Eructation

This behavior, also referred to as belching or burping, is often considered normal in infants. In fact, infants are encouraged to burp during and after feeds in the hope of minimizing gastroesophageal reflux (GER) and feeding intolerance. As in infants, who are liable to swallow air during normal periods of crying and feeding, excessive eructation in older children and adults is almost always secondary to aerophagia. Undue aerophagia may result from excessive gum chewing, use of a straw, clenching on a pencil, or oral breathing as in adenotonsillar hypertrophy or unrecognized H-type tracheoesophageal fistula; patients should be counseled on chewing their food slowly and not gulping. Excessive upper gastrointestinal gas can be associated with consumption of large amounts of carbonated beverages. Rare patients with excessive belching have been found to have eosinophilic esophagitis (personal observation). In adults, chronic eructation is generally thought to be a functional disorder.

Gas-bloat syndrome, seen in children following gastric surgery such as Nissen fundoplication, results from an inability of the patient to belch/eructate effectively. Although this can be a source of significant patient discomfort and family distress, the condition is generally transient and self-resolves. If such patients have a gastrostomy tube, parents can successfully vent the excessive gastric gas.

Abdominal Distension

Bloating refers to a person’s sensation of abdominal fullness, whereas distension connotes visible or measurable increase in abdominal girth. Patients often attribute the feeling of abdominal bloating to excessive gas burden. The relationship between the amount of intestinal gas and symptoms, however, is not linear. Studies of adult patients with complaints of excessive gas have revealed that the quantity of intestinal gas is usually not different between “gassy” and “nongassy” subjects. One study reported that patients with a history of abdominal bloating had significantly delayed transit of small intestinal gas compared to a healthy control population.

Abdominal distension may result from excessive aerophagia or increased gastrointestinal gas production as in malabsorption syndromes. Children with aerophagia often have a nondistended abdomen upon rising, which progressively distends over the day and may be accompanied by crampy abdominal pain. The physical examination may be impressive for abdominal distension and tympany. Plain abdominal films reveal gaseous distension of the bowel. Symptoms and signs may be so intense as to mimic intestinal obstruction or celiac disease. Fatal tension pneumoperitoneum has been reported secondary to aerophagia.

Bloating is part of the symptom constellation of IBS. The discomfort associated with bloating in patients with IBS is likely due to dysmotility and heightened perception. No appreciable differences were found in the volume of gastrointestinal gas in adults with complaints of bloating versus controls, although there was an increased symptomatic response to gas infusion in patients with bloating.

Flatulence

An average adult passes flatus about 10 to 12 times per day, with an upper limit of 20 times a day. The frequency of flatus does not correlate with age or gender, although data on children are lacking. Although flatulence can be a social embarrassment, comfort should be derived from the fact that over 99% of the flatus consists of odorless gases. Increased gastrointestinal gas production, rather than aerophagia, is usually responsible for flatulence in adults, although it is not known if the same can be extrapolated to children. The source of the flatus may be assessed by gas chromatographic analysis of flatus collected via a rectal tube. Aerophagia should be considered the main contributor if N ₂ is the leading component; predominance of H ₂ , CO ₂ , and CH ₄ would suggest increased intraluminal production, for example, secondary to bacterial fermentation of malabsorbed carbohydrates.

An extensive radiologic and endoscopic evaluation of a patient with excessive flatulence alone is generally fruitless and should be avoided. Efforts should instead be directed at eliciting a detailed history ( Table 10-1 ). Appropriate investigation should be considered if the flatulence is accompanied by other symptoms such as diarrhea, hematochezia/melena, abdominal pain, or weight loss. Otherwise, dietary modifications directed toward limiting intake of fruit juices and poorly absorbed carbohydrates, such as cabbage and legumes, may need to be enforced. Excessive consumption of high-carbohydrate–containing beverages (e.g., high fructose corn syrup) is more apt than high intake of cruciferous vegetables such as cabbage to be a culprit in children. A detailed inquiry into intake of liquid medications and “sugar-free” drinks should be undertaken, because these products contain sorbitol, an artificial sweetener that is poorly absorbed and readily fermented by colonic bacteria.

If the patient is bothered by odoriferous flatus, there now are several commercially available charcoal-lined seat cushions and undergarments to help in social situations by effectively absorbing odiferous sulfur gases.

Methane and Constipation

Although traditionally viewed as an inert bystander, methane has recently been linked to and even implicated in the pathogenesis of constipation. Recent studies in both children and adults have revealed strong associations between methane production (as detected on breath testing) and constipation. In a study that examined if methane production was associated with diarrhea or constipation in adults with IBS or inflammatory bowel disease, the researchers noted that methane production on lactulose breath testing was present in all patients with constipation-predominant IBS (C-IBS). Similar studies in children have linked severity of constipation to methane production. Soares et al. reported higher rates of methane production in children with constipation and soiling compared to those with constipation but no soiling. These studies highlight associations but leave questions as to whether methane production is a cause or effect of constipation. However, there is accumulating evidence that methane has direct effects on gut motility. Among patients with constipation, methane production was higher in adults with slow transit constipation than those with normal transit constipation. Animal studies may provide an explanation for this; Pimentel and colleagues infused methane in vivo into canine small intestine and demonstrated delayed transit compared with infusion of room air. In a second phase of the study, they showed that although methane augmented contractility of guinea pig ileum, it had an overall slowing effect by promoting segmental, nonpropagating contractions in the small bowel. The effects of methane on small intestine are important to elucidate further, as patients with IBS may have altered gut flora and small intestinal bacterial overgrowth, as evident on breath testing. These recent advances, at least in adults, suggest that patients with C-IBS may benefit from treatment with neomycin or other similar antibiotics that eradicate methanogenic flora.

Excessive Gastrointestinal Gas

Excessive gastrointestinal gas load may result from aerophagia secondary to the inconsolable crying exhibited by the colicky infant or from increased gas generation from colonic fermentation. There is a paucity of data to support the hypothesis that excessive gastrointestinal gas precipitates a colicky episode. Harley, in 1969, demonstrated radiographically normal gastric outlines at the beginning of a crying episode, and excess gas was found only after the infant stopped crying, indicating that the abdominal distension seen in colicky babies is due mostly to the large amount of air swallowed while the infant is crying. In addition, measures to prevent aerophagia, such as using the upright position, are of little benefit in the management or prevention of infantile colic. Despite these data, simethicone, a defoaming agent, has been proposed for the treatment of infantile colic. A ran­domized, placebo-controlled, multicenter trial of simethicone versus placebo in colicky infants failed to detect a statistically significant difference between the two treatment modalities, thereby refuting, albeit indirectly, this hypothesis.

Carbohydrate Malabsorption

Malabsorption of dietary carbohydrates has been proposed as a possible cause of colic through the production of excess colonic gas with resultant abdominal cramping and discomfort. Investigations aimed at uncovering evidence of malabsorption such as stool α1-antitrypsin levels, pH, reducing substances, and occult blood have been unrewarding, and no significant differences have been found between colicky and noncolicky infants.

In the first year of life, a number of infants may display partial malabsorption of dietary carbohydrate present in human milk or formula. This phenomenon of “physiologic malabsorption” due to enzyme insufficiency may be a cause of colic, especially given that enzyme insufficiency generally resolves at approximately 3 months of age, which coincides with the age that colicky behavior usually subsides. Studies measuring breath H ₂ levels in colicky infants have produced inconsistent results. Two studies showed an association between elevated breath H ₂ levels and infantile colic, although there was a considerable overlap in the H ₂ excretion values between colicky infants and controls. On the other hand, Hyams and colleagues reported no difference in breath H ₂ levels between colicky and noncolicky infants who were fed standardized nonabsorbable carbohydrate. Duro and colleagues demonstrated carbohydrate malabsorption through increased breath H ₂ excretion from fruit juices containing sorbitol and a high fructose-to-glucose ratio in infants with colic.

The role of lactose consumption in infantile colic is controversial. Lack of symptom improvement was demonstrated by two studies that examined the effects of lactase supplementation in infants with colic, and in one study that used low-lactose containing formula in infants with colic. Kanabar et al., however, found symptomatic improvement in a subset of colicky infants following pretreatment of feeds with lactase. Although the available data on the role of malabsorption in infantile colic are limited and contradictory, carbohydrate malabsorption may be the pathogenic factor in a subset of infants with colic.

Mode of Feeding

The prevalence, pattern, and amount of crying associated with infantile colic are reportedly similar in both human milk- and formula-fed infants, although one study reported an earlier peak of colicky behavior in formula-fed infants compared with human milk–fed infants (age 2 weeks versus 6 weeks). Evans et al. compared the effect of two modes of nursing on infantile colic, namely, prolonged emptying of one breast versus equal drainage of both breasts at each feed. The former group had a lower incidence of colic over the first 6 months of life, but the majority of mothers in this group felt it necessary to offer the second breast at the end of a feed to satisfy their infant’s hunger. Based on this study, prolonged nursing from one breast may reduce colic in infants.

Protein Allergy/Intolerance

The immunologic model of colic focuses on possible allergens such as cow’s-milk proteins in human milk or infant formula as an underlying cause, although convincing, reproducible evidence is lacking, or controversial at best. An early study by Jakobsson and Lindberg reported that the exclusion of cow’s-milk protein from the diet of mothers of nursed infants with colic resulted in symptom resolution. Campbell also suggested a role for cow’s milk protein in the pathogenesis of infantile colic. In his study, 68% (13/19) of infants exhibited resolution of colic with dietary modifications that consisted of switching from a cow’s-milk protein–based formula to soy protein–based formula, or switching from the latter to a protein-hydrolysate formula. Oggero and colleagues found similar results with resolution of symptoms in 95.5% (42/44) of formula-fed colicky infants with soy protein–based or protein-hydrolyzed formula. In addition, Lucassen et al. randomized colicky infants to either a whey-hydrolysate or a standard formula, with the former demonstrating decreased crying duration of 63 minutes/day (95% confidence interval = 1 to 127 minutes/day). Forsyth, in contrast, found that the resolution of symptoms witnessed early on was not sustained. He alternated the feedings of 17 colicky infants between a casein-hydrolysate formula and a cow’s milk protein–containing formula. Infants fed the hydrolysate formula had less crying and colic initially, but the effects diminished over time. Although Lindberg reported that approximately 25% of infants with moderate or severe colic responded favorably to a diet free of cow’s milk protein, and Estep and Kulczycki found free amino acid–based formula to be beneficial in infantile colic, their approach has been described as controversial. Hill and colleagues took protein intolerance further and performed a randomized, controlled trial to investigate the effects of a low-allergen maternal diet on colic among nursed infants. Broad maternal dietary modifications that included the exclusion of cow’s milk, eggs, peanuts, tree nuts, wheat, soy, and fish were associated with an objective reduction in colic-like distress among 6-week-old infants.

Conversely, Thomas et al. noted that the prevalence of colic was similar between infants fed human milk, formula, and formula-supplemented human milk, and they concluded that dietary protein hypersensitivity may not be the cause of colic in otherwise healthy infants. These results were supported by a questionnaire-based study of the prevalence of colic among nursed, formula-fed, and formula-supplemented nursed infants, where no associations were shown between the source of infant nutrition and development of colic. Liebman also failed to uncover objective evidence of protein allergy in his study of 56 infants with colic. Despite these results, one study supported the use of pancreatic enzyme supplements in lactating mothers for the treatment of infantile colic. The authors theorized that hydrolysis of human milk protein by pancreatic enzyme supplements would benefit colicky infants with cow’s-milk allergy; no further studies have been reported to support this theory.

Motility

Transient dysregulation of the nervous system during development may cause intestinal hypermotility in infants with colic, particularly during the first few weeks of life. Jorup stated that most cases of infantile colic can be explained by colonic hyperperistalsis and increased rectal pressure, and this hypothesis has been supported by studies reporting the beneficial effects of antispasmodics, such as dicyclomine, on infantile colic. Whether dicyclomine exerts its effect via the relief of gastrointestinal spasms by a direct relaxant effect on the colonic smooth muscle, or through sedative central nervous system effects, is unclear; however, its utility in infants has been limited because of its central effects and potential for respiratory depression. In a controlled trial, an herbal tea preparation containing chamomile, fennel, and balm mint as antispasmodics was shown to benefit colicky infants. It should be noted that fennel tea was recently reported to have mutagenic effects on bacteria and carcinogenic effects in mice. Savino and his group suggested that a phytotherapeutic agent with Matricaria recutita, Foeniculum vulgare , and Melissa officinalis improved colic in infants through its antispasmodic activity.

A double-blind, placebo-controlled clinical trial investigated the use of cimetropium bromide, a quaternary ammonium semisynthetic derivative of the belladonna alkaloid scopolamine, in 86 colicky infants. In this study, cimetropium bromide reduced the duration of crying in the treated group compared with controls, and although treated infants did have more sleepiness, neither respiratory distress nor apnea was observed.

Gastroesophageal Reflux

It is appealing to explore a cause–effect relationship between gastroesophageal reflux (GER) and infantile colic, especially in view of the prevalence of GER during infancy. Similar to infantile colic, GER may present with excessive crying, but the crying is generally less intense in GER. GER often displays other symptoms such as regurgitation and emesis that are not associated with colic.

Few studies have examined the role of pathologic GER in colicky infants, and the results are mixed. In a study of 26 infants with persistent, excessive crying of more than 4 weeks’ duration, who had been labeled colicky, Berkowitz and colleagues detected pathologic GER in 61% (16/23) of the infants using a 24-hour continuous intraesophageal pH monitoring study. Although the data appeared compelling, a cause–effect relationship could not be established because these infants did not exhibit classic symptoms of GER, such as regurgitation and emesis. Moreover, 12 (75%) of the 16 infants with pathologic GER were 4 months or older, by which age infantile colic has generally resolved. In another study of 24 infants younger than age 3 months, who had excessive crying and had presumed GER, only one infant had pathologic GER according to pH study. Therefore, the question remains whether pathologic GER is indeed a causative factor of infantile colic. Although some data suggest that GER is implicated in a small subset of infants with severe colicky symptoms, in the absence of regurgitation and vomiting, GER is not a common cause of infant irritability.

Gut Hormones

The gastrointestinal tract contains a repertoire of hormones, transmitters, and other biologically active proteins, such as prostaglandins, that are involved in the regulation of intestinal motility. Of these, motilin is the most investigated as a player in the etiopathogenesis of infantile colic. Basal motilin levels have been shown to be elevated in colicky infants independent of their diet, and are higher at birth in infants who later develop colic. It is speculated that motilin promotes gastric emptying, which increases small bowel peristalsis and decreases transit time. These could contribute to perceived intestinal pain and lend substance to the hyperperistalsis theory. A recent study showed that colicky infants have higher serum levels of ghrelin compared to their healthy counterparts, which is thought to be implicated in promoting abnormal hyperperistalsis and increased appetite. Random urinary concentrations of 5-hydroxy-3-indoleacetic acid (5-OH IAA), a serotonin metabolite, were measured in infants with and without colic; 5-OH IAA levels were elevated in colicky infants, suggesting that elevated serotonin concentrations may participate in the pathogenesis of infantile colic.

Altered Intestinal Flora

The intestinal microbiota plays an important role in human health by producing nutrients and preventing gut colonization by potentially pathogenic microorganisms. Increasing attention has been directed to the role of intestinal microflora in the pathogenesis of various gastrointestinal processes including infantile colic. According to Lehtonen et al., an aberrant gut microbial composition, such as inadequate lactobacilli level in the first months of life, may affect the intestinal fatty acid profile, thereby favoring the development of colic. However, his study failed to show any detectable differences in the intestinal microflora between colicky and noncolicky infants. A subsequent study by Savino and colleagues demonstrated lower counts of intestinal lactobacilli in colicky infants compared with healthy infants. In a separate study, these investigators reported that Lactobacillus brevis and Lactobacillus lactis were found only in colicky infants, whereas Lactobacillus acidophilus was cultured only from healthy infants. In an additional study by Savino and colleagues, modulation of the intestinal microflora of colicky infants using probiotics was investigated. In this prospective study, a cohort of 90 exclusively nursed colicky infants was equally and randomly assigned to probiotic Lactobacillus reuteri or simethicone treatment. Infants in the L. reuteri– treated group displayed an improvement in crying behavior within 1 week of treatment compared with the simethicone-treated group. Addition of prebiotics to the formula of infants with colic also demonstrated a reduction in crying episodes.

A recent study that evaluated the colonization pattern of gas-forming coliforms in colicky infants and healthy controls by molecular methods found coliform bacteria, particularly Escherichia coli , to be more abundant in colicky infants. Similar results were found by de Weerth et al. Compared to control infants, those with colic had specific microbial signatures in the first weeks of life that were less diverse and contained increased Proteobacteria, which are organisms related to Escherichia , Klebsiella , Serratia , Vibrio , Yersinia , and Pseudomonas . Rhoads and colleagues explored whether gut inflammation could provide a pathophysiologic mechanism for colic. In their study, infants with colic had fecal calprotectin levels twofold higher than in healthy controls, with values in a range comparable to those in children with inflammatory bowel disease. Even Helicobacter pylori infection has been implicated in colic. A case–control study found that colicky infants (N = 55) were more likely than those without colic to have H. pylori antigen found in their stool.

Psychosocial Factors

This aspect of infantile colic has long been proposed, widely studied, and passionately debated. In 1944, Spock had suggested that infantile colic could be due to transmission of anxiety and tension from the mother to the infant. Stewart et al. reported, in a prospective study in 1954, that mothers of excessive criers experienced more psychological conflicts regarding their maternal role and displayed more hostility toward their child. In contrast, two other studies found that maternal emotional factors did not play a role in excessive infant crying; however, an association was found between infantile colic and a history of emotional tension or depression early in the pregnancy. Of interest, Zwart and colleagues in 2007 demonstrated that infants with severe excessive crying show normalization of their behavior during hospitalization and are unlikely to have a medical cause for their colic. The most important risk factor for their crying was a complicated pregnancy or birth, suggesting that these experiences might predispose parents to regard normal crying behavior as excessive.

Various studies have also examined the relationship between maternal smoking and infantile colic. Prevalence of colic was twofold higher in infants of mothers who smoke. A large Danish study with data from more than 60,000 infants not only corroborated the association between maternal smoking and infantile colic, but actually found that nicotine replacement therapy also increased the risk of subsequent colic, thereby suggesting that nicotine itself may be the culprit. Moreover, a Canadian study found increased likelihood of colic with maternal alcohol consumption at 6 weeks of gestation and shift-work during pregnancy. However, being married or having a common-law partner and being employed full-time during the pregnancy were associated with a reduced risk of infantile colic. A recent study by Canivet and colleagues showed psychological and psychosocial factors to be significantly related to an increased risk of infantile colic and that these factors interacted with age, parity, social support, and educational level in a complex manner. The authors suggested lending support and special attention to very young women and single mothers. On the other hand, Rautava et al. demonstrated that socioeconomic factors do not play a role in the cause of colic in Finnish infants. Instead, superior maternal intelligence and higher education were found to be associated with higher incidences of infantile colic.