test was performed and interpreted in accordance with the guidelines of the European Society for Pediatric Gastroenterology and Nutrition (9). Informed written consent was obtained from the parents. Infants whose pH-metry indicated significant GER (9), primarily by a finding of esophageal pH < 4 for longer than the upper percentile value for age (9), received oral treatment with cisapride (0.2 mg/kg, q.i.d.) and cimetidine (10 mg/kg, b.i.d.). Cisapride was given throughout the 3 months of follow-up and beyond, whereas cimetidine was discontinued after 4 weeks. The infants with GER were followed up during a period of 3 months, by daily event-reports handed in by the parents every 10 days, and a monthly evaluation of the infants during a visit at the outpatient clinic. RESULTS Of the 26 infants, 14 were male and 12 were female. Their ages ranged between 2 and 9 months (median 4.8 months), and the age at onset of the symptoms was 3 weeks to 4 months (median 1.8 months). The time from onset of symptoms to performance of pH-metry ranged between 5 weeks and 6 months, and had been longer than 2 months in 21 of the infants. Pathological GER was detected by pH-metry in 16 of the 26 infants (61.5%) (Table 1). Treatment with cisapride and cimetidine of these 16 infants, who were referred with a presumptive diagnosis of “infantile colic” but were found to have pathological GER, induced a reduction in the frequency and in the severity of the events within 5 days in 12 of the infants, whereas after 14 days of treatment all the infants with GER were free of any symptom that could be regarded as a manifestation of “infantile colic.” In the remaining 10 infants, those who did not have GER on pH-metry, the picture of “infantile colic” gradually resolved over a period of 4-6 weeks, throughout which family-intervention measures were continued. DISCUSSION The pattern of the clinical constellation that is termed “infantile colic” tends to be fairly stereotypic, in spite of the diversity of conditions that have been proposed as causative agents. A specific cause cannot be discerned in most instances of genuine(?) “infantile colic.” The initial therapeutic measures that the primary physician will undertake are largely influenced by the contention that overproduction of gas by malabsorbed sugars (4) and food allergies (5) are major causes of “infantile colic,” and will most often consist of parental reassurance and dietary manipulation, perhaps with the addition of a defoaming agent such as simethicone, which has been shown to be no more effective than placebo (10). Our study indicates that the differential diagnosis of “infantile colic” should include GER, which can manifest solely as bouts of crying and restlessness, in the absence of any of the other clinical features that are traditionally associated with GER. In our series of 26 infants, who were studied by esophageal pH monitoring while they were having only attacks of crying and restlessness that were labeled “infantile colic,” 16 (61%) were found to have significant GER. The administration of medications that are recommended for the management of GER disease, namely, H2 block-age (cimetidine) and a prokinetic drug (cisapride) (11), induced a dramatic improvement and disappearance of the “colic” features within 5-14 days. GER that causes symptoms is pathological, and requires appropriate therapy that will allay the symptoms, reduce reflux, heal the esophagitis, and prevent long-term complications (11). We are aware that our series consists of selected patients whose seemed to be refractory to the usual therapies, and that our observations are not based on a double-blind, placebo-controlled study. We are also aware that “infantile colic” may resolve spontaneously with time. However, we may regard our group of infants with GER as being their own controls, inasmuch as the rapidity of resolution of their “infantile colic” following initiation of anti-reflux therapy is strongly suggestive of a putative role for GER in evoking the repeated episodes of inconsolable crying and restlessness. We conclude from our observations, that GER can fully mimic the clinical array termed “infantile colic.” Awareness of this association is warranted in view of the damaging potential of pathological GER that is left untreated (8). It might even be justified to propose that severe “infantile colic” be managed by addressing the possibility of GER, whereas other modes of treatment become warranted if no improvement is apparent after 10 days of antireflux medication.