Infantile colic: Clinical features and diagnosis

INTRODUCTION — Persistent or excessive crying (colic) is one of the most distressing problems of infancy. It is distressing for the infant, the parents, and the clinician [1]. The parents may view the crying as evidence of illness or as an indictment of their caregiving ability [2]. Colic is a benign self-limited condition that resolves with time. However, the family's beliefs concerning the cause of crying and their interactions with the health care system related to the crying may affect the way in which they view the child and the health care system long after the crying has resolved.

The clinical features, etiology, and diagnosis of prolonged or excessive crying in young infants are reviewed here. The management is discussed separately. (See "Infantile colic: Management and outcome".)

DEFINITIONS

Normal patterns of crying — All infants, whether or not they have colic, cry more during the first three months of life than at any other time. The average duration of crying during the first three months of life ranges from 68 to 133 minutes per day.

In a meta-analysis of 28 studies of diaries documenting the duration of fussing and crying in 8690 infants, mean duration of crying was 117 to 133 minutes per day during the first six weeks of life and decreased to 68 minutes per day by 10 to 12 weeks, but varied widely from infant to infant [3].

Few people agree about how much crying is considered excessive. In the meta-analysis of 28 studies described above, the approximate 95^th percentile duration of daily crying ranged from [3]:

●225 to 250 minutes during the first six weeks of life

●210 minutes at 8 to 9 weeks

●145 minutes at 10 to 12 weeks

Definitions based upon duration may not be helpful clinically because "normal" and "abnormal" crying depend upon the context and quality of crying [4]. In addition, adhering to a strict definition is not helpful to the families whose child does not meet the threshold for abnormal crying.

Colic — There is no standard definition for the term "colic." For clinical purposes, we define it broadly as crying for no apparent reason that lasts for ≥3 hours per day and occurs on ≥3 days per week in an otherwise healthy infant <3 months of age. The broad definition considers the variety of parental experiences, thresholds of concern, and perspectives that ultimately shape the relationship between the parent(s) and child. (See "Infantile colic: Management and outcome", section on 'Outcomes'.)

Other terms that may be used interchangeably with colic include "cry-fuss behavior," "excessive crying," "unsettled infant behavior," and "period of PURPLE crying" [5,6].

Stricter definitions for colic, often used in clinical research, may include criteria for minimum duration (eg, one week, three weeks, etc) or associated clinical features. As examples:

●The Wessel criteria specify that episodes of crying must last for ≥3 hours per day, occur on ≥3 days per week, and persist for ≥3 weeks ("rule of three") [7]. Wessel criteria also require that the infant is "otherwise healthy and well fed." The criterion of persistence for three weeks has been dropped by most authors because few parents or clinicians are able to wait three weeks before evaluation or intervention [8].

●The Rome IV criteria, which classify infant colic as a functional gastrointestinal disorder in infants from birth to five months of age, require all of the following: 1) age <5 months when the symptoms start and stop; 2) recurrent and prolonged periods of crying, fussing, or irritability that start and stop without obvious cause and cannot be prevented or resolved by caregivers; 3) no evidence of poor weight gain, fever, or illness; 4) caregiver reports crying/fussing for ≥3 hours per day on ≥3 days/week in a telephone or face-to-face interview; and 5) total daily crying is confirmed to be ≥3 hours when measured by at least one prospectively kept 24-hour diary [9].

●Another definition requires that episodes of crying meet Wessel criteria (including persistence for ≥3 weeks) and at least three of the following: paroxysmal; qualitatively different from normal crying (eg, louder, higher and more variable in pitch, more dysphonic); associated with features of hypertonia; inconsolability [10]. (See 'Clinical features' below.)

EPIDEMIOLOGY — Estimates of the prevalence of colic in infants range from 8 to 40 percent [7,11-16]. The wide range is due to differences in diagnostic criteria, study design, populations, and family perceptions of "excessive and prolonged" crying [11,17]. In a systematic review and meta-analysis of 28 parental diary studies, including 8690 infants, colic (defined as crying/fussing for ≥3 hours per day on ≥3 days in any one week) was documented in 17 to 25 percent of infants age <6 weeks, 11 percent of those age 8 to 9 weeks, and 0.6 percent of those age 10 to 12 weeks [3].

The incidence of colic does not appear to differ among males and females, breast- and formula-fed infants, full-term and preterm infants, or first-born and subsequent-born children [18-20]. It appears to be more common in industrialized countries, White infants, and in areas that are further away from the equator [19,21].

Associations between colic and dissatisfaction in the marital relationship, parental perception of stress, lack of parental self-confidence during the pregnancy, dissatisfaction with the delivery, and levels of family stress have been reported [7,22]. The causal relationship between colic and family stress is difficult to determine because both factors affect parental perception of, and response to, crying.

A complex interaction exists between colic and family dynamics, which also are affected by pre- and postnatal factors. In a case-control study, families with colicky infants had more problems in family structure, functioning, and affective state both during the colicky period and one year later than control families [23]. However, a causal relationship between family dynamics is difficult to determine because both factors affect parental perception of, and response to, crying.

PROPOSED ETIOLOGIES — The etiology of colic is unknown. It probably represents a final common pathway for numerous contributing factors [19]. Proposed etiologies must account for the age of onset, the individual variability, the tendency for crying to occur more commonly in the evening, and the spontaneous resolution [24]. Gastrointestinal, biologic, and psychosocial etiologies have been proposed.

Gastrointestinal — Colic is commonly thought to be a gastrointestinal disturbance; the word "colic" stems from the Greek "kolikos," the adjective of "kolon" [25]. Gastrointestinal factors that are proposed to contribute to colic include:

●Faulty feeding techniques – Underfeeding, overfeeding, infrequent burping, and swallowing air all have been described as possible etiologies of colic.

●Cow's milk protein intolerance – A subgroup of infants with colic may have symptoms that are caused at least in part by cow's milk protein intolerance. Systematic reviews of small randomized trials with methodologic limitations (eg, inadequate blinding) suggest hydrolysate formulas or a hypoallergenic diet for breastfeeding mothers may reduce distress in infants with colic [26-29]. (See "Clinical manifestations of food allergy: An overview" and "Food protein-induced allergic proctocolitis of infancy".)

●Lactose intolerance – It is unclear whether lactose intolerance plays a role in infantile colic. Randomized trials of lactase treatment for infantile colic have conflicting results [30-33].

●Gastrointestinal immaturity – It is uncertain whether colic is related to gastrointestinal immaturity and incomplete absorption of carbohydrates in the small intestine. This hypothesis proposes fermentation of the unabsorbed carbohydrate by colonic bacteria produces excessive gas. However, studies measuring breath hydrogen excretion in infants with and without colic have inconsistent results [34-36].

●Intestinal hypermotility – Evidence supporting an association between intestinal hypermotility due to autonomic imbalance is contradictory [37-39]. In observational studies, motilin concentrations are increased in infants with colic, but vasoactive intestinal peptide and gastrin concentrations are not [40-42]. Motilin stimulates gastric emptying and intestinal peristalsis, reducing transit time in the small intestine.

●Alterations in fecal microflora – Alterations in fecal microflora may play a role in infantile colic. Several observational studies have demonstrated differences in intestinal microflora between infants with colic and control infants, particularly Klebsiella species, anaerobic gram-negative bacteria, coliform bacteria (including Escherichia coli), and Lactobacillus species (L. brevis and L. lactis) [43-47]. Observational studies have also noted an association between colic and gut inflammation (as indicated by increased fecal calprotectin) and altered gut microbiota [43,47]. Others have noted decreased fecal calprotectin levels as colicky symptoms improved over time [48] or in response to Lactobacillus reuteri therapy [49].

The role of fecal microflora is supported by randomized trials in infants with colic in which treatment with L. reuteri reduced crying time and was associated with changes in gut microbiota (eg, increased fecal Lactobacilli, decreased fecal E. coli) [50-54]. (See "Infantile colic: Management and outcome", section on 'Probiotics'.)

Other proposed etiologies

●Biologic — Biologic factors that are proposed to contribute to colic include:

•Tobacco smoke and nicotine exposure – Maternal smoking during pregnancy or in the postpartum period has been associated with an increased risk of infantile colic in several cohort studies [55-57]. In the largest study, the prevalence of colic (using Wessel criteria) was 9.4 percent among infants of smokers versus 7.3 percent among infants of nonsmokers (adjusted odds ratio 1.3, 95% CI 1.2-1.4) [57]. Prenatal exposure to nicotine replacement therapy also was associated with an increased risk of infantile colic.

•Immature motor regulation – Many of the mechanisms that regulate motor activity are immature in infants. The immaturity of these mechanisms may result in increased vulnerability to feeding intolerance [58,59]. Thus, colic may be a common clinical manifestation in the subpopulation of infants who have maturational dysfunction in one or more of the aspects of motility regulation [58].

•Increased serotonin – The hypothesis that infantile colic is related to increased serotonin is supported by an observational study, in which random urinary concentrations of 5-hydroxy-3-indole acetic acid (a serotonin metabolite) were greater in infants with colic than in control infants [60].

•Early form of migraine – Infantile colic may be an early manifestation of childhood migraine. In a prospective cohort, migraine without aura was more common in adolescents with infantile colic than in those without infantile colic (multivariate risk ratio 2.7, 95% CI 1.5-4.7); colic was not associated with an increased risk of migraine with aura [61]. These findings confirm those of retrospective studies [62-66], although it is not clear whether infantile colic is an early manifestation of childhood migraine or a marker of migraine genetics [67].

●Psychosocial — Colic is a psychosocial phenomenon. It is the caretaker's perception of what is excessive and prolonged and the caretaker's response to crying episodes that define whether the crying is seen as a problem. Psychosocial theories of colic focus on temperament, overstimulation, and parental variables.

•Temperament – Healthy behavior and development are believed to be predicted on the "goodness of fit" between the child's environment and their innate characteristics [68-71]. Evidence supporting this theory is limited. The most direct evidence comes from therapeutic trials aimed at modifying parental behavior [72-74]. In one controlled clinical trial, when parents of colicky infants were counseled regarding effective responses to crying, the crying decreased from 2.6 to 0.8 hours per day [73]. In another, parental counseling was more effective than dietary changes (crying decreased from 3.2 to 1.1 hours per day in the counseling group and from 3.2 to 2 hours per day in the dietary change group) [74].

•Hypersensitivity – Another proposed hypothesis is that crying at the end of the day represents discharge after a long day of exposure to environmental stimuli and is a means of maintaining homeostasis [75].

•Parental variables – Various parental psychosocial factors, including family stress, maternal anxiety, and transmission of tension from the mother to the infant, have been proposed to be associated with colic [7,76,77]. Associations between maternal anxiety disorder, maternal history of emotional tension or depression early in the pregnancy, and paternal depressive symptoms during pregnancy are supported by prospective studies [77-80].

CLINICAL FEATURES — There are differences of opinion regarding whether what is called "colic" is the upper end of the normal range of crying or a discrete disorder with unique clinical features [81,82].

We use the following clinical features to distinguish colic from normal crying [10]:

●Paroxysms – The cry/fuss behavior of colic generally is paroxysmal [10,83]. Colicky episodes typically have a clear beginning and end. The onset seems to be unrelated to what the infant was doing just before the "attack." The infant may have been happy, fussy, feeding, or even sleeping. These spells of crying occur suddenly and often cluster during the evening hours.

●Qualitative differences – The cry of colic is qualitatively different from normal crying. It is louder, higher and more variable in pitch, and more turbulent and dysphonic than noncolicky crying [83-85]. Colicky crying may sound as if the infant is in pain or is screaming rather than crying [83]. The mothers of colicky infants describe their infant's cries as more urgent, piercing, grating, arousing, aversive, distressing, discomforting, and irritating than do the mothers of noncolicky infants [2,85,86].

●Hypertonia – Episodes of colic may be associated with physical characteristics associated with hypertonia [83]. These include facial flushing, circumoral pallor, tense or distended abdomen, drawing up of the legs, clenching of the fingers, stiffening and tightening of the arms, or arching of the back.

●Difficulty consoling – Infants with colic can be difficult to console, no matter what the parents do. There may be periods when the crying diminishes, but the infant remains fussy [83]. Relief may be noted after the passage of flatus or feces.

Most of the characteristics of crying in infants with colic also occur in normal infants but with less frequency and shorter duration. The early peak and evening clustering, as an example, have been described in widely disparate societies and in normal preterm infants at two months corrected age.

EVALUATION FOR IDENTIFIABLE CAUSES OF CRYING — The evaluation typically includes a history and examination for identifiable causes of crying/fussiness. Laboratory or imaging studies generally are not necessary. The thoroughness of the history and examination is reassuring to parents and may strengthen the clinician-family relationship [87].

Goals — Colic typically is suspected based on the history but confirmed in retrospect after it has run its characteristic course. In the meantime, colic must be differentiated from other conditions that can cause prolonged crying or irritability in infants and may require specific treatment (table 1). This distinction usually can be made with history and physical examination. (See 'History' below and 'Examination' below.)

Characteristic features of colic include paroxysms of crying that start and stop without obvious cause and normal growth, development, and examination. Thus, it is particularly important to consider other conditions in infants with poor weight gain, abnormal development, or abnormalities on physical examination. Virtually any illness/condition can present with crying [19,20,88].

When to schedule — It can be helpful to schedule the evaluation during the time of day that the infant is fussy (if possible, given that colic often occurs in the evening) [87]. This allows the clinician to observe the crying behavior, the parents' soothing techniques, and the infant's ability to be soothed.

History — The history may provide clues to the etiology of infant's fussiness. It must assess identifiable causes of crying (table 1), as well as psychosocial factors that may be contributing to it. (See 'Other proposed etiologies' above.)

Important aspects of the history in a child with colic include [5,26]:

●The infant's feeding, stooling, urination, and sleeping patterns, including vomiting (helpful in evaluating the possibility of gastrointestinal, cardiovascular, and metabolic conditions) (table 1)

•Bloody stool may indicate cow's milk or soy-induced colitis, anal fissure, intussusception (see "Milk allergy: Clinical features and diagnosis", section on 'Clinical features' and "Food protein-induced allergic proctocolitis of infancy", section on 'Clinical presentation' and "Lower gastrointestinal bleeding in children: Causes and diagnostic approach", section on 'Infants and toddlers')

•Bilious or projectile vomiting may indicate gastrointestinal obstruction (eg, pyloric stenosis, volvulus) (see "Infantile hypertrophic pyloric stenosis", section on 'Clinical manifestations' and "Intestinal malrotation in children", section on 'Clinical presentation')

●Prenatal and perinatal history, including risk factors for sepsis (eg, premature rupture of membranes, maternal fever, maternal colonization with group B Streptococcus) (see "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm neonates", section on 'Maternal risk factors')

●Psychosocial history, including assessment of parent-infant interactions, and the perceptions and interactions of extended family members (eg, grandparents), which may play a role in parenting style and techniques for soothing (see 'Other proposed etiologies' above)

●Specific questions about the crying or fussiness, including [19]:

•When does the crying occur? – Colicky crying typically occurs during the evening. Crying that occurs directly after feeding may be associated with air swallowing or gastroesophageal reflux and may respond to changes in feeding technique (eg, upright positioning, smaller volumes, etc). (See 'Gastrointestinal' above and "Infantile colic: Management and outcome", section on 'Feeding technique'.)

•How long does the crying last? – Duration of crying may help to differentiate normal infant crying from colic. (See 'Definitions' above.)

•What do you do when the baby cries? – The response to this question may provide information about soothing techniques that are helpful, not helpful, may exacerbate crying, or may be harmful (eg, shaking). (See "Infantile colic: Management and outcome", section on 'Soothing techniques'.)

•What does the cry sound like to you? – Parents usually can differentiate different types of crying (eg, hunger, pain). The response to this question may indicate how the parents feel about the crying (eg, empathetic, distressed, angry, helpless). Colicky crying is more often described as "screaming," "piercing," "distressing," or "irritating" than noncolicky crying [2,85,86]. (See 'Clinical features' above.)

•How and what do you feed the baby? – Underfeeding, overfeeding, and inappropriate feeding are proposed etiologies of colic and may respond to changes in feeding techniques. (See 'Gastrointestinal' above and "Infantile colic: Management and outcome", section on 'Feeding technique'.)

•How do you feel when your baby cries? – Responses may range from feeling inadequate as a parent, to feeling responsible for the crying, to fear of harming the infant if the crying continues. (See 'Potential sequelae' below.)

•How has the colic affected your family? What is your theory of why the baby cries? – Understanding what the family fears about the crying is helpful in formulating a management plan, particularly with respect to parental support. (See "Infantile colic: Management and outcome", section on 'Caregiver support and education'.)

Examination — Important aspects of the examination of the infant with colic include [5]:

●Observation of the infant and parent interaction during a bout of crying (provides information about the infant's ability to be soothed and the parents' soothing techniques; allows the clinician to see what the parents are going through) [87,89]

●Assessment of temperament (eg, sensitivity, irritability, soothability, intensity, adaptability [89,90]) and responsiveness to stimuli (ie, does the infant cry in response to touch or movement?)

●Plotting of growth parameters to look for deviations from the normal patterns (which generally preclude a diagnosis of colic); poor weight gain may indicate inadequate nutritional intake, absorption, or utilization; increased losses; or increased requirements (table 2) (see "Normal growth patterns in infants and prepubertal children", section on 'Normal patterns' and "Poor weight gain in children younger than two years in resource-abundant settings: Etiology and evaluation", section on 'Growth trajectory and proportionality')

●Assessment for identifiable causes of prolonged crying in infants (table 1), including:

•Assessment of hydration and subcutaneous fat (to evaluate adequacy of feeding)

•Assessment for tongue-tie (picture 1), which may be associated with breastfeeding problems (see "Ankyloglossia (tongue-tie) in infants and children", section on 'Clinical features')

•Eye examination for foreign body, corneal abrasion, infantile glaucoma (eg, corneal enlargement (picture 2) or clouding), retinal hemorrhage (though fundoscopic examination may be difficult) (see "Corneal abrasions and corneal foreign bodies: Clinical manifestations and diagnosis", section on 'Eye examination' and "Primary infantile glaucoma", section on 'Clinical features' and "Child abuse: Eye findings in children with abusive head trauma (AHT)")

•Ear examination for otitis media (picture 3) (see "Acute otitis media in children: Clinical manifestations and diagnosis", section on 'Diagnosis')

•Oropharyngeal examination for thrush (picture 4) (see "Candida infections in children", section on 'Oropharyngeal candidiasis')

•Cardiovascular evaluation for signs of heart failure or supraventricular tachycardia (eg, tachycardia, tachypnea, poor perfusion, S3 gallop, tachypnea) (see "Heart failure in children: Etiology, clinical manifestations, and diagnosis", section on 'Clinical manifestations' and "Clinical features and diagnosis of supraventricular tachycardia (SVT) in children", section on 'Clinical features' and "Suspected heart disease in infants and children: Criteria for referral")

•Evaluation of the abdomen for tenseness, tenderness, absence of bowel sounds (possible clues to an acute abdominal process such as intussusception, volvulus) (see "Intussusception in children", section on 'Clinical manifestations' and "Intestinal malrotation in children", section on 'Clinical presentation' and "Causes of acute abdominal pain in children and adolescents")

•Evaluation of perineum for diaper rash (picture 5), testicular torsion, hair tourniquet, meatal ulcer, anal fissure, inguinal hernia (see "Diaper dermatitis" and "Inguinal hernia in children", section on 'Clinical features and diagnosis' and "Neonatal testicular torsion", section on 'Clinical presentation')

•Evaluation of the skin and musculoskeletal system for signs of trauma (including abusive trauma) or infection; examples of relevant findings include hair tourniquet or other narrow constricting band (picture 6), bruising or petechiae, decreased range of motion, and pain with passive movement (see "Hair tourniquet and other narrow constricting bands: Clinical manifestations, diagnosis, and treatment", section on 'Clinical manifestations' and "Physical child abuse: Diagnostic evaluation and management", section on 'Evaluation' and "Bacterial arthritis: Clinical features and diagnosis in infants and children", section on 'Clinical features' and "Hematogenous osteomyelitis in children: Clinical features and complications", section on 'Clinical features')

•Evaluation of the nervous system for abnormalities (eg, bulging anterior fontanelle, head asymmetry, increased or decreased muscle tone) that may indicate meningitis or other neurologic condition (see "Bacterial meningitis in the neonate: Clinical features and diagnosis", section on 'Clinical features' and "Elevated intracranial pressure (ICP) in children: Clinical manifestations and diagnosis" and "Approach to the infant with hypotonia and weakness")

DIAGNOSIS — A presumptive diagnosis of infantile colic can be made in an otherwise healthy infant <3 months of age who cries for no apparent reason for ≥3 hours per day on ≥3 days per week. Other causes of crying generally are excluded by the history and physical examination. The diagnosis of colic is confirmed in retrospect, after it has run its characteristic course. (See 'Evaluation for identifiable causes of crying' above.)

POTENTIAL SEQUELAE — Colicky crying is not harmful to the infant in the short- or long-term. However, parents of crying infants may resort to hurting the infant to try to stop the crying [91,92]. In addition, observational studies suggest that infantile colic is associated with increased risk of postpartum depression [93-96] and early cessation of breastfeeding [97]. (See "Postpartum unipolar major depression: Epidemiology, clinical features, assessment, and diagnosis", section on 'Risk factors'.)

In a community-based sample, parents of 3259 infants anonymously responded to a questionnaire about their actions to stop their infant from crying [91]. Among parents of one- and three-month-old infants, 2.2 and 3.7 percent, respectively, reported having smothered, slapped, or shaken their baby at least once because of the crying. In multivariate analysis, these behaviors were more likely if the parents were worried about the crying or judged it to be excessive, and were unrelated to the amount of crying (defined by ≥3 hours per day on ≥3 days per week in the week before the survey).

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Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword[s] of interest.)

●Basics topic (see "Patient education: Colic (The Basics)")

●Beyond the Basics topic (see "Patient education: Colic (excessive crying) in infants (Beyond the Basics)")

SUMMARY

●Definitions

•Normal crying – The average duration of crying during the first three months of life ranges from 68 to 133 minutes per day. The duration of crying is greatest during the first six weeks of life and declines after eight to nine weeks. (See 'Normal patterns of crying' above.)

•Colic – There is no standard definition of the term "colic." For clinical purposes, we define it broadly as crying for no apparent reason that lasts for ≥3 hours per day and occurs on ≥3 days per week in an otherwise healthy infant <3 months of age. (See 'Colic' above.)

●Proposed etiologies – The etiology of colic is unknown. It probably represents a final common pathway for numerous contributing factors. Gastrointestinal, biologic, and psychosocial etiologies have been proposed. (See 'Proposed etiologies' above.)

●Clinical features – Infants with colic have normal growth, development, and examination. Clinical features that are thought to distinguish colic from "normal" crying include paroxysmal episodes; qualitative differences (eg, louder, higher pitched, more dysphonic); hypertonia (eg, facial flushing, clenched fists, etc); and difficulty consoling. (See 'Clinical features' above.)

●Evaluation – The evaluation of a child with suspected colic typically includes a history and examination for identifiable causes of crying/fussiness (table 1). Laboratory or imaging studies generally are not necessary. (See 'Evaluation for identifiable causes of crying' above.)

●Diagnosis – A presumptive diagnosis of colic can be made in an otherwise healthy infant <3 months of age who cries for no apparent reason for ≥3 hours per day on ≥3 days per week. Other causes of crying generally are excluded by the history and physical examination (table 1). (See 'Diagnosis' above and 'History' above and 'Examination' above.)

●Potential sequelae – Potential sequelae of colic include physical abuse, increased risk of postpartum depression, and early cessation of breastfeeding. (See 'Potential sequelae' above.)

●Management – The management of colic is discussed separately. (See "Infantile colic: Management and outcome".)