Infant Colic: A Pediatric Gastroenterologist’s Perspective

CARE OF THE INFANT

0031-3955/94 $0.00 + .20

INFANT COLIC A Pediatric Gastroenterologist's Perspective William R. Treem, MD

Few problems have engendered as much confusion and consternation among practicing pediatricians as the syndrome of infant colic. Faced with anxious, frustrated, often sleep-deprived parents, the pediatrician must try to explain the cause of the infant's excessive crying and offer some rational therapies. The pediatric literature, however, is replete with papers that contradict each other and offer only weak evidence supporting one cause or another. We cannot seem to agree whether colic is an organic or a behavioral problem, whether excessive crying is the result of visceral pain or not, or whether colic is really a problem with the baby or the mother. Gastroenterologists involved in studying colicky infants debate whether lactose or cow's milk protein is more responsible, or whether luminal digestion or abnormalities in gut motility are more important. This article offers a pediatric gastroenterologist's perspective on this contradictory field. It draws upon recent reviews, which have collated and synthesized much of the available data, allowing a more comprehensible framework with which to approach the infant with colic. 21 , 51 A pediatric gastroenterologist regards colic in the majority of infants as the interaction of physiologic factors, which produce crying, with infant behavioral characteristics, which contribute to variability in crying. Only those infants whose crying behavior is excessive, does not conform to the usual daily pattern, lasts longer than the usual natural history, or is associated with findings suggestive of a specific organic problem should be subject to more extensive investigation or trials of specific therapies.

From the Department of Pediatrics, University of Connecticut School of Medicine; and Division of Pediatric Gastroenterology and Nutrition, Hartford Hospital, Hartford, Connecticut

PEDIATRIC CLINICS OF NORTH AMERICA VOLUME 41 • NUMBER 5 • OCTOBER 1994

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The underlying assumptions of this view are (1) that most infants with colic are crying excessively because of a combination of normal physiologic triggers and normal behavioral responses, (2) that most infants with colic will be calmed by changes in parental responses to the crying behavior, (3) that colic is a syndrome describing a heterogeneous group of disorders of which the minority represent specific dysfunctions of the gastrointestinal tract, and (4) that this minority may be recognized by features of the history and presentation or by responses to specific therapeutic interventions (Fig. 1). DEFINITION

The most commonly accepted definition of colic focuses on the duration of infant crying and was offered by Wessel et al74 who described colic as paroxysms of irritability, fussing, or crying lasting for a total of more than 3 hours a day and occurring on more than 3 days in any 1 week, for at least 3 weeks. These periods of crying are more likely to occur in the afternoon or evening in an infant between 2 weeks and 4 months of age. Using these criteria, Wessel identified 49% of a normal nursery population as eventually colicky, thereby raising doubts about the validity of the definition. Brazelton9 and others have documented in prospective studies that the median amount of crying in normal fullterm infants at 6 weeks of age is about 2.75 hours per day and that normal crying behavior is typified by clustering during the evening hours and peaks in the second month of life with a gradual decrease

Normal Variant Crying

Figure 1. The causes of colic. IBS reflux.

=

irritable bowel syndrome, GER

=

.

65%

gastroesophageal

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thereafter. 34, 61, 62 A recent, large English study showed that 29% of Northamptonshire infants cried for more than 3 hours a day during the first 3 months of life declining to 7% to 10% thereafter. 62 These studies support the hypothesis that colic in most infants represents the extreme of the normal spectrum of variability in crying. Recently, investigators have attempted to further characterize infant crying behavior and refine the definition of colic. Diaries prospectively recording five different behaviors, namely crying, fussing, sleeping, awake and content, and feeding, have been used to define normal crying and colicky behavior.21, 34, 62 In some studies, these diaries have been validated with voice-activated recordings of infant cryingM and even with spectral analysis of the infant cry to determine if the cry of the colicky infant sounds different from a normal cry. Although some studies have suggested that the cry is characterized by a higher pitch, greater variability in pitch, and greater dissonance,40 others suggest that different cry morphology reflects a continuum in an infant's level of stress or arousal rather than specific cry types that might distinguish the cries of colicky infants from those without colic.22,77 Using prospective diaries, two recent studies have documented median durations of crying plus fussing of 5.0 and 5.6 hours in colicky infants at 6 to 8 weeks of age. 24, 70 One of these studies simultaneously recorded these behaviors in an agematched control group where the median duration of crying plus fussing was 1.7 hours.24 This finding is in close agreement with previous studies employing prospective diaries in healthy control infants.29 More detailed prospective diaries have also been used to attempt to delineate specific subgroups. By analyzing crying logs, two recent studies have documented distinct patterns in infants labeled by their parents as colicky?' 21 In both studies, a minority of infants was noted to cry intensively most of an hour regardless of parental response. These classic, or Wessel's, colic babies averaged 38 minutes per bout of crying versus 23 minutes for the majority comparison group who had frequent bouts of crying but who calmed quickly in response to parental intervention? Other symptoms and signs have been associated with the syndrome of infant colic (Table 1), Our studies of 54 infants who satisfied Wessel's definition of colic on prospective behavior diaries have confirmed the classic description of the colicky infant as one who suddenly cries for a prolonged time as if in pain and is difficult to console.69,70 In addition, 89% of our study group was said to pass a lot of gas; 56% had feeding problems including spitting, vomiting, and crying with feeding; and half were said to sleep poorly. Physical features usually attributed to colicky infants were not so uniform in our study population: 86% were found to be hypertonic, but only approximately half cried during the physical examination, and only 28% were actually inconsolable. Approximately half the infants were flushed and had abdominal distention or flexion of the legs. Although some of these features have been used as evidence that these infants have pain originating in the gastrointestinal tract, they have also been observed as nonspecific motor behaviors that accompany crying.57

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Table 1. COLIC: SYMPTOMS AND SIGNS No. Patients Presenting

Percentage

Symptoms Cry/scream as in pain Cry/scream sudden onset Cry/scream >15 minutes Hard to console Passes a lot of gas Sleeps poorly Feeding problems

54/54 53/54 54/54 54/54 48/54 24/54 30/54

100% 98% 100% 100% 89% 47% 56%

Signs (at time of physical exam) Crying Drawing up legs Abdominal distention Hypertonic Flushing Arching Inconsolable

31/54 30/54 24/54 46/54 30/54 11/54 15/54

58% 56% 44% 86% 56% 20% 28%

Data from Treem WR, Blankschen E, Etienne N, et al: Effect of soy polysaccharide fiber on stool characteristics and intestinal gas in infants with colic [abstract]. Gastroenterology 102:A581, 1992; and Treem WR, Hyams, JS, Blankschen E, et al: Evaluation of the effect of a fiber-enriched formula on infant colic. J Pediatr 119:695, 1991.

ETIOLOGY Parental/Maternal Factors

Carey and others have promoted an "interactional" model of colicY This model proposes that excessive crying in most infants is the result of normal physiologic events which trigger crying in infants who are temperamentally sensitive to these stimuli, and who then receive a parental response which is not appropriately soothing. Despite its attractiveness, support for the individual elements of this interaction is limited. The associations between colic and infant temperament reported by Carey in 1972 were obtained by parental assessments when infants were 4 and 8 months of age,12 Parents who experience colicky infants might be guilty of reporting bias and a tendency to view subsequent normal behavior as reflecting a difficult temperament. In a prospective study of normal infants, those rated as more difficult at 2 weeks of age by nonparental observers were found to be crying more at 6 weeks, but this rating only accounted for 7% of the variance in crying behavior,s In general, research into the connection between infant temperament and colic has suffered from methodological problems, parental bias, and a lack of reproducibility over time,38,71 Another element of this interactional model is the maladaptive parental (usually maternal) response to the crying behavior, Although several studies have shown an association between infantile colic and maternal postpartum depression, maternal anxiety, and maternal hostility

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toward the infant,13, 28 others have nof56; these efforts have also suffered from a reliance on parental impression as the sole arbiter of the presence of colic, It is therefore unclear whether what has been documented is an association between psychologic risk factors and the actual occurrence of difficult crying or simply negative parental impressions of infant behavior. In a prospective study, Forsyth et aP9 attempted to determine risk factors identified in the perinatal period for later perception of excessive infant crying at 4 months of age. Factors such as concerns about how the infant would feed, a history of a previous child with "allergies," and a low level of maternal education all increased the risk of later maternal perception of colic and feeding problems. There are several arguments against an inadequate caretaker response playing a significant causative role in most cases of infant colic. First, there is a high degree of stereotypic behavior that parents go through in response to infant crying (talking, touching, picking up, cuddling, patting, and walking).23 Second, most studies have not found a birth order effect on crying, which suggests that parental inexperience is not a factor. Third, infants are unstable in their crying pattern and appear to undergo maturational transitions regardless of variations in parental care. 40, 61 A recent study by Barr and colleagues6 failed to demonstrate any advantage of increased carrying of infants with colic over standard office advice in reducing excessive crying in infants with colic. These findings do not rule out a contribution of methods of caring to reducing infant crying. The most direct evidence for an interactional basis for colic has come from therapeutic trials aimed at modifying parental behavior. Taubman65,66 has published two studies that have shown the benefit of rigorous supportive counseling by a concerned pediatrician in ameliorating colic in infants in his practice. Interventions suggested by the counseling included the instruction to never let the baby cry and an ordered set of guidelines for exploring potential reasons for crying and acting to remedy them (Table 2). In one study, crying was markedly reduced among infants 9f parents who received the counseling intervention compared with asymptomatic controls and with a small group of infants whose parents were instructed to let the baby cry and avoid Table 2. PARENTAL RESPONSE COUNSELING IN INFANT COLIC Try never to let your baby cry. In attempting to discover why your infant is crying, consider these possibilities: The baby is hungry and wants to be fed. The baby wants to suck, although he is not hungry. The baby wants to be held. The baby is bored and wants stimulation. The baby is tired and wants to sleep. If the crying continues for more than 5 minutes with one response, then try another. Decide on your own in what order to explore the above possibilities. Don't be concerned about overfeeding your baby. This will not happen. Don't be concerned about spoiling your baby. This also will not happen. From Taubman B: Clinical trial of the treatment of colic by modification of parent·infant interaction. Pediatrics 74:998, 1984, with permission.

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excessive stimulation. In the second study, counseling intervention was compared with the elimination of cow's milk protein from the infant's diet in two small groups of colicky infants with no symptoms of vomiting or diarrhea. Infants whose parents received the counseling had a greater and faster reduction in crying over the 9-day study period than infants whose diet was altered. Subsequent counseling of the parents of infants originally in the altered diet group after their infants resumed consumption of cow's milk protein resulted in a further significant decrease in crying. Criticisms of these studies include the small size of the study population, the patient selection bias inherent in a middle-class private office practice, the less stringent entry criteria for defining colic, and the short duration of follow-up. In spite of these criticisms, these studies clearly show that in the short term, supportive counseling and modification of parental behavior can reduce colicky behavior. The recommended responses, however, may be improving parental effectiveness to modify crying from other causes, and caution should be used before assigning a causal role for ineffective parental responses. Gastrointestinal Factors

For many parents and pediatricians, the colicky infant's shrill crying, passage of gas, abdominal distention, and increased tone suggest that colic is a pain syndrome arising from a disturbance in the gastrointestinal tract. The term colic is derived from the Greek word for colon, and as far back as 1923, White used the term "gastroenterospasm" to describe what he considered an autonomic disturbance affecting the smooth muscle of the intestine?5 Since then, numerous investigations have been undertaken attempting to delineate differences in the function of the gastrointestinal tract in colicky infants versus normal infants. Gastrointestinal Allergy

Evidence that colic is a consequence of cow's milk protein allergy has been most forcefully presented by a group of Swedish investigators. An early study from Malmo, Sweden, reported that removal of cow's milk protein from a breast-feeding mother's diet resulted in the disappearance of colic in 13 of 18 infants.36 This result was contradicted by a study of avoidance of cow's milk by 20 breast-feeding mothers in New Zealand whose infants did not experience a reduction in colicky behavior.16 Subsequently Lothe and colleagues46 reported that a blind trial of soy formula resulted in resolution of symptoms in 11 of 60 colicky infants, and that 32 infants whose colic did not resolve with soy protein responded to an open trial of a hydrolyzed casein formula. This study has been criticized on a number of methodologic grounds including the lack of an adequate double-blind design, the lack of an adequate instrument to ensure a rigorous definition of colic, and the lack of suitable

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controls especially at a time when colic is resolving in most infants regardless of medical intervention. Parents responsible for recording the primary outcome measure (amount of crying) were not blinded as to the intervention. This is of particular significance, because placebo effects may be strongly evident in the treatment of colic.55 Two further studies by the Malmo group have addressed earlier shortcomings with a blind study design. Elimination of cow's milk in the diet of breast-feeding mothers, followed by its reintroduction, reportedly implicated cow's milk protein as the cause of colic in 23 (35%) of 66 colicky infants.37 With a subsequent randomized double-blind crossover trial of capsules containing whey protein or placebo followed by the return of milk to the mother's diet, however, only 9 (13.6%) of the original 66 infants reacted with both the whey protein and the milk but not with the placebo. The lack of information about crying times and the suggestion that colic completely resolved when the mother was on a milk-free diet raise questions about this study. In their most recent study,44 the Swedish investigators have shown that 18 of 24 colicky infants previously responsive to the open substitution of a hydrolyzed casein formula for a cow's milk protein formula subsequently showed increased crying and disturbed sleep when cow's milk whey protein was introduced into their hypoallergenic formula versus a placebo. This phase of the study was a double-blind, randomized crossover trial. The major criticism of this study centers around the selection of infants for participation. In several respects, this appears to have been a separate subgroup of infants with colic consisting of (1) infants who already had failed standard counseling and trials of medication, (2) a majority of infants with vomiting, (3) infants with a severe degree of crying (mean 5.6 hours per day), and (4) some infants who had already exceeded the usual period of infant colic (12 weeks) at the time of the double-blind study. According to the group's own estimates, the 18 infants who reacted to whey protein represented 9% of all colicky infants born in Malmo over the 6-month period of the study and 1.5% of all infants born during this time. Taken in this context, it is not unreasonable to assume that the infants studied were a select group of severely affected infants who represented the small proportion of colicky infants who have cow's milk protein allergy. A recent study of 70 infants from ltaly2 also purported to show that approximately 70% experienced a remission of symptoms when cow's milk protein was eliminated from the diet and a recurrence of severe crying with two successive non-blinded challenges with the allergen. Here again, there appears to be a selection bias, because the 70 infants were selected on the basis of the most severe crying (more than 4 hours per day on at least 5 days per week) from a pool of 270 colicky infants referred to a pediatric gastroenterology clinic. In addition, a significant proportion of these infants had vomiting; a strong family history of atopy; and developed diarrhea, occult blood in the stools, and fecal eosinophils upon rechallenge with cow's milk protein. The presence of increased numbers of IgE-producing plasma cells in the jejunal mucosa of a small group of colicky infants after exposure to cow's milk protein

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is often cited as evidence of a causal relationship between allergy and colic.26 Symptoms of severe crying, vomiting, diarrhea, and poor weight gain in some of these infants who were older than the usual age of resolution of colic also implies a preselection bias. In an attempt to address some of these criticisms, Forsyth18 conducted a double-blind, multiple-crossover study of the effect of changing formulas in infants with colic. He fed 17 colicky infants hydrolyzed casein formula with or without cow's milk protein alternating the two for four periods of 4 days each. Significant decreases in crying and colic were seen with the initial formula change, but the effect of changing the formula diminished with time and only 2 of 17 infants (11.8%) had clinically meaningful changes in crying with each formula change. Marked day to day variability in crying with each subject, independent of the formula consumed, clouded the analysis. Other evidence which suggests that cow's milk protein allergy does not cause colic in the majority of infants includes a similar incidence of colic in formula-fed versus breast-fed infants, a lack of markers of intestinal damage including fecal hemoglobin or a-I-antitrypsin in infants with colic fed cow's milk protein containing formula, and a lack of elevated IgE levels or radioallergosorbent (RAST) tests for cow's milk proteinY· 67 Intestinal permeability to macromolecules, however, long considered a mechanism of acquired food intolerance in infants, does appear to be increased in some infants with colic. Serum levels of human a-lactalbumin, a component of human milk, are elevated in breast-fed infants with colic and in formula-fed infants with colic after ingestion of a breast-milk meal.47 Although this finding implies a difference in gut permeability, there is a significant overlap between controls and colicky infants, and the level of a-lactalbumin does not predict which infants with colic will have a clinical response to the removal of cow's milk protein from the diet. Malabsorption and Gas

Because of the observation that colicky infants appear to pass a large amount of gas and, at times, to be relieved by the passage of gas, a considerable amount of work has been done to determine whether more gas is produced by colonic bacterial fermentation of malabsorbed dietary carbohydrate in colicky infants. Abdominal cramping and excessive flatus is a common accompaniment of carbohydrate intolerance in older children and adults, so it seems reasonable to investigate this possibility in infants with colic. Most term infants cannot fully absorb the lactose load contained in formula feedings or human milk in the first 4 months of life despite having "adult" levels of mucosal lactase activity,53 and they produce large amounts of colonic gases as reflected in high breath hydrogen levels.3. 42 A causal role for gas production fits well with the equal prevalence of colic in breast-fed and formula-fed infants, with the afternoon and evening peak of colicky behavior after a day of ingesting potentially malabsorbed carbohydrate, and with the resolution of symp-

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toms at 4 months of age when decreases in breath hydrogen excretion in response to feeding are also occurring.3 In spite of these parallels, studies of carbohydrate malabsorption, gas production, and breath hydrogen excretion in infants with colic have not been conclusive. Studies of stool pH and reducing substances have not documented carbohydrate malabsorption in infants with colicY Two recent papers have shown an increased breath hydrogen excretion in response to lactose-containing feedings in infants with colic.52,54 In addition, Moore and colieagues54 showed that failure to produce hydrogen in response to lactose was significantly more frequent in noncolicky compared with colicky infants. In these studies, colic was defined and categorized as mild, moderate, or severe purely on the basis of maternal interviews without the aid of a prospective crying log. As a result, 55% and 68% of all infants recruited for the two studies were identified as colicky, a much higher prevalence than usual. In addition, there was a marked overlap in baseline and peak breath hydrogen excretion between the colicky and noncolicky groups. Studies that implicate lactose malabsorption as a cause of infant colic also do not fit with Illingsworth's observation that feeding eases the colicky behavior in a majority of infants. 34 Hyams et apo were unable to show a difference in breath hydrogen excretion in colicky infants defined by prospective crying diaries. In this study, the nonabsorbable carbohydrate lactulose was used as a substrate for breath hydrogen testing to insure that a standardized malabsorbed carbohydrate load was delivered to the colon. Neither colicky nor noncolicky infants showed any irritability at the time of maximum breath hydrogen excretion. An even stronger argument against the role of colonic gas production playing a role in infant colic are studies in which lactose intake has been reduced or lactase enzyme supplied to reduce the amount of undigested carbohydrate reaching the colon in breast-fed and lactose formula-fed infants. Three such studies have failed to show a reduction in crying and fussing behaviors in colicky infants when such treatment was instituted. 2, 51, 63 Interestingly, in one study in which yeast lactase was given with lactose-containing feedings, there was no reduction in breath hydrogen excretion after feeding. 51 This raises the possibility that breath hydrogen excretion may reflect fermentation of substrates other than lactose in the infant colon. Another common dietary carbohydrate that is not completely absorbed in the first several months of life is starch. Again, there are conflicting data in the literature concerning an association between colic and starch consumption. In one study, the prevalence of colic was found to be greater in a group of infants fed cereal in the first 3 months of life compared with infants receiving no solids. 27 Yet, in an earlier report, no difference was found in colicky behavior between infants who received cereal in the first month of life and those who did not. 15 Infants fed rice cereal in the first 3 months of life have no evidence of increased breath hydrogen excretion over those exclusively formula-fed, so it is unclear if ingestion of starch really has any role in increased colonic gas production in infants (Hyams JS, personal communication, 1993).

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Adults with irritable bowel syndrome characterized by cramping and bloating have no evidence of increased colonic gas production but do appear to have increased sensitivity to bowel distention caused by a balloon inflated in the colon.58 Because of the empirical observation that colicky infants are relieved by the passage of flatus, it is attractive to speculate that they too may have a heightened sensitivity to bowel distention by gas from colonic bacterial fermentation of carbohydrate, swallowed air, or other sources. Intestinal Motility

Disordered intestinal motility is suggested by the painful cry, abdominal distention, excessive flatus, straining to stool, and calming with changes in position noted in some infants with colic. Although these symptoms are all nonspecific and not clearly attributable to the gastrointestinal tract, they do invite comparison with symptoms in older children and adults with irritable bowel syndrome in whom abnormalities in intestinal transit, intracolonic pressure, and motility are thought to play a role. 64,76 Mouth to cecum transit time measured by a rise in breath hydrogen after a carbohydrate load has not differed from controls in two studies of infants with colic.3D,54 The effectiveness of the anticholinergic dicyclomine hydrochloride in well-designed clinical trials, however, suggests a role for disordered motility and intestinal smooth muscle spasm.33, 72 Caution must be exercised in attributing a cause-and-effect relationship here, because the therapeutic efficacy of this drug may be due to effects on the central nervous system rather than a direct action on gut smooth muscle. Studies of stooling patterns of normal and colicky infants when fed standard soy protein soy formulas and fiber-supplemented formulas suggests differences potentially related to altered intestinal motility and colonic metabolism of fiber. Infants with colic had significantly fewer stools per day than noncolicky infants when consuming a standard soy protein formula and developed more formed and even hard stools than their noncolicky counterparts when exposed to increased soy-polysaccharide fiber.69 Based on a postulated connection between infant colic and irritable bowel syndrome, Treem et aFD studied the efficacy of a fiber-enriched formula on infant colic. The addition of fiber to the diet has proven beneficial in adults with irritable bowel syndrome and children with recurrent abdominal pain!7,48 and resulted in reduced intraluminal pressures and normalization of colonic motility in some patients.39 In a double-blind, randomized crossover study, there was no significant difference in crying and fussing behavior recorded in detailed logs between colicky infants consuming a fiber-supplemented soy protein formula and those consuming a standard soy formula. Despite these negative findings, the parents of 18 of 27 colicky infants chose the fiber-supplemented formula as most beneficial in reducing colic. Factors other than reduced crying which may have influenced parental choice included an increased frequency of stooling, stools of firmer consistency, or a change in inten-

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sity of the cry while the infants were consuming a fiber-supplemented formula. Gut hormones, particularly motilin, have an important role in the regulation of intestinal motility. Motilin accelerates gastric emptying and reduces intestinal transit time by increasing the motor activity of the gUt.!4,59 Motilin is present in the intestinal mucosa by 25 weeks' gestation, and serum levels of motilin are high in the neonatal period and decrease with increasing age.!' 10 Lothe et al45 studied cord blood motilin levels (prior to any feeding) and levels on day 1 and at 6 and 12 weeks of age in 19 infants with colic and 59 without colic in a prospective fashion. At all time points, infants with colic had higher mean motilin levels than normal controls; however, there was a great deal of overlap. Differences were more significant in formula-fed infants than in those who were breast-fed. Although by no means conclusive, the finding of elevated levels of motilin in neonates long before symptoms of colic develop suggests the possibility of an underlying biologic predisposition to infant colic. Gastroesophageal Reflux

A small number of infants with gastroesophageal reflux will manifest extreme irritability due to the development of peptic esophagitis. 3! Some of these infants may not have pronounced spitting and vomiting; excessive crying may dominate the clinical picture. These infants may manifest aversive feeding behaviors, turning away from the bottle and screaming soon after beginning a feeding. Awakening from a sleep 1 to 2 hours after a feeding with excessive crying may also signify reflux esophagitis is playing a role. Consideration of this possibility is particularly important if these behaviors begin later than the usual colicky symptoms and become worse as the baby approaches 4 months of age when colic often begins to subside. MANAGEMENT OF INFANT COLIC

From the previous discussion, it is evident that there is no single therapy for colicky infants that will be universally effective. The following recommendations are based on the data summarized above and my own experience with infants referred for irritability and excessive crying. Assessment of the Infant with Colic

A complete history and physical examination are essential to assess the irritable infant. Attention to the timing of the onset of symptoms, the daily pattern of crying, and whether it is lessening with time are important parameters. Although symptoms persist into the fourth and fifth months in up to 30% of colicky infants,34 worsening of symptoms during

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those months should raise the possibility of gastroesophageal reflux and esophagitis or other causes of irritability. An infant behavior diary including crying, stooling, and feeding logs kept over a 4- to 7-day period is very helpful in the initial assessment and choice of therapy. The data summarized above appear to support a division of colicky infants into at least two groups. The first group has frequent short bouts of crying and fussing with the expected diurnal variation averaging approximately 3 hours per day on 3 to 4 days per week; the second group has more prolonged, severe bouts of crying occurring throughout the day averaging 4 to 6 hours on most days of the week. The former group is more likely to respond to detailed instructions designed to alter the parentinfant interaction. The latter group is more likely to contain some patients with cow's milk protein allergy, or other organic causes of irritability. The use of a crying diary is also an effective means of enlisting the parents' support in helping to solve the problem of their infant's crying and relieves some of their feelings of helplessness. \ The presence of symptoms of diarrhea, mucousy stools, constipation, or vomiting, although not inconsistent with colic, should raise the possibility of a primary gastrointestinal disturbance. Occult or gross blood in the stool not secondary to an anal fissure signifies the possibility of eosinophilic colitis due to cow's milk or soy protein intolerance. Careful measurement of weight, length, and head circumference should indi. cate normal growth or raise the possibility of an underlying systemic or central nervous system abnormality. A complete physical examination should help rule out other causes of chronic pain and irritability in infants including hydrocephalus, corneal abrasions, otitis media, fractured clavicle, or child abuse.

An Approach to Therapy of Colic

The algorithm in Figure 2 offers a clinical approach to the infant with colic. It is based on the careful assessment previously outlined and a crying diary to define the nature of the colicky behavior. Most infants will respond to the systematic instructions outlined by Taubman in his studies on colic (Table 2) which stress trials of a pattern of responses including feeding the infant, allowing the infant to suck on a pacifier, holding and carrying the infant, playing with the infant, or putting the infant down to sleep. These guidelines stress certain principles: (1) never let the baby cry, (2) carry the baby as much as possible, (3) overfeeding should not be a concern and no feeding schedule should be imposed, (4) parents are the best judges of their infant's needs, and (5) education of the parents about normal infant behavior is essential. Most parents will be reassured by explanations of the normal developmental pattern of infant crying including information about the usual peak at 6 weeks of age and the absence of any underlying disease. Changing the environment to capitalize on the responsiveness of infants to constant rhythmic or repetitive stimulation may be helpful including

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~ ""~"'E""""""."~ Heme + stool (no anal fissure)

Other causes: fracture hip dislocation otitis media corneal abrasion trauma (abuse)

"

Crying. stooling. feeding diary

~

Cries with: high frequency brief duration consolable

+?gass y simethacone

Parental response counseling

Cries with: high frequency long duration inconsolable

~ ?,a,stools

ChrOniC vomiting poor feeding failure to thrive

?GER

fiber

Trial hydrolyzed casein formula

~

Parental response counseling

Trial antacids

?pH probe. endoscopy

Figure 2. Algorithm for an approach to infant colic. GER = gastroesophageal reflux.

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background music or noise, patting or bouncing the infant, rides in the car or stroller, or commercial rocking devices. The effectiveness of pharmacologic intervention in colic may have more to do with sedation or a strong placebo effect than with any specific effect on gastrointestinal smooth muscle. Although some studies support the use of dicyclomine hydrochloride,33, 72 the safety of this agent in children younger than 6 months of age has recently been questioned.4,49 Other agents include the anticholinergic, antispasmodic preparation hyoscyamine sulfate (Levsin); the combined preparation of hyoscyamine sulfate, atropine sulfate, scopolamine hydrobromide, and phenobarbital (Donnato); and the sedative preparations phenobarbital, diphenhydramine hydrochloride (Benadryl) and chloral hydrate. Donnatol elixir also contains 23% alcohol; Levsin elixir 20% alcohol, and Levsin drops 5% alcohol. Combinations of these medications have been associated with apparent life-threatening events in infants presumed to have colic.25 Because of the lack of clear evidence of efficacy and potential serious sideeffects, the use of anticholinergic drugs to treat infant colic is discouraged. Antiflatulents such as simethicone (Mylicon) may be useful in infants who swallow excessive amounts of air and pass flatus frequently.60 Herbal teas containing chamomile, fennel, and balm-mint have weak antispasmodic activity and may be helpful in some infants with colic,73 but little is known about the proper dose of these home remedies, and they may have unknown dangerous pharmacologic effects if given in excess. Occasionally, because of extreme parental fatigue and anxiety, the judicious use of a sedative to induce longer periods of sleep at night in a colicky infant can be entertained. If there seems to be the potential for child abuse, a brief hospitalization to allow a clearer picture of the situation and decompression of the hostility is warranted. If an infant has prolonged severe bouts of crying; a strong family history of allergy; asthma; eczema; or other symptoms such as mucousy stools, diarrhea, occult blood in the stool, or vomiting, a trial of a hydrolyzed casein formula can be considered. Approximately 10% to 15% of infants with colic may benefit from such a change. Parents should not be left with the idea that their infant will have a permanent food allergy or intolerance, because the beneficial response may be the result of a placebo effect, the coincidental resolution of symptoms at the time of the formula change, or some other mechanism. Even if the response is related to protein intolerance, the adverse reactions may be short lived.8 In our' studies on colic, we documented a mean of 3.5 formula changes per infant including 7 of 27 infants who had been fed a hydrolyzed casein formula without success prior to enrollment in the study 7° Forsyth et aFo have shown the negative effect of the practice of formula manipulations on a mother's perception of her infant. With each change and no improvement in symptoms, the parents become more convinced that their infant is seriously ill with a resulting belief in their child's vulnerability when older. They may have a tendency to blame a host of unrelated symptoms later in life such as diaper rashes, nonspecific skin eruptions, chronic nonspecific diarrhea, constipation, poor appetite, and

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behavioral problems on food allergies. This belief can lead to hypocaloric elimination diets and result in weight loss and malnutrition.43 • 68 Supplementation of the formula or expressed breast milk with fiber can be tried in infants who have infrequent stools, hard stools, explosive stools, and appear to strain when stooling. We have used methylcellulose (Citrucel) or extract of barley malt (Maltsupex), one half teaspoon, 3 to 4 times per day. A trial of antacids is warranted in the irritable crying infant who spits and vomits excessively, appears to be developing an aversion to feeding, and whose colicky symptoms are worsening instead of improving in the third and fourth months of life. Such infants may need more extensive investigation for gastroesophageal reflux, including prolonged intraesophageal pH probe testing and upper gastrointestinal endoscopy to document the presence of peptic esophagitis.

CONCLUSION

Colic is a syndrome of excessive crying in infancy with multiple causes. A careful assessment of the history; a complete physical examination; and a careful behavior log including crying, stooling, vomiting, feeding, and sleeping may suggest a likely cause. Infants with less severe, less prolonged bouts of crying unaccompanied by other signs and symptoms of gastrointestinal pathology will usually benefit from modifications in the parental response to infant crying. In contrast, infants with more severe prolonged crying who are difficult to console are more likely to have a specific dysfunction of their gastrointestinal tract including cow's milk protein allergy, gastroesophageal reflux, or gastrointestinal dysmotility. Trials of hydrolyzed casein formulas, antacids, or fiber supplementation may benefit some of these infants. An approach to any infant with colicky behavior includes taking the time to educate parents about the normal variability in infant crying behavior.

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Address reprint requests to William R. Treem, MD Division of Pediatric Gastroenterology and Nutrition Hartford Hospital 80 Seymour Street P.O. Box 5037 Hartford, CT 06102